THE EFFECTS OF ETHYL ALCOHOL

ON CONTRALATERAL AND IPSILATERAL

ACOUSTIC REFLEX THRESHOLDS

Edward N. Cohill

A Dissertation

Submitted to the Graduate College of Bowling Green State University in partial fulfillment of the requirements for the degree of

DOCTOR OF PHILOSOPHY

June 1978 XI

ABSTRACT

Acoustic reflex thresholds were measured at intervals in response to 500, 1000 and 2000Hz pure tones after the

ingestion of a 50% solution of 100 proof vodka. These

measurements were conducted to determine: 1. the effects

of ethyl alcohol on the contralateral and ipsilateral

acoustic reflex; 2. the relationship between acoustic

reflex thresholds and blood alcohol concentration, and; 3. the relationship between acoustic reflex threshold shift following alcohol ingestion and the frequency of the elicit­ ing stimulus. Sight male and eight female normal-hearing adults served as subjects. Acoustic reflex threshold mea­ surements were obtained pre-ingestion and at blood alcohol concentrations of 0.02 to 0.10% in 0.01% increments. Blood alcohol measurements were made by the use of an electronic a 1c ohol-in-breath analyzer. Acoustic reflex measurements continued until blood alcohol concentrations were reduced to

0.02%. The greatest acoustic reflex threshold shifts occurred at 0.10% blood alcohol concentration. The shifts were approximately 11dB for contralateral stimulation and 7dB for ipsilateral acoustic reflexes for all frequencies. Thus, the effects of ethyl alcohol were more pronounced on contralateral than on ipsilateral reflexes. These effects iil

were linear, and the rate of increase in acoustic reflex

thresholds was only significantly different at the extremes

of the measured blood alcohol concentration levels. Acoust­

ic reflex threshold shifts which resulted from the ingestion of ethyl alcohol did not show significant differences as a

function of the frequency of the reflex eliciting stimuli.

This was true for both ipsilateral and contralateral stimulation.

This study concluded that ethyl alcohol affects the acoustic reflex arc neural system, particularly the contra­ lateral pathway to different degrees depending upon the amount of alcohol in the individual. Small acoustic reflex threshold shifts were seen for low blood alcohol concentra­ tions. Thus, interpretation of acoustic reflex threshold data on an individual who is known or suspected to have ingested ethyl alcohol should be done with caution. XV

ACKNOWLEDGMENT

I would like to thank Michigan Auditory Instrument Company, Detroit, Michigan and Doug Vogal of CMI, Inc., Vail, Colorado for the use of their equipment. „ Their concern in this research is appreciated. Also, I would like to thank Mr. Edward Roth, President, W. A, Taylor and Co, for his financial support of this research.

To my committee, Drs, Joyce Statz, Ray Tucker, Jeff Danhauer, and George Herman, I appreciate their time and comments.

Dr, Herbert J. Greenberg, my chairman and friend, a special thanks for his time and companionship. His profes­ sional critisism and help will never be forgotten.

A note of thanks and love to my sister, Donna, for her

H iterailstic review of the work. Also, Mother, Dad, Bart,

D

C ridget, and Kathy, we did it, Many cases, cords, and four years later- »If its to be, its up to me’.

Mary, thanks for so much. Your love, time, patience, a very thing, this work is yours. V

TABLE OF CONTENTS

INTRODUCTION » ...... 1

ACOUSTIC REFLEX...... a,....,,,,,,,.,...,.,...... ,...... 5 Diagnostic importance of the acoustic reflex,...... 5

Psychoacoustic experiments and the acoustic reflex....9

Theories of acoustic reflex activity.,.,.,....,.,,,,..?

Neuroanatomy and neurophysiology.,11

Contralateral and ipsilateral reflex measurements..,,17

EFFECTS CF DRUGS ON THE CENTRAL NERVOUS SYSTEM ...... 19

ACTION Of ALCOHOL ON MAN...... 21

E FFECTS CF M ANIPULATIVE AGENTS ON THE ACOUSTIC EEFLEX. . . . . 24

STATEMENT OF THE PROBLEM..,...... 29 VI

METROE...... 31 Sub jects, ...... 31

Instrumentation...... 32

Test pr ocedure...... 33

RESULTS, ...... 36

Eat a analysis...... 36

Ipsilateral versus contralateral stimuli tion., 39 Blood alcohol concentration.39

Frequency46

DISCUSSION...... 48

Ipsilateral versus contralateral...... 48 Blood alcohol concentration.49

E re q uen cy,...... 51

Effects of drugs on the acoustic reflex51

Conclusions...... ,,..,52

REFERENCES...... 54

APPEN EICES...... 68 vii

LIST OF TABLES

Table 1. Means and standard deviations of contralateral and ipsilateral ear acoustic reflex threshold shifts as a function of blood alcohol concen­ tration and stimulus frequency...... 37

Table 2. Summary of three-way analysis of variance...... 38

Table 3. Mean values for Scheffe Test of Multiple Com­ parisons for ipsilateral and contralateral acoustic reflex threshold shifts at 0.02 to 0.10% blood alcohol concentration...... 42

Table 4» Mean values for Scheffe Test of Multiple Com­ parisons for contralateral acoustic reflex shifts as a function of blood alcohol concen­ tra tion...... 44

Table 5. Mean values for Scheffe Test of Multiple Com­ parisons for ipsilateral acoustic reflex threshold shifts as a function of blood alco­ hol concentration...... 44

Table €. Main effect intervals, formulas, and values for the linear, quadratic and cubic expression of acoustic reflex threshold shift is a func­ tion of blood alcohol concentration...... 45

Table 7. Mean values for Scheffe Test of Multiple Com­ parisons for the rate of change in acoustic reflex thresholds for ipsilateral and contra­ lateral ear stimulation as a function of blood alcohol concentration ...... 47 LIST OF FIGURES

Figure 1. Neuronal organization of the acoustic reflex. ...14

Figure 2. Mean contralateral and ipsilateral acoustic reflex threshold shifts as a function of blood alcohol concen tration...... 41 ISTRODOCT ION

The acoustic reflex in man has been stalled extensively

for almost forty years. It has been define! as the

contraction of the stapedius or tensor tympani muscles that

will usually produce a measureable, time-locked change in

acoustic impedance at the lateral surface of the tympanic

membrane (Lilly, 1972). The reflex is bilateral, that is,

the stimulation of one ear causes a contraction of the

stapedius muscle in both ears (Simmons, 1960; Klockhoff,

1961; Jepsen, 1963; Greisen and Rasmussen, 1970) . Holler

(1962) reported that in 1934, Geffcken showed that a

contraction of the middle ear muscles changed the acoustic

impedance of the hearing mechanism in humans.. The acoustic reflex is due to contraction of the

stapedius or the tensor tympani muscle, with the former

being the most important. The stapedius muscle receives its nerve supply from a branch of the facial na rve (VII CN),

