AAGE R. MOLLER
Distinguished Lecturer Cognition and Neuroscience
Neural plasticity and its role in tinnitus, hyperacusis,
phonophobia, and misophonia, teaching biology of pain,
neuroplasticity, intraoperative neurophsysiology
My first interest in research regarded hearing, and my first published studies concerned the function of the middle ear and the acoustic middle ear reflex. These studies included the physics of sound transmission in the middle ear including the creation of electrical analogue models of the transmission properties of the middle ear. These studies also included the development of techniques for measuring the ear's acoustic impedance. Then I turned to studies of the acoustic middle ear reflex and its effect on sound transmission through the middle ear. These two topics were the basis for my dissertation 1965 at the Karolinska Institut, Stockholm, Sweden. Later I studied the anatomical and physiological basis for the acoustic middle ear reflex and this topic was the theme for a doctoral dissertation of a student of mine.
I then turned to studies of coding of complex sounds in the cochlear nucleus in studies on rats using recordings from single nerve cells a topic I pursued from 1966 to 1997. For this I first used standard neurophysiologic recording processing of the recorded unit responses, but I soon began to use statistical signal analysis methods. For that purpose I used mathematics from communication theory and what later was called cybernetics. I developed a special kind of test signals, pseudorandom noise based on tertiary m-sequences. These were converted into sounds used as stimuli or for modulation of tones or noise. Systems identification methods such as Winer kernel analysis were used to analyze the recorded unit responses for single nerve cells in the cochlear nucleus of rats. This method of studying the dynamic properties of coding in the auditory nervous system made it possible to study phenomena that could not be studied by traditional methods. I also developed a technique to study the width of the tuning of the basilar membrane on the basis of recordings from single cells in the cochlear nucleus. I gave many presentations about these methods and my research results, among others I had three presentations at the UNESCO-IBRO Symposium, Leningrad, U.S.S.R., 1977.
Towards the end of my tenure at the Karolinska Institut my research aimed at the function of the cochlea studied by recording from single auditory nerve fibers. I found that the cochlea is nonlinear. In recording from the single auditory nerve fibers using pseudorandom noise I had developed for studies of the cochlear nucleus I could study the frequency selectivity of the cochlea in a large range of sound intensities. These studies published 1977 constituted the first physiologic proof that the cochlea in a living animal is non-linear and that it is much more frequency selective for weak sound than for loud sounds. I have written books about hearing: "Auditory Physiology" published by Academic Press, 1983, followed by "Hearing: Its Physiology and Pathophysiology" (published by Academic Press 2000), now in its second edition (published by Academic Press, 2006). A third edition was published 2013.
During the years I spent at the Department of Physiology at the Karolinska Institut, I participated in research regarding computerized identification of human chromosome in projects lead by Professor Torbjorn Casperson. Again I used mathematical methods for the purpose, now from an emerging field of pattern recognitions. Using weighted Fourier coefficients in the computer algorithms I developed, we were the first to be able to distinguish each one of all 24 human chromosomes. I was invited to give a presentation at the Genetics Congress in Paris and I was a consultant to the Jet Propulsion Laboratory (JPL) in Pasadena for implementation of these computer routines.
Studies of the function of the submicroscopic protuberances that are present on the surface of the corneas of some night insects (moths) resulted in an understanding that these structures act to decrease the light reflection from the surface. These studies were led by Professor Carl-Gustaf Bernhard and I designed the experiments that revealed the function of these structures using models of the eyes made of beeswax and as test signals I used centimeter radio waves to measure reflections. These studies were described in several publications and I described the physical basis for how these protuberances could act to reduce the light reflection from the surface of these insect eyes.
During the same time I studied the effect of noise exposure on hearing and wrote several papers about the topic. I became involved in legal regulations of noise exposure and I served as an expert for the US Environmental Protection Agency (EPA) in 1975 and I served as a Witness, U.S. Department of Labor's Hearing on Noise Standards, Washington, D.C. I also held a keynote presentation, "Noise as a Health Hazard" at the Science in the Americas Congress in Mexico City 1973. In the 1970s I was engaged in insect research in Africa where I studied sound production by tsetse flies. I was together with 26 other researchers involved in developing a research laboratory, the International Center for insect Physiology and Ecology (ICIPE) in Nairobi, Kenya, financed by the United Nations Development Programmed (UNDP). The ICIPE laboratory still operates a very active research institute in Nairobi, Kenya. My studies of tsetse flies were done in the field in Kenya and in my laboratory at the Karolinska Institute. It resulted in the first acoustical description of these sounds.
