Elyse Sussman - US grants

[unreadable] DESCRIPTION (provided by applicant): The goal of this proposal is to test the hypothesis that nonlinguistic auditory perception is essential for normal speech development. Despite the evidence that children with developmental language disorders (DLD) have deficits in processing low-level acoustic information, the specific nature of the auditory perceptual deficits is not known. The proposal will investigate the ability to segment or group acoustic input because impairments in the ability to organize sound could contribute to poor speech discrimination skills and interfere with learning in common multi-source listening situations, such as the classroom. The ultimate purpose is to ascertain standard measures of the normal development of perceptual sound organization in school-aged children upon which measures in language-impaired children can be compared. School-aged children (6-11 years) and young adults (21-40 years) will be studied. A combination of electrophysiological and behavioral measures will be examined. We will analyze selected components of event-related brain potentials (ERPs) that index different stages and attentional states of auditory processing. ERP analysis will be supplemented by analysis of frequency-specific components in the electroencephalogram (EEG). This approach will enable us to assess developmental features of how cortical sensory representations of sound impact upon perception of multiple sound streams. Assessing the relationship between stimulus-driven and attention-driven processes in typically language developing (TLD) children (via the studies proposed in the current application) is crucial for designing future studies that test whether or not language impairments can be attributed to stimulus-driven cortical sound representations, and to assess the degree to which attentional factors influence perception of sound streams. We will test the following hypotheses: 1) Stimulus parameters determining the segregation of sounds change as a function of age. 2) Electrophysiological indices of stream segregation correlate with behavioral measures in TLD children and adults. 3) Perceptual training facilitates stream segregation, as indexed by changes in electrophysiological and behavioral measures. The use of the ERP and EEG measures to assess developmental markers of sound organization is advantageous because these indices can be obtained in young children and impaired populations. This methodological approach has the potential to be an important non-invasive tool for diagnosis and assessment of central auditory processing deficits that lead to impaired language. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): In natural situations, the sound environment is dynamically and rapidly changing, with multiple sources overlapping in time and competing for attention. The ability to listen to your friend talking while walking down a noisy city street requires brain mechanisms that disentangle the sound mixture, separating your friend's voice from the sounds of the cars and other passing conversations. Auditory scene analysis, the ability to parse and organize the mixture of sound input, is a fundamental auditory process. Yet, the neural mechanisms that subserve perceptual sound organization are still poorly understood, and often rely on theories developed primarily to describe mechanisms of the visual system. Deficits in the ability to select relevant information when there are multiple competing sound sources is a common complaint in aging and in individuals with hearing loss, and can greatly hinder communication ability. There is no computer algorithm or prosthetic device that can mimic what the brain does when there is competing background noise. The overall goal of this proposal is to characterize how the auditory system adapts to dynamically changing multi-stream environments, allowing rapid and flexible shifting to different sound events in one's surroundings. Specific Aim 1 determines how ambiguous input is physiologically stored. Specific Aim 2 characterizes how attention modifies neural activity to support behavior in ambiguous situations. Specific Aim 3 identifies how neural representations of auditory input accommodate to changing multi-stream environments. The aims will be accomplished by obtaining behavioral and multiple electrophysiological indices of sound organization when the input is perceptually ambiguous, thus providing a novel model in normal hearing adults for characterizing how the brain maintains stable sound events in noisy environments. A key strength of the current project is the ability to neurophysiologically assess sound organization in auditory cortex for both attended and unattended sounds. The results of the proposed experiments will elucidate how dynamically changing environments are maintained by brain systems; characterizing how automatic and attentive mechanisms of scene analysis interact in the perception of one among many streams. This will fill a profound gap in our understanding of the neural mechanisms contributing to the perception of stable auditory events in complex and dynamically changing sound environments.

