Nina Kraus, Ph.D. - US grants

The middle latency response (MLR) can be used as a measure of low frequency hearing, a neurologic measure of function of the higher levels of the auditory pathway and an objective index of cochlear implant function. Clinical use of the MLR is currently limited by inadequate understanding of 1) the underlying generator sites, 2) MLR development, and 3) the extent to which the auditory brainstem response (ABR) and MLR can be used to predict low frequency hearing loss in adult and developing subjects. The aims of this grant are: (1) To determine specific generator sites of the MLR in an aminal model using intracranial mapping, neural inactivation techniques and histologic reconstruction. It is expected that these procedures will also further the understanding of inhibitory mechanisms thought to modulate the MLR. (2) To investigate maturational changes in the MLR. In humans, the MLR develops throughout the first decade of life. By using gerbils, the difficulty of adequately sampling a human population over 10 years can be circumvented. The gerbil auditory system develops completely within a few months. To be investigated are developmental changes in spectral content of the EEG and MLR and the use of ABR and MLR to predict low frequency hearing in developing animals. It has been speculated that low frequency noise in the EEG obscures the MLR in children. This work is expected to lead to an optimal MLR recording strategy for use with children. (3) To examine the use of ABR and MLR in the assessment of low frequency hearing in animals with high frequency (noise-induced) hearing loss. The relationship between electrophysiologic measures (ABR and MLR) and the configuration of the hearing loss, as determined by compound action potential (AP) thresholds will be investigated and described mathematically. It is expected that resulting equations can be used clinicallly to predict the behavioral audiogram based on elelctrophysiological measures. Studies will be initiated in adult animals and will continue with developing subjects. A similar approach is problematic in humans because of the difficulty of obtaining complete behavioral and electrophysiologic data in a single test session and the obvious limitations of behavioral testing in children. Aims 2 and 3 are designed so that data on experimental animals will be comparable to ongoing human studies in our laboratory.

DESCRIPTION: (Adapted From The Applicant's Abstract.) The degree of success and satisfaction experienced by cochlear-implant recipients varies greatly and is influenced significantly by the individual's ability to understand speech. It is hypothesized that the wide range of speech perception skills exhibited by cochlear-implant patients may be attributed, in part, to differences in central auditory processing abilities or in the capacity of the central auditory system to adapt to electrical stimulation. It is proposed to characterize speech-evoked cortical potentials in order to develop an objective measure of central auditory function in implant users. The long-term aim of this research is to develop a clinically feasible battery of speech--evoked electrophysiologic measures that can be used to evaluate the function of cochlear implants in deaf individuals. Optimally, that non-invasive test battery will be useful in assessing implant performance in patients who cannot undergo conventional behavioral testing (e.g. young children) and in providing a neurophysiologic basis for the design of rehabilitation programs and future implant signal-processing strategies. Specifically, the mismatch negativity (MMN)- a passively elicited evoked potential that reflects the cortical processing of fine acoustic stimulus differences - and the P300 cognitive potential will be investigated. Synthesized pairs of speech stimuli with well-defined acoustic parameters will be used to elicit the MMN and P300 in normal-hearing listeners and cochlear-implant patients to characterize the central neurophysiologic processes underlying normal and cochlear-implant-mediated speech perception. Those responses will be correlated with behavioral speech discrimination and related to clinical measures of speech perception and implant success. A subset of newly implanted adults and children will undergo the same battery of tests periodically for 12 months immediately after implantation to assess short-term longitudinal changes in electrophysiologic responses, auditory discrimination, and speech perception.

DESCRIPTION (provided by applicant): The overall focus of this research isto understand how speech sounds are represented in the brain and how that representation is related to the conscious perception of speech in quiet and in noise. In order to address those questions, an acoustic-phonetic experimental paradigm has been developed. In this approach, behavioral speech perception and neurophysiologic responses to speech signals are measured in the same experimental subject in order to determine relationships between hearing and its neural substrates. Speech-evoked intracranial responses also are measured in an animal model in order to more definitively characterize the auditory system's response to speech signals. Specifically, the relative roles of auditory midbrain, thalamus and cortex as well as left-brain specialization will be examined. In addition to understanding normal speech processing, the project focuses on understanding the pathologies underlying auditory learning disabilities and attention deficit disorders, which are among the most common disorders found in school-aged children. Typically, these children have difficulty perceiving fine-grained speech signals and speech in noise. Another series of experiments will evaluate the neurobiological processes involved in the perceptual learning of speech sounds. The goal is to impact the design of training regimens that may assist these individuals who have difficulty perceiving speech sounds. Overall, the results of this project will further understanding of how speech is represented neutrally and how the normal and impaired auditory systems respond to speech in quiet and in challenging listening environments. Furthermore, the results will delineate the role of neural synchrony in speech perception, and suggest training protocols that may improve speech perception in individuals with impaired hearing mechanisms.

