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Revealing Insula Functional Circuit(s) and Their Role in Autism with Resting State fMRI

Friday, 3 May 2013: 17:45
Meeting Room 3 (Kursaal Centre)
A. Di Martino1, C. Kelly2, F. X. Castellanos2 and M. P. Milham3, (1)NYU Child Study Center, New York, NY, (2)Institute for Pediatric Neuroscience, NY, NY, (3)Child Mind Institute, Center for Developing Brain at Child Mind Institute, New York, NY

Mounting evidence support the model that patterns of intrinsic functional connectivity (iFC) trace the history of evoked co-activation within distinct neuronal networks. This, along with its high test-retest reliability and feasibility for data collection in more challenging populations, have increasingly placed R-fMRI among the mainstream neuroimaging modalities –particularly to map differences in functional architecture for autism spectrum disorders (ASD). Motivated by our ability to dissect functional units of complex regions such as the anterior cingulate cortex (ACC; Margulies 200X), and the insula (Kelly, 2012), and given their aberrant activation in individuals with ASD (Di Martino et al, 2009), we hypothesize a role of their functional connections in ASD.


Leveraging on the increased recognition of the dimensional nature of autistic traits, we employed the Social Responsiveness Scale-Adult version (SRS-A) as a first step to identify a brain behavioral relationship potentially useful for ASD.


Resting state fMRI scans were collected in 25 neurotypical individuals (26.4 ± 5.6 y) who provided SRS-A completed by an informant who knew the participant in natural social settings. We selected the pregenual ACC (pgACC), typically implicated in theory of mind processes, as a region of interest and mapped its whole brain iFC with and without the SRS-A as a covariate of interest. Voxel-wise analyses were Gaussian random filed corrected for multiple comparisons at Z > 2.3; p < .05. The study has been approved by the IRB of the NYU school of medicine and the NYU.


We found a significant negative relationship between SRS-A and pgACC iFC with the anterior portion of mid-insula. Specifically, low levels of autistic traits were observed when a substantial portion of the anterior mid-insula showed positive iFC with pgACC - an iFC pattern similar to the ventral anterior insula typically implicated in empathy processes. In contrast, elevated levels of autistic traits were associated with negative iFC between the pgACC and the anterior mid-insula.

Conclusions:  Intrinsic FC of the pgACC-insula is dimensionally related autistic traits in neurotypical adults. Application of this approach in individuals with ASD is needed to confirm whether the pgACC- anterior mid insula circuit is a marker of ASD risk. Additionally, given the role of other portions of insula and ACC in cognitive and sensory processes we planned a broader examination of their functional connections in individuals with ASD.

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