(Byrne, 1938; Borg, 1976). The contraction of the stapedius

muscle occurs when stimulation is delivered to the afferent pathway of the acoustic nerve. Following tha synthesis of the stimulation in the brain stem, the efferent, or motor neurons react (Greisen and Rasmussen, 1970). A reflex arc system is the feeder power for the acoustic reflex. The determination of acoustic reflex thresholds can be

employed as a testing procedure in the diagnosis of a

hearing impairment. The utilization of the acoustic reflex

in acoustic impedance audiometry relies on the relationship

between the pure tone thresholds and the acoustic reflex thresholds. Sedenberg ( 1963) cited the importance of

acoustic reflex thresholds in their evaluations of hearing

sensitivity in young children. As Feldman (1967) has

pointed out, such measurements provide information concern­ ing the middle ear mechanism independent of a patient’s subjective response. Also, Lamb and Norris (1969) indicated a similar importance in the hard-to-test individual, such as the mentally retarded. Perhaps the most important implication of acoustic reflex thresholds is the determination of the type and degree of hearing loss that a person may have. Conductive versus sensorineural involvement in a hearing loss can be differentiated by acoustic reflex thresholds (Metz, 1946; Liden, 1S69; Jerger, 197C) . In addition, the presence of either ossicular disarticulation or otospongeosis can be determined (Lilly and Shepherd, 1964; Feldman, 1967; Jerger,

1970; Liden, Peterson and Hartford, 1970; Anderson and Barr,

1971). The existence of recruitment in an individual can also be determined by utilizing the acoustic reflex (Liden, 1969,

2 1 970; Alberti and Kristenson, 1970), in that a difference of

less than 70 to 90dB between the pure tone thresholds and

acoustic reflex thresholds is indicative of recruitment (Thomsen, 1955; Feldman, 1963; Lindstrom and Liden, 1964).

Three factors can contribute to abnormal reflex find­ ings or the absence of an acoustic reflex. First, patholog­

ical changes in the afferent pathway of the reflex arc lead

to moderate or severe hearing loss. Second, changes in the

afferent part are reflected in facial palsy or middle ear

pathologies (Greisen and Basmussen, 1970). The third factor may be any manipulative agent (such as a drug) which, when

ingested by an individual, acts to alter a system, specific­

ally the autonomic nervous system (Metz, 1946; Kissin,

Schenker, and Schenker, 1959). For instance, Bobinette,

Rhoads, and Marion (1974) demonstrated that the administra­

tion of a sedative (secobarbitol) often causes an elevation

of acoustic reflex thresholds. To obtain reliable reflex thresholds, the individual’s system must be free of any manipulative agent that could

serve to alter the reflex system. Researchers have directed their efforts to the effects of certain drugs on the acoustic reflex in man. Differing results have been reported, especially with regard to temporal parameters of the reflex and ipsilateral versus contralateral threshold, measurements.

In 1970, Mendelson demonstrated that the performance of

3 a reflex system can be altered by the introduction of a chemical such as ethyl alcohol into the biological system.

After being ingested orally, it is absorbed very rapidly

(Victor and Adams, 1953). The chemical passes through the

walls of the gastrointestinal tract into the blood stream.

Once in the blood, the alcohol, now greatly diluted, is carried to all cells of the body including the brain.

Ethyl alcohol is medically classified as a chemical agent. Shen ingasted in small doses, it acts as a sedative

(Loomis, 1950; Gonzales, Vance, Helpern, and Omberger, 1954;

Olson, Davis, Eagles, and Longman, 1964) . Asmussen, Raid, and Larsen (1948) and Docter and Perkins (1960) observed that ethyl alcohol acts upon regulatory structures, such as the reticular formation, which in turn modify the activity of the cortex and other parts of the central nervous system.

Sven at low blood alcohol concentrations, the reticular formation not only affects brain functions, but also serves as a relaxing agent to the muscles (Killam, 1 962).

Since it has been shown that ethyl alcohol acts as a depressant on the autonomic nervous system when taken in small doses, this study was performed to investigate the affects of alcohol on certain parameters of the acoustic reflex. The parameters studied were threshold shift and differences between ipsilateral and contralateral reflexes at various blood alcohol concentrations as a result of the ingestion of alcohol.

4 REVIEW OF THE LITERATURE

The review of the literature will be presented in four

sections; (1) the application of the acoustic reflex to

audiolcgical diagnostic procedures , and psychoacoustic

experiments, the neuroanatomy and neurophysiology of the stapedius reflex, and, ipsilateral versus contralateral

acoustic reflex measures; (2) the effects of central depre­

ssants cn central nervous system activity; (3, the effects

of ethyl alcohol in man ; and, (4) the effects of manipula­

tive agents (drugs) on the acoustic reflex..

THE ACOUSTIC REFLEX

Acoustic reflex threshold data have been used in the

iiagnosis of hearing sensitivity for over thirty years, A landmark publication by Metz (1946) marked the initiation of research into impedance measurement techniguas. Five special applications of acoustic reflex threshold data exist in the repertoire of the diagnostician. First, recovery from 7th nerve tumors can be monitored by the use

5 of acoustic reflex thresholds (McCandless and Jacobson,

1975). Second, thé acoustic reflex has been employed in the

selection of a hearing aid. By â comparison of the loudness

discomfort level and acoustic reflex threshold, the maximum

power output of the hearing aid can be determined for

optimum efficiency and usefulness by the hearing-impaired

individual (McCandless and Miller, 1972). Third, the indi­

vidual who attempts to feign a hearing loss can be disco­

vered by the involuntary response procedure of the acoustic

reflex (Lamb and Peterson, 1967), Fourth, Wedenbarg (1963)

and Jerger ( 1970) cited the importance of acoustic reflex

thresholds in their evaluation of hearing sensitivity in

young children, As Feldman (1 967) stated, such measurements provide information concerning the middle ear mechanism independent of a patient* s subjective response. Also, Lamb and Norris ( 1969) indicated a ; similar importance in the hard-to-test individual, namely, the mentally retarded..

Fifth, Jerger, Burney, Mauldin, and Crump (1974) proposed, the use of the acoustic reflex as a predictor of the amount of hearing loss. This concept was carried further into a technique designated »'Sensitivity Prediction from Acoustic

Reflex" (SPAR). SPAR is a very simple arithmetic computa­ tional procedure, but the prediction is invalid if a middle ear pathology exists (Jerger, 1977),

Anderson and Barr ( 1966, 1971) showed that patients with ctospongeosis were seen to have reflexes although the

6 severity of the pathology would seem to be of sufficient

magnitude to increase the acoustic reflex threshold. The

verification of this "conductive recruitment", (Anderson and

Barr, 1971) , could be analyzed further by using bone conduction acoustic stimulation (Djupesland, Flottorp, Sund- by et al. , 1973), In addition, the presence of ossicular disarticulation can be determined by acoustic reflex thre­ shold measurement (Lilly and Shepherd, 1964; Feldman, 1967; Jerger, 1970; Liden et al. , 1970; Anderson and Barr, 1971).

Sensorineural hearing losses reveal diversified acoustic reflex thresholds with the site of lesion dictating the variance in reflex data (Wilber, 1976),

The existence of recruitment in an individual can be determined by using the acoustic reflex (Metz, 1952; Liden,

1 969, 1970; Alberti and Kristensen, 1970), A difference of less than 70 to 90dB between the pure tone thresholds and acoustic reflex thresholds is indicative of recruitment (Thomsen, 1955; Feldman, 1963; Lindstrom and Liden, 1964),

Cochlear lesions produce reflexes as low as 5dB sensation level with a white noise stimulus (Wilber, Goodhill, and Bettswcrth, 1976). The acoustic reflex threshold in the pathological ear differs significantly from that of the normal. Contralater­ al stimulation in a normal ear yields acoustic reflexes at

7 0 to 95dB SPL (Metz, 1946; Thomson, 1955; Klockhoff, 1961;

Lindstrom and Liden, 196 4; Peterson and Liden, 1972; Chi-

7 veralls and Fitzsimons, 1973),

Wilber (1976) noted four possibilities that could exist in an ear with normal pure tone thresholds and without

measureable acoustic reflexes. They are: (1) with contra­

lateral stimulation, the monitored ear may have too severe a

hearing loss to exhibit a measureable reflex; (2) 8th nerve

damage in the stimulated ear; <3) 7th nerve damage in the

monitored ear; or (4) absence of the stapedius tendon in the

monitored ear. These four possibilities demonstrate the diagnostic importance of acoustic reflex measurements.

