UNIVERSITY OF CINCINNATI Date: 1-Feb-2010 I, Lisa D. Cahill , hereby submit this original work as part of the requirements for the degree of: Doctor of Philosophy in Communication Sciences and Disorders It is entitled: Cortical responses to speech stimuli in hearing impaired infants measured by fMRI and auditory evoked potentials Student Signature: Lisa D. Cahill This work and its defense approved by: Committee Chair: Robert Keith, PhD Robert Keith, PhD David Brown, PhD David Brown, PhD Scott Holland, PhD Scott Holland, PhD Peter Scheifele, PhD Peter Scheifele, PhD 5/6/2010 369 Cortical responses to speech stimuli in hearing impaired infants measured by fMRI and auditory evoked potentials 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 Ph.D. in the Department of Communication Sciences and Disorders of the College of Allied Health Sciences 2010 Lisa D. Cahill, M.A., CCC-A B.A. Indiana University – Bloomington, 1996 M.A. University of Cincinnati – Cincinnati, 1998 Committee Chair: Robert W. Keith, Ph.D. Committee Members: Scott K. Holland, Ph.D. Peter Schiefele, Ph.D. David Brown, Ph.D. ABSTRACT Many brain regions respond and adapt to early exposure to sensory experience. Long periods of auditory deprivation, particularly during critical or sensitive periods of neurodevelopment, are known to produce cortical reorganization including functional and/or structural deficits at all levels of the human auditory system. Auditory evoked potentials have been used as an index of maturation of both normal-hearing and hearing impaired auditory cortical networks, as well as neuronal recovery time upon initiation of auditory stimulation (Sharma, Dorman, & Spahr, 2002a). However, the relationship between neuronal and vascular cortical activity in the developing impaired auditory nervous system has not been fully characterized. The overall aim of the present research was to perform an exploratory analysis of the relationship between the P1 auditory evoked potential response and residual auditory cortical function as shown by fMRI activation maps in moderate or severe to profoundly hearing impaired subjects. Electrophysiologic and functional neuroimaging evaluations using speech stimuli were conducted on fourteen subjects ages 9-24 months with residual hearing ranging from 85 dBHL to 100 dBHL pure tone average (PTA), in the .5 to 2 KHz range. Subjects who met the study’s eligibility requirements were made available through the Cincinnati Children’s Hospital Medical Center Departments of Otolaryngology and Radiology. Electrophysiological testing included evaluation of P1 cortical auditory evoked response with a hearing aid on using a Klatt generated /ba/ stimulus in the soundfield at 75 dBSPL. Subjects unable to wear an amplification device during the testing were stimulated using an Eartone 3A insert earphone at a minimum of 10 dB sensation level based on aided audiometric results. An ii fMRI paradigm consisting of Narrow Band Noise (NBN) and stories was administered under sedation at the end of a clinical scan in a 3 Tesla system using sound presentation levels of 10 dB sensation level based on audiometric results. Stimuli were interleaved with silence in a block- periodic counterbalanced fMRI design with 30-second on-off intervals. Results were subjected to a correlation analysis to search for a relationship between P1 characteristics and the number of activated fMRI pixels detected within specified regions of interest in the auditory cortex. In addition, a multiple regression analysis was conducted to assess the prediction of the P1 latency in our sample based on duration of hearing aid use and age at the time of the fitting. The importance of early intervention for congenital hearing loss has been well established using a variety of measures, including speech and language outcome, cognitive and educational assessment techniques, and electrophysiologic measures. The P1 auditory evoked potential has been acknowledged and characterized as a biological indicator of auditory neurodevelopment in normal hearing children and in children with cochlear implants. (Sharma, et al., 2005). In this sample of infants with hearing aids, multiple regression analysis results suggest that the age of hearing aid fitting and duration of hearing aid use are significant predictors of shifts in P1 latency even during very early stages of development (F (2,8) = 10.266, p= .006). Combining both predictors in the model explained 72% of the overall variance (R2 = .720). These findings provide additional support for the essential influence of early sensory exposure on auditory neuromaturation during the first year of life using a non-invasive physiological measure. Activity related