Human communication, from classroom learning to friendly conversation, involves the integration of auditory and visual speech information, and understanding when and how this integration occurs in the brain is a fundamental question in communication science. Moreover, virtually nothing is known about how visual influences affect auditory processing of music. With support from the National Science Foundation, Dr. Nina Kraus will conduct three years of research investigating how visual information modulates auditory inputs to the brain. Of primary interest is the fact that seeing a talking face greatly improves the ability of a listener to understand speech. The question of when and where in the brain the auditory and visual speech information is integrated is poorly understood. Preliminary findings from the Kraus laboratory suggest that it occurs earlier in the neural processing network in the brain than previously thought, thus challenging prevailing views of sensory integration. These questions will be addressed by recording brain responses (EEG) in normal adult listeners at different levels of the central nervous system. Two experiments will be conducted. The first experiment will address visual influences on auditory processing of speech by comparing brain responses to auditory-only speech with responses elicited by audio-visual speech, provided by a talking face. In the second experiment, visual influences in music perception will be investigated by comparing brain responses elicited by a cello note to responses elicited by a cello note accompanied by a video of a musician bowing a cello. To assess the effect of experience on audiovisual interaction, the latter study will employ non-musicians and professional musicians as subjects: professionally trained musicians may use visual musical information, such as viewing the bowing of a cello, to enhance their perception of musical sounds in a manner similar to the enhanced perception of speech provided by seeing a talking face. This study will also investigate the extent to which speech and music are processed by different networks in the brain, which will provide important information about how the brain is programmed to process different types of acoustic signals. This work could have broad impacts. It will provide a better understanding of the sensory processes that are necessary for successful human communication, which may inform the development of improved techniques and practices of communication for schoolteachers and public speakers as well as for those learning foreign languages and those learning to play musical instruments. Furthermore, an understanding of how the normal auditory and visual systems interact in the brain will provide an essential baseline for future studies addressing audiovisual interactions in disabled populations, such as hearing and reading-impaired individuals, and could lead to improvements in the identification and remediation of these disabilities.

The ability to produce and understand the intricacies of human speech has a large impact on quality of life. Auditory communication often involves learning; for example, identifying a new friend's voice over the telephone, perceiving and producing words in a foreign language, or understanding the meaning of words used in different contexts. The traditional view of the auditory system emphasizes a feed forward pathway starting from the inner ear in the cochlea, progressing to the various brainstem nuclei, the thalamus, and finally up to the auditory cortex. As acoustical and/or functional complexities of the auditory signal increase, the more likely ?higher-level? structures are to be involved. Although the existence of this corticofugal (descending) system is acknowledged in the literature, relatively little research, especially in terms of physiology, has been conducted. The functions of individual auditory-neural structures have been studied in isolation yet researchers lack an understanding of the simultaneous contributions of these structures in performing auditory functions in humans. With support from the National Science Foundation, Dr. Patrick Wong and his research team will explore whether learning speech (particularly the lexical tones of Mandarin) and music can result in changes in lower level circuitry, which could potentially then influence processing upstream that is associated with auditory encoding. Investigations on brain anatomy and physiology will be conducted using brainstem electrophysiologic and functional magnetic resonance imaging (fMRI) procedures at various time points in a training paradigm, in which participants will learn to use pitch patterns to identify English pseudo words. This study contributes to the ongoing effort to explore the plasticity of lower and higher level structures across different stages of learning, and how these functions may differ in successful and less successful learners.