One abnormality in acoustic reflex threshold data is

abnormal adaptation or decay of the reflex in the patient with a retrocochlear lesion. A reflex decay test was developed by Anderson, Barr, and Wedenberg (1969, 1970) as a clinical test for the early detection of eighth nerve tumors. It was noted that subjects with multiple sclerosis or acoustic neuromas showed 50% adaptation in less than 5 seconds for pure tones at 10dB above the acoustic reflex threshold. Extensive research into the effects of 8th nerve pathologies on the acoustic reflex has been performed by

Jerger. He reported that only 23% of his patients with 8th nerve disorders showed normal reflexes (Jerger and Jerger, 1974). Similar results were seen in other studies by

Jerger, Harford, Clemis and Alford (1974), Jerger and Jerger

(1975), Starr and Achor (1975), Jerger, Neely, and Jerger

8 ( 1975), Olsen, Noffsinger and Kurdziel (1975), and Jerger and Jerger (1977).

The role of stapedius contraction has been employed in the resolution of certain psychoacoustic phenomenon. Djupe- sland and Zwislocki (1971) stated that the action of the stapedius reflex and temporal summation are related. In

1971, flottorp, Djupesland, and Ninther revealed that a decrease in reflex threshold of 3 to 6dB per octave was apparent as the bandwidth of the signal was increased. The authors stated that the responses were indicative of a subcortically controlled neuromuscular response, in contrast to cerebral responses which are employed in psychophysical measurement methods. These results were investigated furth­ er by Ijupesland and Zwislocki (1 973), Using a tone-on-tone masking stimulus, the investigators found that there was a sharp transition at each frequency using a masker with its center frequency at the same test frequency. The combina­ tion tones enhanced the threshold by 3 to 63B when compared to thresholds elicited by a single tone (Djupesland and

Zwislocki, 1973). From the above mentioned psychoacoustic experiments and others, several theories of the function of the stapedius reflex have been postulated. They are: (1) labyrinthine pressure theory; (2) fixation theory; (3) protection theory; and, (4) frequency selectivity theory.

The labyrinthine pressure theory was postulated by

9 Jepsen (1963). This theory states that a stapedial reflex

»ill cause a change in the pressure of the labyrinthine fluid and therefore change the mechanical performance of the ear {Jepsen, 1963). No experimental evidence supports this

theory.

Sever and Lawrence (1954) stated that the function of the tympanic muscles is to suspend the ossicular chain in its ncrmal anatomical position and as a result, provide a proper tension for effective signal transmission.

The protection theory has been the most widely accepted theory fcr the function of the tympanic muscles. According to Jepsen (1963) and Smith (1967), the muscles contract as part of the impedance matching device to prevent overstimu­ lation of the inner ear fluids and neural network. Simmons,

¿alambcs, and Rupert (19 59) and Fletcher and Riopelle (1960) have attempted to validate this theory in animals and humans, respectively. In the Fletcher and Riopelle study, certain subjects were exposed to a 1000Hz pure tone stimulus of sufficient magnitude to produce an acoustic reflex. All subjects were subjected to rapid gun fire. Those who were axposed to the activating 1000Hz pure tone signal showed greater protection as measured by the acoustic reflex than those net exposed to the pure tone. Simmons et al. (1959), showed that the stapedius muscle was the main reactant for protec ticn to loud sounds in non-anesthetized cats.

According to the frequency selection or accomodation

10 theory, the role of the tympanic muscles is to enhance the transmission of certain frequencies to the inner ear (Jep- sen, 196 3) . The high frequencies are enhanced and low frequencies are attenuated during contraction of the muscles

(Wever and Lawrence, 195 4) . It should be noted that although all of the theories are based on contraction of both the tensor tympani and the stapedius muscles, the tensor tympani is present in the reflex in humans only at high stimulation intensities

(Jepsen, 196 3).

Neuroanatomy and Meuroph ysiology of the Stapedius Reflex

The origin of the stapedius muscle, which lies within the lumen of the pyramidal eminence, is within the walls of the bcny canal of the posterior wall of the tympanic cavity (Zemlin, 1971). The muscle peoceeds in a vertical direc­ tion, joins with its tendon, and continues in a horizontal direction to join with the neck of the stapes (Kobrak, 1959;

Zemlin , 1971). The stapedius is a pennate type muscle showing the characteristic action of large amounts of tension with very little displacement (Jepsen, 1963). Weyer and Lawrence

(1954) found the average length of this muscle to be 6.3mm with an average cross sectional area of 4.9mra2.

11 Major research into the neural pathway of the stapedius

reflex has been performed on animals (Borg and Holler, 1968; Borg, 1971, 1972a, 1972b, 1972 c, 1972d, 1973, 1976, 1977;

Bosatra, 1977) . These studies on the rabbit revealed

basically a direct and an indirect neural chain (Borg,

1973). A neuronal organization of the midile ear reflex pathway is summarized in Figure 1, The following are the observations cited by the aforementioned Borg studies on the direct and indirect middle ear reflex pathway.

Direct

First synapse

1. Located in the ventral cochlear nucleus;

2. Dorsal cochlear nucleus and neurons of posteroventral nucleus which give rise to stria of Held not involved in muscle activation for pure tones;

3. No primary fibers pass the cochlear nucleus in the trapezoid body to higher auditory cen­ ters, the ventral cochlear nucleus is the only possible location of the first synapse; 4. Thin fiber component of the trapezoid body is the most likely pathway, since if originates in the ventral cochlear nucleus and has bilat­ eral connections to the medial superior olive.

Second synapse

1. The lateral superior olive, medial superior clive and lateral preolivary nucleus are the wain sites of the ipsilateral termination of trapezoid body fibers;

2. The trapezoid body transmits the reflex actively, therefore the position of the second synapse is most likely to be found in the area of the trapezoid body termination (lateral

12 Figure 1 Neuronal organization of the acoustic rafiex.

13 ACOUSTIC REFLEX ARC

Right Left------superior olive, medial superior olive and lat­ eral preolivary nucleus) ;

3. The pathway of the contralateral stapedius has a synapse in either the ipsilateral or the contralateral medial superior olive; 4. Ipsilateral and contralateral connections from the medial superior olive and a small direct pathway from the ventral cochlear nuc­ leus to the ipsilateral facial motor nucleus exists.

Third synapse

1» The fourth neuron of the reflex pathway is the motoneuron; 2. The facial nerve innervates the stapedius muscle;

3, Direct connections from the ventral cochlear nucleus for the stapedius muscle are few.

I ndirect

1. Lies parallel to the direct pathway; 2» Slower and probably multisynaptic connections;

3. Relays are unknown; 4. The slope of the stimulus-response curve is decreased after lesions specific to the direct pathway, without influence of the reflex thre­ shold, The reason is that the direct connec­ tions have higher thresholds than slow indirect connections;

f. Non-linear dynamic characteristics of mid­ dle ear reflex responses are partially explained by the direct and indirect arrange­ ment (Borg, 197 3).

