UNIVERSITY OF CINCINNATI
DATE: 2/21/02
I, Donna Russell Scarborough , hereby submit this as part of the requirements for the degree of:
Doctor of Philosophy in: Communication Sciences and Disorders
It is entitled: Consequences of Interupting Normal Neurophysiologic Development: Impact on Pre-Swallowing Skills
Approved by: Suzanne Boyce, Ph. D. Jean Neils-Strinjas, Ph. D. Sonya Oppenheimer, M.D. Anna August, M.D. Gail McCain, Ph. D.
CONSEQUENCES OF INTERRUPTING NORMAL NEUROPHYSIOLOGIC DEVELOPMENT: IMPACT ON PRE-SWALLOWING SKILLS
A dissertation submitted to the Division of Research and Advanced Studies of the University of Cincinnati in partial fulfillment of the requirements for the degree of
DOCTOR OF PHILOSOPHY
in the Department of Communication Sciences and Disorders of the College of Allied Health Sciences
2001
By
Donna Russell Scarborough
M.S., University of Louisville, Louisville, KY B.S., University of Illinois, Urbana-Champaign, IL
Committee Chairman: Suzanne Boyce, Ph. D.
Committee Members: Jean Neils-Strinjas, Ph. D. Sonya Oppenheimer, M.D. Anna August, M.D. Gail McCain, Ph. D.
ABSTRACT
This project tests the hypothesis that full-term infants and toddlers who are deprived of oral feedings during the first 3-months (13 weeks) of life show altered physiologic responses to touch. Such children often suffer from Failure-to-Thrive of the “Mixed” type (MFTT). This hypothesis developed from a clinical conundrum—the frequent observation that although such infants may have a variety of medical diagnoses, they share a common profile of difficulty tolerating touch. Because normal oral feeding requires tolerance for the touch of a spoon or food in the mouth, along with the touch of a parent’s arms, etc. touch intolerance can directly result in interference with oral feeding skills. The MFTT group of children also shares a clinical history of oral deprivation as a result of medically necessary tube feedings. Typically, this fact has not been considered significant within the medical profession. However, several converging lines of evidence in the literature of psychology, neurobiology and neonatology suggest that early oral deprivation can result in aberrant neurophysiological development. This study compares the responses to touch (firm pressure) of a group of MFTT children and a matched control group of children with a normal medical history. Children were examined for response to touch along a hierarchy of body points (e.g. legs, trunk, lips, etc.) and responses were assessed through state behavior changes and/or abnormal gag reflex responses. A chi-square analysis revealed that the group of MFTT children showed response patterns to firm pressure that significantly differed from the normal control group. These response patterns confirmed the original clinical observation and suggest that a history of early oral deprivation can result in aberrant response to touch. These findings have significant implications for the current understanding of physiologic development, the identification of specific behavioral manifestations within the feeding/swallowing population, and the prevention of feeding difficulties in this vulnerable population. Further, the results of this study challenge us to critically review current intervention models.
ACKNOWLEDGEMENTS
I feel so fortunate that I was able to pursue a project that reflects my life’s passion. I would like to thank the families of all of the children whom I have had the honor of working with over the years. It was observing your triumphs and tribulations that inspired this project.
Thank you.
I feel privileged that I was able work with such a supportive and knowledgeable committee. I want to thank Dr. Suzanne Boyce who served as my dissertation committee advisor for her invaluable input, continuous support and expert guidance throughout this process. Furthermore, thank you for the countless times that you gently pushed me back from going over that edge and when necessary you pushed me over one. I will be forever grateful for all of the lessons that I learned under your mentoring. I want to thank my committee member Dr. Jean Neils-Strinjas who served as my academic advisor for her constant support and encouragement throughout this process. I also thank Dr. Gail McCain, who took me under her wing and provided invaluable encouragement and direction. I am grateful to Dr.
Sonya Oppenheimer and Dr. Anna August for their willingness to provide their time and expertise for my benefit.
I would like to extend a special thank you to my department head, Dr. Nancy
Creaghead for her support throughout this process. To my outside readers, Dr. Bruce Giffin,
Dr. Susan Stanton and Susan Meiser I want to extend my deepest appreciation for taking the time to offer constructive feedback and reading more than you ever wanted to on this topic.
To Dr. Rick Divan, I would like to offer my sincere gratitude for helping me through the technical aspects of this project. I would also like to thank the entire Communication
Sciences and Disorders faculty and support staff for their encouragement over the years.
I would like to thank all of the individuals who helped make this research project possible. Thank you to all of the families that participated. I cannot tell you how much I appreciated your willingness to accept me into your home as part of the study. Thank you to
Erin Zink, my friend and cohort who participated as my fellow investigator. Thank you to all of the students (all of whom are now practicing clinicians) who participated as observers.
Thank you to Debbie Highhouse of the High Risk Clinic, Dorthyann Feldis of CCDD, Pam
Morgan and Joanne Mitchelle of the GI Clinic, Dr. Lichtenstein and Dr. Boling local pediatricians, and Mary Carol Heidrich of First Steps in Northern Kentucky for your tireless effort to find subjects for this project.
Finally I want to acknowledge the dedication and support of my friends and family.
To my wonderful husband, Jim, without your love and support I would not have been able to perservere to the end. To my beautiful daughter Morgan, I am so grateful that you came into my life during this entire process and I hope you too will find a passion in life. To my family and friends thank you for supporting me in the good times and the not so good times. I love you all.
TABLE OF CONTENTS
CHAPTER 1
1.1 RATIONALE...... 1
1.1.1 Themes of the Clinical Profile ...... 1
1.1.2 Unique Characteristics of the Population With This Profile ...... 3
1.1.3 Potential Explanation for Abnormal Responses in this
Heterogeneous Population ...... 3
1.1.4 Introduction of the “Behavioral Organization” Model as it Relates to the Clinical Profile ...... 4
1.1.5 Logic ...... 5
1.1.6 Clinical Example...... 7
1.2 HYPOTHESIS ...... 8
1.3 EXPERIMENTAL DESIGN...... 8
CHAPTER 2: LITERATURE REVIEW
SECTION 1: CLASSICAL THEORY OF DEVELOPMENTAL LEVELS
2.1.1 Interpreting (Feeding) Behaviors: A Developmental Perspective...... 9
2.1.2 Learning and Memory: A Brief Review ...... 9
2.1.3 Piagetian Stages of Development ...... 12
2.1.4 Stages of Development by Mahler, Pine and Bergman ...... 14
2.1.5 Stages of Development by Greenspan and Lourie...... 16
2.1.6 Stages of Development by Claire Kopp...... 17
2.1.7 Feeding Behaviors Outlined by Developmental Levels ...... 19
SECTION 2: DEVELOPMENT OF NEUROLOGIC ORGANIZATION: A COMPREHENSIVE REVEW OF THE PERIOD OF “HOMEOSTASIS”
2.2.1 The Period of “Homeostasis”: Convergence in the Literature...... 20
2.2.2 Developmental Psychobiology: What is Stress? An Endocrine...... 21
2.2.3 What is calming? An endocrine perspective:...... 24
2.2.4 Development of Neurological Organization...... 25
2.2.5 Continued research conducted within the neonatal period confirms the idea that specific nervous system responses are fluid (plastic) 26
2.2.6 Other research was completed which supports the idea that specific nervous system responses are fluid and appear to develop on a continuum...... 28
2.2.7 Two other important concepts emerged from the literature on homeostasis ...... 28
2.2.8 Another approach to understanding a child who presents with a regulatory disorder symptom is to study autonomic nervous system response patterns would facilitate homeostasis within the autonomic nervous system after a disruption...... 29
2.2.9 Developmental Levels by Porges...... 30
SECTION 3: POSTNATAL DEVELOPMENT OF THE AUTONOMIC NERVOUS SYSTEM: AN IN-DEPTH REVIEW OF THE NUCLEUS TRACTUS SOLITARIUS
2.3.1 Animal studies supporting postnatal development of the autonomic nervous system ...34
2.3.2 The NTS: An In-Depth Review……… ...... 37
2.3.3 Parallel medullary structures which course with portions of the NTS...... 38
2.3.4 Cytoarchitecturally the NTS is a very complex...... 41
2.3.5 The NTS participates in a number of critical brain activities including ...... 46
2.3.6 Brief review of the neurochemical components of the NTS: ...... 58
2.3.7 Normal development of the NTS...... 61
2.3.8 Deprivation at birth and the effects on postnatal development of the NTS …………...66
SECTION 4: POSTNATAL DEVELOPMENT OF THE AUTONOMIC NERVOUS SYSTEM: AN IN-DEPTH REVIEW OF THE NUCLEUS TRACTUS SOLITARIUS
2.4.1 Classification of Feeding and Swallowing Disorders………………………………….68
2.4.2 Classification Based on Levels of Development………………………………………68
2.4.3 Organic vs. Non-Organic Dichotomy...... 69
2.4.4 Multi-Dimensional Classification System ...... 69
2.4.5 Classification Based on a Biopsychosocial Model ...... 70
2.4.6 Current Clinical Theories: A Brief Review ...... 70
2.4.7 The Team Approach ...... 70
2.4.8 Behavioral/ Interaction Theory...... 72
2.4.9 Developmental Theory ...... 72
2.4.10 Occupational Therapy Approaches ...... 74
2.4.11 Regulatory Disorder Theory ...... 78
CHAPTER 3: METHODS AND RESULTS
3.1.1 SUBJECTS: INTRODUCTION……… ...... 80
3.1.2 SUBJECTS: MIXED FAILURE-TO-THRIVE (MFTT) GROUP...... 80
3.1.3 SUBJECTS: CONTROL GROUP...... 88
3.1.4 STANDARDIZATION OF THE PROTOCOL...... 91
3.1.5 Independent Test of Bias………………………………………………………………92
3.2 RESULTS ...... …93
3.3 Validity/Reliability………………………………………………....……………………99
CHAPTER 4: SUMMARY AND DISCUSSION
4.1 SUMMARY...... 105
4.2 DISCUSSION...... 106
4.2.1 Relevance of the findings to the Neuro-Orgnizational Literature ...... 107
4.2.2 Relevance to the Psychological Literature in Identifying Specific Feeding...... 107
4.2.3 Discussion of the physiologic responses selected for this thesis ...... 108
4.2.4 Discussion about the four subjects with MFTT who demonstrated normal response patterns: Why don’t these children have altered response patterns ...... 109
4.2.5 Discussion of future basic science research that would allow for brain mapping of specific brainstem nuclei (i.e. Nucleus Tractus Solitarius)…...………………………..111
4.2.6 General future research ideas: What is the next step?……………………………… 112
REFERENCES…………………………………………………………………………….115
APPENDICES Appendix A: Introduction of “Mixed” Failure-to-Thrive…………………………………..133
Appendix B: Behavioral States State Control and Self Calming Abilities ………………..135
LIST OF FIGURES AND TABLES
Figure 2.3.3a The NTS in the dorsal medulla with the obex as the reference point ……....38
Figure 2.3.3b Schematic representation of a coronal slice taken 1.8 mm below the level of the obex……………………………….…………………………………………….39
Figure 2.3.3c Schematic representation of the surrounding structures of the NTS 3.2 mm above the level of the obex…………………………………………………………..40
Table 2.3.3 Medullary structures and beginning level which parallel the NTS………..…..41
Table 2.3.4a NTS Afferent Projections…………………………………………………….44
Table 2.3.4b NTS Efferent Projections…………………………………………………….45
Table 2.3.6 Review of neurotransmitters and relationship with the NTS………………….60
Table 2.4.7 Team Approaches (Leifton-Greif & Arvedson, 1997) ………………………71
Table 3.1.2a Descriptive information for the MFTT group………………………………..81
Table 3.1.2b A Priori inclusion/exclusion factors for the MFTT subjects…………..…….83
Table 3.1.2c General age appropriate oral feeding milestones…………………………….86
Table 3.1.2d Summary of reported feeding difficulties for MFTT subjects……………….87
Table 3.1.3a Comparison of weight, length of gestation, type of delivery and sex Between matched normal control subjects and MFTT subjects …………….89
Table 3.1.3b Summary of normal subjects including matched controls and additional subjects……………………………………………………………………….90
Table 3.1.4 Numeric value assigned to corresponding body type…………….…………...92
Table 3.2a Summary of scores for the matched normal control group……….…………...94
Table 3.2b Summary of MFTT scores …………………….……………………….……..95
Table 3.2c Abnormal vs. normal physiologic responses of MFTT group and matched normal control group: Investigator’s results……………………….…………96
Table 3.2d Abnormal vs. normal physiologic responses of MFTT group and matched normal control group: Observer’s or Occupational therapists results …………97
Table 3.2e Frequency of physiologic responses for the MFTT and matched normal control subjects…………………………………………………………… ……98
Table 3.2f Distribution of scores obtained by the investigator…...………………………..101
Table 3.2g Distribution of scores obtained by the observer or occupational therapist……………………………………………………………………………………..102
Table 3.3a Comparison of investigator and occupational therapist scores....……………...104
Table 3.3b Comparison of investigator and observer (student) score……………………..105
CHAPTER 1
1.1 RATIONALE
The hypothesis for this project tests whether full-term infants and toddlers who are deprived of oral feedings during any portion of the first 3 months (13 weeks) of life can develop altered physiologic responses to tactile (firm pressure) stimulation. This hypothesis was developed from a frequently observed clinical conundrum—the observation that a heterogeneous group of infants/toddlers (known as Mixed Failure-to-Thrive [MFTT] see section 1.1.2 below) shares a common profile of difficulty with tolerating touch. This touch intolerance can directly result in interference with oral feeding skills. The MFTT group of children also shares a clinical history of oral deprivation as a result of medically necessary tube feedings. Typically, this fact has not been considered significant within the medical profession. Several converging lines of evidence in the literature of psychology, neurobiology and neonatology suggest that feeding problems in this population derive primarily from immature and/or aberrant neurophysiological development, a result of early oral deprivation. This thesis explores the link between oral deprivation and neurophsyiological development as a predictor of clinical symptoms.
1.1.1 Themes of the Clinical Profile
Normal physiologic response to all types of tactile input proceeds along a developmental continuum; however only firm (pressure) touch will be addressed in this thesis. The behavioral response pattern of neonates and very young full-term infants
(younger than 3 months of age) includes a variety of autonomic nervous system responses.
For example, it is not uncommon to observe gagging and/or “state” behavior changes (such
as uncontrolled crying, fussiness, drowsiness or falling asleep, see Appendix A) in young infants while processing touch input. Touch input refers both to touch to the body such as general physical handling (Brazelton, 1973) (Als, 1982), and/or oral touch associated with feeding (Comrie & Helm, 1997). Over time as the infant develops beyond 3 months of age these autonomic nervous system responses become less generalized and more appropriate to environmental situations. For instance, gagging is a normal protective reflex when elicited by touch to the posterior oral regions; however, gagging to anterior oral touch or touch to more peripheral areas of the body is seen as a sign of immature physiological (autonomic) processing (Als, 1982). Thus in infants older than 3 months of age autonomic nervous system responses to touch are unusual. Interestingly, there have been a number of reports describing negative feeding behaviors such as rejection of food, rapid “state” behavior changes, and/or gagging to oral touch in children older than three months of age with a history suggesting
MFTT [(Arvedson, 1997); among others]. A number of clinicians (the investigator included) report even more extreme reactions, such as a gag response to touch on shoulders, arms, neck, and other more peripheral regions of the body. The degree of abnormality seems to be proportional to the distance from the oral cavity—in other words, gagging as a response to touch on the trunk appears to be more abnormal than gagging as a response to touch on the external cheek. Thus, a child who has an extreme aversion to oral touch is likely to have a less extreme, but still abnormal response to touch on the shoulders or trunk as manifested through an abnormal gag response or “state” behavior change.
1.1.2 Unique Characteristics of the Population With This Profile
MFTT is a relatively new term utilized to describe a group of children who are born with a medical condition that prevents oral feedings for a certain period of time and who persist with feeding difficulties following remediation of the medical problem (Arvedson,
1997) (see Appendix A for a complete definition of failure-to-thrive). Clinical experience has shown that most children with MFTT require the use of alternative feedings for at least two weeks during the first three months of life. In addition, infants and toddlers with MFTT are typically the product of a full-term gestation and often follow a normal cognitive course of development. However, the medical conditions involved with MFTT children can be disparate. For instance, non-oral feedings are common in cases of early cardiac malformations, respiratory ailments, craniofacial abnormalities, etc. Furthermore, because the diversity of the medical conditions and subsequent interventions involved are unique to each individual child, MFTT children are introduced to oral feedings at a range of developmental ages. In spite of these medical and intervention differences, MFTT children show similar difficulties in feeding behaviors, including inappropriate gagging, etc., as detailed above.
1.1.3 Potential Explanation for Abnormal Responses in this Heterogeneous Population
One explanation is the lack of early normal oral sensory experience. Although the development of the autonomic system is often considered complete at birth (full-term), there is considerable support from animal research and some human post-partum studies that suggest continued structural, neurochemical and electrophysiological changes take place
(Azmitia & Whitaker-Azmitia, 1991; Carpentier et al., 1997; Denavit-Saubie et al., 1994;
Goya, Alaez, & Pascual-Leone, 1990; Jaquin, Rhoades, & Klein, 1995; Takashima &
Becker, 1986; Takemura et al., 1996; Tomlinson & Coupland, 1990; Vincent & Tell, 1997).
These changes are dependent on the existence and quality of input (Bornstein, Terry,
Browde, Assimon, & Hall, 1987; Lasiter, 1995; Lasiter & Diaz, 1992; Salas, Torrero, &
Puliso, 1986; Young & Morrison, 1998). Therefore, altered sensory input during the first 3 months of could theoretically impede normal response patterns. For this reason, it is reasonable to assume that altered physiological development could cause similar feeding behaviors in a medically heterogeneous group of children.
1.1.4 Introduction of the “Behavioral Organization” Model as it Relates to the Clinical
Profile
Development of altered physiological responses through a lack of access to oral feeding is consistent with current approaches to the study of neurological maturation. In the
“behavioral organization” model, which has been adopted as standard in most neonatal literature, neurologic organization is a process in which an infant demonstrates an increasing ability to regulate internal responses to external stimuli (Als, 1986; Als & Gilkerson, 1995;
Comrie & Helm, 1997; VandenBerg, 1990). This model assumes that infants achieve
“behavioral organization” by neurophysiologic modulation “techniques” including modulation of primitive reflexes, such as the gag and startle reflexes and “states” of consciousness (Boner & Perlin, 1984; Brazelton, 1973; Kopp, 1982). In normal infant development “behavioral organization” implies the ability to modulate states of behavior and to integrate reflexes, thus allowing the infant to attain a calm, alert state more often and for longer periods of time while being touched and handled. This calm, alert state is a critical
precursor for learning more advanced skills (Als & Gilkerson, 1995; Brazelton, 1973, 1990;
Comrie & Helm, 1997; DiPietro & Porges, 1991; Einarsson-Backes, Keitz, Price, Glass, &
Hays, 1994; Johnston, Stevens, Craig, & Grunau, 1993; Johnston, Stevens, Yang, & Horton,
1995; Miller & Quinn-Hurst, 1994; Porges, 1992; Ramsey, Gisel, & Boutry, 1996; Ramsey
& Zelazo, 1988; Stengel, 1980; Stevens, Johnston, & Horton, 1994). Other simple examples of infant behavior that reflect behavioral organization include grasping objects to limit the movement of extremities or looking away to decrease the level of interaction (Miller &
Quinn-Hurst, 1994). These primitive mechanisms assist the infant to stabilize biological functions, to safeguard against intrusive or strong stimulation (Kopp, 1982), and/or to support the neonate to self-calm (Hoffman & Ison, 1992; Kopp, 1982) .
A number of studies have shown that tolerance for oral touch is a predictor of success in oral feeding. If a child cannot achieve tolerance for touch then the child is unlikely to thrive via oral feedings (Comrie & Helm, 1997; Einarsson-Backes et al., 1994). (Tolerance for the purpose of this document is defined as behaviorally maintaining a calm, alert state while being physically touched.) Clinical experience with children that present with MFTT suggests that this same tolerance of touch, especially oral touch, is a necessary prerequisite for successful transitions to oral feedings in this mixed FTT population.
1.1.5 Logic
In the behavioral organization model, neonates and young infants are expected to have difficulties with state behaviors and reflexes because of immaturity of the autonomic nervous system (Als & Gilkerson, 1995; Comrie & Helm, 1997; Kopp, 1982). Current clinical practice does not consider this model applicable to older infants and children because
they are assumed to have successfully negotiated through the period of time that the autonomic nervous system fully matures (i.e. birth to three months, also known as the period of “homeostasis”). This leads to the following clinical intervention model often utilized with older MFTT children:
• Physiologic development proceeds normally along a biologically predetermined pattern; thus, children older than 3 months of age must have completed the period of “homeostasis”.
• Because the child is prevented from normal oral feeding only by medical bypass devices, i.e. tube feedings, remediation of the medical problem that necessitated bypass feeding—i.e. the physical problem—is enough to enable normal oral feeding.
• Abnormal reflexes or immature regulation of state behaviors is seen as evidence of some other process. Because the physical and physiologic factors are now “normalized”, other external factors must be causing the persistent feeding difficulties. Hence, behaviors in the neonate which are ascribed to immature behavioral organization, such as poor regulation of state or gagging to touch, are attributed in the older child to cognitively modulated manipulation of the environment and/or breakdown of caregiver-child interaction (Babbitt et al., 1994; Chatoor, Schaefer, Dickson, & Egan, 1984).
Clinicians following the above clinical model, however, have reported a low success rate (Tolia, 1995). Furthermore, a number of investigators have noted that the representational memory skills required for manipulation of the environment do not emerge until late in the second year of life (Bauer, Hertsgaard, & Dow, 1994; Greenspan & Lourie,
1981; Kopp, 1982; Piaget, 1952). Therefore clinical techniques that rely on representational memory skills are perhaps best applied after 18 months of age. Clearly other techniques need to be developed for younger ages. To do this we need to reassess clinical practice in light of what we know about development, normal and abnormal, in this age period.
This study aims to provide an explanation for feeding/swallowing problems in the
MFTT population. A gap in the current literature regarding feeding/swallowing
problems in the MFTT population between 3 and 18 months of age has been identified.