This research will lead to a more comprehensive understanding of brain plasticity as it pertains to auditory learning. On a broader level, this research is directly relevant to music and foreign language instruction. Regarding clinical applications, this research may shed light on hearing-related disorders which occur throughout the auditory pathway (e.g., peripheral hearing loss and central processing disorders). Additionally, the research focuses on a type of language (tone language) that is spoken natively in many parts of the world. The topic of second language learning is also important to global competitiveness, and this research should lead to improvements in our understanding of the process of learning Mandarin tones.

Generalization of musical experience to listening in noise

Noise is ubiquitous in our lives: the whir of a computer, the chatter of a busy classroom, the din of a noisy restaurant. Children, older adults, and the hearing impaired are especially vulnerable to the disruption that background noise has on listening and learning. The degree to which noise affects the ability to understand spoken words differs from individual to individual. Why? One theory is that musical experience may be a key to success in overcoming noisy environments. In this project, brain responses will be measured using sensitive recording electrodes while participants listen to speech embedded in background noise. The degree to which the brain is able to ?pull? the speech out of the noise will be discernable in the brainwaves. This ability will be examined with respect to the amount of musical training that each participant has had in the course of their lives. The brainwave results will be complemented with thorough listening-in-noise testing. As such, this study stands at the crossroads of two previously nonintersecting lines of research: musical experience?s effect on the nervous system and the effects of noise on the neural processing and perception of speech.

The proposed project will provide a better understanding of the role of music training on the sensory processes that are necessary for successful communication and learning. Understanding how the ?normal? auditory system is impacted by musical training will provide a baseline for future studies addressing music?s role in disabled populations, such as hearing- and reading-impaired individuals. Hearing words accurately and forming associations between sounds and letters are keys to learning to read. If it turns out that musicianship affects the ability to hear words accurately, there would be profound ramifications for advocating music education in public schools. At the other end of the age spectrum, music may prove to be a check for the well-known speech-in-noise perception decline in older adults. Finally, the proposed work will provide diverse scientific training opportunities in human perception and neurophysiology for graduate, undergraduate and area high school students.

Musical experience during childhood profoundly influences how the brain processes sound, even with just one year of training. Enhancements in musicians' brains often relate to the very neural impairments seen in children with language, learning and literacy disorders. Musical experience might therefore boost impaired systems in children with such disorders. Little is known about how musical experience brings about changes in the brain and about how these changes relate with behaviors such as language, learning and literacy. With support from the National Science Foundation, Nina Kraus and her laboratory will provide initial evidence for musical training's impact on both cortical and subcortical auditory processing in children and adults, defining the roles different parts of the brain play in shaping cognitive and perceptual capabilities related to language, learning and literacy. To accomplish this work, the researchers will recruit musician and non-musician participants from 3 to 35 years of age and assess them at three age groups, with child musicians recruited in collaboration with Chicago's Suzuki-Orff School of Music. Using scalp electrodes, the researchers record brain responses to speech and music sounds from both the auditory brainstem and the cortex. Electrodes are also used to measure auditory attention in the brain while participants are asked to listen to a spoken story and ignore competing sounds. Participants additionally complete listening and learning tests by which researchers assess cognitive and perceptual abilities and relate them with brain activity.

This work has the capacity to explain how brain changes occur with musical experience in the auditory system and to define relationships these changes have with language, literacy and attention. Understanding of the cognitive benefits of music could influence public policy regarding music education and music therapy. Outcomes of this project will also expand clinicians' toolkits for addressing language, literacy and attention disorders in addition to influencing policy-makers to incorporate music into classrooms, particularly for schools with at-risk children demonstrating high concentrations of language, learning and literacy disorders. The principal investigator has established a track record of broadly disseminating findings to the research community and the public, and expects new findings to be further translated into practice on an international scale.

What is the impact of musical training on brain development? This project will determine how the subcortical transcription of speech and cortical attention indices are affected by musical training during adolescence and how these neural processes drive language, learning and literacy abilities. Music's inherent activation of neural attention mechanisms provides a distinct advantage for engendering subcortical and cortical plasticity and learning. However, children from low-income families have little access to musical training. The researchers thus hypothesize that by undergoing musical training to boost processes of auditory attention, low-SES youths will demonstrate improved educational performance and underlying neural processes. Specifically, musical training may close the gap between students of low- and high-SES by strengthening neural underpinnings of language, learning and language development. Scientific partnerships with educational institutions can be difficult to form. Through a relationship with local high schools this project provides the opportunity to produce longitudinal findings as the investigators follow students throughout their four years of high school.