15' The understanding of the neural pathway has been 'both

reinforced and confused by inducing lesions to various areas,

of the pathway and recording the neural activity at that and

other locations. In a recent study by Borg (1977) -, it was

found that by inducing retrocochlear pathologies in rabbits,

distinct changes were noted in the reflex properties. By

inducing lesions to the auditory nerve, the investigators induced trauma much like that of an eighth nerve tumor.

Upon inducing the lesion, reflex thresholds increased and

sometimes returned to normal upon dispersion of the edema. Furthermcre, the effects of the trauma were seen only’

ipsila terall y. Lesions induced in the cochlear nucleus showed a systematic relationship to the position and the

extent of the lesion. None of the animals showed variation

f rom normal when the lesion was confined to the dorsal

cochlear nucleus and the pathway below the nucleus and

iorsal to the dorsal and intermediate strias (Borg, 1977). Lesions to the ventral cochlear nucleus showed both ampli­ tude, latency and decay changes. The decay phenomenon is variable. Lesions in the lateral jiarts of the trapezoid

body affected the latency and amplitude to a great extent Jf whereas ether pathway lesions from the cochlear nucleus did

not influence the reflex at all (Borg, 1977). Even exten­

sive lesions to the midline, which would be expected to remove contralateral responses, produced a change, but did not obliterate reflex response in the rabbits. In spite of

16 extensive lesions, some contralateral reflex response always remained {Borg, 1977).

The information from the Borg studies has been employed by other researchers for clinical application. By monitor­ ing acoustic reflex threshold activity, the severity of a pathology can be investigated, Also by ascertaining acoust­ ic reflex threshold data on patients with brain stem disorders, the diagnostic value of contralateral versus ipsilateral neural activity was confirmed. . Jerger et al. ,

( 1975), monitored the change in acoustic reflex thresholds in a patient with an intra-axial brain stem tumor. A pattern of systematic recovery was noted in acoustic reflex thresholds as the brain stem lesion responded to therapy.

This procedure of diagnosis and monitoring was confirmed as an important tool for differentiating eighth nerve disorders from the brain stem site (Jerger and Jerger, 1977).

1 C ontrala teral versus Ipsilateral Reflex Measurements

Mcller (1961) and Fria, leBlanc, Kristensen et al.

(1975) reported that the stapedius reflex could be elicited at lower intensities using ipsilateral stimulation rather J than centralateral stimulation. The difference was found to be 2 tc 16dB. Also, Holler (1962) stated that the dif­ ference between ipsilateral and contralateral stimulation

.17 was greater at 300 and 525Hz than at 1200Hz. He concluded I that the difference between frequencies was due to "... the

change in transmission through the middle ear caused by the muscle contraction.”

The comparison of ipsilateral to contralateral measure­ ment methods is of importance in the diagnostic setting. In the cochlear pathology with contralateral stimulation, the reflex will be present bilaterally (Anderson and Hedenberg,

1 968; Jerger, Jerger and Hauldin, 1972). With the pathology beyond the cochlear hair cells but peripheral to the trapezoid body, acoustic reflexes will be present in both the pathological and healthy ear if the stimulus is of sufficient intensity. A pathology in the 8th nerve region will exhibit decay (Greisen and Rasmussen, 1970).

One of the most important diagnostic implications of the acoustic reflex is the diagnosis of a central lesion.

Upon ipsilateral stimulation, reflexes would be present in both ears (Jerger and Jerger, 1974), Greisen and Rasmussen

( 1970) reported evidence that in central lesions contralat­ eral stimulation revealed no reflexes in the ear contralat­ eral to the lesion. It was revealed through histological studies that there was an interruption of the reflex arc.

It was concluded that the contralateral reflex pathway was degenerated, thus contributing to the characteristic acoust­ ic reflex data.

18 THE EFFECTS OF DRUGS ON THE CENTRAL NERVOUS SYSTEM

The effects of drugs on man have been studied primarily

by electroencephalographic (EEG) techniques. The effects

monitored when a drug has been ingested alone or in

combination with another manipulative agent have been cen­

tered cn changes in reticular formation activity. ,

Auditory inputs have been identified in the reticular formation (Rossi and Zanchetti, 1957). Modifications of

reticular potentials can be demonstrated by following stimu­

li applied to many points in the central nervous system.

There has been evidence of facilitatory (Brodal, 1943) and

inhibitory interaction (French, Verzeano, and Magoun, 1953)

between incoming stimuli from differing sources. ;

There is a widespread reticular influence on the propagation of sensory stimuli from receptor to receiving

area of the primary systems. Early evidence of alterations

in sensory potentials within the central nervous system at

the first synaptic relay was obtained by Hagbarth and Kerr

(1954). They demonstrated an inhibitory effect of the l reticular formation on afferent potentials elicited by dorsal root stimulation. Similar data were reported by

Linblom and Ottosson (1956), and evidence of reticular influence at various other sensory relays appeared rapidly.

Sensory signals were shown to be blocked at the nucleus

19 gracilis and in the sensory nucleus of the fifth nerve (Hernandez-Peon, Jouvet and Schemer, 1955; Hernandez-Peon, Schemer and Velasco, 19 56). Following reticular formation stimulation, auditory responses to clicks were depressed at

the geniculate and at the cochlear nucleus (Galambos, 1956).

The investigation of the selective sensitivity of the reticular formation and central nervous system to pharmaco­ logical agents has employed two criteria. First, neurophy­ siological approaches have been used to detect alterations in the electrical activity of the reticular formation and central nervous system or of structures or pathways func­ tionally related to the reticular formation and central nervous system. Secondly, behavioral studies have been concerned with drug-induced alterations of unpatterned or conditional behavior. There is little evidence available for any biochemical substratum of activity of drugs on specific brain areas. Further, the accumulation of a drug in any area does not necessarily indicate activity at that site. The importance of experimental control of influences of body temperature, blocd pressure and local blood flow, oxygenation, etc., have been emphasized as a part of any drug experimentation.

Tie Influence of nonbarbiturate depressants on poly- synaptic mechanisms has been studied extensively. All results revealed that it is possible to differentiate certain central depressants by their actions on various

20 segments of the neural pathway.

In summary, although most of the depressants seem to

exert their anesthetic or sedative effect through action on

the brain stem reticular formation, their specificity might be due to many different effects on other systems,

ACTION OF ALCOHOL IN HAN

Ethyl alcohol is classified as a general depressant.

Therefore, Ingestion of alcohol affects the central nervous system and manipulates the action of nerve cells.

It has become evident that the pharmacological and metabolic effects of ethyl alcohol on any organism are very different at high and low levels of consumption. Shen consumed in moderate quantities, alcohol is a relatively innocuous nutrient that can be tolerated without harm to an organism.