It is known that a level of neurological (organization) maturity is required for
successful processing of oral touch (and thus feeding). However, the presence of key
indicators of neurophysiological development (i.e. gag reflex, state behavior changes) in
the MFTT population suggests that neurological maturity has not yet been achieved.
1.1.6 Clinical Example
As noted in the clinical model above, behaviors such as poor regulation of state or gagging to touch, are often attributed in the older child cognitively modulated manipulation of the environment and/or breakdown of caregiver-child interaction (Babbitt et al., 1994;
Chatoor, Schaefer, Dickson, & Egan, 1984). If we believe instead that normal physiologic development has been altered, an entirely different clinical approach becomes apparent.
Consider the proposition that an infant is placed on a feeding tube because of an underlying cardiac condition. The medical team anticipates only minimal adjustments to oral feedings because a cardiac condition is not typically associated with the anatomy, physiology or neurology of the swallowing mechanism. Since it is assumed that the child has the neurologic foundation to alter his/her behavior a typical recommendation might be to target mealtime interactions between the child and caregiver and to alter the environment as appropriate
(Arvedson, 1997; Kopp, 1982). However, if the evidence shows the child's neurological foundation is immature, then the focus of clinical practice should be shifted to rebuilding the appropriate neurological responses.
Techniques for improving behavioral organization exist and are currently used in neonatal clinical settings (Comrie & Helm, 1997). However, prior to making any alterations
in diagnostic or treatment techniques it will be necessary to establish that differences in response patterns between normal and the “mixed” failure-to-thrive children exist.
1.2 HYPOTHESIS
Lack of oral experience in the first 3-months (13 weeks) of life affects development of neurological organization for tactile sensory input thus compromising the ability of a child with MFTT to become a successful oral feeder.
1.3 EXPERIMENTAL DESIGN
This study compares the responses to touch in normal and children with MFTT. A graded system of tactile input will be presented to each child, and responses will be assessed through state behavior changes and/or abnormal gag reflex responses.
CHAPTER 2:
LITERATURE REVIEW
Introduction:
The subsequent chapter is divided into four sections. Readers with an interest in classical theory of developmental levels might focus attention on sections 2.1.1 to 2.1.7. Readers with an interest in the development of neurologic organization with an emphasis on the period of homeostasis might focus attention on sections 2.2.1 to 2.2.9. Readers with an interest in postnatal development of the autonomic nervous system - more specifically a review of the nucleus tractus solitarius-may want to focus attention on sections 2.3.1 to 2.3.8. Finally, for a reader with more clinical interest, sections 2.4.1 to 2.4.11 describe clinical implications.
SECTION 1: CLASSICAL THEORY OF DEVELOPMENTAL LEVELS
2.1.1 Interpreting (Feeding) Behaviors: A Developmental Perspective
The field of pediatric feeding and swallowing is complex for a number of reasons. 1)
Infants/toddlers express themselves by indirect, non-verbal means. Thus, all diagnosis and treatment depend on appropriate interpretation of behavior. 2) Theoretically feeding behaviors transition from wholly physiologic responses to cognitively learned responses or combinations of both. 3) Finally, to compound the issue, a human infant undergoes a dramatic transformation in all aspects of development during the first two to three years of life. These areas include neurologic, anatomic, motor, sensory, physiologic, feeding/swallowing skills, speech/language, cognitive, social-emotional and play skills. Each
of these areas is interdependent, much as the pieces of an intricate jigsaw puzzle can be viewed piece by piece or as a whole. Thus, it is important to briefly review what is known.
2.1.2 Learning and Memory: A Brief Review
Before levels of development can be reviewed, basic definitions about learning and memory will be summarized. Learning can occur in the absence of overt behavior, but it can only be inferred from changes in behavior. Memory is the retention of stored knowledge
(Kupfermann, 1991). Over the past 20 years of research into the neurological basis of learning and memory, some basic principles established: a) multiple memory systems are present in the brain, b) short-term learning and memory require changes in existing neural circuits, and c) long-term memory requires new protein synthesis and growth (Beggs et al.,
1999).
Learning is typically broken down into non-associative and associative types. Non- associative, one of the more basic learning processes occurs when a human is exposed one time or repeatedly to a single type of stimulus. This type of learning will result in habitiation or sensitization (Kupfermann, 1991). Habitiation is a decrease in a behavioral response to a repeated non-noxious stimulus. Sensitization, on the other hand, is an increase in response to a wide variety of stimuli following an intense or noxious stimulus. It is important to note that sensitization can override the effects of habitiation (Kupfermann, 1991).
The associative type of learning involves the formation of associations among stimuli and/or responses. This type of learning has been studied extensively and it includes two categories: classical conditioning and instrumental conditioning (Carlson, 1994). Classical conditioning occurs when one stimulus, the conditioned stimulus (CS) is paired with a second stimulus, the unconditioned stimulus (US). The US reliably elicits a response termed
the unconditioned response (UR). Repeated pairings of the CS and the US result in the conditioned stimulus eliciting a response called the conditioned response (CR). Some critical aspects of this type of learning include: a) the CS precedes the US, b) limited time period between the presentations, and c) the established conditioned response decreases in intensity if repeated presentations of the CS occur without the US (Kupfermann, 1991).
Unlike classical conditioning, which is restricted to the specific reflex responses that are evoked by specific stimuli, instrumental or operant conditioning involves behaviors that occur spontaneously. Thus instrumental behaviors are said to allow for an organism to adjust its behavior according to the consequences of that behavior. That is, if a behavior is followed by favorable consequences (reward), the behavior tends to occur more frequently; when it is follow by unfavorable consequences (aversive stimuli or punishment) it tends to occur less frequently (Carlson, 1994). These two types of associative learning demonstrate how an individual begins to learn about predictive relationships. For classical conditioning, the subject learns that a certain stimulus predicts a subsequent event. For instrumental conditioning subjects learn to predict the consequences of their own behavior.
Learning and memory can be classified as reflexive or declarative on the basis of how information is stored and recalled (Kupfermann, 1991). For the purpose of this thesis, only two types of memory will be reviewed, reflexive (or procedural) and declarative memory.
Typically, reflexive, procedural or implicit memory is defined as an increasing ability to detect or identify a stimulus as a result of prior exposure, and it is not dependent on awareness, consciousness or cognitive processes. This type of memory is dependent upon sensorimotor functioning and was thought to be the first type of memory acquired
(McDonough & Mandler, 1994). In one study, infants as young as 3 months of age,
demonstrated reflexive memory for a foot-kicking activity that involved operant condition
(Ruff, 1984). Alternatively, declarative, explicit or representational memory generally refers to one’s own previous experiences, recognition of scenes and objects and depends on conscious reflection (Beggs et al., 1999; Kupfermann, 1991). It has been found that this type of recall is in place (even if not fully mature) early in the second year of life (Bauer et al.,
1994).
A direct reflection of developmental changes in learning and memory can be easily observed in newborn infant behavior as compared to the significantly different behavior repertoire of a toddler. Anna Freud (1946) first proposed the concept of the developmental continuum to describe different aspects of development in a sequential progression (Chatoor,
Schaefer, Dickson, & Egan, 1984). Since that time a number of researchers have described development as proceeding in a sequential manner (Epstein, 1974; Erikson, 1950; Fisher,
Murray, & Bundy, 1991; Greenspan & Lourie, 1981; Kopp, 1982; Lecours, 1975; Luria,
1973; Mahler, Pine, & Bergman, 1975; Piaget, 1952; Porges, 1983; Porges, Doussard-
Roosevelt, Portales, & Greenspan, 1996) A detailed review of the four most frequently utilized levels of development within the current feeding/swallowing literature will ensue.
This review will include developmental stages by Piaget (1952), Mahler, Pine &
Burgman(1975), Greenspan and Lourie (1981) and Kopp (1982) from pre-term through 36 months.
2.1.3 Piagetian Stages of Development
As early as 1952, Piaget classified developmental stages for birth through three. The
Piagetian approach postulated that sensorimotor skills were the foundation for the development of social, communicative, self-care, and play behaviors during the first 2 years
of life (Dunst & Gallagher, 1983). This sensorimotor period was divided into 6 stages that
include (Piaget, 1952):
Stage 1 Reflexes- (0-6 weeks) – The child in this stage is dominated by reflexive behaviors and simply reacts physiologically to external stimuli.
Stage 2 Primary Circular Reactions– (1-4 months) - The child learns to integrate sensory and motor behaviors and begins to interact with the external environment. Actions observed in this stage are focused on their own bodies not directed towards objects. Interactions that the child may have are pleasurable in experience, but the results from this experience are accidental in nature.
Stage 3 Secondary Circular Reactions– (4 to 8 months) – Children notice that their actions produce pleasurable results and begin to repeat behaviors systematically to continue the pleasurable results. The discoveries that children have in this stage remain random, with no pre-established goal in mind.
Stage 4 Coordination of Secondary Circular Reactions- (8-12 months)- Children in this stage become goal directed and are able to chain behaviors together to achieve a desired goal. However, if the goal is not achieved using their familiar scheme, then the child is not able to find an alternative method at this time.
Stage 5 Tertiary Circular Reactions- (12-18 months)- The foundation for deductive reasoning skills are established in this phase. Children in this stage now have the skills to try something different if their first attempt to achieve a goal is unsuccessful.
Stage 6 Combinations of New Means through Mental Combinations- (18-24 months)-The primary characteristic of this stage is that children acquire insight into their problems rather than using trial and error. Symbolic thought during this stage remains primitive and is only just emerging.
Throughout the development of these six sensorimotor stages, children simultaneously acquire more complex forms of the following six domains. These include: visual pursuit and object permanence, means-ends relationships, causality, spatial relationships, imitation skills and behaviors related to objects. Within each of these domains children begin by using rudimentary motor and sensory skills and advance towards more complex, symbolic abilities. Therefore, in order for the child to develop in an optimal manner
progression within each of these six, parallel but separate domains, is critical (Langley,
1989).
The Piagetian theory categorizes children between 24-36 months as being in the pre- operational phase. Piaget (1952) places children 2-7 years in this group. It is subdivided into the preconceptual phase and the intuitive phase. During the preconceptual phase the use of language expands and logical reasoning remains limited. For the purpose of this thesis there are three key aspects of the preconceptual phase: (1) an inable to distinguish easily between
“self” versus “other” perspective, (2) a recognition that inanimate objects have human qualities and are capable of human action, and (3) continuing difficulty with conservation
(e.g. understanding that liquid poured from one cup into another remains the same despite varying the size of the cup) (Langley, 1989).
2.1.4 Stages of Development by Mahler, Pine and Bergman
A number of papers written in the 1940’s by Mahler (1975) discuss phases of development. According to these authors the observation of motor, kinesthetic and gestural phenomena of the entire body during the first year of life provides critical information about the inner workings of a child. These authors wrote that the motor and kinesthetic pathways are the principal expressive, defensive and discharge pathways for the infant. Furthermore, the psychological birth of the infant thus occurred as a separation-individuation process. In other words, the infant establishes a sense of separateness from, and relations to, a world of reality, particularly with regard to the experiences of their own body. No longer is the infant in the symbiotic relationship with their caregiver.
In this approach the period from approximately 4-5 months to the 30-36 months is particularly significant (Mahler et al., 1975). These authors distinguish 4 sub-phases of
separation-individuation including: 1) Differentiation and development of the body image, 2)
Practicing, 3) Rapprochement and 4) Consolidation of individuality at the beginning of emotional object constancy.
Phase 1- Differentiation and development of the body image- (4-5months to 10-12 months) Symbiosis of infant and mother are at a peak at the beginning of this stage. At approximately 6 months of age experimentation occurs where the child begins to differentiate his body from his mother’s. Between 7-8 months the child acquires a “checking back” pattern in which the infant visually checks back to his mother, which is a sign of somatopsychic differentiation. During this stage the most important normal pattern of cognitive and emotional development occurs: Begins with the simple discrimination task of differentiating mother vs. others.
Phase 2- Practicing- (10-12 months to 16-18 months) Develops in 2 parts: 1) Early practicing period-this stage is marked by the infants earliest ability to move away physically from his mother by crawling, paddling, climbing and righting himself, yet still holding on to things or people. 2) Practicing period proper is characterized by free, upright locomotion. During this stage there are 3 interrelated yet distinct developments that contribute to the child’s first steps toward awareness of separateness and toward individuation including: a) Rapid body differentiation from the mother, b) Establishment of a specific bond with the mother, and c) Growth and functioning of the autonomous ego apparatuses in close proximity to the mother.
Phase 3- Rapproachement (15-24 months) This stage the child makes a deliberate search for, or avoidance of intimate body contact. During this phase separation reactions are noted with two types of behavior patterns observed: a) “shadowing” of the mother and b) “darting away” from the mother. Concomitant with the acquisition of primitive skills and perceptual cognitive faculties, an increasingly clear differentiation between “interpsychic” representation of the object and the self-representation occurs.
Phase 4- Consolidation of individuality at the beginning of emotional object constancy (24-36 months) The task of this stage is two-fold: achievement of a definite (lifelong) individuality and attainment of a certain degree of object constancy. In other words a stable sense of self-boundaries is attained.
It is very interesting to note that Mahler, Pine and Bergman (1975) purposefully omitted the first four months of life from their developmental stages. These authors reasoned that in very young infants (i.e. less than 4 months of age) changes like modulation, inhibition, stylization and defensive distortion of bodily expressions have yet to be learned, therefore,
cannot adequately be studied. However, these authors did acknowledge the importance of
the first four months of development in that it sets up a healthy process through which to best
achieve subsequent phases (Mahler et al., 1975).
2.1.5 Stages of Development by Greenspan and Lourie
Two decades ago, Greenspan and Lourie utilized a developmental structuralist approach
to describe developmental stages of infancy and early childhood. Each developmental stage
outlined characteristics/abilities that would allow an infant/child to organize and differentiate
various experiences. This construct was unique for that time because it focused on
integrating behaviors rather than on an isolated or single behavior that may be less stable and
more sensitive to minor environmental changes. The first 3 years are divided into 5 stage-
specific capacities including: 1) “Homeostasis”, 2) Attachment, 3) Somatopsychological differentiation, 4) Behavioral organization, initiative, and internalization, and 5)
Representational capacity, differentiation and consolidation.
Stage 1 Homeostasis (Birth to 3 months)- Adaptation to the external environment while maintaining a state of internal regulation including regulating state and basic rhythms such as sleep/wake and hunger cycles.
Stage 2 Attachment (2-7 months)- Increasing central nervous system regulation (between 2-4 months of age) allows the infant to respond to the external environment and to form a special relationship with the significant primary caregivers.
Stage 3 Somatopsychological differentiation (3-10 months) A process of differentiation begins to occur along a number of developmental lines such as sensorimotor integration, affects, relationships, etc. This process is demonstrated through flexible, wide-ranging affective, multi-system reciprocal interactions particularly with the primary care givers.
Stage 4 Behavioral organization, initiative and internalization (9-24 months) By 12 months the infant is able to begin connecting behavioral units to form larger organizations. Further into the second year of life in the practicing sub-phase of the development of individuation (see Mahler et al, latter half of the second phase) there is a capacity for forming
behavioral schemes and increased imitative activity and intentionality. Imitation, which is evidenced earlier, now takes a dominant role.
Stage 5 Representational capacity, differentiation and consolidation (18 months to 4 years) Toward the end of the second year when the toddler’s central nervous system matures further, there is an increased capacity to form and organize mental representations. Representational capacity refers to the ability to organize and evoke internal multi-sensory experiences of the animate object.
Greenspan and Lourie’s developmental structuralist approach was distinctive in that it
outlined both a diagnostic scheme and provided a high-order construct for a variety of
behaviors. In addition, this method outlined levels and patterns of integration of behaviors
that incorporate the history and meaning that the infant/child has ascribed to events as well as
the way in which the infant/child has organized these meanings into stable, coherent patterns
(Greenspan & Lourie, 1981).
2.1.6 Stages of Development by Claire Kopp
Claire Kopp (1982) presented phases of a development for self-regulation. Self-
regulation is defined as the ability to comply with requests, initiate and cease activities
according to situational demands, modulate the intensity, frequency and duration of motor
acts in social and educational settings and to generate socially approved behaviors in the
absence of external monitors. Typically self-regulation does not begin to fully emerge until
after 3 years of age, however, antecedents to self-regulation begin in infancy. Kopp (1982)
established 5 phases of development leading to self-regulation including: 1)
Neurophysiologic modulation, 2) Sensorimotor modulation, 3) Control,
4) Self-control and 5)Self-regulation. (Note that the use of phase was specifically chosen to suggest gradual transitions rather than sharp boundaries).
Phase 1- Neurophysiologic Maturation- (Late prenatal period to 3 months) The term neurophysiological modulation subsumes processes that safeguard the immature organism form intrusive or strong stimulation. By 3 months of age, infants show the emergence of clearly defined sleep-wake cycles that are congruent with the social definitions of day and night. In addition this growth is accompanied by other maturational changes as seen in electroencephalograms and habituation.
Phase 2- Sensorimotor modulation- (3 to 9-12 months) During this phase the modulation of a voluntary motor act cannot occur until component aspects of a sequence are coordinated and performed non-reflexively. Modulation does NOT involve consciousness, prior intention or awareness of the “meaning” of the situation. There is action, but not conscious reflection of that action. Infants cannot move out of this phase until differentiation of their own actions from others emerges and an intact sensorimotor system is in place.
Phase 3 Control (9-12 months to 18 months) The control phase characterizes the emerging ability of children to show awareness of social tasks or demands (that have been defined by caregivers). In this phase children begin to initiate, maintain, modulate or cease physical acts, communication and emotional signals accordingly. This phase is subdivided into two sub- phases including: a) Compliance and b) Self-initiated inhibition of a previously prohibited behavior. Features of the compliance control phase involve: 1) Appraisal of different features of the environment, 2) Subsumes intent, 3) Only an elementary awareness of what is acceptable/not acceptable to caregivers. Children are dependent upon the presence of key signals because the child does not have the capacity to recall events. Finally, 4) the cognitive capacity of reflection does NOT exist. Features of self-initiated inhibition involve children taking an active role in guiding their own behavior. This involves a child approaching a desired object, recognizing the object was associated with prohibition or inhibition of a prohibited act. It is not until the child is 15-16 months of age that they are capable of producing patterns of situational appropriate self-initiated behavioral controls. It should be noted that limits in the child to develop this phase of control includes memory and pleasurable input that competes with awareness of “correct” behavior (i.e. Locomotion).
Phase 4 Self-control (24 months +) This phase immediately precedes self-regulation. The child begins to develop skills that act on caregiver request and to behave according to caregiver and social expectations without external monitors.
Phase 5 Self-regulation (36 months +) Flexibility of the control processes emerges allowing the child to meet changing situational demands.
One of the features that Kopp (1982) outlined within the first level of development, neurophysiologic modulation, was that it began in the prenatal phase (i.e. while the fetus was in utero). This is quite a contrast to Mahler et al. (1975) who chose not to address the first few months of life, much less speculate on perinatal influence. At the time that Mahler, et al.
(1975) made this claim there was very little research that had been done with newborns and premature infants.
2.1.7 Feeding Behaviors Outlined by Developmental Levels
These four developmental levels have traditionally been utilized to outline feeding behaviors. One set of researchers looked at behaviors related to a combination of Greenspan and Lourie’s (1981) and Mahler’s (1975) levels of development (Arvedson, 1997; Chatoor,
Schaefer, Dickson, & Egan, 1984; Satter, 1990, 1995). By combining these two perspectives feeding behaviors were outlined from three levels of development: homeostasis (0-2 months), attachment (2-6 months) and separation/individuation (6 months – 3 years). Only one article used the first three phases of Kopp’s (1982) self-regulation development to describe a feeding disorder (Pridham, 1990).
These various levels of development have historically been important for classifying feeding behaviors as well as providing a foundation for current clinical theories. Regardless of the many differences between these developmental levels, all of the investigators seem to agree on this period of “homeostasis”. Because this thesis is looking at children between 3 months and 18 months who have persistent feeding difficulties due to difficulties within the first 13 weeks of life, it is critical to review the period of homeostasis in depth. This review will cover the development of neurologic organization and neonatal theories leading into this period.
SECTION 2: DEVELOPMENT OF NEUROLOGIC ORGANIZATION: A
COMPREHENSIVE REVIEW OF THE PERIOD OF HOMEOSTASIS
2.2.1 The Period of “Homeostasis”: Convergence in the Literature
After reviewing the various continuums of development, it becomes apparent that there was a convergence in the literature as a specific time period beyond normal gestation where certain neurologic responses continue to be fluid. This period can be best described as the “Period of Homeostasis”. Most investigators identify this critical period as the timeframe of development from birth (40 weeks gestation) to the first 2-3 months of life. This period of
“homeostasis” represents the normal stage of development when the infant stabilizes biological functions such as sleep-wake cycles, state behavior, feeding, and excretion patterns (Chatoor, Schaefer, Dickson, & Egan, 1984; Greenspan, 1990; Porges et al., 1996;
Pridham, 1990).
Although this period of “homeostasis” is noted in the literature to be fluid (plastic) and an important part of development, typically it has NOT been viewed as a critical time period for feeding development. Many of the authors who postulated levels of development have indicated that disruption of any of the early developmental levels may impede normal ability to get through subsequent phases of development (Arvedson, 1997; Pridham, 1990; Satter,
1990; Tolia, 1995). However, the preponderance of studies focusing on cases of failure-to- thrive or persistent feeding difficulties has stressed the caregiver-child interaction as related to the attachment/sensorimotor phase of development, that is the phase that immediately
follows homeostasis (Breunlin, Desai, Stone, & Swilley, 1983; Chatoor, Schaefer, Dickson,
& Egan, 1984; Chatoor, Schaefer, Dickson, Egan et al., 1984; Satter, 1990; Tolia, 1995;
Ward, Kessler, & Altman, 1993; Whitten, Pettit, & Fischhoff, 1969). This literature assumes that the period of “homeostasis” is successfully completed and that aberrant child feeding behaviors should be traced to inadequate relationship formation.
