This past year we have continued to evaluate the neural characteristics and associated behavioral consequences of Autism Spectrum Disorders (ASD). Prevailing theories suggest that ASD results from impaired brain communication due to aberrant timing or coordination of neuronal firing patterns (impaired synchrony). However, it remains debated whether synchrony abnormalities in ASD are among local and/or long-range circuits, are circuit-specific or are generalized, reflect increased (hyper-) synchrony and/or decreased (hypo-) synchrony, and whether they are frequency band specific or are distributed across the frequency spectrum. In previous studies, we used data driven techniques in conjunction with both fMRI and structural data to show that the abnormalities in ASD brain networks are most prominent within brain regions that support social functions. To provide an additional test of this hypothesis, as well as determine how oscillatory neural dynamics are affected in ASD, we recorded spontaneous magnetoencephalography (MEG) data in 17 high functioning adolescents and adults with ASD and 18 controls matched on age, IQ, and sex, and equated for motion during the scanning session. We used a method we recently developed to look at all-to-all synchronization across the brain in conjunction with data driven analyses to compare local and long-distance synchrony in a frequency-specific manner. We found that individuals with ASD showed local increased or hypersynchrony in the theta band (4-7 Hz) in lateral occipitotemporal cortex. We also observed long-range decreased or hyposynchronous activity in the alpha band (10-13 Hz) that was most prominent in neural circuitry underpinning social processing. The magnitude of this alpha band hyposynchrony was correlated with social symptom severity. These results suggest that while ASD is associated with both decreased long-range synchrony and increased posterior local synchrony - with each effect limited to a specific frequency band - impairments in social functioning may be most related to decreased alpha synchronization between critical nodes of the social processing network (Ghuman et al., 2017). To extend our understanding of these social deficits, we evaluated developmental changes in social functioning in 324 individuals with ASD, without intellectual impairment, compared to 438 typically developing subjects ranging in age from 4 to 29. We found that as they approach adolescence/adulthood the subjects with ASD fell increasing behind their age-matched peers in their social-communicative skills, indicating that social difficulties become more, rather than less pronounced in ASD during development (Wallace et al., 2017). We also completed two studies of higher-order executive functions, such as planning, organization skills, and cognitive flexibility, that strongly impact activities of daily living. In one of these studies (Wallace et al., 2016) we found that impairments of executive functions persist into adulthood and are associated with both depression and anxiety in ASD. We also evaluated executive functioning and adaptive behaviors in the largest study to date of sex differences in executive functions in ASD (White et al., 2017). Our study included 79 females and 158 males with ASD. Our results indicated relative weaknesses for females compared to males diagnosed with ASD on executive function and daily living skills. These differences occur in the absence of sex differences in our sample in age, IQ, clinician ratings of core ASD symptomatology, parent ratings of ADHD symptoms, and parent-reported social and communication adaptive skills on the VABS. These findings indicate specific liabilities in real world executive functions and daily living skills for females with ASD and have important implications for targeting their treatments.

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Ratto, Allison B; Kenworthy, Lauren; Yerys, Benjamin E et al. (2018) What About the Girls? Sex-Based Differences in Autistic Traits and Adaptive Skills. J Autism Dev Disord 48:1698-1711
Crutcher, Jason; Martin, Alex; Wallace, Gregory L (2018) Dissociations in the neural substrates of language and social functioning in autism spectrum disorder. Autism Res 11:1175-1186
Power, Jonathan D; Plitt, Mark; Gotts, Stephen J et al. (2018) Ridding fMRI data of motion-related influences: Removal of signals with distinct spatial and physical bases in multiecho data. Proc Natl Acad Sci U S A 115:E2105-E2114
Avery, Jason A; Ingeholm, John E; Wohltjen, Sophie et al. (2018) Neural correlates of taste reactivity in autism spectrum disorder. Neuroimage Clin 19:38-46
Ghuman, Avniel Singh; van den Honert, Rebecca N; Huppert, Theodore J et al. (2017) Aberrant Oscillatory Synchrony Is Biased Toward Specific Frequencies and Processing Domains in the Autistic Brain. Biol Psychiatry Cogn Neurosci Neuroimaging 2:245-252
Power, Jonathan D (2017) A simple but useful way to assess fMRI scan qualities. Neuroimage 154:150-158
Wallace, Gregory L; Dudley, Katerina; Anthony, Laura et al. (2017) Divergence of Age-Related Differences in Social-Communication: Improvements for Typically Developing Youth but Declines for Youth with Autism Spectrum Disorder. J Autism Dev Disord 47:472-479
Power, Jonathan D; Plitt, Mark; Laumann, Timothy O et al. (2017) Sources and implications of whole-brain fMRI signals in humans. Neuroimage 146:609-625
Ramot, Michal; Kimmich, Sara; Gonzalez-Castillo, Javier et al. (2017) Direct modulation of aberrant brain network connectivity through real-time NeuroFeedback. Elife 6:
White, Emily I; Wallace, Gregory L; Bascom, Julia et al. (2017) Sex differences in parent-reported executive functioning and adaptive behavior in children and young adults with autism spectrum disorder. Autism Res 10:1653-1662

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