The elimination of alcohol from the organism takes place largely through metabolic removal. It has been difficult to explain how much of the total alcohol metabo­ lism takes place in the liver and how much takes place in other tissues (leloir and Munoz, 1938) . Tygstrup, Winkler and Lundquist (1965) and Lieber (1968) revealed that more than 7C% of alcohol metabolism is accounted for by oxidation in the liver, But other routes cannot be neglected. The

21 two most important processes are elimination through the

lungs ano kidneys. The amount of alcohol lost in this way is proportional to the concentration in the blood. In man,

pulmonary and renal elimination contributes 10 to 15% to the overall elimination rate at blood levels of 200 to 300 mg/IGGirl (Jacobsen, 1952). The type of experiment most often performed on human subjects involves the intake of relatively small doses of ethanol followed, after a suitable equilibration period, by the rénovai of a series of venous or capillary blood samples. In nearly all cases, the blood alcohol concentra­ tion obtained is low, and the disappearance is caused by the metabolic conversion of ethanol. In some cases, the forma­ tion cf carbon dioxide (CO2) from carbon-14 (14C) ethanol has been measured instead of the change in alcohol concen­ tration (Jacobsen, 1952; Mendelson, 1968) . Such measure­ ments do not estimate the rate of alcohol oxidation, but indicate to what extent the primary oxidation products, acetaldehyde and acetate, are further oxidized in the body. The conclusion of Nyman and Palmlov (1934) and Carpenter and Lee (1938) was that the blood alcohol concentration, after completion of absorption and distribution in the body decreased at a constant rate, wAS virtually independent of physiological factors, such as physical work. Ethanol is not metabolized to a significant extent in the brain, and this tissue does not contain alcohol dehydro­

22 genase activity (Kinard and Hay, 1960; Wallgren and Kulonen,

1960; Towne, 1964) . In a study by Battey, Heyman and

Patterson (1953), it was shown that ethanol in concentra- I t ions of about 300 mg/100ml of blood, significantly reduces the brain oxygen consumption by 30%. Ethanol and higher alcohols inhibit the utilization of glucose in KCL- stimulated brain cortex slices (Machronicz, 1962, 1965).

There is a three step process leading to an increased oxygen and glucose consumption in the stimulated nerve cell, The first is that there is a depolarization which produces changes in the nerve cell membrane that lead to the production of an action potential. Sodium ions enter the cell and potassium is removed (Hodgkin, 1964; Huxley, 1964).

Second, this action is followed by an increased active transport of sodium and potassium with a hydrolysis of ATP (Cummins and Mcllwain, 1961). Third, the availability of

ADP is increased and oxygen consumption is increased (Atkin­ son, 1 96 €) .

The most marked effects of ethanol in the nerve cell seem to be exerted on the resting potential and in the active transport of sodium and potassium ions (Wright, 1947;

Gallegc, 1948; Knutsson and Katz, 1967). Although alcohol: at very low concentrations has activating effects in the neuromuscular junction, these seem not to occur in the central nervous system.

23, EFFECTS OF MANIPULATIVE AGENTS ON THE ACOUSTIC REFLEX

Having established temporal parameters of the acoustic

reflex fcr both the normal and the pathological hearing individual, investigators of the acoustic reflex have directed their investigations to the effects of manipulative agents, i.e., drugs, on the acoustic reflex. Berg and Holler (1967) investigated the effects of ethyl alcohol and pentobarbital sodium on the acoustic reflex in roan. With blood alcohol concentrations of 0.12%, the researchers found diminished responses. In response to stimuli cf 500 and 1450Hz, with a duration of 500msec, the acoustic reflex threshold increased as a function of blood alcohol concentrations. For example, at 500Hz, the stimulus intensity was Increased about 10dB at a blood alcohol concentration of 0.13%. This shift decreased to 2dB at a concentration of 0,0 2%. No differences were noted between ipsilateral and contralateral reflex measurements when com­ paring pre- and post-ingestion tracings. However, upon careful examination of figures presented by the authors, pre- and post-ingestion differences between the contralater­ al and ipsilateral acoustic reflex measurements can be a oted. . ' An example is a recording of pre- and post-alcohol threshold measurements (Figure 1, pp. 118, Borg and Holler,

24 1 967). While contralateral and ipsilateral reflexes are I 1 distinctly different on the recording for pre-alcohoi inges­

tion, the tracings overlap at blood alcohol concentrations of 0.12%, Similar results were seen when subjects were

given 3.0 mg /kg of pentobarbital sodium. Reflexes under

this condition were characterized by decreased amplitude and

a rise in threshold. Contralateral reflexes were more

susceptible to the drug than ipsilateral reflexes.

Liden, Nilsson, Laaskinen, Roos, and Miller (1974)

investigated the effects of pentymal, diazepam, and a placebc cn the threshold latency, rise time and threshold of

the acoustic reflex. It was concluded that these drugs

cause little effect on the acoustic reflex parameters

measured. In response to one second stimuli of 500 and

2000Hz pure tones, higher doses did result in prolonged

latency and rise time. As stated earlier, the acoustic reflex is a valuable iiagncstic tool in the hard-to-test individual, such as a

child. In 1974, Robinette et al., conducted an investiga­

tion whereby ten normal hearing children were given secobar­ bital, a sedative-hypnotic drug. They state three reasons for sedation of children during tympanometry and acoustic reflex threshold measurements; if there are movements, (1)

the prcbe tip may become dislodged; (2) the position of the

probe tip changes, thus volume and pressure in the canal will be altered; and <3) artifacts can be recorded on

25 equipment as a result of movement. All measurements were performed 60 minutes after administration of the secobarbit­ al. The results revealed that there was no effect on tympancmetric measurements. For acoustic reflex thresholds, in response to 500 and 2000Hz pure tone stimuli, there were no significant differences between frequencies, but all subjects showed a desensitization on the order of 4dB as a result of the drug (Robinette et al., 1974).

Phenobarbital has been demonstrated to have an effect upon some of the brain structures involved in the auditory pathway. An investigation by Richards, Mitchel and Speights

(1975) sought to determine if phenobarbital could have measurable effects on the acoustic reflex. All of the subjects had normal hearing and demonstrated reflexes at 500, 1000 and 2000Hz. The results showed that 83% of the reflex measurements with phenobarbital were identical to pre-drug measurements, plus or minus 5dB. Threshold shifts of 9dE or more were observed 17% of the time. The highest threshold shift for any one ear was 15dB, and return to normal never occurred (Richards et al., 1975). Other drugs which have been investigated are chloro- promazine (Simon and Pirsig, 1973), pentobarbital (Bosatra,

Russolc and Poli, 1975), and alcohol (Cohill and Greenberg, 1977) , Adults sedated with chloropromazine (.76 to 1.89 mg/kg) were found to elevate acoustic reflex thresholds approximately 4 to 7dB (Simon and Pirsig, 1973). Following,

26 the ad ninist ration of pentobarbital, Bosatra et al. <1975)

showed that their subjects’ acoustic reflex thresholds and

latency increased. Upon the ingestion of 30 ml of alcohol,

an elevation of 11dB at 90 to 110 minutes in response to 500 and 2000Hz pure tones and white noise was noted for eight

female subjects (Cohill and Greenberg, 1977) ,

Correlations have been made between the acoustic reflex

and susceptibility to noise induced threshold shift.

Robinette and Brey (1977) demonstrated that blood alcohol

levels above 0.09% may result in an elevation of the

acoustic reflex threshold for 500Hz and for a low frequency narrow band noise. Also, temporary threshold shift at

1 000Hz, measured three minutes following noise exposure, increased under blood alcohol concentrations from 0.12 to

0.14%.

het all research on the effects of drugs on the acoustic reflex has been performed on man. Borg and Holler (1975), investigated the effects of five central depressants on the acoustic reflex in rabbits. The effects of Nembutal on the reflex was shown to be a function of the dosage.

Nembutal produced a decrease in the sensitivity of the reflex above 4 mg/kg. Also, a more pronounced effect on the contralateral reflex than on the ipsilateral was noticed for doses greater than 12 mg/kg. Elevations in acoustic reflex threshold were evident when Norcotal

27 sensitive to stimulation than the ipsilateral for 25 minutes after the induction of the drug. The contralateral reflex was mere susceptible to Urethane and Urethane chlorolose, particularly at higher doses. Xylocain was responsible for a 3dB shift for both contralateral and ipsilateral reflexes following a 10 mg/kg administration (Borg and Holler, 1975).