Many recent authors have recognized that the child may present with altered physiology that may be impacting the ability of the child to develop normal feeding behaviors (Polan & Ward, 1994; Rudolph, 1994; Senez et al., 1996), yet no specific timeframe was offered. Only one article to date has specifically connected altered physiology with chronic feeding difficulties with the period of homeostasis. Ramsey, Gisel and Bountry
(1996) have proposed that aberrant feeding behaviors and interactions may be a consequence of long standing feeding difficulties rather than an indication of a psychological disorder in the caregiver-infant pair. Furthermore, these authors also noted that these feeding difficulties appear to have an onset during the “reflexive” phase of development that is the first 2-3 months of life (assuming 40 weeks gestation). Therefore, the Ramsey et al. (1996) article was distinctive in making a connection between early infant behavior and the period of homeostasis. Before we move into a discussion of the development of the neurological organization, a review of what constitutes “stress” vs. “soothing” from the endocrine perspective will be reviewed.
2.2.2 Developmental Psychobiology: What is Stress? An Endocrine
Perspective
An understanding of the neuroendocrinology of stress, including those endocrine systems that counteract the response to stressful experiences, provides a starting point for
explaining the mechanisms underlying human behavior (Carter & DeVries, 1999).
Neuroendocrine regulation of homeostasis and stress responses involves a complex brain- pituitary-adrenal axis (also known as the hypothalamus-pituitary-adrenal gland axis, or HPA axis) (Akil et al., 1999; Carter & DeVries, 1999). The HPA is a key player in response to stressful stimuli. Other participants include the adrenal medulla (which produces norepinephrine and epinephrine) and the autonomic nervous system (which activates this axis through neurotransmitters) (Akil et al., 1999). To better understand the HPA axis it should be viewed, not as an alarm system that is only activated by stress, but as a system that has a continuous baseline with daily oscillations (Akil et al., 1999).
Although the basal activity of the HPA has a daily rhythm and fluctuates, this system can be activated under stressful conditions through neuronal input (Best & Taylor, 1985a). The hypothalamus, which is the ventral part of the dinecephalon that form the floor and part of the lateral wall of the third ventrical, is a major structure involved with this HPA axis.
Information is received by the periventricular nucleus (PVN) of the hypothalamus from several areas of the brain including such areas as: select brainstem nuclei (i.e. NTS, sensory systems), the limbic system, circumventricular organs (i.e. subfornical organ) and from within the hypothalamus itself (Akil et al., 1999; Martin & Jessell, 1996). In order for the
HPA axis to be activated, the PVN of the hypothalamus appears to sum and integrate input from these loci (Akil et al., 1999). If triggered, the HPA axis will result in a cascade of endocrine events. In other words, a specific nuclei within the hypothalamus (a deep structure in the brain) receives information from many areas of the brain that involves sensory and emotional targets. If the amount of information or the intensity of what is received exceeds a
particular threshold then the hypothalamus will send a message to the pituitary gland (a structure also deep the brain, but near by) to activate.
Neuoropeptides within the hypothalamus, including corticotropin releasing hormone
(CRH) and arginine vasopressin (Whitnall, Kiss, & Aguilera, 1993) regulate the release of adrenocorticotropin hormone (ACTH) from the anterior pituitary gland into the bloodstream
(Carter & DeVries, 1999). The ACTH circulates and binds to receptors on the surface of the adrenocortical cells to stimulate the synthesis and secretion of cortisol (Best & Taylor,
1985a). The cortisol then acts as a negative feedback control on ACTH synthesis by suppressing transcription of the ACTH gene in the pituitary and by suppressing formation of
CRH in the hypothalamus (Best & Taylor, 1985a). Therefore net synthesis of ACTH is a result of the relative strength of CRH, which stimulates production, and cortisol that inhibits production (Best & Taylor, 1985a). In addition to the adrenal cortex being activated by
ACTH, the adrenal medulla is activated as well. The adrenal medulla secretes catecholamines, including epinephrine (adrenaline) and norepinephrine(Carter & DeVries,
1999). One result of these catecholamines being released into the bloodstream is that that the sympathetic portion of the autonomic nervous system is activated (i.e. flight/fight response).
In other words, the hypothalamus activates the pituiatary gland to send a specific hormone
(ACTH) into the bloodstream. This hormone then binds to two different portions of the adrenal gland (which is found near the kidney) to release a gluccocortoid called cortisol and catacholamines such as adrenaline. The release of both of these agents are important because the cortisol acts as the means to tell the system that enough ACTH has been released, and the adrenaline is the agent which puts the body into the fight or flight response.
2.2.3 What is calming? An endocrine perspective
The homeostatic processes that down regulate the response to stressors or actively allow soothing have not yet been fully determined in animals or humans. However, it is hypothesized by (Carter & DeVries, 1999) that a specific neural system, dependent in part by oxytocin is capable of modulating stress responses. Oxytocin is a hormone created by peptide synthesized in cell bodies of neurons located mainly in the periventricular nucleus, and in smaller amounts in the supraoptic nucleus of the hypothalamus. The traditional role of oxytocin is to stimulate the uterus, breast and other smooth muscles to regulate birth and the ejection reflex of milk (Kupfermann, 1991; Lawrence & Lawrence, 1999). In addition to this traditional role, levels of oxytocin have found to increase within a variety of positive social interactions, including infant and maternal attachment, and in the exploration of novel situations (Carter & DeVries, 1999; Unvas-Moberg, 1997). Oxytocin has also been shown to play a major role in the regulation of the parasympathetic nervous system (“rest and digest” portion of the autonomic nervous system) (Unvas-Moberg, 1997). In rats, tactile contact, such as massage, vibration, electroacupuncture and emersion into warm water produce increased levels of oxytocin (Carter & DeVries, 1999).
Oxytocinergic and vasopressinergic systems may interact to modulate behavioral states.
For example, both hormones have been implicated in the control of the ANS, with oxytocin having parasympathetic actions and vasopressin serving the sympathetic nervous system
(Carter & DeVries, 1999). It is postulated that oxytocin and its vagal activities may integrate a variety of metabolic and behavioral systems that may serve to counteract the defensive behavioral patterns associated with stress and the central release of vasopressin (Carter &
DeVries, 1999; Unvas-Moberg, 1997). Therefore, dynamic interactions of oxytocin and
vasopressin may be part of a larger system that integrates neuroendocrine and autonomic changes associated with stress and maintaining homeostasis (Carter & DeVries, 1999).
A question was then posed by Akil and collegues (Akil et al., 1999), “What would happen if this system, involving the interplay of several circuits, is disrupted?”. These authors theorized that stress responses might be initiated in response to the “wrong” stimulus.
In other words, a stimulus might be coded as stressful despite not being perceived as such by most individuals or by that same individual at other times. They continued by saying that one might also imagine that appropriate stress responses might not be terminated in a timely manner and basic functions (i.e. eating, sleeping, etc.) that are often superseded by these stress responses, become disregulated. This perspective was substantiated by a number of clinical researchers who observed this pattern within neonatal and infant behaviors.
2.2.4 Development of Neurological Organization
Historically, the development of neurological organization began with observations from the infant and neonatal literature. In 1973, after several years of development,
Brazelton published the Neonatal Behavioral Assessment Scale (NBAS). The basic premise underlying NBAS was to develop an examination tool that would classify infant behaviors when demands were placed on his/her immature physiological systems (Brazelton, 1973).
The concept that the individuality of the infant may have a powerful influence on the caregivers replaced the notion that the infant was a passive participant in the early months of life (Brazelton, 1973). Brazelton (1973; 1987) identified 6 “states” of consciousness within the newborn (see Appendix B). These states consist of 2 sleep states and 4 awake states (deep sleep, light sleep, drowsy, alert bright, increasing agitation and intense crying), and according to Prechtl(1987), these “states” develop around 36 weeks gestational age. As part of his
original research, Brazelton (1973) postulated that the baby’s state of consciousness or
“state” behavior was the single most important element in the NBAS examination. States are seen as reflections of autonomic nervous system maturation, as well as reactions to incoming stimuli (Brazelton & Cramer, 1990). Over time it has become recognized that only in an alert, bright state does the newborn orient to external sources of input and take in information
(Brazelton, 1990; Kaufmann-Hayoz, 1987). In addition, changing state behaviors can also provide a mechanism for an infant to avoid overstimulation (Miller & Quinn-Hurst, 1994).
2.2.5 Continued research conducted within the neonatal period confirms the idea that specific nervous system responses are fluid (plastic)
Als (1982) developed the synactive theory of development, also known as the
“behavioral organization” model. This model expanded the work of Brazelton and distinguishes behavior and development according to separate but interdependent subsystems
(Als, 1982, 1986). These subsystems of development include not only state organization, but also autonomic-physiologic, motoric, attentional interactive, and self-regulatory systems
(Als, 1982). Als (1982; 1986) also developed characteristics of each subsystem and labeled them as unstable or self-regulated. For example, alterations in breathing, color changes, gagging, and/or yawning, etc. are all considered autonomic system stress signs. Well- regulated tone and efficient motor strategies such as hand to mouth are signs of stability of the motor system (Als, 1982). Als expanded Brazelton’s 1973 hypothesis Als (1982; 1986) indicated that the goal for all pre-term infants was to achieve regulation and modulation between these subsystems (Miller & Quinn-Hurst, 1994). This model also assumes that infants achieve “behavioral organization” by neurophysiologic modulation “techniques” including modulation of primitive reflexes, such as the gag and startle reflexes and “states”
of consciousness (Boner & Perlin, 1984; Brazelton, 1973; Kopp, 1982). Some simple examples of infant behavior that reflect “behavioral organization” include grasping to limit the movement of extremities or looking away to decrease the level of interaction (Miller &
Quinn-Hurst, 1994). These primitive mechanisms assist the infant to (1) stabilize biological functions, (2) safeguard the immature organism from intrusive or strong stimulation (Kopp,
1982), and (3) to allow the child to self-calm (Hoffman & Ison, 1992). This model also assumes that an increasing level of neuorlogic maturation will occur with increasing gestational age, therefore, improved “behavioral organization” skills would be expected the closer to term (i.e. 40 weeks) that the child was born (Hoffman & Ison, 1992; Nijhuis, 1995).
Duffy, Als & McAnulty (1990), supports this finding by showing that pre-term infants with a gestational age of 26-32 weeks showed the most difficulty with autonomic and motor organization, as compared with pre-term infants of 33-37 weeks gestation, and that normal, full-term infants (38-41 weeks) were the most organized. Primarily, this “behavioral organization”model has been applied to infants through 42 weeks gestation with significant evidence for support (Als & Gilkerson, 1995; Brazelton, 1973; Comrie & Helm, 1997;
DiPietro & Porges, 1991; DiPietro, Porges, & Uhly, 1992; Einarsson-Backes et al., 1994;
Johnston et al., 1993; Johnston et al., 1995; Stengel, 1980; Stevens et al., 1994).
Therefore, to summarize, in normal infant development “behavioral organization” implies the ability to modulate state behavior and reflexes appropriately, thus allowing the infant to attain a calm, alert state more often and consistently. This calm, alert state, in turn, is a critical pre-cursor for learning more advanced skills such as successful transitioning to oral feedings (Brazelton & Cramer, 1990; Miller & Quinn-Hurst, 1994; Porges, 1992; Ramsey &
Gisel, 1996).
2.2.6 Other research was completed which supports the idea that specific nervous system responses are fluid and appear to develop on a continuum.
Using both ultrasound technology for fetal monitoring and observations of pre-term infants, Prechtal(1987) dissected the very early development of motor movements and developed a continuum of neural functions from prenatal to postnatal life.
2.2.7 Two other important concepts emerged from the literature on “homeostasis”: homeostasis can have lasting effects on future development, and “homeostasis” is the period of time that the autonomic nervous system matures.
Until the last decade very little research has been published outlining difficulties that might be observed in infants if these infants do not successfully complete the developmental stage of “homeostasis”. However, Greenspan (1992) has suggested that certain “regulatory” disorders may stem from aberrant development during the period of homeostasis. By definition, children may present with a regulatory disorder if it is first evidenced in infants older than 6 months of age who demonstrate difficulties with regulating physiological, sensory, attentional and motor or affective processes, and organizing a calm, alert or positive state (DeGangi, 1991; Greenspan & Lourie, 1981; Greenspan & Weider, 1992). Ultimately these children can present with sleep or feeding difficulties, deficits in their speech and language development, play skills and/or regulation of emotional state (Greenspan, 1990;
Greenspan & Weider, 1992). These “regulatory” difficulties were organized and classified into four categories following observations of children in Dr. Greenspan’s clinical practice, including hypersensitive type, underreactive type, active-aggressive type, and a mixed type.
In addition, DeGangi and Greenspan (1988) documented that infants with regulatory disorder symptoms had a higher incidence of sensory processing dysfunction. This dysfunction
included a hypersensitivity to tactile and vestibular stimulation. However, Greenspan (1992) indicated that the causes of these disorders continued to be “unclear”.
2.2.8 Another approach to understanding a child who presents with a regulatory disorder symptom is to study autonomic nervous system response patterns (DeGangi,
1991).
According to DeGangi, et al. (1991) as early as 1915, Eppinger and Hess investigated the relationship between psychosomatic symptomatology and the reactivity of the vagal system. Based on this idea, DeGangi et al.(1991) developed a hypothesis that the regulatory disordered infant might exhibit autonomic hyperirritablity caused by defective central neural programs and mediated via neurotransmitters through the vagus nerve. These authors then designed an experimental tool that measures a physiologic response called “vagal tone”.
“Vagal tone” according to Porges, Doussard-Roosevelt, Portales & Greenspan (1996) is a construct that describes the functional relationship between the heart and the brainstem, and physiologically plays two roles. First, during states of low environmental demand, vagal tone fosters physiological homeostasis to promote growth and restoration. Second, during states characterized by environmental challenges, the vagus nerve acts as a brake to rapidly regulate metabolic output. Subsequently, the results presented by DeGangi, et al. (1991) was the first preliminary evidence that children with regulatory disorders present with atypical physiological response patterns. Other studies began to appear in the literature to substantiate this primary evidence found by DeGangi et al.(1991). DiPietro, Porges and Uhly
(1992)compared full-term and premature infants to a surprise stimulus using vagal tone as the measurement for changes observed. It was predicted that the activation of the nervous system would be the more adaptive regulatory response because it would facilitate
homeostasis within the autonomic nervous system after a disruption. DiPietro et al.(1992)found that vagal reactivity is associated with exploratory competence for both pre- term and full-term infants and suggest that measurement of infants’ behavioral and autonomic reactivity may provide access to aspects of development that reflect processing of environmental stimuli.
DeGangi, Porges, Sickel and Greenspan (1993) completed a four-year follow-up study on a sample of infants presenting with regulatory disorders. Cardiac vagal tone was used as their measurement tool. These authors found that normal infants with high vagal tone had better behavioral organization than infants who had been diagnosed with regulatory disorders and who also presented with high vagal tone. This was the first formal substantial evidence that untreated regulatory disordered infants with moderate to severe regulatory difficulties do not outgrow their difficulties. In fact this group of infants were found to be at high risk for later perceptual, language, sensory integrative, and behavioral difficulties in the pre-school years (DeGangi et al., 1993; Porges & Doussard-Roosevelt, 1997). Porges,
Doussard-Roosevelt, Portales and Greenspan (1996) found support for this leading evidence in a study that found a relationship between aberrant vagal tone responses in infants who are
9 months old who then presented with significantly more behavioral problems at 3 years of age.
2.2.9 Developmental Levels by Porges
In 1996, Porges generated a model that identifies the importance of neural regulation of autonomic state as an antecedent substrate for emotional, cognitive and behavioral regulation. This model, although focuses on the high-risk infant, may be generalized into the study of older children and adults with behavioral and psychological problems. Some key
points presented by Porges (1996) include: a) Prior to the infant mastering complex behavioral interactions with the environment, the infant must competently regulate autonomic processes. b) Current means of studying normal physiological and behavioral development emphasized the importance of the external environment. c) Homeostasis is not a passive process in which physiological systems remain constant. Rather it is an active, neurally modulated process in which physiological systems vary within viable ranges. d)
The feedback from internal sensors and their interaction with the vagus nerve inputs is interpreted by brainstem structures that contribute to the regulation of autonomic state (i.e. nucleus tractus solitarius, nucleus ambiguus, etc.). e) Finally, self-regulatory processes characterize various domains ranging from the overt behavioral strategies of the infant demanding caregiver attention, to subtle physiological shifts related to changes in temperature, digestion, or cardiopulmonoary function.
Using the model as a theoretical base, Porges (1996) developed the Polyvagal Theory in order to substantiate specific clinical assessments and interventions in the Neonatal
Intensive Care Unit (NICU). This theory describes two distinct types of vagal responses that infants may present to stressors. The first vagal system described is called the “neo- mammilian” system. This system is considered the healthy means that an infant utilizes to maintain physiologic homeostasis. The initial response of the mammalian system is characterized by a rapid withdrawal of vagal tone that instantaneously increases heart rate, thus in turn the metabolic output. This type of response increases the strength and speed of response to the stress, however it also reduces the control of the motor systems. Therefore a common physiologically normal stress sign of infants is the difficulty in coordination of the suck-swallow-breathe triad. Although the mammalian system is considered the normal or
healthy response pattern to stress, if this system is frequently being challenged (i.e. medical interventions such as gavage feeding) it could become detrimental to the developing infant system. If the infant is in the mammalian system and homeostatic functions are compromised, the child is in a heightened physiological or aroused state. In addition, if this aroused state is elicited too frequently, the infant is then at risk for going into one of two more primitive types of response patterns (Doussard-Roosevelt & Porges, 1999). The first of these two response patterns involves the spinal sympathetic system working in conjunction with motor pathways characterized by a fight or flight response pattern. There is typically a massive increase in heart rate and the fostering of mobilization occurs (Doussard-Roosevelt
& Porges, 1999).
In some infants, however, a second primitive response pattern may be observed. This second type of vagal response has been deemed as the “reptilian” vagal system. Basically with this type of response pattern the system shuts down by eliciting a mass increase in vagal tone that in turn slows the heart and constricts the bronchi (Doussard-Roosevelt & Porges,
1999; Porges, 1996; Porges et al., 1996). Clinical observations of infants who are utilizing maladaptive strategies in response to stress can range from a potentially lethal bradycardia
(slow heart rate) and/or apnea to cardiac arrhythmias. In other words, some infants respond abnormally to stress by shutting down and other infants present with hypermotility and other fight/flight responses (McCulloch, Panneton, & Guyenet, 1999; Porges, 1996).
Utilizing the Polyvagal Theory and clinical experience, Porges (1983; 1996) developed a hierarchical model of four developmental stages of self-regulation. This model assumes that behaviors are dependent upon a more primary physiological substrate related to the systematic regulation of the autonomic state. In addition, this model of self-regulation
provides important information pertaining to the details of both the period of homeostasis and a new level established prior to this stage.
Level I. (Pre-term infants) Neurophysological processes are characterized by bi-directional communication between the brainstem and peripheral organs to maintain physiologic homeostasis. The brainstem structures interpret sensory information and regulate the visceral state by triggering motor pathways that either directly manipulate (through heart rate changes, facilitation of peristaltic activity, etc.) or trigger the release of hormones or peptides (i.e. adrenaline, oxytocin, gastrin, etc.). In this stage typically only a single physiologic system can be evaluated at a time.
Level II. (Homeostasis) “Cost of doing business” This stage represents the coordination of multiple physiologic systems. For example, it is conceivable that on a single variable level each individual system reflects appropriate organizational qualities (i.e. temperature is regulated, sleep/wake cycles are regulated, etc.) However, coordination between these physiologic systems may be disorganized. Because the autonomic nervous system services the needs of the internal viscera and responds to external challenges, response strategies to environmental demands and homeostasis are interdependent.
Level III (No age specified) This level reflects the organization of overt behavior. At this level a deficiency in the organizational characteristics of the nervous system as reflected in underlying physiological activity would be manifested in dysfunctional overt behavior. Measurable and observable motor processes including body movements and facial expressions can be evaluated in this stage in terms of quantity, quality and appropriateness.
Level IV (No age specified) Processes that reflect the coordination of motor behavior, emotional tone, and bodily state that successfully negotiate social interactions. Unlike those of Level III, these processes are contingent with prioritized cues and feedback from the external environment. This level reflects the pinnacle of organization.
According to Porges (1983) these levels of neurobehavioral organization force us to evaluate the methods available to answer our research questions. Porges (1983) continued by asserting that researchers typically have two views when studying behavior and nervous system interactions. These include either 1) a monotonic relationship between a global construct of nervous system status and behavior or, 2) independence between behavior and neurophysiological mechanisms. Neither view, however, supports that neurobehavioral
systems are dynamic and interactive. This recent work, led by Porges, has been ground
breaking for substantiating the importance of the period of homeostasis as a critical time for
autonomic nervous system maturation and the potential lasting effects on future development
if not successfully achieved.
It is interesting that autonomic nervous system connections have been made within
the neonatal literature regarding both “behavioral organization” and “regulatory” disorders.
Brazelton (1990) broached this point by postulating that autonomic immaturity is at the core
of “state” instability. In addition, Greenspan (1992) provided several examples of poorly
organized or modulated responses including: irregular breathing, startles, hiccups, gagging,
attention and/or affective disorganization, and poor sleeping, eating or elimination patterns,
all which have a direct connection with the autonomic nervous system. However, neither the
behavioral organization literature nor the regulatory literature takes an in-depth look into
postnatal development of the autonomic nervous system as supported through animal or early
human studies.
SECTION 3: POSTNATAL DEVELOPMENT OF THE AUTONOMIC NERVOUS SYSTEM: AN IN-DEPTH REVIEW OF THE NUCLEUS TRACTUS SOLITARIUS
2.3.1 Animal studies supporting postnatal development of the autonomic nervous system: An Introduction
This investigator, like many clinical researchers, faced a challenge of having observed clinical phenomenon in which there was no literature tying the observations together. Yet, clinical experience has clearly demonstrated that certain populations of both neonates and children with mixed FTT can present with three different responses to touch
(firm pressure). These responses include: a) a normal response (no response or calming response), b) state behavior changes and c) an abnormal gag reflex.
Two specific questions arose: 1) “What similarities exist between the neonatal
population and the population of children with mixed FTT in regards to presenting
with these responses to touch?”The similarities between the infants/toddlers who presented
with these abnormal responses to touch within the neonatal population and mixed FTT
population were notable. First, both populations of infants had received medical procedures
that interfered with normal orosensory input. In addition, these populations of children also
presented with persistent feeding difficulties once the medical intervention had stopped.