After moving to the University of Gothenburg 1976 I continued studies of the effect of noise exposure and together with a postdoctoral fellow we studied the effect of antioxidants on the function of the cochlea after exposure to noise.
After immigrating to the USA 1978 and obtaining a position in the Department of Otolaryngology at the University of Pittsburgh School of Medicine where I continued electrophysiological studies in animals. During this time I became interested in pathologies such as tinnitus and the use of electrophysiological methods for diagnosis of disorders of the ear and the auditory nervous system. In particularly I worked on development of ways to use evoked potentials such as the auditory brain stem response (ABR). I developed computer programs for processing such recordings using Finite Impulse Response Zero-Phase digital filters (FIR digital filters). Soon I became interested in the neural generators of the auditory evoked potentials and I found that I could study where the different components of these potentials were generated by recording from structures of the auditory nervous system in patients undergoing neurosurgical operations where these structures became exposed. For that I initiated collaboration with Professor Peter Jannetta, Chairman of the Department of Neurosurgery, University of Pittsburgh School of Medicine where I resolved some basic problems in interpretation of the ABR that were related to the difference between results obtained in animals and in humans. We obtained a complete description of the generators of the different components of the ABR. Others later confirmed these results, which are now widely accepted.
Studies in the operating room in patients undergoing operations (microvascular decompression) have confirmed one of the two competing hypotheses regarding the pathophysiology of the disorder hemifacial spasm (HFS). I showed evidence that activation of neural plasticity is an important factor in creating the symptoms of HFS and that the location of the pathology is the facial motor nucleus and not the nerve root as was earlier believed. Later I studied other disorders and found evidence that many common disorders such as many forms of chronic pain and of tinnitus are caused by maladaptive plastic changes.
My studies of tinnitus showed evidence that some individuals with severe tinnitus have signs of use of other auditory pathways than individuals who do not have tinnitus, thus a sign of that activation of neural plasticity plays a role in creating the pathologies of some forms of tinnitus. I was interested in the similarities between some forms of tinnitus and chronic pain and in studies of individuals with pain we found that the temporal integration of painful electrical stimulation of the skin was different from that of individuals who did not have pain. This was taken as another sign of activation of neural plasticity. During this time I wrote a book on "Neural Plasticity and Disorders of the Nervous System", published 2006 by Cambridge University Press. It was followed 2009 by another book "The Malleable Brain", published by Nova Scientific Publishers.
Doing research in the operating room I soon understood that the electrophysiological methods I used could also be used for clinical purposes namely for reducing the risk of inadvertent damage to the nervous system during many kinds of surgical operations. I developed several methods for such intraoperative monitoring and I wrote the first comprehensive book on the topic ("Evoked Potentials in Intraoperative Monitoring, published by Williams and Wilkins, 1988). This book was followed by another book, "Intraoperative Neurophysiologic Monitoring", published by Harwood Academic Publishers, 1995, that provided more detailed description of methods developed during the first few years of this era. This book is widely used, it is in its second edition and I am now preparing its third edition.
This was soon established as a new field of medicine known as intraoperative neurophysiological monitoring (IONM). I soon became much involved not only in developing methods for IONM but also in academic and administrative aspects regarding this new field of health care. I took an active role in creation of a professional society, the American Society for Neurophysiologic Monitoring (ASNM) and later I participated in the creation of a certification board for IONM, the American Board of Neurophysiological Monitoring (ABNM).
IONM soon became an important part of many operations and the need for skilled people to perform IONM increased rapidly. I took great interest in teaching people who could perform IONM as a service, first teaching in the operating room in Pittsburgh, and after I 1977 moved to Dallas to take apposition at The University of Texas at Dallas School of Human Development (now the School of Behavioral and Brain Sciences) I created a two semester course on the anatomical and physiological basis for intraoperative monitoring in our neuroscience program. I have taught these courses every year since 1999.
Based on experience from my time at the University of Pittsburgh School of Medicine I became interested in other reasons for injuries to patients treated for various kinds of disorders and I wrote a book about such problems "A New Epidemic: Harm in Health Care", published 2007 by Nova Scientific Publishers. My research activity after moving to The University of Texas at Dallas involved studies of neurophysiologic abnormalities in individuals with autism, where I found evidence that autistic individuals have signs of using a different auditory neural pathway than individuals who do not have autism. Studies in children who did not have autism showed similar differences in the auditory pathways with involvement of non-classical pathways. Animal studies by a doctoral student done with Dr. Tres Thompson regarded the effects of noise exposure on other systems of the brain than structures that are associated with hearing. The study showed that hippocampal place cells behave abnormally after exposure to noise that normally causes tinnitus.