28 STATEMENT OE THE PROBLEM

The action of the stapedius reflex in normal and

pathological ears has been studied by numerous investiga­

tors. Variability of various parameters of the acoustic

reflex has been evident when any drug was introduced. _ Only a few investigations have been performed on the effects of

ethyl alcohol on the acoustic reflex.

Ecrg and Moller (1967) investigated the effects of ethyl alcohol on the acoustic reflex threshold. The authors stated that “the ipsilateral and the contralateral reflexes seem to be equally susceptible to ethanol, although occa­ sionally the contralateral reflex is more depressed” (Borg and Holler, 1967) . As stated in the review of the litera­ ture, differences were noted in their data. Since no statistical analysis was presented but differences in acoustic reflex data were observed, further observations are seeded into the effects cf ethyl alcohol on the contralater­ al and ipsilateral reflexes. Three limitations were noted in the Cohill and Green­ berg (1977) study. First, blood alcohol concentrations were aof assessed at regular intervals. Second, the effects òf alcohol cn only female subjects were note!. Third, the

29 affects . of contralateral and ipsilateral reflex activation were net investigated. Ecbinette and Brey (1977) limited their acoustic reflex threshold measurements only to contralateral reflexes.

Also, only four subjects were used.

Since varying results have been reported on the effects of ethyl alcohol on the acoustic reflex, the present study investigated the following:

1. Does ethyl alcohol have different effects on the

contralateral or ipsilateral acoustic reflex?

2. Shat is the relationship between acoustic reflex

threshold variation and blood alcohol concentration?

3. Are acoustic reflex threshold shifts resulting from

alcohol ingestion different according to the frequency

cf the eliciting stimulus? ’

30 METHOD

Subjects

Eight male and eight female normal hearing adults

between the ages of 21 and 28 years with a mean age of 24.8

years served as subjects. Normal hearing was characterized

by: (1) no history of otologic disease; (2) bilateral pure tone air conduction thresholds no poorer than 15dBHTL

(ANSI-1970) at the octave frequencies of 500 to 4000Hz; and,

(3) the presence of normal middle ear function, that is, static compliance within 0.4-0.9 cc of air as specified by

Zwislocki (1976), and tympancmetric curves showing maximal

admittance within ± 50 mm of water pressure (Alberti and Kristersen, 1970) ,

No subject was a heavy drinker in that the average of each individual’s alcoholic consumption was no greater than 5 drinks per week. At the time of the experiment, all subjects had less than 0,02% blood alcohol concentration..

31 Instrumentation

Stimuli and acoustic reflex thresholds were measured by

a compliance and acoustic reflex meter (Amplaid, model 702).

This instrument was also used for pure tone and tympanometry measurements. The output of the stimulus generator was

directed through a 1dB step attenuator (Hewlett Packard,

model 3501) , which was inserted in the system before the

earphone to allow for fine control of stimulus intensity.

The reflex eliciting stimulus and the output of the reflex

meter were recorded on a two channel strip chart recorder

(Brush, model PB2522). Blood alcohol measurements were made by the use of an

electronic alcohol-in-breath tester (CHI INT3XILYZEH, model

4011). The instrument uses a measurement technique based on

infrared absorption. Its operating principle is that every

molecule absorbs light of a specific wavelength depending on its physical size and structure. Ethyl alcohol absorbs light at 3.39 micron wavelength. Materials capable of

absorption at 3.39 microns are not found in sufficient

quantities in human breath to produce a false positive reading. The instrument measures alcohol in breath by detecting the decrease in intensity of the 3.39 micron light passing through the breath sample. When the light beam exits the sample chamber, it is filtered to remove all

32 wavelengths other than 3.39 microns. The remaining 3.39

light energy is converted by a photosensor to an electrical

signal directly proportional to the concentration of alcohol

in the subject’s breath (CMI, Manual, 1977).

Test Procedure

Subjects were tested in a sound treated booth (IAC,

model 4O2A). All subjects abstained from any alcoholic

consumption twenty-four hours prior to the experiment. They were provided with a plain doughnut and a four ounce glass of orange juice as a substitute for breakfast.

Pre-experimental audiolcgical measurements were taken prior to the ingestion of the alcohol. These tests included a pure tone air conduction test and tympanometry. The point of maximum compliance (in mm water) was recorded. This value was used throughout the study for all acoustic reflex threshold measurements. A meter deflection of 0.5% of maximum compliance in response to signal presentation was considered significant.

The subjects drank a 50% solution of 100 proof vodka in less than 15 minutes. The amount of alcohol was determined by applying the Widmark Formula (Appendix A). The amount given was that needed to achieve a blood alcohol concentra­ tion of 0.10%. The value was calculated by the use of a

33 computer program to minimize error in the calculations

(Appendix B).

Thirty minutes were allowed for stabilization after all

of the alcohol was consumed. Acoustic reflex threshold

testing was done at blood alcohol concentrations of 0.02 to 0.10% in 0.01% increments. Blood alcohol concentrations

were measured every five minutes. Stimuli were 500, 1000, and 2000Hz pure tones as the reflex is generally most

sensitive at these frequencies (Peterson and Liden, 1972),

and these stimuli are routinely used in the clinical setting

(Woodford, Feldman, and Wright, 1975). The rise/decay time

was 50 msec, stimulus duration was one second and a five

second inter-stimulus interval was used. Blood alcohol

concentrations were measured immediately before and after

each reflex threshold procedure. Acoustic reflex threshold

measurements continued until blood alcohol concentrations

were reduced to 0,02%. This represented concentrations

aelow a level that would impair any psychophysical function­

ing (Weed, 1966). Reflexes were obtained in ascending 2dB steps. The intensity was increased to 15dB above pre-alcohol acoustic

reflex thresholds. Acoustic reflex threshold interpretation

was performed by an individual other than the principle investigator. The examiner noted the first point at which a

2 mm pen deflection was coincident with signal presentation.

This level (in dB), was subtracted from pre-ingestion

34 acoustic reflex thresholds and was recorded is the shift in t hr esheld.

35 RESULTS

Table 1 represents the means and standard deviations of contralateral and ipsilateral ear acoustic reflex threshold

shifts as a function of blood alcohol concentration and

stimulus frequency. The greatest shifts occurred at 0.10%

blood alcohol concentration. The shifts were approximately

11dB for contralateral stimulation and 7dB for ipsilateral

acoustic reflexes for all frequencies. No reflex shifts occurred at 0.02% blood alcohol concentrations for contra­ lateral reflexes and at 0,02% and 0.03% for ipsilateral reflexes. The analysis of variance for a three-way analysis of variance with repeated measures on three factors (Dixon,

1977) is shown in Table 2. The Table represents the mean squares, degrees of freedom, F-value, and the probable F exceeded. Significant differences were realized for ipsi­ lateral versus contralateral stimulation and blood alcohol concentration. Significant statistical interactions were also found for the ipsilateral-contralateral/f requency and ipsilateral-contralateral/blood alcohol concentration analyses,

36 Table 1. Means ana standard deviations of contralateral ana ipsilateral ear acoustic reflex threshold shifts as a function of blood alcohol concentrations and stimulus frequency.