Furthermore, the population of mixed FTT children who present with these abnormal
responses have received at least 2 weeks of alternative feedings during the first three months
of life. This time frame of the first three months of life is a critical component because it is
well documented to be the “Period of Homeostasis” (see sections 2.20-2.28). This period of
“homeostasis” represents the normal stage of development when the infant stabilizes
biological functions such as sleep-wake cycles, state behavior, feeding, and excretion
patterns (Chatoor, Schaefer, Dickson, & Egan, 1984; Greenspan, 1990; Porges, 1996). As we
know, the autonomic nervous system (ANS) is the neurologic substrate that acts to maintain
homeostasis in the body (Wilson-Pauwels, Stewart, & Akesson, 1997). Therefore, the
common denominator between the two specific subpopulations of neonates and mixed FTT is
that both groups have an interruption of normal sensory input while the autonomic nervous
system is continuing to mature. Based on this first answer a second question arose.
2) “Is there a specific part of the autonomic nervous system which may be directly
affected by the lack of normal orosensory input and could trigger these aberrant ANS
responses to touch?” In order to best answer this question it had to be determined if a common denominator between the gag reflex and state behavior changes within the ANS
existed as the most likely source for these aberrant responses to touch. This common denominator was the nucleus tractus solitarius (NTS), the principal medullary coordinating center for autonomic function (Dodd & Role, 1991). Basic science research has shown that a gag reflex response is mediated by afferent fibers received by the NTS with the efferent branch by the nucleus ambiguous (Martin & Jessell, 1996). This information was combined with the work of Porges (see section 2.2.9) that discusses the vagal system as a means to maintain “homeostasis”. Basic science research has also shown us that the majority of vagal afferent information is brought into the NTS (Brining & Smith, 1996; Kalia & Sullivan,
1982; Travers & Norgren, 1995; Zhang, Fogel, & Renehan, 1995). Therefore, the NTS is the most logical part of the autonomic nervous system to review. Many may argue that this brainstem portion of the autonomic system is not the likely source of difficulty because until recently it was assumed to be complete at birth. However, it has become increasingly clear through animal studies and human postpartum studies that continued changes persist well into the first year of life (Azmitia & Whitaker-Azmitia, 1991; Bornstein et al., 1987;
Carpentier et al., 1997; Denavit-Saubie et al., 1994; Goya et al., 1990; Jaquin et al., 1995;
Ma, 1993; Salas et al., 1986; Takashima & Becker, 1986; Takemura et al., 1996; Tomlinson
& Coupland, 1990; Vincent & Tell, 1997; Young & Morrison, 1998).
Recent animal studies have been completed that specifically review changes within the NTS during periods of oral deprivation (Lasiter, 1995; Lasiter & Diaz, 1992). Some key factors were noted from this research including: 1) altered development of afferent terminal fields, 2) specific orochemical stimulants were necessary to promote normal development
(other types had no effect) and 3) a specific number of days of artificial stimulation were required to produce normal development. Therefore, altered development of the NTS may
play a significant role in the behavioral profile of the population being studied. However, the exact mechanism within the NTS is left for further research.
2.3.2 The NTS: An In-Depth Review
This section will first review the structure, function and development of the NTS and then discuss research examining deprivation and the effects on the NTS.
The NTS is an important component of the autonomic system that also has ties with the somatosensory system, visceral and special sensory information systems, cardiac and respiratory centers, and is associated with a variety of reflexes (i.e. salvation, fluid homeostasis and thirst, food intake, vomiting, swallowing, gagging and coughing). In addition, the NTS has been linked to the regulation of sleep states and behavioral states and can influence learning and memory skills (Allen, Barbrick, & Esser, 1996; Boughter, St.
John, & Smith, 1999; Card, Swanson, & Moore, 1999; Dodd & Role, 1991; Jean, 1984a;
Larson, Yahima, & Ko, 1994; Martin & Jessell, 1996; Matsuo, Yamamoto, Yoshitaka, &
Morimoto, 1989; Miller & Ruggiero, 1994; Smith & Shepherd, 1999; Steinbacher & Yates,
1996; Sved, 1999; Widdecombe, 1995; Yates, Siniaia, & Miller, 1995). The NTS is considered one of the most critical brainstem areas involved in coordination of reflexive activity although higher centers can influence this complex medullary region. In other words the NTS has two means of modulating autonomic function: 1.The NTS can control simple autonomic function by means of a set of reflex circuits (Chan, Chan, & Ong, 1986; Matsuo et al., 1989; Menetrey & Basbaum, 1987; Yu & Gordon, 1996) or, 2. The NTS coordinates elaborate homeostatic adjustments by transmitting information from autonomic targets to both higher and lower brain regions. These regions then relay integrated information required
for more complex autonomic control back to the NTS (Dodd & Role, 1991; Gu & Ju, 1995;
Halsell, Travers, & Travers, 1996; Hayward & Felder, 1995; Jean, 1984a; Jean & Car, 1979;
Valentino, Pavcovich, & Hirata, 1995).
2.3.3 Parallel medullary structures which course with portions of the NTS
The NTS is a component of the solitary complex which is located in the dorsal medulla (see Figure 2.3.3a). This complex is made up of the solitary tract that terminates into the solitary nucleus. The NTS extends from the dorsal column nucleus and somatosensory decussation in the caudal medulla superiorly to the rostral medulla.
Figure 2.3.3a: The NTS in the dorsal medulla with the obex as the reference point (Martin, 1996)
In a review article by Kalia and Mesulam (1980) the NTS of several animal species was outlined and consolidated in order to provide precise measurements of the NTS and define its surrounding structures. As described in the review article the NTS extends bilaterally from approximately 1.8 mm below the level of the obex to approximately 3.2mm above the level of the obex (see schematic representation in Figure 2.3.3b) (Kalia & Mesulam, 1980). (Note:
The obex is a reference point within the medulla that is marked by the v-shaped caudal portion of the fourth ventricle where it narrows into the central canal [see Figure 2.3.3a]).
The surrounding structures of the NTS at its origin can be reviewed in a schematic representation as seen in Figure 2.3.3b.
Figure 2.3.3b: Schematic representation of a coronal slice taken at 1.8mm below the level of the obex.
At this level in the medulla the pyramids (P) and inferior olives (IO) can be seen at the ventral end of the slice. The most medial structure is the central canal (CC) with the hypoglossal (nXII) nucleus just adjacent, bilaterally. The dorsal motor nucleus of the vagus nerve (dmnX) can be observed just dorsal to these structures. Finally the NTS (3 subnuclei) and solitary tract can be observed just dorsal and lateral to the dmnX.
Some of the structures that surround the NTS at the most rostral level at 3.2 mm above the level of the obex, is different than those at the origin. Figure 2.3.3c shows a schematic representation of a coronal slice taken at 3.2mm above the level of the obex.
Figure 2.3.3c: A schematic representation of the surrounding structures of the NTS at 3.2mm above the level of the obex.
At this level the pyramids and inferior olives remain at the ventromedial most portion of the slice. The medial longitudinal fasciculus now resides in the medial portion of the slice. The hypoglossal nucleus (nXII) can now be observed in a dorsomedial position with the NTS adjacent laterally. The relative position of the dorsal motor nucleus of the vagus nerve
(dmnX) remains unchanged from Figure X, thus remains in its ventral position relative to the
NTS. Two additional structures can be observed in Figure Y which were not present in the more caudal slice. The nucleus ambiguous (NA) can now be observed ventral to the dmnX that is ventral to the NTS. And the spinal trigeminal nucleus (spV) is lateral and slightly ventral to the NTS with some overlap observed.
Therefore, as the NTS courses its 5mm within the medulla from –1.8mm below the level of the obex to 3.2 mm above the level of the obex, several main structures can be identified that run parallel with the entire length or portions of the NTS (see Table 2.3.3 below). As noted earlier, both the dorsal motor nucleus of the vagus nerve and the
hypoglossal nucleus have their beginnings in more caudal regions than that of the NTS.
These two structures however, will run parallel with the entire course of the NTS and beyond.
Table 2.3.3 Medullary Structures and Beginning Level which to Parallel the NTS
Structure: Course: Dorsal motor nucleus of X entire length Hypoglossal Nucleus entire length Pyramids entire length Inferior Olive (IO) entire length Medial Longitudinal Fasciculus -1.2mm from obex beyond apex Spinal Trigeminal Nucleus at level of obex (0.0mm)beyond apex Nucleus Ambiguous 0.6mm from obex beyond apex
(Kalia & Mesulam, 1980)
Two other structures also run the entire length of the NTS, and these include the inferior olives and the pyramids. Portions of other structures that will course with the NTS include: the medial longitudinal fasciculus from –1.2mm, the spinal trigeminal nerve begins at the level of the obex(0.0mm) and the nucleus ambiguous begins at .6mm above the obex.
All of these structures run parallel with the NTS past the apex of where the NTS ceases at
3.2mm above the obex. Therefore, although some of the reference points change as the NTS courses through the medulla, many of the structures and the relative positions of those structures to the NTS remains unchanged.
2.3.4 Cytoarchitecturally the NTS is a very complex system
In its simplest form the NTS is divided into two functionally distinct parts: a rostral gustatory nucleus and a caudal cardiorespiratory nucleus. However, a review article by Kalia and Sullivan (1982) reveals a number of animal/human models that have displaced this rudimentary division and nine distinct subnuclei were identified. These subnuclei include: the dorsal nucleus (dnTs), dorsolateral nucleus (dlnTs), medial nucleus (mnTs), commissural
nucleus (ncomm), intermediate nucleus (nI), interstitial subnucleus (ni), subnucleus gelatinosus (sg), ventrolateral subnucleus (vlnTs), and ventral subnucleus (vnTs).
Although this paper will utilize the nomenclature outlined by Kalia and Sullivan (1982), it should be noted that one of the challenges of studying the NTS and its subnuclei has been the wide interpretations across various animal types studied (i.e. cats, rats, birds, rabbits, humans etc.). For example, variations between cat and rat studies have found that the rat does not have a subnucleus gelatenosus, yet in the cat it is a prominent subnucleus (Kalia & Sullivan,
1982). In addition, in some of the various animal types, specific categorization can be difficult because of adjacent or overlapping structures. For example in the caudal medulla there is a circumventricular organ that overlies this portion of the NTS called the area postrema that is often poorly differentiated from the NTS ((Hayward & Felder, 1995).
Another example of the challenges with creating specific nomenclature for NTS subdivisions can be found specifically with rat models. In this case the NTS is poorly delineated from the reticular formation (RF), which it overlays thus preventing an accurate view of each subdivision (Kalia & Sullivan, 1982).
Like many areas of the brain, the NTS is arranged with a general pattern of viscerotopic organization. The rostral or “gustatory” portion of the NTS receives taste information from the chorda typani branch of the facial nerve, greater superficial petrosal nerve of the glossopharyngeal and superior laryngeal nerve of the vagus (Brining & Smith,
1996). This information regarding taste is organized in a rostral to caudal manner (Dodd &
Castellucci, 1991; Patrickson, Smith, & Zhou, 1991; Smith & Shepherd, 1999).
The caudal or “cardiorespiratory” portion of the NTS has been implicated for afferent and efferent projections related to blood pressure regulation and respiratory rate (Martin &
Jessell, 1996). Typically this information is carried via the vagus and glossopharyngeal nerves, which also appear to be arranged in an organized fashion. Another example of viscerotopic organization within the NTS specifically can be observed from the visceral afferents from the gut for regulating gastrointestinal (GI) motility and secretions (Zhang et al., 1995). From the tip of the tongue to the cecum, afferent information from these structures has been represented from a caudal to medial position within the NTS (Travers & Norgren,
1995). In addition to these highly arranged systems, there are also numerous local connections among neurons within the NTS and with cells of the oral, facial, phayngeal and motor nuclei (including the nucleus ambiguus, cranial nerve V, VII, and XII) either directly or via interneurons of the reticular formation (Allen et al., 1996; Furusawa, Yasuda, Okuda,
Tanaka, & Yamaoka, 1996; Smith & Shepherd, 1999). Table 2.3.4a provides a summary of the afferent projections received by the NTS and Table 2.3.4b provides a summary of the efferent projections from the NTS.
Table 2.3.4a NTS Afferent Projections______Afferent Projections: subnuclei or region (if specified) Chorda Tympani (of CN VII) rostral central Carotid Sinus Branch (of CN IX) mnTs, vlnTs, dnTs, ncomm, ni, ap Aortic Nucleus dnTs, ni Recurrent Laryngeal Nerve (of CN X) ni, mnTs Inferior Ganglion of X lnTs, mnTs Glossopharyngeal nerve (in general) rostral central, ncomm, mnTs Mandibular Branch (of CN V) dlnTs Intermediate Nuc of Geniculate Ganglion (VII) sg, lnTs, dlnTs Petrosal ganglion (of CN IX) mnTs, ncomm Nodose ganglion (of CN X) lnts, ncomm, mnTs and caudal NTS Superior Laryngeral Nerve (all branches, CN X) ni, rostral central Cervical Trunk (of CN IX) mnTs, ni, (ipsilateral NA, Vsp) Barrington’s Nucleus of the Pons rNTS Nucleus Ambiguus cNTS Fastigial Nucleus of the Cerebellum entire NTS Dorsal Parabrachial Nucleus of Pons ------Paraventricular Nucleus of the Hypothalamus ------Central Nucleus of the Amygdala ventral rNTS Gustatory Neocortex rNTS Medial Prefrontal Cortex ------Bed of Nucleus of Stria Terminalis ------Medial and Lateral Portions of Hypothalamus ------Stomach (gastric portions) sg Esophageal cNTS Stomach/Caudal Intestine mNTS Cecum/Caudal Intestine ncomm Lingual Branch of V (trigeminal nerve) rostral central Interneurons ------References: (Beckstead, Morse, & Norgren, 1980; Block & Kapp, 1989; Brining & Smith, 1996; Conteras, Beckstead, & Norgren, 1982; DiLorenzo & Monroe, 1995; Furusawa et al., 1996; Gu & Ju, 1995; Halsell et al., 1996; Jean & Car, 1979; Menescal-De-Oliveria & Hoffman, 1995; Nomura & Muzuno, 1982; Panneton & Loewy, 1980; Patrickson et al., 1991; Seiders & Stuesse, 1984; Steinbacher & Yates, 1996; Valentino et al., 1995; Walker, Easton, & Gale, 1999; Xu & Frazier, 1995; Zhang et al., 1995)
Table 2.3.4b NTS Efferent Projections______
Efferent Projections: Medial and lateral Portions of Parabrachial Nucleus (PBN) Reticular Formation Central Nucleus of the Amygdala Superior Salvitory Nucleus “Oromotor” nucleus Medial Vestibular Nucleus Spinal Trigeminal Nerve Caudoventrolateral Medulla (CVLM) Dorsal PBN Paraventricular nucleus of the Hypothalamus Nucleus Ambiguus Entorhinal Cortex Endopyriform Nucleus Insular Cortex Bed of Stria Terminalis Substantia Innominata Nucleus ventralis posterior medialis pars parvocellular of the thalamus Subfornical Organ Spinal Sympathetic and Adrenal Medullary Outflow Locus Ceruleus Medial Frontal Cortex
References: (Beckstead et al., 1980; Block & Kapp, 1989; Brining & Smith, 1996; DiLorenzo & Monroe, 1995; Gu & Ju, 1995; Halsell et al., 1996; Hayward & Felder, 1995; Jean & Car, 1979; Martin & Jessell, 1996; Matsuo et al., 1989; Menescal-De-Oliveria & Hoffman, 1995; Seiders & Stuesse, 1984; Walker et al., 1999; Yates et al., 1995; Yu & Gordon, 1996)
2.3.5 The NTS participates in a number of critical brain activities including (see the outline below of this section)
2.3.5a BLOOD PRESSURE REGULATION( Short-Term Cardiovasuclar Homeostasis) Baroreceptor Reflex Chemoreceptor Reflex Postural Adustments Stressful Stimuli/Reaction to a Percieved Threat
2.3.5b WATER REGULATION and REGULATION of BLOOD VOLUME
2.3.5c NEURONAL REGULATION OF RESPIRATION Introduction Respiratory Mechanoreceptors Slowly Adapting Receptors Rapidly Adapting Receptors Bronchopulmonary c-Fibers Respiratory Chemoreceptors Respiratory Protective Reflexes Coughing Gagging Sighing Sneezing Yawning Other Respiratory Phenomena
2.3.5d CONTROL OF FOOD INTAKE (Caloric Homeostasis) Introduction Salivation Swallowing
2.3.5e MISCELLANEOUS NTS INVOLVEMENT Nociception Learning/Memory Seizure Regulation
2.3.5a BLOOD PRESSURE REGULATION (Short-Term Cardiovascular
Homeostasis)
In order for our systems to maintain a narrow normal range of blood pressure within a
variety of situations, a number of neurologic regulatory systems are in place. The majority of
these neurologic regulatory systems have a direct connection with the NTS including: the
baroreceptor reflex, chemoreceptor reflex, postural changes and behavioral alerting to a
perceived threat.
The baroreceptor reflex is an example of a negative feedback system that is in place to detect acute changes in blood pressure as arterial walls become distended. In other words, as blood pressure deviates from a narrow normal range, the change is detected by stretch receptors or baroreceptors found within 2 major blood vessels: the carotid sinus and aortic arch, and are compensated by this reflex (Sved, 1999). Afferent information about the distension of the arterial walls is carried to the caudal NTS via the carotid sinus branch of the glossopharyngeal nerve and the aortic branch of the vagus nerve (Panneton & Loewy, 1980;
Seiders & Stuesse, 1984). Depending on the type of change that was detected, the NTS will activate either a sympathetic or parasympathetic response. In a situation where blood pressure is too low and needs to be increased, the NTS will send impulses in order to activate the sympathetic portion of the baroreceptor reflex. Information from the NTS is sent to the caudal ventrolateral medulla (CVLM), which in turn sends to inhibitory projections to the rostral ventrolateral medulla (RVLM) which in turn influences the interomedolateral (IML) zone of the thoracic spinal cord. This in turn causes peripheral vasoconstriction which causes an increase in systemic BP (Steinbacher & Yates, 1996; Yu & Gordon, 1996). The parasympathetic system is activated if information from the baroreceptors to the NTS
indicates that blood pressure is too high. Information from the NTS is sent to the vagal
cardiomotor neurons of the nucleus ambiguous (NA) and dorsal motor nucleus of the vagus
nerve (DM NucX). Information from these nuclei will, in turn, inhibit sympathetic vasomotor
via the CLMV and RLMV thus reducing systemic blood pressure (Sved, 1999). Therefore,
cardiovascular homeostasis via the baroreceptor reflex is the result of opposing controls
between the tonically active sympathetic innervation and the negative feedback loop to the
RVLM via the NTS (Sved, 1999).
The chemoreceptor reflex detects sensitivity changes to blood oxygen levels. In other words, when there is a decrease in blood oxygen levels (called hypoxemia) it requires blood pressure and circulatory changes to preserve the oxygen delivered to the brain. This reflex is similar to the baroreceptor reflex in the sense that the information is carried from the carotid sinus branch of the glossopharyngeal nerve to the caudal NTS, where the sympathetic response to increase blood pressure through the CVLM, RVLM to the IML of the thoracic spinal cord is activated. However, because the chemoreceptor activates both a blood pressure response and circulatory changes the afferent information from the carotid sinus nerve is taken to a different location within the caudal NTS to allow for more complex, higher order efferent projections (Sved, 1999). These projections allow for reflex vasoconstriction in most tissues to redirect blood flow to the brain as well as sending information to the parabrachial nucleus (PBN) of the pons in order to integrate signals between blood pressure and respiratory activities (Hayward & Felder, 1995; Sved, 1999). In addition it has been documented that some of the signals to the PBN reportedly connect to activate the central nucleus of the amygdala, which is a structure that modulates emotional behavior and its autonomic correlates (Block & Kapp, 1989).
The vestibular system is also known to participate in cardiovascular control of blood pressure (Yates, 1992). This system, through a vestibulo-sympathetic reflex appears to play a critical role in making immediate changes in blood pressure during postural adjustments.
Animal research has shown that when vestibular inputs are removed there is a decreased ability to maintain normal blood pressure (Doba & Reis, 1974). The vestibulo-sympathetic reflex appears to work in conjunction with the baroreceptor reflex at the level of the CVLM.
In other words, if the NTS receives information from the carotid sinus branch of the glossopharyngeal nerve that blood pressure is too low because of a postural position, the
NTS will activate the sympathetic baroreceptor reflex sending the signal to the CVLM. It is at the CVLM that the information from the NTS and medial and inferior vestibular nuclei will converge (Siniaia & Miller, 1996; Steinbacher & Yates, 1996). This information will then be sent to the RVLM which will then project to the preganglionic neurons of the IML of the thoracic spinal cord, causing appropriate peripheral vasoconstriction that will result in an increase in blood pressure (Steinbacher & Yates, 1996).
Finally, blood pressure changes occur when a stressful stimulus or a reaction to a perceived threat is activated. During this “fight or flight” response the sympathetic nervous system is activated by the hypothalamopituitary-adrenal axis (HPA) to produce an integrated and coordinated cardiovascular response (Sved, 1999). In order to achieve this coordinated response directed from the hypothalamus, two specific mechanisms must be activated. First there is an inhibition of the baroreceptor reflex at the level of the NTS (Sved, 1999). Then, input to the RVLM directly will activate the sympathetic response to the IML of the spinal cord (Hilton, Marshall, & Timms, 1983; Sved, 1999).
2.3.5b WATER REGULATION AND REGULATION OF BLOOD VOLUME
Circulatory volume can be impacted in two ways: 1). Osmotic dehydration (lack of adequate
body fluid, i.e. water), and 2). Hypovolemia, or loss of blood volume. Both situations can also
directly impact blood pressure regulation. The afferent information thus is sent to the NTS (as
well as other brain areas). Water regulation can be monitored by cholecystokinin (CCK), which
will, in turn, act on gastric afferents which then are found to terminate in the NTS (Verbalis,
Hoffman, & Sherman, 1995). Hypovolemia on the other hand is initially detected by
baroreceptors of the right atrium of the heart, and if the blood loss is great enough other
baroreceptors are also activated (Stricker & Verbalis, 1999). Information is sent from the
baroreceptor or gastric afferents to the NTS which in turn will send information to a number
of specific brain regions including: paraventricular nucleus of the hypothalamus, subfornical
organ and parabrachial nucleus of the pons (Gu & Ju, 1995). Information provided to these
areas will then mediate neuroendocrine responses for thirst and NaCl (salt) appetite (Ciriello
& Calaresu, 1980; Gu & Ju, 1995; Herbert, Moga, & Saper, 1990; Shioya & Tanaka, 1989;
Tanaka & Seto, 1988).