By defining the impact of musical experience in shaping language and literacy skills this work could provide objective biological evidence for the support of music education delivered in schools that serve low-SES populations. Educators and policy makers, in the face of tough fiscal decisions, may be encouraged to maintain and promote, rather than cut, musical education at the secondary school level, potentially decreasing the prevalence and economic stresses of language, learning and literacy impairment.

DESCRIPTION (provided by applicant): Many older adults experience excessive difficulty perceiving speech in background noise. Why this occurs for some, but not all older individuals is a question that currently has no answer. Our long-term goal is to understand the biological bases of speech-in-noise perception in older adults and to use that knowledge to improve perception through training. Converging evidence indicates that the auditory sensory system (including cochlear mechanics and brainstem) is dynamic and can be shaped by short-term (training) and lifelong (language and music) experience. Normal verbal communication depends on the accurate transcription of sound by the nervous system, especially in noisy backgrounds. Failure of this transcription process in the aging population represents a huge social and financial cost, and considerable resources are invested in treatments that may not work. Little objective assessment exists in diagnosis and evaluation of treatment options. Further, there is emerging evidence that the auditory periphery is modulated by higher centers via the efferent system to aid listening in background noise. This contribution remains to be characterized and/or quantified in any detail in the human species. Accordingly, our objectives are to determine brainstem transcription of speech sounds in noise in older adults, how this transcription relates to measures of cochlear mechanics, and the plasticity of transcription with training. Our central hypothesis is that disruption of transcription accuracy and cochlear mechanics are factors in listening-in-noise impairments, and that disruption can be remedied by intervention. The outcome of the proposed work will reveal sensory mechanisms linked to speech perception in noise in older adults and determine plasticity of basic sensory circuitry arising from short-term training. This outcome will have a positive impact on our understanding and objective assessment of sensory function in aging adults. PUBLIC HEALTH RELEVANCE: Normal verbal communication depends on the accurate transcription of sound by the nervous system, especially in noisy backgrounds. Many older adults experience excessive difficulty understanding speech in background noise because, at some level, the transcription process has broken down. Our first objective is to investigate the earliest levels of transcription-cochlear mechanics and brainstem encoding - and determine the extent to which they may contribute to the problem, thereby potentially leading to an objective metric. The second objective is to investigate the extent to which a training-based remedy affects these early processing levels. This outcome will have a positive impact on our understanding and objective assessment of sensory function in aging adults.

Many cognitive and perceptual skills are negatively affected by aging. One critical concern for older adults is an age-related decrease in speech understanding, especially in noisy environments such as restaurants. Dr. Nina Kraus, at Northwestern University, will examine whether musical training can protect against age-related deterioration in the ability to perceive speech in noise. Dr. Kraus will record the subcortical processing of speech in noise in musicians and non-musicians who are 45 to 65 years of age to determine whether lifelong musical training results in enhanced brainstem tracking of speech in noise. In addition, the influences of musical training on a variety of behavioral measures will be examined, including perception of speech in noise, short-term memory, and attention.

As life circumstances change, including loss of job or spouse, maintaining social contacts becomes ever more important for social and emotional health. It would be of great benefit if speech understanding could be improved at the source of difficulty by increasing the brain's ability to represent the speech signal accurately and to separate speech from background noise. If musical experience can lessen or slow the negative effects of age on cognitive skills, perceptual acuity and neural encoding of speech in noise, it would have substantial scientific and societal impact, emphasizing the importance of music as a rehabilitation strategy.
 
 

