Despite a general consensus that autism has biological causes, the specific links between brain loci of abnormality and cognitive-behavioral impairments remain unknown. Functional neuroimaging studies do not provide a clear picture, possibly due to etiological heterogeneity of autism samples. We will explore potential abnormalities of functional brain organization in autism with specific focus on individual variability, using functional MRI (fMRI) -- an imaging technique with sufficient power for individual analyses. Thirty verbal individuals with autism, 24 subjects with Asperger syndrome (AS), and age, gender, and handedness-matched controls will be studied. Our project will focus on language -- a domain which not only differentiates autism and AS in terms of delay and deficit, but is also characterized by a wide spectrum of abilities within the adult autistic population. FMRI will be performed during auditory and phonological discrimination, and lexical semantic association. Several complementary data analysis paths (groupwise and intraindividually; in normalized and native space) will enable us: (i) to identify consistent abnormalities of functional maps for autism and AS groups; (ii) to quantify activation foci in each subject in terms of spatial divergence from normal and individual variability within patient groups; (iii) to relate varying patterns of abnormal functional maps with measures of language skill; and (iv) to distinguish effects of pathological disturbance of functional maps from those of compensatory plasticity. We will test hypotheses, according to which in autism (and to a lesser extent in AS) pathological disturbance of neural differentiation and impoverished interactive language experience during critical developmental periods result in aberrant neurofunctional maps and abnormally pronounced individual variability. Language delay in autism is further hypothesized to be associated with atypical hemispheric dominance for language. Finally, we expect that individually variable patterns of abnormal functional maps will be correlated with level of language outcome. Identifying such links between brain maps and level of functioning achieved in adults will elucidate the significance of individual variation in autism in terms of different pathways of etiology and abnormal development.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BBBP-6 (01))
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Cooper, Judith
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San Diego State University
Schools of Arts and Sciences
San Diego
United States
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Jao Keehn, R Joanne; Sanchez, Sandra S; Stewart, Claire R et al. (2017) Impaired downregulation of visual cortex during auditory processing is associated with autism symptomatology in children and adolescents with autism spectrum disorder. Autism Res 10:130-143
Keehn, Brandon; Nair, Aarti; Lincoln, Alan J et al. (2016) Under-reactive but easily distracted: An fMRI investigation of attentional capture in autism spectrum disorder. Dev Cogn Neurosci 17:46-56
Stewart, Claire R; Sanchez, Sandra S; Grenesko, Emily L et al. (2016) Sensory Symptoms and Processing of Nonverbal Auditory and Visual Stimuli in Children with Autism Spectrum Disorder. J Autism Dev Disord 46:1590-601
Keehn, Brandon; Shih, Patricia; Brenner, Laurie A et al. (2013) Functional connectivity for an ""island of sparing"" in autism spectrum disorder: an fMRI study of visual search. Hum Brain Mapp 34:2524-37
Shen, Mark D; Shih, Patricia; Öttl, Birgit et al. (2012) Atypical lexicosemantic function of extrastriate cortex in autism spectrum disorder: evidence from functional and effective connectivity. Neuroimage 62:1780-91
Shih, Patricia; Keehn, Brandon; Oram, Jessica K et al. (2011) Functional differentiation of posterior superior temporal sulcus in autism: a functional connectivity magnetic resonance imaging study. Biol Psychiatry 70:270-7
Muller, Ralph-Axel; Shih, Patricia; Keehn, Brandon et al. (2011) Underconnected, but how? A survey of functional connectivity MRI studies in autism spectrum disorders. Cereb Cortex 21:2233-43
Shukla, Dinesh K; Keehn, Brandon; Müller, Ralph-Axel (2011) Tract-specific analyses of diffusion tensor imaging show widespread white matter compromise in autism spectrum disorder. J Child Psychol Psychiatry 52:286-95
Shukla, Dinesh K; Keehn, Brandon; Smylie, Daren M et al. (2011) Microstructural abnormalities of short-distance white matter tracts in autism spectrum disorder. Neuropsychologia 49:1378-1382
Keehn, Brandon; Lincoln, Alan J; Muller, Ralph-Axel et al. (2010) Attentional networks in children and adolescents with autism spectrum disorder. J Child Psychol Psychiatry 51:1251-9

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