2.3.5c NEURONAL CONTROL OF RESPIRATION
Introduction
Respiration is a very complex process that ultimately requires a patterned motor output with appropriate timing and magnitude of muscle contraction and relaxation. Neuroscientists believe that a simple rhythm generating system lies at the core of neural circuits for breathing. Spinal motor neurons innervate muscles of the respiratory “pump” and cranial motor neurons innervate muscles that modulate airway resistance (Feldman & McCrimmon,
1999). However, there are a number of variables that can directly influence respiration
including posture, swallowing, sleep, phonation, emotions, temperature, exercise, defecation,
emesis and cardiovascular changes (Feldman & McCrimmon, 1999; Travers & Norgren,
1995). Despite the complexity of this system this section will focus only on the sensory
inputs, respiratory protective reflexes and pre-motor outputs that have a direct connection
with the NTS.
Respiratory Mechanoreceptors and Chemoreceptors
There are two broad types of respiratory sensory receptors that send information directly to the NTS: mechanoreceptors and chemoreceptors. Mechanoreceptors convey
information about lung volume, lung inflation rate and pulmonary tissue status. There are
three different types of afferent mechanoreceptor fibers: slowly-adapting stretch receptors
(SAR), rapidly-adapting pulmonary stretch receptors (RAR) and brochopulmonary c-fibers.
All of these fiber types bring the specific information through the jugular and nodose ganglia
of the vagus nerve to 3 distinct regions of the NTS.
Slowly-adapting stretch receptors are myelinated A-fibers found in the airway
smooth muscle and respond to the distention of the airway. Activation of these fibers can
trigger the “Breuer-Hering” reflex in which inspiration is prematurely terminated and
expiration is prolonged. In addition, activation of these fibers also relaxes the airway smooth
(Feldman & McCrimmon, 1999). Information from these receptors terminate ipsilaterally in
the NTS, in a position slightly rostral to the obex (Kalia & Richter, 1985).
Rapidly adapting pulmonary stretch receptors are myelinated A-fibers found in the
airway epithelium that are stimulated by rapid lung inflation/deflation, chemical irritants or
swelling in the walls of large airways. These receptors trigger a cough, a sigh, a decrease
airway expiration or an airway constriction (Feldman & McCrimmon, 1999). These fibers
terminate bilaterally in the same region of the SAR fibers with additional fibers also terminating ipsilaterally in the region just caudal to the obex (Davies & Kubin, 1986;
Feldman & McCrimmon, 1999). Finally, bronchopulmonary c-fibers are unmyelinated fibers that are found in the airways and alveolar walls. These receptors are stimulated by irritants and edema and can trigger reflex responses of apnea, shallow breathing, airway constriction and mucous secretion (Feldman & McCrimmon, 1999). These fibers terminate in the dorsomedial aspects of NTS distributing rostral/caudal to the obex (Bonham & Joad, 1991;
Kubin & Davies, 1995).
Chemoreceptors measure information about oxygen and carbon dioxide levels using two distinct pathways. Oxygen changes are detected at the carotid bodies (the bifurcation of the carotid artery which are the areas through which most of the oxygen enters the brain) and brought through the carotid sinus branch of the glossopharyngeal nerve to the caudal region of the NTS (Seiders & Stuesse, 1984). Specific information about the exact neurologic sensor and subsequent processing for carbon dioxide and acid/base balance (pH) information is unclear at this time. However, it is known that when carbon dioxide levels become too high an increase in respiration is observed which, in turn, implicates a connection with the NTS
(Feldman & McCrimmon, 1999).
Respiratory Protective Reflexes
Sensory receptors in the lungs and airways have an important role in not only the control of breathing but also with pulmonary defense reflexes. The following 5 reflexes, all with NTS connections, will be reviewed: coughing, gagging, sighing, sneezing and yawning.
Coughing is a pulmonary defense reflex that can be evoked by mechanical, chemical, electrical or thermal stimulation of the airways (Korpas & Tomori, 1979). The components
of the cough include a deep initial “preparatory” inspiration followed by an active expiratory effort produced by contraction of the diaphragm and abdominal muscles (Korpas & Tomori,
1979; Perlman & Schulze-Delrieu, 1997). A cough is elicited when RAR fibers are activated from the larynx and/or tracheobronchial tree or when sensory receptors in the distal oesophagus are stimulated (Widdecombe, 1995). Interestingly, c-fibers will inhibit the cough unless the stimulus is so strong that there is a neurochemical release of tachykinin that, in turn, will stimulate the RAR response, thus stimulating a cough (Widdecombe, 1995).
Afferent pathways of these receptors include the glossopharyngeal nerve for stimulation in the oropharynx and superior laryngeal nerve branch of the vagus nerve for all other stimulation (Perlman & Schulze-Delrieu, 1997) with the information carried to the NTS
(Widdecombe, 1995). The NTS then effectively disperses the information to produce the desired motor or respiratory functions.
Gagging is the other pulmonary defense reflex that prevents foreign objects from entering the pharynx, larynx or trachea. The gag reflex is a protective reflex which is elicited upon stimulation of the posterior tongue, pharyngeal & velar regions. This reflex is characterized by the lowering of the mandible with forward and downward movement as well as velar and pharyngeal constriction (Leder, 1996). The afferent pathway is the glossopharyngeal nerve to the NTS (Logemann, 1983). Information from the NTS is then sent to the nucleus ambiguous which then activates the vagal efferent fibers order to produce the specific motor response (Martin & Jessell, 1996).
Yawning is a phenomenon that subserves arousal. It is characterized by a coordinated motor pattern including a deep inspiration with wide mouth opening and stretching of the trunk. Changes in autonomic function such as lacrimation (tears), decrease in blood pressure
and inhibition of the sympathetic nervous system activity can also be observed. It appears that the paraventricular nucleus of the hypothalamus (PVN) activates both the behavioral and autonomic components associated with yawning. The PVN sends descending axons to the locus coeruleus, NTS, dorsal motor nucleus of the vagus nerve, ventrolateral medulla and spinal cord in order to produce the respiratory, cardiovascular, motor and arousal sequence of events associated with yawning (Sato-Suzuki, Kita, Oguri, & Arita, 1998).
Sighing is characterized by shallow breaths that are interrupted by occasional spontaneous deep breaths. It is hypothesized that the sigh is triggered as a result of activation of vagal irritant (Thach & Taeusch, 1976). Although Widdecombe (1982) reported that RAR fibers are responsible for the sigh reflex. Regardless of the specific sensor involved, information is carried from a branch of the vagus nerve to the NTS. The NTS then activates the dorsal motor nucleus of X in order to elicit the appropriate motor responses ((Korpas &
Tomori, 1979).
Sneezing is a powerful defense mechanism of the respiratory tract. It is characterized by a brief enhanced expiration against a closed glottis, preceded by one or several deep inspirations (Wallois, Bodineau, Macron, Marlot, & Duron, 1997; Wallois & Macron, 1994).
The glottis participates in the high intrapulmonary pressure generated for the explosive expiratory effort by closing completely at the outset of the expiratory phase of sneezing. A sneeze is generated by the combination of a strong expiratory airflow in conjunction with the relaxation of the upper airways which will cause air to be forced through the mouth and nose
(Wallois & Macron, 1994). Due to the complexity of the sneeze, both the nasal (trigeminal nerve) and vagal afferents are involved. Sneezing is initiated by stimulation of the nociceptive fibers of the trigeminal nerve and the SAR and RAR fibers of the vagus nerve
shape this response Ganong, 1975; (Korpas & Tomori, 1979; Wallois et al., 1997; Wallois &
Macron, 1994; Widdecombe, 1982). Information is then carried the “sneezing center” of the
brainstem which include the ventromedial margin of descending trigeminal nucleus, the
medullary reticular formation and the NTS (Korpas & Tomori, 1979; Wallois & Macron,
1994). Information from these regions then activate a number of brainstem nuclei including
the nucleus ambiguous, facial nucleus, dorsal motor nucleus of the vagus as well as
bulbospinal efferents in order to produce the patterened motor output (Korpas & Tomori,
1979; Wallois et al., 1997; Wallois & Macron, 1994).
Other respiratory phenomenon related to the NTS:
Premotor neurons also seem to have a connection with the NTS. The primary source of respiratory neurons are found with two specific groups, the ventral respiratory group
(VRG) and the dorsal respiratory group (DRG). The VRG is located in the ventrolateral medulla and is known to provide the excitatory drive to expiratory motor neurons. The VRG also contains inspiratory bulbospinal neurons to the phrenic and thoracic inspiratory motor neurons (Feldman & McCrimmon, 1999). Additional inspiratory bulbospinal motor neurons are found in the vlNTS. These premotor neurons do not appear to participate in rhythm generation, but they transform the rhythmic drive they receive in a pattern of output appropriate for motor neurons they innervate (Feldman & McCrimmon, 1999). Neurons of the dorsal respiratory group (DRG) lie in and close to the NTS and have a discharge pattern rate primarily to inspiration (Larson et al., 1994). Finally, as part of respiratory control, the entire NTS receives information from the fastigal nucleus of the cerebellum. Since respiratory timing is believed to be generated and modulated in the brainstem the effects of activation of the of the fastigal nucleus on both inspiratory and expiratory timing suggests a
cerebellar effect on this medullary connection rather than on spinal motoneurons (Xu &
Frazier, 1995).
2.3.5d CONTROL OF FOOD INTAKE (caloric homeostasis)
The NTS and area postrema (AP) receive sensory information from gustatory (taste) receptors as well as afferent information from the stomach, esophagus, intestines, pancreas and liver (Altschuler, Bao, Bieger, Hopkins, & Miselis, 1989; Travers & Norgren, 1995;
Woods & Stricker, 1999; Zhang et al., 1995). The rNTS receives topographical gustatory afferent information (in a rostral to caudal sequence) from the facial, glossopharyngeal and vagus cranial nerves. An interesting note by Travers and Norgren (1995) indicates that there are two sub-specialized types of neurons found within these specific cranial nerves called
“G” neurons and “M” neurons. The “G” neurons carry information regarding taste, somatosensory and thermal stimulation to the rostral NTS. The “M” neurons transmit information regarding mechanical stimulation, airflow and thermal information that fires in synchrony with respiration and are found in the caudal NTS, specifically the ni & nI subnuclei.
The NTS is where sensory input from the viscera is first integrated with input from the tastebuds (Zhang et al., 1995). In addition, a study on decerebrate rats revealed that there is enough neuronal control within the caudal brainstem at the level of the NTS in order for animals to sufficiently control their food intake without higher center involvement (Grill &
Kaplan, 1990). However, in typical situations there are connections to and from the NTS to the hypothalamus, amygdala, thalamus and gustatory cortex that allows for emotion and cognition to influence the control of eating (DiLorenzo & Monroe, 1995).
Other food-related activities in which the NTS participates include, salivation and swallowing. The NTS reportedly sends information to the superior salivatory nucleus as part of a gustatory relay in order to elicit salivation (Matsuo et al., 1989). In addition, the NTS has been implicated with having a very prominent and complex role with swallowing.
Swallowing is characterized by 3 broad phases: the oral phase, pharyngeal phase and esophageal phase (Jean, 1984a; Logemann, 1983). The first phase is typically divided into an oral preparatory phase where the food is chewed and organized into a bolus and an oral transit phase where the bolus is moved posteriorly into the oropharynx. The pharyngeal phase includes the actual “swallow” patterned response. Finally the esophageal phase transports the food through the esophagus into the stomach. It is generally accepted that the NTS contains higher order sensory neurons concerned with the initiation and coordination of neuronal activity underlying these sequential stages of swallowing (Altschuler et al., 1989; Jean,
1984a; Miller, 1986). In addition the interaction between respiration and swallowing is also regulated through the NTS (Furusawa, 1996; MacFarland & Lund, 1993). Simply stated, afferent information specific to the pharyngeal swallow is carried through the glossopharyngeal and vagus nerves to the NTS [Jean, 1979 #139; (Perlman, 1991). Efferent information is then sent to the motor nuclei of the trigeminal and hypoglossal nuclei and nucleus ambiguous in order to coordinate the muscles involved with eliciting the swallow in synchrony with respiration (Halsell et al., 1996; Jean, 1984b).
2.3.5e MISCELLANEOUS NTS INVOLVEMENT
Nociception (Pain)
It has been shown recently that the NTS is an important relay for the modulation of nociception produced by vagal afferent stimuli (Menescal-De-Oliveria & Hoffman, 1995).
More specifically, electrical stimulation of the NTS inhibits spinal dorsal horn neurons and nociceptive reflexes while electrical stimulation of the NTS inhibits spinal dorsal horn neurons and nociceptive reflexes (Menescal-De-Oliveria & Hoffman, 1995). Furthermore, these researchers found that the NTS and area postrema interact with the parabrachial nucleus of the pons for nociception modulation. More specifically, a reciprocal inhibitory action of the NTS and pons controls the analgesic effect. It is hypothesized that the temporal modulation of the analgesic response may have an important adaptive function in confrontation situations because the longer/shorter duration of analgesic affect may reinforce the defensive responsiveness depending on external conditions (Menescal-De-Oliveria &
Hoffman, 1995; Ren, Randich, & Gebhart, 1990).
The NTS has been also been implicated in learning and memory as part of the autonomic-emotional coordination (Walker et al., 1999). These same authors have also noted that the mNTS regulates seizures of forebrain origins. Although forebrain and NTS connections have been identified ((Bagaev & Panteleev, 1994), Walker et al. (1999) (1999) propose that inhibition of ascending outputs from the mNTS to the forebrain mediated the anticonvulsant properties of vagal stimulation.
2.3.6 Brief review of the neurochemical components of the NTS
Because of the structural and functional complexity of the NTS the neurochemical make-up of the also appears to be complex. The NTS contains a variety of differing traditional and non-traditional neurotransmitter types including: GABA, glutamate, epinephrine, substance
P, serotonin, dopamine, opioids, nitric oxide, glycine and somatostatin (Block & Kapp, 1989;
Carpentier et al., 1997; Chigr et al., 1991; Gingras, Lawson, & McNamara, 1995; Housley,
Martin-Body, Dawson, & Sinclair, 1987; Kawai, Takagi, Kyoko, & Tohyama, 1988; Kessler
& Jean, 1986; Kinney, Ottoson, & White, 1990; Langercrantz, Holgert, Pequignot, &
Srinivasan, 1992; Takemura et al., 1996; Walker et al., 1999; Zec, Filiano, Panigrahy, White,
& Kinney, 1996). Table 2.3.6 will provide a brief review of the neurotransmitters found within the NTS.
Table 2.3.6: Review of the neurotransmitters and the relationship with the NTS
GABA is a known inhibitory amino acid neurotransmitter. GABA has a role in the processing of respiratory, cardiovascular and other information within the visceral portion of the NTS. GABAergic cells are also distributed within caudal regions of the NTS. Glycine is a known inhibitory amino acid neurotransmitter which is similar to GABA. Animal studies indicate that glycine has a role in stabilizing respiratory rhythm via spinal cord and brainstem respiratory activies Glutamate is a known excitatory amino acid neurotransmitter involved in the control of swallowing, baroreceptor reflexes and the respiratory motor output through the activation of NMDA receptors. Glutamate also acts as a neurontransmitter between gustatory afferent fibers and taste-responsive cells in the NTS Epinephrine is a known catecholamine found within the NTS. It plays a crucial role in neuroendicrine regulation and autonomic functions. A study by Kawai et al. (1988) found evidence that the NTS has more than one type of adrenalin neuron. One type appears to directly influence breathing, blood pressure regulation and swallowing. The second type projects directly to the hypothalamus. Substance P is a known neuroactive peptide found within the tachykinin family. Substance P is an important respiration-stimulating neuropeptide in the NTS and may contribute to the onset of continuous breathing after birth. Abnormalities in the distribution of Substance P in the infant brainstem may be related to sudden infant death syndrome (respiratory) or familial dysautonomia (pain). In addition, evidence also indicates that taste responsive cells in the NTS are excited by Substance P. Serotonin (5-HT) is a known biogenic amine within the indolaminergic family. Serotonin has been found to participate in a variety of functions including: sensory processing, homeostasis, neuroendocrine and visceral control, mediation of central pain-regulation mechanisms and regulation of cerebral bloodflow. The actions of 5-HT may occur in concert with other early developmental unmylinated systems such as the dopaminergic and cholinergic systems. Dopamine is a known catecholamine or biogenic amine. The effects of dopamine are mediated by various subtypes of receptor, including the D1 that is known to be stimulating to the system or D2 which is a known inhibitor. Endogenous Opioid Peptides and their receptors are related to processing or modulation of nociception. The opioid system has been found to be located in brainstem sites including the NTS, parabrachial nucleus and the ventrolateral medulla This complex system has specifically been found to influence important braistem-mediated functions such as respiration, analgesia, cardiovascular stability and arousal. Nitric Oxide (NO) has been implicated in participating in a variety of physiological functions including orofacial sensorimotor functions from a distinctive group of neurons within the rostrolateral portion of the NTS and the subnucleus oralis of the spinal trigeminal nucleus. Somatostatin is a known neuroactive peptide that may be an important regulator of respiratory activity. The density of binding sites within the brainstem is typically much higher in fetuses than in adults, thus suggesting an involvement of this peptide in the maturation of the respiratory centers of the brainstem
(Azmitia & Whitaker-Azmitia, 1991; Carpentier et al., 1996; Carpentier et al., 1997; Chigr et al., 1991; Dashwood, Gibley, & Spyer, 1985; Kawai et al., 1988; Kessler & Jean, 1986; Langercrantz et al., 1992; Pokorski, Grieb, & Wideman, 1981; Salas, Ghilini, & Denavit Saubie, 1993; Santiago & Edelman, 1985; Schwartz, 1991; Smith & Shepherd, 1999; Takemura et al., 1994; Wilson-Pauwels et al., 1997)
2.3.7 Normal development of the NTS
During normal development, the final number of neurons to reach maturity within individual brainstem nuclei is determined by the combined effects of neuron proliferation during neurogenesis and neuron loss during the regressive phase of programmed cell death
(Dentremont, Ye, D'Ercole, & O'Kusky, 1999). In addition there are many other aspects of cell structure and function that can also influence development. The majority of these changes in neurologic growth is thought by many to be completed in utero. However, there is an abundance of evidence that supports specific changes within the NTS during the postnatal period.
2.3.7a Neurotransimitter and Receptor Studies
During the first postnatal weeks in humans dramatic changes are found in receptor sensitivity, response to neurotransmitters and expression and/or alterations of ionic channels within the human brainstem (Paton, Ramirez, & Richter, 1994). Following birth, in general there is an enhanced release of neuropeptides (i.e. somatostatin) and catecholamines (i.e. dopamine, epinephrine) which appears important following the significant changes surrounding birth such as respiration of air and establishment of sleep/wake cycles
(Langercrantz et al., 1992). Carpentier et al. (1997) studied somatostatin binding sites in the human brainstem from 19 post-conception weeks to 6 months postnatally. This study found high densities of somatostatin binding sites in discrete respiratory nuclei as early as 19-21 weeks of gestation and that the intensity of labeling decreases between midgestion and the postnatal period. In most brainstem nuclei studied (including 4 subnuclei of the NTS) the density of somatostatin binding sites was approximately 2 times higher in 4-6 month infants than in adults (as compared to the 1996 study from Carpentier, et al.). This increased number
of binding sites in the postnatal period compared to adults suggests an involvement of this peptide in the maturation of the respiration centers of the brainstem.
The daily rhythms in the concentration of dopamine and norepinephrine were studied within the rabbit NTS in order to increase the understanding of sleep/wake cycle development (Gingras et al., 1995; Gingras, Lawson, & McNamara, 1996). Analysis of the data suggests that daily variations in norepinephrine are established by the third day of life and continues to shift in a pattern that occurs with development through adulthood (Gingras et al., 1996). Dopamine was also demonstrated to shift with age. The data showed a progressive peak from the early light phase in the 3-day old animal, to late light phase in
21day old animals to a sustained peak during the dark phase in adult animals (Gingras et al.,
1995).
Changes in glutamate and GABA receptor expression and/or binding characteristics have also been demonstrated in the NTS (Paton et al., 1994; Rao, Jean, & Kessler, 1995;
Rao, Jean, & Kessler, 1997; Rao, Pio, & Kessler, 1999; Takemura et al., 1996). In addition, a major change in glycinergic mechanisms during maturation of the respiratory network over a relatively short time period being the first two weeks of life in the rat and mouse has also been demonstrated (Paton et al., 1994). During this time frame the expression and clustering of glycine receptors increase, thus it appears that a mature respiratory motor pattern coincides with both the structural and dendritic distribution of the glycine receptor. These changes in the glycine receptor may account for the differences in the role that glycine plays in respiratory rhythmogenesis in neonates and adults. It is suggested that the maturation of glycine receptors within the respiratory network might be important for stabilizing the
rhythm when complex reflex adjustments of the motor output have to occur during, for example, speech, gagging, sneezing, swallowing, coughing and vomiting (Paton et al., 1994).
Takemura et al. (1996) have also shown that the number and size of the labeled cells for nitric oxide (NO) in the NTS increase in a linear fashion into adulthood. These researchers also found that the ontogeny of NO labeling differs between the spinal trigeminal nucleus and involves changes in both cell number and size. Interestingly the development of the spinal trigeminal neurons containing NO were found to mature in the embryonic stage of development, whereas the NTS continued postnatally.
Two specific neurochemical receptor systems have been reported to decrease during the postnatal period including the opiate and seratonin receptors. Opiate receptors were found to decrease within individual nuclei between midgestation and early postnatal period (4-5 months), including the NTS. This is not a surprising finding since opioids are postulated to serve as developmental trophic factors influencing connectivity, including neuronal and spine number and dendritic length. Once this is complete these “trophic” opioid receptors may be eliminated and only those necessary for neurotransmission is retained (Hannah, et al., 1990).
