There is converging evidence to support an investigation of basal ganglia (BG) structure, function and circuitry in autism as a possible core neurobiological component of the disorder;a finding which may help target better interventions for the treatment of autism. This system is an attractive target area for dysfunction in autism spectrum disorders, as it has been implicated in learning and memory, language, motor behaviors and social communication, all of which are disrupted in autism. The proposed study will provide an in-depth and comprehensive investigation of the BG in autism, specifically reward and implicit learning systems, using both structural and functional magnetic resonance imaging. Our lab has investigated other neural systems in autism and found differences in striatal activity during certain tasks as measured by fMRI between typically developing (TD) children and children with autism (ASD). I would like to further examine these differences in activity as well as any structural differences that may be related. Using fMRI, I will adapt an established implicit learning task, which has been shown to rely on the BG, for children and add a reward component to test the hypothesis that ASD children will show less activity in this area compared to TD children. I will also conduct novel structural analysis on sub-regions within the BG. We will use a structure deformation approach described by Thompson et al. (2003) to create spatial maps of structural displacement to correlate with the functional maps from the fMRI task. We predict that areas of greatest structural displacement will correlate with decreased functional activity during reward processing and implicit learning. Beyond investigating functional deficits in the basal ganglia, this research will also explore the underlying link between neural structure to behavior by relating the functional and structural measures to measures of repetitive behaviors, restricted interests, and overall severity of autistic symptoms. Specifically, we will create spatial cross-correlation maps relating the structure/function correlation and behavioral measures. By addressing relationships between behavior, structure and function of one system in both children with and without autism, a clearer picture of how implicit learning and reward system dysfunction may contribute to some of the core deficits in autism will emerge.
| Scott-Van Zeeland, Ashley A; McNealy, Kristin; Wang, A Ting et al. (2010) No neural evidence of statistical learning during exposure to artificial languages in children with autism spectrum disorders. Biol Psychiatry 68:345-51 |
| Scott-Van Zeeland, Ashley A; Abrahams, Brett S; Alvarez-Retuerto, Ana I et al. (2010) Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP2. Sci Transl Med 2:56ra80 |
| Scott-Van Zeeland, Ashley A; Dapretto, Mirella; Ghahremani, Dara G et al. (2010) Reward processing in autism. Autism Res 3:53-67 |