DESCRIPTION (provided by applicant): Funds are requested to help support the Sixth International Conference on Mismatch Negativity (MMN) and its Clinical and Scientific Application that will be held May 1-4, 2012 at the Graduate Center of the City University of New York. This is the first time the meeting will be held in the United States. The MMN has become a key neurophysiological tool for studying auditory perception, memory, attention, speech and music. Recently, there has been increased focus on its clinical use in detecting and monitoring cerebral and psychological dysfunctions, and, as a result, increased interest in gaining greater clarification of its neural substrate, with this new focus leading to an increase in animal studies The four-day conference is focused on bringing together a diverse group of scientists, clinicians, postdoctoral fellows and students who use, or who are interested in using this electrophysiological technique to investigate clinical and basic science questions related to auditory function and their disorders. This forum will allow attendees to exchange ideas and foster collaborations, and to discuss and share recent research advances in using the MMN as a tool for scientific investigation. The conference will be comprised of symposia, keynote addresses, poster presentations, and workshops for professional skill development. Support is requested to defray the cost of student awards, travel for the keynote speakers, publication costs, and venue rental fees. PUBLIC HEALTH RELEVANCE: This conference will bring together a diverse group of scientists and clinicians and provide a forum for exchanging information and developing collaborations that enhance knowledge of auditory system function and disorders. These interactions are aimed at developing improved diagnostic and interventions for disorders that impact auditory cognition across the lifespan.

? DESCRIPTION (provided by applicant): In line with the strategic plan of the NEI, this project is focused on filling a profound gap in our understanding of neural mechanisms of visual perception. Specifically, we aim to understand how the adaptation of visual cortical circuits contributes to perception. Adaptation is a ubiquitous process by which neural processing and perception are dramatically influenced by recent visual inputs. However, the functional purpose of adaptation is poorly understood. Based on preliminary data, this project tests the hypothesis that visual adaptation instantiates a form of predictive coding, which is used to make unexpected events salient. We posit that cortical circuits learn the statistical structure of visua input in a manner that extends beyond previous fatigue- based descriptions of adaptation effects. This learning is used to discount expected features and signal novel ones. Our project will test this hypothesis through the collaborative effort of three investigators with expertise in human EEG, animal neurophysiology, and computational modeling. Aim 1 will assess the ability of cortical circuits to adapt to temporal sequences of input and to signal deviations from expected sequences. Aim 2 will evaluate the effect of stimulus uncertainty on adaptation and responses to novel events. Aim 3 will determine how adaptation dynamics and responses to novel stimuli are influenced by the temporal constancy of stimulus statistics. Each of these aims involves an experimental manipulation that yields distinct behavior from fatigue- based and predictive coding mechanisms. Thus, together our aims will provide a robust test of our core hypothesis, and provide a much richer understanding of the adaptive properties of cortical circuits. Results from our project will contribute to answering one of the continuing puzzles in visual research, which is to understand the functional purpose of adaptive mechanisms in visual perception.

Project Summary Between 40-70% of children treated for acute lymphoblastic leukemia (ALL) on contemporary protocols exhibit measurable deficits in cognitive functioning, which negatively impacts school and occupational performance, and diminishes quality of life. However, the specific processing deficits contributing to poor cognitive functioning in survivors of childhood ALL and the implications for ongoing brain development are poorly understood. The goal of this project is to characterize treatment-related effects on brain functions (Aim 1), identify abnormal patterns of neural connectivity (Aim 2), and assess chronic effects of chemotherapy treatment on the development of cognitive skills (Aim 3) in childhood survivors. We achieve these aims by using a combination of behavioral, electrophysiological, and neuroimaging measures to demonstrate effects on neurocognitive function, brain activity and brain development following chemotherapy compared to healthy, matched controls. Our study is designed to identify the relative contributions of sensory processes, memory, and attentional mechanisms, and cortical-maturation delays to poor performance on standardized tests of cognition function. Our approach will lead to the development of a powerful set of tools for identifying children with persistent treatment-related changes in cognitive functioning due to exposure to toxic therapy. Results will differentiate the level at which processing deficits occur (Aims 1 and 2), and longitudinally assess cognitive development (Aim 3) and the associated development in brain function and pathways in survivors of childhood ALL. This contribution is significant because defining the loci of neurocognitive dysfunction caused by ALL treatment would guide the development of novel preventive, treatment, and intervention strategies.