Serotonergic (i.e. 5-HT) receptors also show a marked decrease between midgestation and infancy in the NTS (among other brainstem nuclei). It is speculated that the rapid change in these receptor binding in the perinatal period may lead to changes in serotonergic control of cardiorepiratory functions between fetal life and infancy. A fetal peak in ([H3] LSD) binding to these serotonergic receptors is consistent with a trophic role of serotonin of modulation of vegetative functions controlled by the brainstem (Zec et al., 1996).
2.3.7b Neuron Proliferation Studies
During the neuron proliferation phase of postnatal development the NTS neurons also undergo rapid and dramatic changes in morphology. Some of these changes include an increase in complexity of dendritic tree from bipolar to multipolar, increase in spine densities, formation and/or maturation of synaptic contacts, rapidly developing synpatic boutons and synpatic shift from cell body to dendrites (Denavit-Saubie et al., 1994; Kalia,
Schweitzer, Champagnat, & Denavit-Saubie, 1993; Kalia & Sullivan, 1982; Miller, McKoon,
Pinneau, & Silverstein, 1983; Rao et al., 1999; Vincent & Tell, 1997). In addition, developmental changes are observed with the intrinsic electrophysiologic properties of the
NTS which leads to the maturation of integrated synapses and subsequent firing patterns of these neurons. Although these developmental alterations in electrophysiologic properties of
NTS neurons may account for postnatal maturation of autonomic functions (Vincent & Tell,
1997), the specific nature of these developmental electrophysiologic changes is beyond the scope of this thesis.
A comprehensive review of the specific electrophysiologic changes that occur in the rat can be found in Vincent & Tell (1997). Human fetus studies reveal that neuronal maturation is less developed in the dorsal vagal nucleus and the NTS than in the reticular formation. The dendrites of neurons in the reticular formation are mature at 24 weeks post conception age unlike the NTS which are still immature at that time. Spine density in the dendrite 50-150 mm from the soma differed significantly between 40 weeks postconception age and 2-18 months of age (Takashima & Becker, 1986). It is hypothesized in the rat that the shape of the dendritic tree is secondary to the maturation of vagal afferents during the 1st
week postnatally (Denavit-Saubie et al., 1994), perhaps there is this influence in the human as well.
NTS and taste studies in sheep show that the sheep brainstem grows from 85 days
(gestation) to 2 months postnatally (Mistretta & Labyak, 1994). The first half of growth is noted with steep changes observed for cell body growth, dendritic branching, length volume and area of influence, number of spines. The second half of growth up to 2 months postnatally demonstrates an increased number of branch points, dendritic length, dendritic volume, and spine density being maintained. In addition, from 130 days gestation to perinatal stages there is a convergence of 1st order taste afferents onto second order neurons of the
NTS. The nature and extent of afferent input to the NTS neurons alters after this period because the extent of presynaptic innervation is directly related to dendritic complexity of post synaptic neurons in other systems (i.e., autonomic) (Mistretta & Labyak, 1994).
A study performed on 108 NTS neurons in animals 0-9 days postnatally found that the development of presynaptic terminals of in these regions does not abruptly end after the first 9-10 postnatal days, as suggested by the use of volumetric fraction or numerical density values, but slows down progressively over the first postnatal month (Denavit-Saubie et al.,
1994). For the NTS this finding is in agreement with electron microscope observations which show a 2.5 fold increase in the number of boutons per dendrite length within this region between the tenth and 15th postnatal day (Rao et al., 1999). The present data indicate that most of the synaptic development of the rat NTS occurs after birth. This is in agreement with several observations showing that newborns are still immature concerning central organization of autonomic functions and responses to visceral stimulation including: respiratory rhythm, swallowing motor drive, and cardiorespiratory responses to hypoxia.
2.3.7c Programmed Cell Death Studies
In normal development neuron proliferation is only one aspect of a nuclei reaching full maturity. More recent literature has pointed to a second aspect of development identified as programmed cell death (PCD). PCD represents the normal differentiated fate of many developing cells that is regulated by cell to cell interactions and therefore is conditional
(Oppenheim, 1999). With few exceptions PCD occurs in all populations of developing neurons and can take place at all stages of development from the time of proliferation to until the establishment of synaptic connections (Oppenheim, 1999). According to Dentremont, Ye,
D’Ercole & O’Kusky (1999) (1999) the time course for most non-motor brainstem nuclei extends to early postnatal development for rodents. However, specific studies have not yet been completed to establish PCD within the NTS for rodents or other animals.
2.3.8 Deprivation at birth and the effects on postnatal development of the NTS
Early studies had shown primary gustatory fibers arising from the facial nerve synapse in rostral NTS at birth with the axons migrating caudally and ramifying within the intermediate levels of NTS between postnatal days one to twenty-five, with the critical period being between days two and ten. Furthermore, early postnatal receptor damage to fungieform papillae of anterior tongue (i.e. those innervated by the facial nerve) causes a decrease in the volume of afferent terminal fields within the (Lasiter, 1992; Lasiter, Wong, & Kachele,
1989). This reduction, in turn, appears to affect second order relays to PBN with as much as
30% reduction in projections as well significant alterations in dendritic length and complexity (Lasiter & Kachele, 1990, 1991). However, these early research studies looked only at receptor damage which raised a fundamental question of the observations. Were the
observations a result of the reduction of gustatory activity or a direct result of the receptor damage (i.e. differentiation models). In order to address this issue, Lasiter & Diaz (1992) began to use artificial rearing as a means to manipulate the input that the animals were receiving (i.e. altered activity with no cell death-receptor or neural).
This first study by Lasiter & Diaz (1992) examined rats, 5 of which were fed via a g- tube. A g-tube is a type of feeding tube that is inserted directly into the stomach thus, when utilized, the structures from the mouth to the stomach are bypassed (i.e. including the oral cavity, throat and esophagus). This group of rats was called the artificial rearing group (AR group). For this study, and this type of artificial feeding was presented four to fourteen days following birth. On day fourteen, these rats were then returned to a lactating mother for another week (until day 21). The rats were then sustained on laboratory chow until day forty- nine to fifty-six. At this time the animals were sacrificed and the NTS was evaluated. These
AR rats were then compared to a second group of 5 rats that were all reared by the mothers
(MR group). One of the five AR rats was omitted from the study because the overall volume of the NTS (all regions) were significantly different than other AR animals and MR animals.
The results show artificial rearing (without normal stimulation from mother’s milk) is sufficient enough to produce altered development of primary gustatory afferent terminal fields in specific portions of NTS.
A follow-up study was then completed by Lasiter (1995), which had two specific aims. The first objective was to evaluate the qualitative nature of orochemical stimulation that was necessary to regulate axonal and terminal development within the NTS. The second objective was to evaluate the amount of stimulation necessary to induce normal development of the facial nerve axons in animals receiving artificial rearing. This study was much more
involved than the previous study, using 189 rats in various combinations of AR with supplemental oral stimulation of water, sodium, lactose, milk. This stimulation occurred both partially and for the entire study. Controls of MR rats were then used for each of the various combinations. The results proved to be very interesting. First, different orochemical stimulants were found to promote VII development in rats that were being artificially reared.
For example, water alone was not effective, however both the sodium taste stimulations and various lactose concentrations normalized the neuronal development. The second important finding was that there was minimal number of days that the rat had to be stimulated in order to produce normal development (i.e. the rats had to be stimulated at least 3 days, two days were not enough).
SECTION 4: CLASSIFICATION OF FEEDING/SWALLOWING DISORDERS AND A
BRIEF REVIEW OF CURRENT CLINICAL MODELS
2.4.1 Classification of Feeding and Swallowing Disorders
Because pediatric feeding and swallowing disorders is very multifaceted with many interlocking aspects, a number of attempts have been made to classify the disorders. A brief summary is given below of the four most common systems utilized clinically.
2.4.2 Classification Based on Levels of Development
A review of 3 pieces of literature that utilized a combination of the work of
Greenspan and Lourie (1981) and Mahler et al. (1975) (Please refer to section 2.20), by dividing feeding disorders based on the period of homeostasis, attachment and separation/individuation (Arvedson, 1997; Chatoor, Schaefer, Dickson, & Egan, 1984; Satter,
1990, 1995). In addition, Pridham (1990) utilized Kopp’s levels of development (1982) as a
means of dividing feeding disorders. However, a more in-depth review of the literature demonstrates that utilization of the levels of development to classify feeding/swallowing disorders is a unique perspective.
2.4.3 Organic vs. Non-Organic Dichotomy
The most common classification system is that which utilizes the “organic” vs. “non- organic” classification system (see Appendix A). Recall that an organic feeding problem is ascribed to a major illness or organ system dysfunction (Frank & Ziesel, 1988). In contrast, feeding disorders classified with a non-organic origin are typically attributed to “maternal deprivation” and or an insufficiently nurturing environment in a home or institution (Frank &
Ziesel, 1988; Goldstein & Field, 1985; Polan & Ward, 1994; Powell & Battes, 1992). But as noted in Appendix A, this type of classification fails to account for feeding problems related to a blend of this dichotomy. Hence the term, “mixed” was utilized instead to account for more complex pediatric feeding cases (Homer & Ludwig, 1981). Because this “mixed” term typically has not been well defined, it is infrequently utilized in current research and clinical use.
2.4.4 Multi-Dimensional Classification System
A new classification system was introduced by Burklow, Phelps, Schultz, McConnell and Rudolph (1998), which allowed for non-mutually exclusive categories. This new system was proposed because the rigidity of the current dichotomy of organic vs. non-organic classification system typically oversimplified complex feeding problems. This new classification system identified five components of pediatric feeding disorders including: structural abnormalities, neurological conditions, behavioral issues, cardiorespiratory problems and metabolic dysfunctions (Burklow et al., 1998). These authors not only
classified feeding issues by the five individual categories, but identified combinations of these categories as well. This allowed the authors to generate a more descriptive, multidimensional classification system that may more accurately identify complex feeding disorders (Burklow et al., 1998).
2.4.5 Classification Based on a Biopsychosocial Model
A third model was reviewed from Bithany and Dubowitz (1985) that schematically represents the complexity of factors which are dynamic and ongoing within a feeding relationship. This model was based on the bio-psychosocial model of Engel (1977), which viewed the role of the health care provider as weighing the social and psychological factors as well as biological factors. Thus, this model proposed that feeding behaviors were the result of physical and psychosocial stressors and supports that simultaneously impacts the child and caregiver (Bithoney & Dubowitz, 1985).
2.4.6 Current Clinical Theories: A Brief Review
Because the focus of this dissertation is related to the sensory and behavioral components of feeding, only summaries of the current clinical theories that address these components will be reviewed. These perspectives include: behavioral psychology, neonatology, occupational therapy and regulatory disorder. However, preceding this review of the clinical theories, a brief section on utilization of the team approach in order to best serve infants and children with feeding disorders will be provided
2.4.7 The Team Approach
As indicated earlier, one of the difficult challenges facing pediatric feeding/swallowing specialists is that infants and toddlers cannot adequately verbally express themselves. Therefore as clinicians, we are forced to interpret their behaviors to obtain the
information needed to diagnose the areas of deficit. Depending on the perspective of the professional these behaviors can be interpreted in a multitude of ways. This in turn leads to treatment techniques based upon each professional’s perspective with only a cursory look at other possible indicators for the same behavior. This is why it is so important to utilize a team approach when handling pediatric feeding and swallowing problems. Typically there are three different types of team approaches. The type of team chosen is often dependent upon the setting of services and funding source. Table 2.4.7 gives a brief review of the different types of teams as outlined by Leifton-Greif and Arvedson (1997).
Table 2.4.7_Team Approaches (Lefton-Greif & Arvedson, 1997) Multidisciplinary Approach -Team members assume responsibilities related to own expertise -One discipline may have no influence with other team members -Family participation is not guaranteed -Easiest to implement, Cost and time effective
Interdisciplinary Approach -Team members provide services consistent with own expertise, but also work toward common goal with other members of the team -Family involvement is encouraged -Time and cost restraints may limit productivity of team
Transdisciplinary Approach -Team members evaluate child according to own discipline, but the team meets collectively to develop goals for treatment -This model is encouraged in settings where patient contact is limited -Time consuming ______
All of the team models allow the child to be observed by a multitude of professionals in order to best view the overall picture and to more clearly define the symptoms or behaviors noted.
2.4.8 Behavioral/ Interaction Theory
This literature has an extensive research base that assists in providing information to the clinician about a variety of areas related to feeding (Arvedson, 1997; Babbitt et al., 1994;
Ottenbacher, Dauch, Grahn, Gevelinger, & Hassett, 1985; Powell & Battes, 1992; Ramsey &
Zelazo, 1988; Reau, Senturia, Lebailly, & Christoffel, 1996; Satter, 1990, 1995). For example, it recognizes that the infant/child is dependent upon an outside source to assist with obtaining adequate nutrition and the importance of this person within the feeding arena. This theory also provides extensive information involving the emotional pressures surrounding feeding times and overwhelming emotions that may emerge. Most feeding specialists who approach treatment from this theory also assist the caregiver in using appropriate reinforcement and establishing healthy feeding routines.
This perspective acknowledges that specific feeding problems can arise if critical periods are not met. However, in many cases when this technique is applied, attempts to “fix” the behavior is related to the current, age-related developmental stage rather than addressing gaps which may have occurred previous stages. In addition, many children can also be conditioned to eat specific textures regardless if the child is physically safe to manage that particular consistency. Another limiting factor involves carryover. The child may eat a specific consistency that was behaviorally managed, but because the underlying issue wasn’t addressed then other varied consistencies may not be accepted.
2.4.9 Developmental Theory
In the “behavioral organization” model, which has been adopted as standard in most neonatal research, neurologic organization is a process in which an infant demonstrates an increasing ability to regulate internal responses to external stimuli (Als, 1986; Als &
Gilkerson, 1995; Comrie & Helm, 1997; VandenBerg, 1990). However, in addition, this theory establishes important information regarding the environment and care-giver interactions to maximize the infant’s ability to appropriately respond to developing physiologic systems.
In reviewing feeding/swallowing issues of the neonate, many of the observed behaviors are explained with information regarding physiologic functioning and sensory processing. This model views behavior as an expression of the underlying maturation and integrity of the infant’s autonomic, motor and state subsystems. An organized “behavioral response” to any stimulation would include maintaining stable physiological functioning, motor control and state control. Examples of a response indicating disorganization would include disrupted function or loss of control, e.g. irregular breathing patterns, pale or dusky coloring, gagging, coughing, hiccupping, spitting up (rumination), flaccid or stiff muscle tone, frantic movements, going to sleep or becoming fussy (poor state control).
Appropriate sensory experiences are considered challenging to provide to pre-term infants because of the nature of an NICU experience that is often overloaded with sensory input. This sensory overload often overwhelms the pre-term infant causing them to either exaggerate their response or under-respond to the sensory input (again, state regulation). For pre-term infants tactile stimulation, particularly oral stimulation, may affect feeding most directly. These infants (not so unlike a medically fragile infant) may have to be hospitalized for long periods of time, thus missing out on opportunities for oral exploration. Medical equipment and or poor muscle tone/control may interfere with these infants in bringing hands to mouth. The lips and tongue have a rich supply of sensory receptors. However, both are often exposed to noxious sensory input from such procedures as oral or nasogastric tubes,
oral or nasoendotrachial tubes, suctioning and facial tape. The long-term effect noted with pre-term infants is tactile defensiveness and oral hypersensitivity which may result as a conditioned response (as with a medically fragile child).
Caregivers’ use of comforting tactile input can help replicate the sensory input typically experienced by a healthy full term infant and support organized development. In many NICU’s parents are assisted in “kangaroo care” (skin-to-skin contact) which facilitates the infants organization, self- regulation and temperature control. For pre-term infants comforting perioral /intraoral stimulation and opportunities for typical oral exploration can facilitate organization, increase healthy reactions to oral stimulation and modify sucking responses. Non-nutritive sucking (i.e. pacifier use) during gavage feeding in pre-term infants has been shown in several studies to improve respiratory and GI function, decrease energy expenditure and behavioral stress (state control), facilitate pharyngeal peristalsis, increase absorption, decrease irritability (state control), increase organization, increase weight gain and promote earlier transition to nipple feeding (Als & Gilkerson, 1995; Comrie & Helm,
1997; Einarsson-Backes et al., 1994; Glass & Wolf, 1994; Pickler, Frankel, Walsh, &
Thompson, 1996; VandenBerg, 1990). Many of these same types of considerations perhaps should also be given to the child who is medically fragile or who is tube fed at an early age and like the pre-termers, miss out on the physiologically calming behaviors of oral stimulation.
2.4.10 Occupational Therapy Approaches
The following theories have evolved out of the OT literature and address the issues regarding motor and sensory development. This literature as a whole is not easily accessible
and much of the literature that is referenced comes from either the work of one individual or practitioners who are trained only by certified instructors in specialized courses.
2.4.10a Neurodevelopmental Treatment (NDT) Approach
This approach was developed by the Bobaths in the 1940’s to rehabilitate adults with central nervous system damage. It has evolved since that time to use with infants and children who have movement disorders as a result of damage to the central nervous system.
The premise of the NDT theory is that movement disorders are based on atypical postural tone, the inability to maintain normal postural stability against gravity and the use of compensatory and atypical patterns of movement (Bobath & Bobath, 1972; DeGangi, 1983).
This model addresses the motor aspect of a developing infant that can directly impact safe and efficient swallowing patterns. From this model the use of a graded level of sensory stimulation evolved which acknowledges that the child’s impaired neurological system may only be able to process a limited amount of information and abnormal responses are minimized. In addition, this theory recognizes that early intervention is key for development of early skills which subsequently impact future development. One of the major limitations of this theory is that it technically applies only to infants and children who have gross central nervous system damage but does not explain the children with feeding and swallowing problems unrelated to central nervous system damage.
2.4.10b Sensory Integration
This approach was developed by A. Jean Ayres, PhD., OTR in the 60’s and 70’s its theory is grounded in the following assumptions: a) neuronal plasticity, b) sensory integration as a developmental sequence, c) the nervous system is organized in a hierarchical fashion, d) an adaptive behavior interaction occurring and e) an inner drive is present. This
approach also explores the relationship between tactile processing and sensory defensiveness
(Ayres, 1979; Fisher et al., 1991).
The first of these assumptions, plasticity, refers to the ability of the brain matter to be modified. Under this assumption, speculation regarding improved functional outcomes following treatments is possible through controlled tactile, vestibular and proprioceptive input (Ayres, 1979). In neuroscience literature, there is interesting information regarding the topic of plasticity and using rehabilitation treatments as a way to reinforce appropriate connections to avoid development of otherwise abnormal circuits (Berne & Levy, 1988c).
The assumption that the sensory integrative process occurs in a developmental sequence is critical for supporting the need to identify negative behaviors (observed in a feeding/swallowing assessment) early, because they may help explain an underlying source for the functional difficulty (Ayres, 1979). In normal development, increasingly complex behaviors develop as a result of a circular process. At each stage certain behaviors need to be present in order for the next, more complex stage, to successfully be achieved. As such, if certain critical behaviors are not achieved then dysfunction will occur. Therefore if the child cannot regulate physiologically and increase the alertness level to his/her environment, then the child would be unable to process even small amounts of sensory stimulation. Thus, stressors and abnormal physiologic responses would be reinforced.
The third assumption is that the brain functions as a whole, but it is composed of systems that are organized in a hierarchy. In many of the articles written by Ayres cortical development is dependent on sub-cortical processing. In this theory, the “lower” parts of the brain (i.e., sub-cortical regions) matured before the “higher” cortical centers. Therefore
optimal cortical processing was dependent on optimal functioning of the sub-cortical regions
(Ayres, 1979).
Adaptation of our behaviors relies on sensory integration. This learning theory postulates that individuals learn movements from past experience only if recognition that the prior movements were successful. Knowledge of the outcome of the adaptive behavior provides the basis for developing neuronal “memories” of what is achieved. Learning from previous experience thus depends on sensing and moving, not just on sensing alone (Brooks,
1986). Inner drive is the final assumption of the sensory integration theory. This assumes that individuals have internal motivation to develop sensory integration through participation in sensorimotor activities (Ayres, 1979). This model provides an excellent foundation for may clinicians to direct diagnostic and treatment techniques. This study is an effort to bridge the gap between the neonatal model (i.e. behavioral organization) and this model.
2.4.10c MORE Integrating the Mouth with Sensory and Postural Functions Theory
In the early 1990’s, the MORE theory was developed by three licensed occupational therapists, Patricia Oetter, Eileen Richter and Sheila Frick (Oetter, Richter, & Frick, 1993).
This theory postulates that the primary oral motor mechanism is the suck/swallow/breathe
(SSB) synchrony, and that development of the synchrony is critical to many elements of sensorimotor and cognitive development including: speech and language development, state regulation, postural control, feeding/eating behavior, ego development and eye/hand coordination. This theory also purports that as a fundamental sensorimotor pattern, SSB serves as an organizer for neuromotor behavior, and with appropriate assessment and planning can be used in treatment to successfully modify behaviors.
The MORE model provides an extensive, well-organized, review of impact of sensory, postural and behavioral states and their impact on behaviors. However, specific feeding behaviors are not the emphasis rather this model focuses on oral motor skills and respiratory organization.
2.4.11 Regulatory Disorder Theory:
The regulatory disorder theory was developed by Stanley Greenspan, M.D. and
Serena Weider, Ph. D. (Greenspan & Weider, 1992). According to this theory, regulatory disorders are first evident in infancy and early childhood. They are characterized by difficulties the infant has in regulating physiological, sensory, attentional and motor or affective processes and organizing a calm, alert or affectively positive state. As part of the criteria to be classified with a regulatory disorder, a distinct behavioral pattern coupled with difficulty in sensory, sensorimotor, or organizational processing that affects daily adaptations and interactions-relationships. Based on the interactions of the criteria, four types of regulatory disorders have been identified: Hypersensitive type, Underreactive type, Active- aggressive type and Mixed type. This regulatory disorder model provides specific information to the parent based upon what category the individual child’s input needs was identified. This model also recognized that children may have differing sensory reactions and physiologic regulation to various inputs. In addition, this model attempts to organize behaviors systematically to assist with improved family dynamics.
However, although recognized as a common regulatory problem, feeding issues are very underdeveloped within the context of diagnosis and management. In addition, this model ignores graded sensory needs of the children and a discussion of the anatomy,
physiology, neuroanatomy of the swallow; critical time periods or any information regarding the impact of past medical history related to feeding/swallowing disorders.
