Autism spectrum disorders (ASD) are characterized by deficits in executive functions, an umbrella term for cognitive processes that enable flexible, goal-directed behavior. We propose to study the neural basis of deficits in two important executive functions: Inhibition and task-switching. We will use an antisaccade paradigm in which ASD patients consistently show performance deficits. We hypothesize that participants with ASD will show abnormal task preparation, as indexed by reduced frontal eye field and anterior cingulate activity in preparation to antisaccade trials compared to prosaccade and No-GO trials and during a task-switch between prosaccade, antisaccade and No-Go trials. We also hypothesize that deficient task preparation will be related to diagnostic ratings of restricted, repetitive behaviors, one of the hallmarks of ASD. In this multimodal project, we will combine the spatial precision of event-related functional magnetic resonance imaging (fMRI) with the high temporal resolution of magnetoencephalography (MEG) and electroencephalography (EEG) to identify the regions involved and the timing of their contribution at various stages of antisaccade performance. Since executive functions are the product of coordinated activity across a distributed network, we will also assess the functional connectivity of the anatomical components of these networks using fMRI and the integrity of white matter tracts that connect them using Diffusion Tensor Imaging (DTI). Together, these methods will identify functional and structural neural correlates of abnormal executive function in ASD that contribute to a disabling symptom - restricted and repetitive behavior. The findings can guide the search for neuropathology and provide targets for intervention in ASD. In order to adapt to the environment, it is necessary to suppress inappropriate behaviors and use contextual cues. Brain networks that are critical for flexible control of behavior are compromised in Autism Spectrum Disorders, and this likely contributes to restricted, repetitive, and maladaptive patterns of behavior. Using complementary neuroimaging techniques, this research will identify the neural basis of cognitive dysfunction that gives rise to restricted, repetitive behavior in Autism Spectrum Disorders. The findings will guide investigations of neuropathology and provide targets for intervention to improve function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32MH088081-03
Application #
8197155
Study Section
Special Emphasis Panel (ZRG1-F01-W (22))
Program Officer
Anderson, Kathleen C
Project Start
2009-11-16
Project End
2012-11-15
Budget Start
2011-11-16
Budget End
2012-11-15
Support Year
3
Fiscal Year
2012
Total Cost
$54,570
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Agam, Yigal; Vangel, Mark; Roffman, Joshua L et al. (2014) Dissociable genetic contributions to error processing: a multimodal neuroimaging study. PLoS One 9:e101784
Gregory, Michael D; Agam, Yigal; Selvadurai, Chindhuri et al. (2014) Resting state connectivity immediately following learning correlates with subsequent sleep-dependent enhancement of motor task performance. Neuroimage 102 Pt 2:666-73
Agam, Yigal; Carey, Caitlin; Barton, Jason J S et al. (2013) Network dynamics underlying speed-accuracy trade-offs in response to errors. PLoS One 8:e73692
Dyckman, Kara A; Lee, Adrian K C; Agam, Yigal et al. (2011) Abnormally persistent fMRI activation during antisaccades in schizophrenia: a neural correlate of perseveration? Schizophr Res 132:62-8
Agam, Yigal; Hamalainen, Matti S; Lee, Adrian K C et al. (2011) Multimodal neuroimaging dissociates hemodynamic and electrophysiological correlates of error processing. Proc Natl Acad Sci U S A 108:17556-61