Prefrontal-Related Functional Connectivities within the Default Network Are Modulated by COMT val158met in Healthy Young Adults

Previous studies have supported the concept that the default network is an intrinsic brain system that participates in internal modes of
cognition. Neural activity and connectivity within the default network, which are correlated with cognitive ability even at rest, may be
plausible intermediate phenotypes that will enable us to understand the genetic mechanisms of individuals’ cognitive function or the risk
for genetic brain diseases. Using resting functional magnetic resonance imaging and imaging genetic paradigms, we investigated whether
individual default network connectivity was modulated by COMT val 158met in 57 healthy young subjects. Compared with COMT heterozygous
individuals, homozygous val individuals showed significantly decreased prefrontal-related connectivities, which primarily
occurred between prefrontal regions and the posterior cingulate/restrosplenial cortices. Further analyses of the topological characteristics
of the default network showed homozygous val individuals had significantly fewer node degrees in the prefrontal regions. This
finding may partially elucidate previous reports that the COMT val variant is associated with inefficient prefrontal information processing
and poor cognitive performance. Our findings suggest that default network connectivity that involves the prefrontal cortex is modulated
by COMT val 158met through differential effects on prefrontal dopamine levels.