CHAPTER 3
METHODS AND RESULTS
3.1.1: SUBJECTS: INTRODUCTION
Prior to collecting any data for this study a sample size estimate (approximated from
clinical experience) was run based on the mean difference in scores between the mixed
failure-to-thrive (MFTT) and normal control groups (x = 4.2 +/- 2, α = .05, and 90% power). Results showed that a minimum sample size of 20 controls and 20 MFTT subjects were needed in order to test the null hypothesis. Ultimately 20 subjects were recruited for the
MFTT group and 20 matched (by age and gender) normal subjects for the control group. To be assured that a sufficient number of normal controls to match to the MFTT subjects was obtained, 5 “extra” normal subjects were also tested. Two additional subjects were tested as an independent test of bias (see section 3.1.5).
The information collected for the study typically fell under two types: A) Descriptive
Information and B) A Priori Inclusion/Exclusion Factors. All of the information was gathered via parental report that was then confirmed with medical records. Approval from the
University of Cincinnati and/or Children’s Hospital Medical Center Internal Review Board(s) and informed consent documents were obtained for all participants.
3.1.2 SUBJECTS: MIXED FAILURE-TO-THRIVE GROUP (MFTT)
3.1.2a Descriptive Information
Information that was purely descriptive in nature and did not evoke any limiting
factors include (see Table 3.1.2a):
• sex of the child • birth weight • type of delivery • type of alternative (tube) feedings
Table 3.1.2a Descriptive Information for the MFTT group
Subject Sex Weight (lbs) Delivery Type Type of Alternative Feeding S1 F 4-1 Cesarean ng tube S2 F 7-5 Cesarean g-tube S3 M 6-10 Cesarean ng tube (sporadic) S4 F 6-5 Cesarean ng tube S5 M 8-2 Vaginal ng tube S6 M 7-0 Vaginal g-tube S7 F 3-2 Vaginal ng-tube S8 F 7-12 Vaginal nd-tube S9 M 5-4 Cesarean ng-tube S10 M 8-11 Vaginal g-tube S11 M 6-4 Vaginal g-tube S12 M 6-12 Cesarean nj-tube S13 F 7-13 Vaginal g-tube S14 M 7-0 Cesarean g-tube + Nissan fundoplication S15 F 5-6 Cesarean ng-tube S16 M 5-2 Vaginal ng-tube (sporadic) S17 M 8-1 Vaginal ng-tube S18 M 5-10 Vaginal ng-tube S19 M 6-13 Cesarean tpn/ng-tube S20 F 4-10 Vaginal ng-tube
The MFTT subject pool had eight females and twelve males. The average birth weight for the MFTT subject group is 6 pounds 4 ounces with a standard deviation of 1 pound 5 ounces. Almost equal numbers of cesarean births (9/20) to vaginal births (11/20)
were represented. Six MFTT subjects (S2, S6, S10, S11, S13 and S14) had feeding histories with gastrostomy tubes (g-tube), a tube placed directly into the stomach. Nine subjects (S1,
S4, S5, S7, S9, S15, S17, S18, S20) had feeding histories of naso-gastric tube feedings (ng feeds), a tube inserted into the nose and threaded to the stomach. Two subjects (S3, S16) had sporadic ng- tube feedings. Subject 19 had TPN feedings (feeding directly into the veins, not involving the GI tract at all) for 4 weeks then was transferred to continuous ng-tube feedings.
Subject 12 had a feeding history of naso-jejunum tube feedings (n-j tube), a tube inserted into the nose and threaded to the jejunum of the small intestine. Finally, Subject 8 had a feeding history of naso-duodenal tube feedings (n-d tube), a tube inserted into the nose and threaded into the duodenum of the small intestine.
3.1.2b A Priori Inclusion/Exclusion Factors for the MFTT Subjects
The second type of information was clearly defined prior to the collection of any data and provided specific exclusion/inclusion guidelines in selecting MFTT candidates for the study. The specific criterion related to the following areas (see Table 3.1.2b):
• age • length of gestation • primary diagnosis • length of alternative feedings • current oral intake (current feeding difficulties)
Age-related criterion: Subjects utilized for the study fell between the ages of 3 months and 18 months (adjusted) age. Both the 3 month and the 18 month values were selected for specific reasons. Recall, as outlined in Chapter 1 (section 1.1.5), this study aims to provide an explanation for feeding/swallowing problems in the MFTT population. A gap in the current literature regarding feeding/swallowing problems in the MFTT
Table 3.1.2b: A Priori Inclusion/Exclusion Factors for the MFTT Subjects
Subject Age Gestation Primary Diagnosis Length of Alternative Current Oral Intake Feeding S1 14months 32 weeks Cardiac 14 months Smooth puree/only; No Liquids S2 8 months 37 weeks Diaphragmatic Hernia 8 months Smooth puree/only; No Liquids S3 9 months 37 weeks Respiratory Complications 6 months (on/off x2) Smooth puree/only; No Liquids S4 5 months 37 weeks Diaphragmatic Hernia 5 months Refuses Tastes S5 6 months 37 weeks Cardiac 3 weeks Smooth Purees/ Liquids via bottle S6 8 months 40 weeks Treacher Collins Syndrome 8 months Tastes Only S7 12months 32 weeks Cardiac/Respiratory 12 months Tastes Only Complications S8 9 months 40 weeks Transplant (Stem Cell) 5 weeks (began at 8 Breastfeeding Only/ Nothing by weeks) Spoon S9 9 months 39 weeks Tracheal Web/Tracheostomy 5 weeks Bottle Only S10 4 months 38 weeks Micrognathria/Respiratory 10 weeks (began at Breastfeeding Only 6 weeks) S11 13months 38 weeks Cardiac/Reflux 13 months Smooth Purees/ Beginning Liquids via Cup S12 5 months 39 weeks Diaphragmatic Hernia 5 months Refuses Tastes S13 3 months 40 weeks Pierre Robin Sequence 3 months 10-15 cc’s Breastmilk from Bottle S14 5 months 34 weeks Cardiac/Respiratory 5 months Refuses Tastes Complications S15 3 months 35 weeks Diplastic Kidneys/Reflux 3 months Refuses Tastes S16 18months 39 weeks Cardiac 8 weeks (on/off x 2) Smooth Puree/Liquid Only via Bottle/No Textures S17 6 months 40 weeks Cardiac 4 months Tastes Only S18 15months 38 weeks Cardiac 6 weeks Smooth Purees Only/No Textures S19 3 months 37 weeks Cardiac 3 months Tastes from Bottle S20 7 months 32 weeks Cardiac 3 weeks Smooth Purees Only population between 3 and 18 months of age has been identified. It is known that a level of neurological (organization) maturity is required for successful processing of oral touch (and thus feeding). However, the presence of key indicators of neurophysiological development (i.e. gag reflex, state behavior changes) in typically developing infants and infants with MFTT alike who are younger than 3 months (13 weeks) of age are in the period of “homeostasis” and thus would be expected to have difficulty with autonomic nervous system regulation. Likely outcomes of firm pressure testing in this age group might include state behavior changes or gagging leading to false positive results.
According to a number of developmental specialists, 18 months of age is the approximate time in development that children acquire the representational memory skills to purposefully utilize behaviors (i.e. gag, state behavior changes) that manipulate the environment (Bauer et al., 1994; Greenspan & Lourie, 1981; Kopp, 1982; Piaget, 1952).
Therefore, children older than 18 months as with those younger than 3 months of age were excluded from the study to limit false positive results.
Criterion related to length of gestation: Another potential source of false positive data might arise from the fact that gestational age is not a wholly reliable indicator of neurological development. Therefore, participants qualified for the study only when an
“adjusted” age of 3 months or 13 weeks was reached. This “adjusted” age technique was incorporated in order to ensure that the candidates for the study had a consistent number of weeks of neurologic development in the immediate postnatal time period. Recall that children born between 37-42 weeks are considered to be products of a full-term pregnancy
(with 40 weeks being the mean). An “adjusted” age was used in this study for infants whose gestation was less than 37 weeks. “Adjusted” age is calculated by using the mean length of a
typical gestation (40 weeks) and subtracting the number of weeks that the infant was born prior to forty-weeks (i.e. chronologic age + number of pre-term weeks). For example, if the child was born at 32 weeks gestation the child was not eligible for the study until 20 weeks after birth (40 weeks –32 weeks = 8 weeks; 8 weeks + the 13 week minimum = 21 weeks).
Criterion related to the primary diagnosis: Specific exclusion factors in relation to the subjects’ primary diagnosis included: subjects who demonstrated gross neurologic involvement (i.e. severe anoxia, specific types of seizures, a history of periventricular leukomalacia, and documented brain bleeds [greater than grade 3]), or gross abnormalities of the gastrointestinal tract (i.e. short-gut syndrome, missing structures, pyloroplasty procedure, known damage to the spinal cord that interfered with gut motility). In other words, excluded populations would be expected to show difficulties with persistent feeding problems. Two procedures involving the GI tract were included with some children (4 of the 20 studied).
One subject, who had a surgical procedure called a Nissan fundoplication procedure (used to reduce reflux) was included in the study. A second group of three children from the study were included who had a diaphragmatic hernia repair. Both of these groups were included in the study because children are expected to be able to orally eat without difficulty following these procedures.
Criterion for length of alternative tube feedings: A minimum length of time that the child received alternative feedings was required. The two-week minimum was based on clinical observations from the investigator. No maximum time limitations for receiving alternative feedings were placed on the subject, as long as the subject was medically cleared to begin oral feeding trials at the time the study was conducted. Furthermore, the child could be enrolled in the study if those two weeks of alternative feedings were received during any
part of the first 13 weeks of life. For example, the child could have been thriving with oral
feeds for the first 8 weeks of life, undergone a medical procedure, placed on alternative
feedings for at least 2 weeks, was medically cleared for oral feedings again, and then,
presented with feeding difficulties.
Criterion of current oral intake: In order to be candidates for the study, all of the
MFTT subjects had received medical clearance for oral feedings. However, the subject’s
specific current oral intake was not a limiting factor other than the child must present with
some type of persistent feeding difficulties with some, and/or all consistencies of foods
(liquid, purees, solids). It is important to understand that feeding difficulties are defined
according to age-appropriate behavior. See Table 3.1.2c for a brief review of age-appropriate
feeding milestones.
Table 3.1.2c General Age Appropriate Oral Feeding Milestones
Approximate Age Oral Feeding Skill
0-4 months Exclusive breast or bottle feeding
4-6 months Introduction of pureed foods; Initiation of spoon feeding
7-8 months Introduction of soft solid table foods; Introduction of a cup
One year Transition from bottle to cup drinking
A typical behavioral disparity is taking liquids from a cup at 13 months, and yet reacting to
pureed foods with gagging.
All of the subjects from the MFTT group met the strict a priori guidelines as outlined above regarding age, length of gestation, primary diagnoses, length of alternative feedings and current feeding difficulties (see Table 3.1.2a and 3.1.2b). The twenty subjects ranged in
age from 3 months to 18 months (adjusted) age with a mean age of 8.1 months and an average length of gestation of 37.1 weeks. The majority of subjects had a normal gestation of
36 to 42 weeks (15/20 subjects). However, five other subjects born between 32-35 weeks gestation were admitted into the study because there was no history of interventricular hemorrhages (IVH’s), or gross neurologic difficulties The subjects all had significant medical histories which could be classified into 4 broad groups: cardiac (10/20), diaphragmatic hernia
(3/20), craniofacial anomalies (2/20), respiratory (3/20) and other (2/20). All but two of the subjects (S8, S10) received the alternative tube feedings within the first couple of days of life. For Subject 8 and Subject 10 the alternative feedings began at 8 weeks and 6 weeks, respectively. Subjects received the alternative feedings over periods ranging from 3 weeks to
14 months, with a mean length of about 5 months. However all of the subjects complied with the guidelines of having been alternatively fed for at least 2 weeks during the first 3 months
(adjusted age).
Finally, Table 3.1.2d provides an overview of the feeding difficulties reported which are consistent with difficulties typically observed in the MFTT group.
Table 3.1.2d: Summary of Reported Feeding Difficulties for MFTT subjects
Feeding Difficulties Subject (age in months) Refusal (4/20) S4 (5), S12 (5), S14 (5), S15 (3) Tastes Only (3/20) S6 (8), S7 (12), S17 (6) Bottle/Breastfed exclusively (5/20) S8 (9), S9 (9), *S10 (4), *S13 (3), *S19 (3) Smooth Puree Only (4/20) S1 (14),S2 (8), S3(9), S20 (7) Smooth Puree/Liquids via Bottle (5/20) S11 (13), S16 (15), S18 (18) Other (1/20) **S5 (6)
*Age appropriate behavior; currently receiving tube feedings, oral intake is less than 5% of nutritional needs ** This subject technically has age appropriate behavior; however, referred for continued need of a “premie” fast-flow nipple, poor tolerance of food volume and frequent gagging with spoon feeding
3.1.3 SUBJECTS: CONTROL GROUP
Each experimental subject was matched by (adjusted) age and sex with a normal control. See Table 3.1.3a for a comparison of the mean and standard deviation of the two groups weight, type of delivery and average length of gestation. All matched normal controls fit the following criteria:
• product of a full term pregnancy (over 36 weeks gestation) • history of normal pediatric examinations • age between 3 months (13 weeks) to 18 months • no significant past medical history (i.e. consistently normal Apgar scores at birth, no major infections, no history of minor surgeries, no severe jaundice, etc.)
Seven additional normal subjects were included in the study. Two of the controls
(N23, N24) were in the study as part of an additional test of reliability and did not meet the strict criteria of the other twenty-five children. See Table 3.1.3b for a summary of the 27 subjects utilized including: the child’s age at the time study was completed, sex, length of gestation, type of delivery and birth weight.
Sources of Subjects:
All of the control subjects were recruited through the following means: the high-risk clinic and GI clinic of Children’s Hospital Medical Center (of Cincinnati), the Kentucky
Birth-to-Three program and the Parent Infant Nurturing Group (PING) of the Cincinnati
Center for Developmental Disorders. The control subjects were recruited through local pediatrician offices.
Table 3.1.3a Comparison of weight, length of gestation, type of delivery and sex between matched normal control subjects and the MFTT subjects
Weight (lbs) Gestation (weeks) Type of Delivery Sex
Mean Stand Dev. Mean Stand Dev. Vaginal Cesarean Male Female
Normal 8.2 1.2 39.1 1.6 15 5 12 8 Controls
MFTT 6.4 1.5 37.1 2.7 11 9 12 8 Subjects
Table 3.1.3b: Summary of Normal Subjects Including Matched Controls and Additional Subjects
Subject Age Sex Gestation Delivery Type Weight (lbs) *N1 7 months M 39 weeks Cesarean 7-6 *N2 15 months M 40 weeks Vaginal 8-7 N3 9 months M 37 weeks Vaginal 7-14 N4 14 months F 40 weeks Vaginal 6-13 *N5 12 months M 40 weeks Vaginal 9-15 N6 6 months M 38 weeks Vaginal 9-4 N7 12 months F 36 weeks Vaginal 6-14 N8 15 months M 39 weeks Cesarean 8-13 N9 4 months M 37 weeks Cesarean 9-8 N10 9 months F 40 weeks Vaginal 7-14 *N11 4 months M 40 weeks Cesarean 7-2 N12 9 months M 40 weeks Vaginal 10-10 N13 5 months M 40 weeks Vaginal 8-7 N14 5 months F 41 weeks Vaginal 8-15 *N15 12 months F 41 weeks Vaginal 8-10 N16 3 months M 41 weeks Vaginal 10-4 N17 13 months M 39 weeks Cesarean 8-8 N18 6 months M 37 weeks Vaginal 7-15 N19 8 months M 39 weeks Vaginal 6-8 N20 3 months F 39 weeks Cesarean 7-10 N21 5 months M 42 weeks Vaginal 9-8 N22 18 months M 37 weeks Vaginal 5-7 **N23 10 months M 35 weeks Cesarean 5-13 **N24 10 months M 35 weeks Cesarean 4-14 N25 3 months F 40 weeks Vaginal 8-3 N26 7 months F 40 weeks Cesarean 7-11 N27 8 months F 40 weeks Vaginal 8-0 * “Extra” 5 Normal Subjects (see section 3.1.1) ** Two subjects included for independent test of bias (see section 3.1.5)
3.1.4 STANDARDIZATION OF THE PROTOCOL:
Data on the child’s medical history was collected from the caregiver. Consent was obtained as required by the University of Cincinnati and Children’s Hospital Medical Center
(of Cincinnati).
The experimental treatment consisted of a brief diagnostic examination using firm tactile pressure on 10 pre-selected parts of the body in the following order: (1) the lower extremities, (2) the hips, (3) trunk, (4) upper extremities, (5) shoulders, (6) face
(external cheeks), (7) lips, (8) gums, (9) palate and (10) tongue. These points were selected based on dermatome regions and cranial nerve organization. The protocol for this examination was originally created by the feeding team of the University Medical Center-
Las Vegas. This exam is used in current clinical practice in Cincinnati and continuing in Las
Vegas. It has been modified slightly for the purpose of this study.
Two different examiners completed the testing (the investigator and an occupational therapist), in order to control for examiner-specific factors. Consistent procedures were followed. The caregiver was asked to hold the child on his/her lap. Two favorite toys were placed near the caregiver and given to the child if a distraction was needed. State behavior changes (see Appendix B for a brief description of behavior states) and abnormal gag response were the two types of physiologic responses being judged at the 10 predetermined dermatome sites listed above. The examination did not begin until the child was in a calm, alert state. Beginning the exam with the child in a calm, alert state is critical for the following reasons: 1) One of the experimental data outcomes records the physiologic measurement of the child state behavior, 2) The calm-alert state is the baseline for behavior state change measurement, 3) Beginning the exam anywhere but at the baseline can produce
erroneous results. Therefore, the study was rescheduled if the child could not achieve a calm alert state prior to initiating the examination.
The experiment began once the child was in a calm, alert state. The experimental test was scored in the form of a judgment about the child’s physiologic reaction to touch at the 10 pre-selected regions. If the child did not change from a calm, alert state, and/or present with a gag response, the score for touch at that point was zero. If the child’s state changed or a gag response was observed, a “yes” was recorded for that point and the study stopped. The “yes” was then converted to a point scale according to the part of the body that was touched (see
Table 3.1.4a).
Table 3.1.4a Numeric value assigned to corresponding body part
10 Legs 9 Hips 8 Trunk 7 Arms 6 Shoulders 5 Cheeks 4 Lips 3 Gums 2 Palate 1 Tongue (anterior 1/3) 0 No Abnormal Response
3.1.5 Independent Test of Bias:
Two subjects were included in the study in order to test for potential bias on the part of the examiner based on external physical features of a subject and/or referring agency. In order to control for these potential biases, a set of twins were selected for the occupational therapist to examine. The twins were enrolled in the First Steps Program of Northern
Kentucky, a program designed to identify and treat high-risk infants and toddlers. One of the two twins (N23) had a significant past medical history for hemophilia, a malformed
extremity and a distinct physical appearance. The other twin (N24), had no distinctive
external features, was on target in all areas of development and only enrolled in First Steps to
be monitored for developmental milestones. Neither child had a history of any feeding
related problems (see Table 3.1.3b for further descriptive information).
The occupational therapist was informed of the twins’ enrollment status in the First
Steps Program. However, the occupational therapist was blind to the past medical history of
the two subjects and was thus unaware if she was examining a normal subject or a child with
MFTT. Despite a difference in the outward appearance and knowledge of First Steps
involvement, the occupational therapist found a 0-score (i.e. normal physiologic processing)
for both of the children.
3.2 RESULTS
Please see Tables 3.2a and 3.2b for a summary of the scores given by the investigator (Score 1), the observer or occupational therapist (Score 2) and the comments noted during the examination. Please see Table 3.2c for a summary of the investigator’s results of the overall number of normal vs. abnormal physiologic responses for the control group compared with the MFTT group. Table 3.2d is a summary of the observer’s and
occupational therapist’s results of the overall number of normal vs. abnormal physiologic
responses between the two groups.
Table 3.2a Summary of Scores for Matched Normal Controls
Subject Score 1 Score 2 Observer Comments N3 0 0 Student Tired/mild very brief protest with touch to palate/no gagging
N4 0 0 Student Giggled N6 0 0 OT Smiled throughout N7 0 N/A None Happy throughout N8 0 N/A None Happy throughout N9 0 0 Student Happy throughout N10 0 0 Student Smiled throughout N12 0 0 Student Smiled; chewed on fingers; teething N13 0 N/A None Cooing N14 0 0 OT Smiled throughout N16 0 0 Student Smiled/sucked with touch to the tongue N17 0 0 Student Frowned/No behavior state changes N18 0 0 Student Smiled/Opened mouth and leaned towards investigator’s hand N19 0 0 OT Happy throughout N20 0 0 Student Smiled/Sucked on fingers in mouth N21 0 0 OT Smiled throughout N22 0 N/A None Smiled throughout N25 0 N/A None Smiled/Sucked with touch to the tongue N26 0 0 OT Smiled throughout N27 0 N/A None Opened mouth and leaned towards investigator’s hand
Table 3.2b Summary of MFTT Scores
Subject Score 1 Score 2 Observer Comments S1 3 3 Student Initially smiled; pushed investigator’s hand away at lips, distracted, then continued, gagged with touch to the gums S2 0 0 Student Weekly OT since birth S3 0 0 Student Smiled throughout S4 1 1 Student Initially smiled; tongue retraction at palate; gagged with touch to tongue S5 1 1 Student Initially smiled; tongue retraction at palate; gagged with touch to tongue S6 3 N/A None Smiled through cheeks; became distressed at lips and gagged at gums S7 5 5 OT Smiled initially; distressed at arms/shoulders; strong gag at cheeks S8 7 6 OT State behavior changes very apparent; investigator though child exhibited Level 6 Distress at arms; OT continued to shoulders where strong gag was observed S9 1 4 Student Atypical response; fussy, calmed; repeated S10 0 0 OT No gagging/state behavior change noted; brief tongue retraction with touch to tongue S11 1 1 OT Smiled initially; strong gag with touch to tongue S12 1 1 Student Smiled initially; distressed at palate; gagged with touch to the tongue S13 1 1 Student Smiled initially; distressed at gums and palate; gagged with touch to the tongue S14 1 3 Student Behavior state changes began at gums; student thought child exhibited Level 6; Investigator continued; Strong gag noted at the tongue S15 1 1 Student Strong gag noted with the tongue; No state behavior changes S16 1 1 Student Smiled initially; attempted to push investigator away at gums; distracted; attempted To bite investigator with touch to palate; strong gag on tongue S17 2 6 Student Behavior state changes began at shoulders (student marked Level 6); Gagged Strongly at the palate S18 1 1 Student Calm throughout then gagged on tongue S19 1 2 Student Smiling initially; arched back with touch to trunk, cough with touch to palate; Strong gag on tongue S20 0 0 Student Smiled throughout; weekly oral intervention since birth
Table 3.2c Abnormal vs. Normal Physiologic responses of MFTT group and Matched Normal Control Group: Investigator’s Results
20
15 MFTT 10 Subjects Matched 5 Controls
0 Normal Abnormal Response Response
Table 3.2d Abnormal vs. Normal Physiologic responses of MFTT group and Matched Normal Control Group: Observer’s or Occupational Therapist’s Results
16 14 12 10 8 MFTT Group 6 Matched 4 Controls 2 0 Normal Abnormal Response Response
The study asked two distinctive questions:
Part 1: Do children who have been classified as mixed FTT demonstrate
abnormal physiologic responses to touch more frequently compared with a normal
control group? The current theoretical and medical expectation is that the MFTT group should demonstrate normal physiologic responses to touch reflected by a 0 score per child.