DESCRIPTION (provided by applicant): As many as one in ten children have the poor reading and spelling skills that comprise developmental dyslexia. It is widely accepted that there is a neurological basis; however, the nature of that basis is hotly debated. Nevertheless, one consistent view is that poor phonological processing-the ability to access and manipulate the sound units of language-is involved in dyslexia. Indeed, a majority of children with reading deficits exhibit difficulties on an array of phonological processing tasks. A growing body of research has discovered that speech-sound transcription, as measured by electrophysiology, shows striking relationships with phonological processing skills and reading ability in school-age children. As such, we have developed a suite of subcortical and cortical physiological tests that probe some of the core deficits that researchers have postulated as the root elements of poor phonological processing. We will target the subcortical processing of time-varying signals and stimulus regularities, and cortical hemispheric specialization to both fast and slow signals. In a longitudinal cohort of four- to eight-year-olds, we will model the normal neurological speech transcription process, quantify its development, and examine its relationship with the development of literacy-related skills. Our intention is that by leveraging these electrophysiological probes to a pre-reading age group, a biomarker, in preschoolers, may be found that predicts a child's eventual reading skill as he/she progresses through the primary grades. If such a biomarker is found, it would pave the way for earlier and more effectively targeted intervention. PUBLIC HEALTH RELEVANCE: As objective neurophysiological measures of literacy become available, a logical step is to apply what has been learned about subcortical and cortical physiology and their relationships with reading to young pre- readers. The outcome of the proposed work will be a deeper understanding of the biological underpinnings of literacy, particularly in pre-literate children, and a means to exploit objective biological responses as biomarkers of future literacy. This outcome will positively impact our understanding of the core deficits leading to poor reading, and has the potential to spur early intervention programs to head off the potential onset of developmental dyslexia.

Learning to read is the cornerstone of education. Recently, it has been discovered that the better you are at keeping a beat (e.g., accurately tapping along to a metronome or tapping out a beat in music) the better you are at reading. This raises fundamental questions about the overlapping brain and behavioral bases of reading and rhythmic abilities. This project measures sound-induced brainwaves in the auditory neural system in a search for "neural signatures" that are shared between people who are good readers and those who are good at keeping a beat. Once these signatures are established, they can be used to hone programs such as school-based music instruction that emphasize rhythmic skills in order to best encourage the parts of the brain that support reading and literacy.

The investigators will examine the overlap in the neural resources drawn upon by reading and rhythm. By measuring neural responses they will test the hypothesis that two types of rhythmic skills, synchronizing to a metronomic beat and extracting a beat from a complex rhythm, involve different brain regions, subcortical and cortical, respectively. The hypothesis is that the two rhythmic skills relate to temporal precision in the brainstem and phase-locking of ongoing cortical oscillations and contribute independent sources of variance to reading ability. By comprehensively testing rhythmic and reading skills in secondary school students, an age group old enough to perform the required rhythmic tasks but in whom reading skills are continuing to emerge, the investigators hope to further our understanding of reading and rhythm in relation to the unique contributions of subcortical and cortical auditory areas. In so doing, this work might guide the development of teaching strategies to optimize language skills for all children and remediation programs for poor readers.

Abstract Because diagnostic criteria of concussion rely upon self-reporting?which may be unreliable in a recently concussed individual?the goal of this project is to identify a neural marker of concussion that does not require effort from the patient. Concussion adversely affects many domains and there is strong reason to believe, and preliminary data to support, that neural processing in the auditory system is negatively influenced by sports- related concussion. By using an objective electrophysiological measure of auditory processing, this work has strong potential to broaden the understanding of concussion's effect on sensory processing and to eliminate a major pitfall in diagnosis and management of concussion. This proposal uses a novel approach to understand the impact of head injury on sensory processing: the frequency-following response (FFR) to speech. The central hypothesis is this objective neurophysiological measure of auditory processing serves as a marker of disruptions to central nervous system function following concussion. In collaboration with Northwestern University Athletics, this is a prospective, longitudinal study of concussion and prolonged participation in contact/collision sports that follows ~500 student-athletes annually (~875 total) within and across sports seasons. In a typical year up to 15% of student-athletes are diagnosed with a concussion by a sports medicine physician. This provides a potent opportunity to investigate the impact of concussion on auditory processing in both the short-term (immediately after injury) and long-term (after a one- to four-year college athletic career). In the large group of non-concussed athletes, this project will establish whether, as hypothesized, auditory processing is more compromised over time in individuals participating in contact/collision sports. This project can elucidate the physiological mechanisms by which concussions and long-term participation in contact sports disrupt the central nervous system. The FFR will provide fine-grained insight into the nature of the physiological imprint of concussion. The longitudinal design in a large cohort provides powerful within- and between-subject controls for tracking head injuries and risk of injury based on sport in the short- and long-term stages, and opportunities for within-study replications. If successful, the FFR could one day serve as a fast, objective, and scalable clinical adjunct to assist in concussion diagnosis and management by indicating an individual's auditory processing profile following one or more concussions.