Blood Alcohol Contralateral Ear Ipsilateral Ear Concentration Frequency (HZ) Frequency (Hz) (percent) 500 1000 2000 500 1000 2000 0.02 0,0 0.0 0,0 0,0 0.0 0.0 0,0 0.0 0,0 0,0 0.0 0.0 0.03 1, 1 1.1 0.8 0,0 0.0 0.0 1.0 1.3 1.0 0.0 0.0 0.0 0.04 2.6 3.3 2,5 0.4 0.5 0,1 1.0 1.0 1.4 0, 8 0.9 0,5 o.os 4.6 5.4 4.1 2.0 1. 6 0.8 1,0 1.2 1,2 1.0 1. 1 1.0 0 .06 6. 1 6.5 5,8 3. 5 3. 1 2.8 1.3 1.2 1.2 1.4 1.0 1.0 0.07 7. 1 8. 1 7.8 4.9 4.3 4.0 1.2 1.2 1. 2 1.0 1. 2 1.3 0.0€ 8.8 9.3 8.5 6.0 5,6 5.5 1.2 1.4 1. 5 1.3 1.5 1.7 0.09 9. 6 10,4 10.0 7. 3 6. 8 6.9 1. 1 1.5 1.8 1.0 1,6 1.6 0.10 1 1. 1 11.5 11. 1 7. 9 7. 1 7.4 1.6 2.3 1.5 0.9 1.0 1.4

37 Table 2» Summary of three-way analysis of variance

Source MS dF F £

Mean 17894.2 1 1056.5* .000 Error 16.9 15 Contralateral/ Ipsilateral (E) 1420.9 1 337.8* ,000 Error 4.2 15 Frequency (F) 9.5 2 3.1 .063 Error 3. 1 30 Blood Alcohol Concentration (BAG) 1159.4 8 880.9* ' .004 Err or 1.3 120 g/F 11 .8 2 6,6* .000 Error 1.8 30 g/BAC 37.3 8 45.8* .000 Error 0.8 120 F/BAC 1.2 16 1. 6 .066 Error 0.7 240 E/F/BAC 0.8 16 1,1 .274 Error 0.7 240

*£< »01

38 IPSILATERAL VERSUS CONTRALATERAL- STIMULATION

The effects of ethyl alcohol were more pronounced on contralateral than on ipsilateral stimulation. The mean shifts for all frequencies at the blood alcohol concentra­ tions of 0.03 to 0. 10% are shown in Figure 2. A Scheffe Test of Multiple Comparisons (Neter and

Wasserman, 1974) was calculated to validate the statistical evidence that contralateral reflexes were affected to a greater extent than ipsilateral acoustic reflexes. Table 3 represents the differences in means for all frequencies at

0.02 to 0,10% blood alcohol concentrations. This analysis verified the observation that ethyl alcohol affects contra­ lateral reflexes more than ipsilateral reflexes.

BLOOD ALCOHOL CONCENTRATION

A blood alcohol concentration of 0,10% produced the greatest shift in acoustic reflex threshold for both ipsi­ lateral and contralateral reflexes, The different affects of ethyl alcohol at various blood alcohol concentrations on the acoustic reflex threshold were easily

39 Figure 2. Mean contralateral and ipsilateral acoustic reflex threshold shifts as a function of blood alcohol concentration.

40 THRESHOLD SHIFT IdSl U 1 Table 3. Mean values for Scheffe Test of Multiple Compari­ sons for ipsilateral and contralateral acoustic reflex threshold shifts at 0,02 to 0.10% blood alcohol concentration.

i ont ra la te ra l Ipsilateral 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09 0.10 0.02 0.0 0. 03 3 . 0* 0.04 7.0* 0. 05 9.8* 0.06 9.0* 0.07 8.6* 0.08 9. 8* 0.09 9.2* 0. 10 11.4*

*£< .01

4 2 seen in Figure 2 and were responsible for a large F-score

(Table 2) .

A Scbeffe Test of Multiple Comparisons was calculated

to verify the observation that each blood alcohol concentra­

tion produced a significantly different threshold shift.

Tables 4 and 5 represent the results of tha analysis for

contralateral and ipsilateral measurements, respectively.

Significant differences in threshold shifts were seen for

each blood alcohol concentration measured with the exception of the 0.03 and 0.04% blood alcohol concentration levels

during ipsilateral stimulation. The similarity of the tracings between contralateral*

and ipsilateral threshold shifts prompted an investigation

into an orthogonal polynomial expression of the curve, and

into the significance of the shape and rate of change of

acoustic reflex thresholds as a function of blood alcohol

concentration (Winer, 1962). The blood alcohol concentra­ tion main effect intervals and formulas, and values for the

calculation for the linear, quadratic and cubic expression

are shewn in Table 6. Although both the linear and cubic expressions were justified, the latter can be attributed to

the absence of a threshold shift at 0,02% blood alcohol concentration. Therefore, the rate of change of acoustic reflex thresholds as a function of blood alcohol concentra­

tion appears to be linear.

43 Table 4. Mean values for Scheffe Test of Multiple Compari­ sons for contralateral acoustic reflex shifts as a function of blood alcohol concentration.

Blood Alcohol Concentration

0.02 0,03 0,04 0.05 0.06 0,07 0.08 0,09 0.02 0.03 3.0* 0.04 5. 4* 0.05 5, 8* 0.0€ 5,3* 0.07 3.7* 0.08 3.6* o.os 3.3* 0,10 3.8*

*£< ,01

Table 5. Mean values for Scheffe Test of Multiple Compari­ sons for ipsilateral acoustic reflex threshold shifts as a function of blood alcohol concentration,

Blocd Alcohol Concentration

0.02 0.03 0,04 0,05 0.06 0.07 0.08 0.09 0, 10 0.02 0.03 0.0 0. 04 1.0 0.05 3. 4* 0.06 5.0* 0.07 3.8* 0.06 4.0* 0.09 3,8* 0.10 1.5*

*£< ,01

44 fable 6, Main effect intervals, formulas, and values for the linear, quadratic and cubic expression of acoustic reflex threshold shift as a function of blood alcohol concentration,

Expression L s2 S2 Interval

Linear 455.0 4. 94 10.27 444,73,465.27* Quadratic 38.0 228.03 69, 79 -31.79, 107,79 Cu b ic 158.1 81. 44 41.71 116.39,199. 81* L = c (i) x(i) s2 = (1) = MSE/N (c(i))2 S* = k(1-J,8,120) Interval = L± SQRT(s2( 1) S2) W he re : c (i) = sum of the orthogonal components x(i) = sum of the mean differences MSE = mean square error N = number of subjects k = number of observations investigated J = confidence level 8,120 = degrees of freedom

*£< .01

I. 45 Significant differences in the rate of change were investigated by using the Scbeffe Test of Multiple Compari­ sons (Meter and Wasserman, 1974) , The results reported in

Table 7 show that significant differences in the rate of change in acoustic reflex thresholds were evident only when comparison was made at adjacent blood alcohol concentration levels of 0.03/0.02, 0.04/0. 03, 0.05/0.04 and 0.09/0.10%.

FEICUENCY

Acoustic reflex thresholds for both ipsilateral and contralateral stimulation were not significantly different from each ether for the 500, 1000, and 2000Hz pure tones.

46 Table 1, Mean values for Scheffe Test of Multiple Compari- sons for the rate of change in acoustic reflex thresholds for ipsilateral and contralateral ear stimulation as a function of blood alcohol concentration.

Blood Alcohol Concentration

0.02 0.03 0.04 0.05 0.06 0.07 0.08 0,09 0.10 0.02 0.03 3.0* i 0.04 4.4* 0.03 2.4* 0.06 0.8 0. 07 0.9 0,08 0,2 0.09 0.6 0. 1C 2. 3*

*£< .01

47 DISCUSSION

The results have demonstrated that ethyl alcohol

affects contralateral reflexes to a greater extent than ipsilateral acoustic reflex thresholds. Reflex shifts were

more prominent at higher blood alcohol c oncen tra tions,

These effects were linear and the rate of increase in

acoustic reflex thresholds was only significantly different

at the extremes of the measured blood alcohol concentration

levels. Threshold shifts as a result of the ingestion of

ethyl alcohol did not show significant differences as a

function of the frequency of the reflex eliciting stimulus.