A chi-square analysis was used to analyze the data for the following reasons: 1) The data is ordinal in nature and, 2) a chi-square analysis allows for the comparison of matched subjects and can statistically determine if there is a difference between the two groups.
Results from the chi-square analysis reveals that there is a difference between the two groups. Table 3.2e summarize the Yes vs. No responses of the MFTT group and the matched normal controls.
Table 3.2e: Frequency of physiologic responses for MFTT and Matched Normal Control Subjects
Mixed FTT Controls Scored 16 0 “Yes” Response Scored 4 20 “No” Response
Calculations were completed with the following results: Χ2= 26.67, df = 1, p<.05 (.001).
A priori α was set for .05, therefore, the scores between the mixed failure to thrive and the normal controls are significantly different.
Part 2: Is there a pattern to the responses?
Another purpose of the study was to develop a severity rating roughly based on broad
dermatome regions and clinical experience. Table 3.2f shows the distribution of scores of the normal control group and mixed failure to thrive given by the investigator. Table 3.2g shows the distribution of scores of the two groups given by the observer or occupational therapist. Visual inspection of these two graphs reveals that the MFTT responses falls along a positive skew curve. This means that the majority of the responses fall close to the normal response (0, in this case) with fewer observations the further away from 0. This type of response would be expected if a severity rating or sub-categorization would be an appropriate tool to classify the responses of children with MFTT where it would be expected to see a greater number of children who are only “mildly” involved (i.e. score 1 and 2) and fewer
MFTT children “severely” involved (scoring 5+). However, formal statistics to determine specific trends could not be completed due to the number of subjects used in this study.
3.3 Validity/Reliability:
The investigator performed 72% (34 of 47) of the study examinations. For the purpose of checking reliability, an occupational therapist who has experience working with children and who is familiar with sensory systems performed the remaining 28%(13 of 47).
All of the examinations were scored by the investigator. In addition, observers (students) who were unaware of the purpose of the study scored 25 of 47 or 68% of the examinations performed by the investigator. Nine of the 47 (19%) examinations were completed by the investigator only. Please see Table 3.3a located at the end of this chapter for a summary of these results.
All of the normal control subjects received a zero(0) score by the occupational therapist and investigator indicating a normal response. In other words, for this group of scores there was
9/9 or 100% reliability between the occupational therapist and the
Table 3.2 f: Distribution of Scores Obtained by the Investigator
20 18 16 ects j 14 12 10 MFTT Subjects 8 Matched 6 Controls Number of Sub Number 4 2 0 012345678910
Measurement Values
Table 3.2g Distribution of Scores Obtained by Observer or Occupational Therapist
12
10 ects j 8 MFTT 6 Subjects Matched 4 Controls Number of Sub Number 2
0 012345678910
Measurement Values
investigator responses. The scores for the MFTT group varied between the occupational therapist and the investigator. Both scorers found 3/3 subjects to have an abnormal physiologic response and 1/1 to have a normal physiologic response. However, the severity or place of response varied in 1/4 of the MFTT subjects. For example, S8 received a score of
7 by the investigator because it was felt that the child exhibited Level 6 distress at the arms.
However, because the occupational therapist was directing this examination, it was continued to the next level, the shoulders (scored a 6). The occupational therapist had stopped the examination at this point due to both a state behavior change and a strong gag reflex was noted. Overall, including both groups, the occupational therapist and investigator agreed on
12 of the 13 scores resulting in a reliability of 92%.
All of the normal control subjects also received a zero (0) score by both the investigator and the observers indicating a normal response. In other words, for this group of scores there was 10/10 or 100% reliability between the investigator and the observers. The scores for the MFTT group also varied between the investigator and the observers. Although both groups of scorers were in 100% agreement of whether or not an abnormal response or normal response occurred (3/3 were found to have a normal response and 12/12 demonstrated an abnormal response), scores disagreed on the level of severity for 4/15 examinations.
• For S19, the observer noted a cough response with touch to the palate and was unclear if a gag response also occurred. The investigator, however, noted the cough response. The examination was continued because this was not a measure of abnormal physiologic response for this study. A strong gag was then noted at the next level of the tongue.
• The final three subjects (S9, S14 and S17) demonstrated a similar pattern. The observer marked that the child demonstrated “significant” behavior
state changes for each of these subjects (distressed, but not crying) However, the investigator continued for all three beyond these state behavior changes because, per definition established a priori these state behavior changes were not strong enough to warrant stopping the examinations. All three subjects eventually demonstrated a gag response before escalating into a Level 6 state behavior change, and the examinations were terminated at that time.
Overall, the investigator and observers agreed on 21 of 25 specific scores resulting in a reliability of 84%. Please see Table 3.3b for a summary of these results.
Table 3.3a Comparison of Investigator and the Occupational Therapist Scores
Normal Control Investigator Score (Score 1) OT Score (Score 2) N6 0 0 N11 0 0 N14 0 0 N19 0 0 N21 0 0 N23 0 0 N24 0 0 N26 0 0
Mixed FTT Investigator Score (Score 1) OT Score (Score 2) S7 5 5 S8 7 6 S10 0 0 S11 1 1
Table 3.3b Comparison of the Investigator and the Observers (Students) Scores
Normal Control Investigator Score (Score 1) Observer Score (Score 2) N3 0 0 N4 0 0 N5 0 0 N9 0 0 N10 0 0 N12 0 0 N16 0 0 N17 0 0 N18 0 0 N20 0 0
Mixed FTT Investigator Score (Score 1) Observer Score (Score 2) S1 3 3 S2 0 0 S3 0 0 S4 1 1 S5 1 1 S9 1 4 S12 1 1 S13 1 1 S14 1 3 S15 1 1 S16 1 1 S17 2 6 S18 1 1 S19 1 2 S20 0 0
CHAPTER 4
SUMMARY AND DISCUSSION
4.1 SUMMARY
The results of this study demonstrate that the group of MFTT children showed response patterns to firm pressure that differ from those of a normal control group. Sixteen of the twenty (20) experimental subjects reacted to firm pressure at some point on their bodies by a change in state behavior or by gagging. In contrast, none of the 27 normal subjects reacted to firm pressure in any way that could be interpreted as indicating distress or by gagging. The study showed that the two study groups fall into dichotomous categories.
As noted in Chapter 3, for most sessions the child’s response to firm pressure was recorded by the examiner and by an independent observer. Two different people served as examiners, the investigator (Examiner 1) and an experienced colleague trained as an occupational therapist (Examiner 2). The investigator was present for all sessions, but in cases where Examiner 2, the occupational therapist, conducted the firm pressure test, the investigator served as the independent observer. At various times in the course of the study, students training to become speech-language pathologists served as the independent observer to the investigator.
Again, as noted in Chapter 3 above, most sessions with a subject generated two independent ratings of the child’s reaction, one by the Examiner and one by the Observer.
On the categorical issue of whether the child’s response was normal or abnormal (a rating of
0 vs. a rating of 1-7), inter-rater reliability between these pairs of raters was 100%. This degree of agreement between observers is striking, but would be expected if the two
populations have different physiological profiles. As expected given the heterogeneity of the
MFTT population tested, severity ratings differed across the 20 experimental subjects (from
0-7 on the designated “dermatome” scale). For any one subject, there was also some disagreement between observers and examiners with regard to severity. However, when the severity ratings are compared, the results show an inter-rater reliability of 87% across all examiners and observers. The two experienced clinicians, the investigator and the occupational therapist, had an inter-rater reliability rate of 92%, while the inter-rater reliability rate between examiners and student raters was 84%. These levels of cross-rater agreement (84-92%) are considered reasonable when selecting a measurement tool (Barley &
Wholer, 1989; Ottenbacher, Dauk, Grahn, Gevelinger & Hassett, 1985).
4.2 DISCUSSION
This section will be divided into 6 main categories including: Section 4.2.1,
Relevance of the findings to the neuro-organization literature; Section 4.2.2, Relevance of the findings to the psychological literature in relation to identifying specific feeding behaviors;
Section 4.2.3, Discussion of the physiologic responses selected for this thesis. Section 4.2.4,
Discussion about the four subjects with MFTT who demonstrated normal response patterns:
Why don’t these children have altered response patterns?. Section 4.2.5, Discussion of future basic science research that would allow for brain mapping of specific brainstem nuclei (i.e. the Nucleus Tractus Solitarius). Section 4.2.6, General future research areas: What is the next step?
4.2.1 Relevance of the findings to the Neuro-Organizational Literature
The autonomic nervous system matures during a critical period which ends around 3 months of age (Als, 1982, 1986; Brazelton, 1973; Greenspan & Lourie, 1981; Kopp, 1982;
Porges, 1996). It is logical that an interruption of this maturation process may lead to a variety of developmental difficulties. Among those the following have been suggested: regulatory disorders, perceptual difficulties, language delays and sensory integrative deficits
(DeGangi et al., 1993; Doussard-Roosevelt & Porges, 1999; Greenspan, 1990). The results of this study supports adding feeding behaviors, including an abnormal gag reflex and poor regulation of state to tactile input, to this list of difficulties affected by poor autonomic system development. In addition, this study joins the studies by Greenspan (1992) and
DeGangi et al. (1993) that documented effects of the interruption of this maturation process lasting into the first year of life.
4.2.2 Relevance to the Psychological Literature in Identifying Specific Feeding
Behaviors
The results of this study demonstrate that children with persistent feeding difficulties and MFTT differ in response to tactile input when compared to subjects of a normal population. Clearly, children with a history of altered oral input in the first 3 months of life demonstrate persistent autonomic behaviors (e.g. distress, immature regulation, gagging in response to touch). Further, these behaviors can profoundly impact their ability to feed successfully by mouth during the first year. These findings have a significant bearing on both the current understanding of physiologic development in and the identification of specific behavioral manifestations within the feeding/swallowing population. Because
children with MFTT may present in clinic with a physiological history and response profile that is different from that of normals, the results of this study challenge us to critically review current intervention models, which typically focus on the period of attachment such as child- caregiver interactions.
Has this study contributed to the clinical knowledge base? Clinicians have often noted that children with feeding disorders have some component of “behavioral” difficulties.
However, a systematic description of these “behaviors” in terms of normal and abnormal developmental stages has not been available. Burklow et al. (1998), for instance, expands the typical classification of organic vs. non-organic failure-to-thrive feeding disorders into four medical “organic” causes and one broad “behavioral” (i.e. environmentally influenced) category, and notes that 87% of children with feeding disorders had “behavioral” difficulties, but does not specify the nature of these difficulties. Given the results of this study, however, it seems likely that the “behavioral” problems referred to included state behavior changes indicative of system distress and gagging. Thus, from a clinical standpoint, it is now possible to define specific behaviors the observation of which is an indicator of possible altered physiological development. Many cases for which the current diagnosis includes poor environmental support by a caregiver may in fact be better categorized as cases of altered physiological development.
4.2.3 Discussion of the physiologic responses selected for this thesis.
State behavior changes and abnormal gag reflex responses were selected as physiologic indicators for abnormal autonomic processing for this thesis. These two physiologic indicators had been selected by the investigator to use in the study because in
clinical practice these two tools seemed to be equal in sensitivity. Therefore, it was an unexpected finding that of the 16 abnormal responses that were observed by the investigator,
15 of those responses were an abnormal gag reflex. Only one of the subjects demonstrated a state behavior response change (to Level 6, see Appendix B) and the study was stopped at that point. However, the family reported that any oral stimulation would typically stimulate a strong gag response.
Another interesting finding is that of the 15 subjects who demonstrated an abnormal gag reflex response, 11 of the subjects demonstrated some less extreme state behavior change
(to Level 5) on the selected body parts from 1-4 points away from where the gag reflex was elicited. However, because the study was specific in using only extreme state behavior changes (i.e. to Level 6) as an abnormal physiologic response perhaps other less extreme forms of state behavior changes (i.e. to Level 5) may precede more significant abnormal responses (i.e. abnormal gag reflex). Although there is currently no literature linking state behavior changes and abnormal gag reflex responses it may be interesting for a future study to more carefully observe moderate state behavior changes (Level 5) in relationship to abnormal gag reflexes or Level 6 state changes as part of the same continuum.
4.2.4 Discussion about the four subjects with MFTT who demonstrated normal response patterns: Why don’t these children have altered response patterns?
As noted above, four of the subjects (S2, S8, S10 and S20)who were predicted to demonstrate altered response patterns appeared to have a normal response. A cursory review of the descriptive features of the four subjects does not appear to reveal any significant factors linking these four subjects. For instance there are two males and two females, two
subjects were delivered via c-section and two were delivered vaginally, two were g-tube fed and two were ng-tube fed. In addition, these four subjects birth weights ranged from below average (4 lbs, 10oz) to above average (8 lbs, 11 oz). Furthermore, each of these four subjects had a different diagnosis and the gestation length ranged from 32 weeks (the youngest participating in the study) to 38 weeks gestation.
A more thorough review of the history of these four subjects was completed in order to explore possible oral sensory influences that may have offset or normalized the responses obtained from these children. This review led to three different potential areas of influence including: aggressive therapy, breastfeeding and intermittent tube feedings. First, two of the four subjects (S2, S20) had received weekly Occupational Therapy services to specifically address orosensory processing since birth. None of the other 18 subjects had received this consistent type of service from birth. One of the parents was even quoted as saying to the investigator, “I wish you would have done this study last week, because she just stopped gagging this week” (sic).
One of the subjects with a normal response (S10) was exclusively breastfed and did not begin receiving tube feedings until Week 6 of life. Although the breastfeeding attempts continued while the tube feedings were utilized, the mother reported that she was required to pump her milk because S10 was not able to suck milk directly from the breast. This mother reported that she was only attempting to latch her baby for “the stimulation”.
Subject 8 demonstrated one of the more “severe” abnormal response patterns during this study, yet has a similar history to S10. Subject 8 did not begin tube feedings until Week
8 and had also been exclusively breastfed to that time. However, due to the medical treatment (which included chemotherapy) and inability to safely handle the breast milk, S8
was removed from the breast until her medical condition stabilized. After a five-week period,
S8 was then re-latched onto the breast and continued successfully with breastfeeding. Both children were admitted into the study because of persistent feeding difficulties and failure-to- thrive. Furthermore, since the study questions have arisen about the level of neurologic involvement presented by both children. Further research is warranted which looks at breastfeeding, orosensory input into the oral cavity and ramifications if this stimulation is interrupted.
The fourth subject (S3) who did not demonstrate an abnormal response to touch had received sporadic nasogastric tube feedings on/off (x2) for 6 months. It is possible that perhaps this subject received enough oral stimulation during the “off” periods or these “off” periods occurred during critical neurologic growth times that normal sensory development was able to take place. Future studies specifically looking at this type of sporadic alternative feeding would be warranted.
4.2.5 Discussion of future basic science research that would allow for brain mapping of specific brainstem nuclei (i.e. Nucleus Tractus Solitarius).
Chapter 2 includes an in-depth review of the Nucleus Tractus Solitarius (NTS) (see
Section 3). The NTS is the most likely candidate for interaction between autonomic and sensory nervous systems (specifically the vagal sensory system). It has been shown that a gag reflex response is mediated by afferent fibers received by the NTS with the efferent branch by the nucleus ambiguous (Martin & Jessell, 1996). This information was combined with the work of Porges (see section 2.2.9) that discusses the vagal system as a means to maintain
“homeostasis”. Basic science researchers have also noted that the majority of vagal afferent
information is brought into the NTS (Brining & Smith, 1996; Kalia & Sullivan, 1982;
Travers & Norgren, 1995; Zhang, Fogel, & Renehan, 1995). Therefore, the NTS is one area of the brain that if altered could potentially produce both an altered state behavior response and/or an abnormal gag reflex response.
Future animal experiments to specifically review changes within the NTS during periods of oral deprivation are warranted which would specifically investigate alterations of vagal nerve subnuclei. To date, only one researcher, Lasiter (1995, 1992) has looked at the
NTS in relation to oral deprivation. However, this research focused on changes in subnuclei of the NTS involved with gustation (not focusing on the vagus nerve input) following oral deprivation in rats. This work produced some very interesting findings. Specific orochemical stimulants were necessary to promote normal development (other types had no effect) and a specific number of days of artificial stimulation were required to produce normal development. Based on these findings it would be interesting to model techniques utilized from these studies and expand to a different animal population and to focus on the subnuclei of the NTS specifically involved with the vagus nerve afferents. An example of a controlled animal study would allow the investigator to use tube feedings for various lengths of time, provided controlled external stimulation (i.e. various degrees of positive and negative tactile sensory input), and then to compare the structural changes within the NTS.
4.2.6 General future research areas: What is the next step?
One logical sequence for the next study would be to obtain a greater number of children involved with the study. One flaw of the current study is the small number of MFTT subjects who were included. Although using this small number of subjects was enough to
obtain statistical significance, a larger study would allow for a statistical analysis of any trends that may be important for direct clinical applications. For instance, using direction from the current study, designing a larger study that would involve five specific subgroups may prove to be beneficial. These five subgroups would include: a control group, a group of
MFTT subjects who received continuous alternative feedings without treatment, a group of
MFTT subjects who received continuous alternative feedings with treatment, a group of
MFTT subjects who received intermittent alternative feedings and any MFTT subject who was exposed to breastfeeding. The desired result of this research would be to gather enough research data to develop a model of oro-sensory input development and the impact on feeding skills. Furthermore, it will be important to complete clinical research in order to generate techniques that would eliminate the development of these abnormal autonomic nervous system responses or eliminate the responses once the abnormal processing had begun.
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Appendix A: Introduction of “Mixed” Failure-to-Thrive
Failure-to-thrive (FTT) can be defined as any child with a feeding and/or swallowing problem who presents with the symptom of an inadequate growth rate typically consistently below the third percentile (Kover, 1997). In some reports, FTT has been directly linked to retarded motor and social development (Pemberton et. al., 1988; Kover, 1997). According to
Tolia (1995) and Arvedson (1997), FTT is a common problem in infancy and childhood, accounting for 3-5% of pediatric tertiary hospital admissions and 10-20% of pediatric outpatient visits.
FTT has been classified into three categories: 1) Organic failure-to-thrive (OFTT), which is defined as growth difficulties due to identifiable medical conditions, 2) Non-organic failure-to thrive(NOFTT) does not have a universally accepted definition, but typically attributes growth difficulties to a breakdown in normal caregiver-child interaction, and 3)
“Mixed” failure-to-thrive (“Mixed” FTT) is defined as growth difficulties persisting aftr remediation of a medical condition (Arvedson, 1997; Corwin, Isaacs, Georgeson, Bartolucci,
Cloud & Craig, 1996; Ramsay & Zelazo, 1988; Chatoor, Kerzner, Zorc, Persinger, Simenson
& Mrazek, 1992; Goldstein & Field, 1985). Remediable medical conditions of this nature include, for instance, children who had a compromised respiratory system at birth and who were prevented from taking food by mouth due to the presence of a tube in the airway.
Another example involves children whose heart condition makes oral feeding physically exhausting. In such cases, infants may become accustomed to receiving nourishment entirely through alternative feeding methods, such as nasogastric tubes (ng-tubes) or gastrostomy
tubes (g-tubes). If tube feedings are utilized for extended periods of time, i.e. beyond 15-20 days (Senez et al., 1996), therapy is typically necessary to restore oral feeding skills.
Clarification of Failure-to-Thrive Terms:
One challenge with focusing on the “mixed” FTT group is the way in which children within this type of FTT are classified, or rather “re-classified”. The flow chart presented in
Figure 1 summarizes this re-classification. All “mixed” FTT children are initially classified as OFTT because of their initial medical condition. When a child’s medical condition is resolved to the point at which oral feeding is possible, and the child is not successfully transitioned to feeding per os (i.e. by mouth, or P.O.), the child is classified as “mixed” FTT.
However, this re-classification presents formidable problems in terms of the literature, because many studies do not distinguish between these subsets of the medically fragile population. For instance, many studies of NOFTT children do not differentiate between children that have never had a documented organic medical condition and “mixed” FTT children. As above and for clarification purposes, the term “mixed” FTT will be used to refer to children with an initial diagnosis of OFTT, whose remediated medical condition makes them eligible for oral feeding but who continue to exhibit FTT. NOFTT in this document will only refer to children who demonstrate “failure-to-thrive syndrome” because of documented and persisting environmental factors.
Appendix B: Behavioral States State Control and Self Calming Abilities
(Brazelton, 1973)
State control is the child’s ability to regulate his/her internal arousal system in order to maintain a quiet/alert bright state. This alert state is the goal for any therapy session and it is critical for optimal learning of new information. For infants and toddlers there are six levels of state control as identified including:
Level 1-Deep Sleep
Level 2-Light Sleep
Level 3-Drowsy but Quiet
Level 4- **Quiet, Alert, Bright
Level 5- Awake Alert, Aroused Fussy
Level 6- Intense Crying State
Control should be assessed at the initiation of the evaluation and at various increments throughout the assessment to identify the child’s ability to control their state levels.
Self-calming techniques are utilized by a child to maintain an optimal control state in order to maximize their abilities.