cortical signals reflecting higher auditory cortical function could be more clearly understood by interrelating electrophysiologic findings with non-invasive mapping techniques. iii fMRI evaluation of the central auditory system prior to cochlear implantation may offer a possible means of objective assessment of auditory nervous system pathways. Auditory cortex activation observed in this sample of hearing impaired toddlers was highly variable between subjects. Group and individual maps of BOLD activation were also markedly dissimilar from what has been observed in normal hearing subjects within the same age range (Smith, et al., 2008). In all subjects, common areas of BOLD activity outside of auditory regions included positive BOLD within the medial frontal gyrus and anterior cingulate cortex, and negative BOLD responses in the inferior frontal gyrus. Areas that were shown to possess a positive correlation with shifts in P1 latency included the left middle frontal gyrus and inferior frontal gyrus, the anterior cingulate, and bilaterally in insular and occipital areas. Results indicated that although fMRI activation patterns do not exhibit a predictive relationship with P1 latency (r(10) = .038, p = .456), the strength of the auditory BOLD response was inversely correlated with P1 amplitude (rS = -.85, p = .001), suggesting more localized regions of cortical responsivity in subjects with robust P1 waveforms. This finding was difficult to interpret in light of fMRI sedation effects, and may be a reflection of normal cortical maturational processes that are known to influence the anatomical generators of the P1 response. In order to verify and further characterize a possible inverse connection between neural and vascular activity in thalamocortical and primary auditory cortical regions, more information is needed regarding developmental effects auditory deprivation on P1 amplitude. iv Lisa Dawn Cahill, 2010 All rights reserved v ACKNOWLEDGEMENTS I gratefully acknowledge my family as the most important contributors to the completion of this dissertation. The emotional and moral support of my husband, and the patience and endurance of my children have helped make this research possible. I’ve been amazed by their ability to adapt and understand the time I have spent pursuing this goal. Many thanks to my in-law family who has consistently offered assistance and support, and to my parents for motivating me and instilling in me a strong work ethic and concern for what is right and good. Thanks to my sister for being my best friend, and to my aunts, uncles, and cousins for their constant encouragement and interest in my work. I would also like to thank the entire faculty of the department of Communication Sciences and Disorders at the University of Cincinnati. I have received invaluable support in at least one instance from nearly every member of the department. My dissertation committee specifically, Dr. Robert Keith, Dr. Scott Holland, Dr. David Brown, and Dr. Pete Scheifele all provided immeasurable expertise and motivational support throughout my research and educational endeavors. I owe enormous gratitude to Dr. Scott Holland, who accepted me into this research project and invited me to share in his immense knowledge, and the opportunity of a lifetime for a doctoral student. Dr. Keith also served on my academic committee with Dr. Laura Kretschmer, both of whom have been instrumental in the development of my career and providing much needed words of encouragement since I was a Master’s student. Dr. Susan Stanton was the chair of my academic committee as well as an admired role model and mentor. Dr. Nancy Creaghead has made it possible for me to stay in this program over the years by providing me with assistance and opportunities, not only to remain financially stable throughout the program but vi also to develop my skills as an educator. Dr. Ernest Weiler, may he rest in peace, supervised my Master’s thesis in my introductory research effort, and was a most wonderful educator and a motivational person for me. I acknowledge the Cincinnati Children’s Hospital Medical Center departments of Otolaryngology, Audiology, Radiology, and the Pediatric Neuroimaging Research Consortium for their participation and efforts toward my project. Additionally, I wish to thank all of my personal friends, my colleagues in the Audiology community, and my fellow doctoral students in Communication Sciences and Disorders who reminded me why I chose this path and encouraged me to keep going, even in the face of adversity and personal challenges. Also deserving of an acknowledgement are those who gave me flexible employment throughout my studies, affording me a reasonable balance