Common CNTNAP2 Variant Relates to Altered Functional Connectivity of the Striatum
Objectives: Examine how a common CNTNAP2 variant (rs2710102) relates to functional connectivity of the striatum, an important structure for implicit language learning.
Methods: Thirty-seven children and adolescents with ASD and 30 matched TD controls completed a 6-minute resting-state functional MRI scan. Resting-state functional connectivity analyses were conducted using the left caudate and the left putamen as seeds. As prior imaging genetics studies have used either dominant or recessive modes of inheritance (Dennis et al., 2011; Scott-Van Zeeland et al., 2010a; Whalley et al., 2011), we analyzed the data separately using each model. Initial group comparisons were completed in FSL, prethresholded with a joint mask of the within group results and thresholded at Z>2.3 with a cluster threshold of p=.05.
Results: Under the dominant and recessive models, the risk and non-risk groups both displayed robust functional connectivity between the left caudate and frontal, temporal, and parietal regions. In the dominant model, the non-risk group displayed significantly greater connectivity than the risk group to the medial prefrontal cortex, a region in which CNTNAP2is known to be expressed (Abrahams et al., 2007). When using a recessive model, the risk group showed significantly greater connectivity to bilateral frontal pole regions than the non-risk group. With regards to left putamen connectivity, both groups displayed robust connectivity to frontal and temporal areas for the dominant and recessive models. There were no significant between-group differences in putamen functional connectivity regardless of model.
Conclusions: Connectivity of the striatum, an area previously associated with language learning differences between ASD and typical development, is significantly modulated by a common genetic variant that has been linked to language in ASD.