Atypical integration of multisensory inputs has been suggested as a major component of autism, with some clinical and behavior-based empirical support for this view. Where and when in the neural processing stream these sensory integration deficits occur is as yet unknown, and gaining an understanding of this will be essential in defining the neuropathology of autism. In fact, there is precious little understanding of the basic development of healthy sensory integration mechanisms in typically developing children, although recent work in animal models is beginning to shed some light. Under this project, we will use established electrophysiological metrics of multisensory integration that we have developed in our laboratory in healthy adults, to test the hypothesis that multisensory integration is impaired in autism. The high-density electrical recordings of neural activity that we record will provide a precise measure of when in the information processing stream sensory integration differs from typically developing matched controls, as well as a good model of the underlying brain processes that are affected. We expect that there are profound developmental effects on how multisensory inputs are treated and we will therefore also characterize the """"""""normal"""""""" developmental trajectory of multisensory integration in typically developing children, using a cross-sectional approach. Specific hypotheses about when and where multisensory processes will be affected in autism are made based on the thesis that there is impoverished connectivity between distant cortical regions in this population, and our predictions are predicated on a rudimentary three-stage model of multisensory integration that we have developed in light of the extant literature. The data acquired under this project will provide a strong empirical test of deficits in multisensory integration processes in autism. Understanding how multisensory integration develops and changes over childhood will significantly inform models of multisensory integration, and provide an initial benchmark against which predictions about possible disordered multisensory integration in a host of developmental disorders can be made.

Public Health Relevance

The failure of integration across the sensory modalities is thought to be a core deficit in a number of clinical populations, especially in autism spectrum disorders but also in schizophrenia. In order to understand how it is that sensory integration goes awry in such patients, we must first develop a clear understanding of how the healthy brain integrates auditory, visual and somatosensory inputs from the environment. This project sets out to delineate the developmental trajectory of the neurophysiological processes underlying multisensory processing in the human cortex in children from 6 to 15 years of age, and to test the integrity of multisensory processes in children with autism. The results will have implications both for the clinical management of individuals with autism, as well as for models of autism.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH085322-05
Application #
8384852
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Gilotty, Lisa
Project Start
2009-01-01
Project End
2014-11-30
Budget Start
2012-12-01
Budget End
2014-11-30
Support Year
5
Fiscal Year
2013
Total Cost
$524,517
Indirect Cost
$208,543
Name
Albert Einstein College of Medicine
Department
Pediatrics
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Ross, Lars A; Del Bene, Victor A; Molholm, Sophie et al. (2017) Common variation in the autism risk gene CNTNAP2, brain structural connectivity and multisensory speech integration. Brain Lang 174:50-60
Butler, John S; Molholm, Sophie; Andrade, Gizely N et al. (2017) An Examination of the Neural Unreliability Thesis of Autism. Cereb Cortex 27:185-200
Murphy, Jeremy W; Foxe, John J; Molholm, Sophie (2016) Neuro-oscillatory mechanisms of intersensory selective attention and task switching in school-aged children, adolescents and young adults. Dev Sci 19:469-87
Uppal, Neha; Foxe, John J; Butler, John S et al. (2016) The neural dynamics of somatosensory processing and adaptation across childhood: a high-density electrical mapping study. J Neurophysiol 115:1605-19
Brandwein, Alice B; Foxe, John J; Butler, John S et al. (2015) Neurophysiological indices of atypical auditory processing and multisensory integration are associated with symptom severity in autism. J Autism Dev Disord 45:230-44
Andrade, Gizely N; Butler, John S; Mercier, Manuel R et al. (2015) Spatio-temporal dynamics of adaptation in the human visual system: a high-density electrical mapping study. Eur J Neurosci 41:925-39
Foxe, John J; Molholm, Sophie; Del Bene, Victor A et al. (2015) Severe multisensory speech integration deficits in high-functioning school-aged children with Autism Spectrum Disorder (ASD) and their resolution during early adolescence. Cereb Cortex 25:298-312
Banerjee, Snigdha; Frey, Hans-Peter; Molholm, Sophie et al. (2015) Interests shape how adolescents pay attention: the interaction of motivation and top-down attentional processes in biasing sensory activations to anticipated events. Eur J Neurosci 41:818-34
Morie, K P; De Sanctis, P; Foxe, J J (2014) Reward contingencies and the recalibration of task monitoring and reward systems: a high-density electrical mapping study. Neuroscience 273:100-17
Molholm, Sophie; Mercier, Manuel R; Liebenthal, Einat et al. (2014) Mapping phonemic processing zones along human perisylvian cortex: an electro-corticographic investigation. Brain Struct Funct 219:1369-83

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