Borg and Holler (1967) noted an increase in acoustic

reflex thresholds resulting from an administration of pure ethanol. At a blood alcohol concentration of 0.12%, the ipsilateral and contralateral effects did not differ signi­ ficantly. Nembutal was shown to have a greater effect on contralateral acoustic reflex thresholds rather than ipsi­ lateral» The present study showed that tha contralateral reflex was more susceptible to the ingestion of alcohol. The contralateral and ipsilateral acoustic reflex dif­ ferences can be attributed to unique properties of the acoustic reflex arc. The main difference between the

48 contralateral and ipsilateral reflex pathway is the presence

□ fa direct connection from the ventral cochlear nucleus to

the ipsilateral 7th motor nucleus (Borg and Holler, 1975).

The contralateral pathway lacks a direct route to the facial

motor neuron which is the center for reflex action. A

connecticn is made through the medial superior olive,

ventral cochlear nucleus and facial motor neuron to the same

contralateral nuclei. In this way, the neural organization

□ f the contralateral pathway demonstrates a more complex

network which is more susceptible to the effects of chemical agents (lorg and Holler, 1967). As discussed in the literature review section, ethyl

alcohol affects neural transmission in three stages. All of

these changes are centered primarily at the nerve axon

(Moore, Ulbrict, and Takata, 1964). Because the contralat­ eral acoustic reflex neural pathway consists of a greater number of synaptic junctions than the ipsilateral pathway, the effects of ethyl alcohol would certainly be more pronounced on the contralateral pathway of the acoustic reflex. The effect of a chemical agent on acoustic reflex threshold changes can be attributed to two factors: the chemical composition and the amount ingested. Research has been performed on central depressants, general anesthetics, barbi turates, and ethyl alcohol. The effects of ethyl alcohol are easily measured by using an alcohol-in-breath

49 analyzer, therefore the amount of alcohol in the system at the time of acoustic reflex threshold measurement can be measured quickly and accurately. Borg and Holler (1967) and

Robinette and Brey (1977) showed that the effects of alcohol on both ipsilateral and contralateral acoustic reflex thre­ sholds increased as the blood alcohol concentration increased. Similar effects on the rate of change in reflex threshold as a function of blood alcohol concentration were found in this study and by Borg and Holler (1967). That is, the change in acoustic reflex threshold occurred at a constant rate except at the extreme of the measurement levels. The elimination of alcohol from an organism takes place through metabolic removal at a constant rate (Jacobsen,

1 952). After alcohol is completely metabolized in the system, elimination from the organism is at a constant rate, virtually independent cf physiological factors (Nyman and Palmlov, 193 4). Battey et al. (1953), showed that as blood alcohol concentration increased, brain oxygen consumption also increased. Their experiments revealed that the amount of oxygen utilization varied linearly with the concentration of ethanol in the blood. The present study demonstrated linear shifts for both the ipsilateral and contralateral acoustic reflex thresholds as a function of blood alcohol concentration. In 1967, Borg and Holler showed a linear relationship

50 between blood alcohol concentration and acoustic reflex

threshold shift. The results of this study are similar to

other studies which investigated the effect of drugs on the acoustic reflex. Borg and Holler (1975), revealed that threshold shifts were greater after administration of 16mg/ kg cf pentobarbitol than after the consumption of 8mg/kg,

Also, similar effects were seen when the amount of Nembutal,

Narcotal, Urethane and Urethane-chloralose were varied (Borg and Heller, 1975).

Elevations in acoustic reflex thresholds did not vary as a function of the frequency of the stimulus. The threshold shifts as a result of ethanol ingestion for the

5 00 and 1450Hz pure tones measured by Borg and Holler (1967) were similar also. Other studies in which chemical agents were induced and acoustic reflex thresholds were recorded have net reported any differences in the reflex threshold as a function of the stimulus frequency (Robinette et al., 1 974; liden et al, , 197 4; Richards et al., 1975; Cohill and

Greenberg, 1977). The effects of chemical agents on acoustic reflex thresholds are known. The reasons for these effects have not been explained,. Different reasons have been postulated, but because of the complexity of a reflex arc, reliable conclusions have not been reached. Borg and Holler (1967) believe that the neural pathway of the contralateral acoust­ ic reflex is more complex than the ipsilateral. These

51 researchers found their results to be in agreement with

other studies which showed polysynaptic reflexes to be more

sensitive to barbiturates than monosynaptic reflexes.

Robinette et al. (1974) attributed the elevation in acoust­

ic reflex threshold that occurs with secobarbitol to the inhibition of an enzyme required for normal neural transmis­ sion (Grcllman and Grollman, 1970). These drugs may be active cn the acoustic reflex arc that depresses the activity of the motor portion of the facial nerve (Giomelli and Mezzo, 1965), Borg and Holler (1975) concluded from their study of drugs and the acoustic reflex that it is uncertain which changes in threshold are due to the reflex arc and which are due to other parts of the central nervous system. In summary, this study showed that acoustic reflex thresholds are elevated when an individual ingests ethyl alcohol. The average threshold shifts at 0,10% blood alcohol concentration were 11 and 7dB for contralateral and ipsilateral reflex thresholds, respectively. The difference in contralateral and ipsilateral measurements supports the knowledge of the complexity of the acoustic reflex arc.

Also, because of this difference, the more direct or ipsilateral neural pathway was shown to be less susceptible to ethyl alcohol. Alcchol is similar to other drugs investigated and affects the acoustic reflex neural system to differing

52 levels depending upon the amount of the chemical in the

organism. Small acoustic reflex threshold shifts were seen for low blood alcohol concentrations, and the shifts increased as the concentration of the alcohol increased.

Threshold shifts at each blood alcohol concentration did not vary as a function of the frequency of the eliciting stimulus.

Interpretation of acoustic reflex threshold data when an individual is known or suspected to have ingested ethyl alcohol should be done with caution, It was shown that at low blood alcohol concentrations both contralateral and ipsilateral acoustic reflex thresholds are elevated. Future research should be directed to a wider variety of chemical agents. Studies should also be performed with subjects who axhibit abnormal acoustic reflex thresholds. Research per­ formed with these subjects could provide invaluable informa­ tion on the acoustic reflex neural network.

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67 APPENDIX A

68 Widmark Formula

A = WRCT/0.8

N here: A = Ethyl alcohol (milliliters) H = Weight of subject (grams)

E = Relative amount of fluid in the body (70%)

CT = % blood alcchol concentration desired

C. 8 = Specific gravity of alcohol.

69 APPENDIX B

70 MIX 19:16 MAY 2j.1978

100 PRINT*NEICRT’j • 101 PRINT'’MILLI’> . 102 PRINT ’OUNCES’ 110 PRINT ~ : • 120 PRINT 130 FORI =90 TO 250 . 140 M = I / 2.2 4= 1000 * 0.70 *0-0012 / 0.8 / 0.50 150 0 = M / 30 160 PRINT I>M,0 •;. ? \ ■ 165 PRINT ' ■ • ' 17 0 NEXT I 180 PRINT' 190 PRINT - - - '•••' . ' . . 200 print 210 STOP ■ / 220 END , -

7 1