Decreased Interhemispheric Functional Connectivity in Autism

Abstract

The cortical underconnectivity theory asserts that reduced long-range functional connectivity might contribute to a neural mechanism for autism. We examined resting-state blood oxygen level-dependent interhemispheric correlation in 53 males with high-functioning autism and 39 typically developing males from late childhood through early adulthood. By constructing spatial maps of correlation between homologous voxels in each hemisphere, we found significantly reduced interhemispheric correlation specific to regions with functional relevance to autism: sensorimotor cortex, anterior insula, fusiform gyrus, superior temporal gyrus, and superior parietal lobule. Observed interhemispheric connectivity differences were better explained by diagnosis of autism than by potentially confounding neuropsychological metrics of language, IQ, or handedness. Although both corpus callosal volume and gray matter interhemispheric connectivity were significantly reduced in autism, no direct relationship was observed between them, suggesting that structural and functional metrics measure different aspects of interhemispheric connectivity. In the control but not the autism sample, there was decreasing interhemispheric correlation with subject age. Greater differences in interhemispheric correlation were seen for more lateral regions in the brain. These findings suggest that long-range connectivity abnormalities in autism are spatially heterogeneous and that transcallosal connectivity is decreased most in regions with functions associated with behavioral abnormalities in autism. Autism subjects continue to show developmental differences in interhemispheric connectivity into early adulthood.

Functional connectivity-based subtypes of individuals with and without autism spectrum disorder

“…Atypical static FC of sensorimotor regions has reported in previous studies (Anderson et al, 2011a;Mostofsky et al, 2009;Turner et al, 2006). Our findings suggest that despite the broad range of sensorimotor difficulties experienced by individuals with ASD (Minshew et al, 1997;Perry et al, 2007;Whyatt & Craig, 2013), atypical functioning with the SMN may be common across the autism spectrum.…”

A network of genetic repression and derepression specifies projection fates in the developing neocortex

“…This role for Tbr1 in callosal development is also intriguing in the context of autism. Autistic patients seem to have callosal abnormalities (19)(20)(21)(22)(23)(24)(25)(26), and in this context it is relevant that Auts2, a gene associated with autism, is regulated by Tbr1, which in turn is regulated by Satb2, a callosal fate specification gene. Recent studies suggest that a mutation in CAv1/2 (an L-type calcium channel) that is associated with Timothy syndrome, a form of autism, results in lower numbers of Satb2-expressing cells and an increase in Ctip2-expressing cells (31).…”

“…The functional significance of this relationship has been puzzling because Tbr1 regulates corticothalamic identity, and there have been no reports of defects in corticothalamic tracts in autistic patients. However, imaging studies in patients with autism have revealed defects in callosal tracts (2,(19)(20)(21)(22)(23)(24)(25)(26). A recent publication highlights a deficit in long-range connections (such as callosal connections) and excess of short-range cortical connections in patients with autism spectrum disorder (27).…”

Brain anatomy of autism spectrum disorders I. Focus on corpus callosum

“…Recent investigations have employed a threedimensional volumetric measurement of CC in ASD and frequently reported a reduction in the overall structure McAlonan et al 2009;Duan et al 2010;Anderson et al 2011;Frazier et al (Vidal et al 2006). The reductions in the CC volume is present over a wide age-range, since it is reported in ASD studies involving children (Vidal et al 2006;Hardan et al 2009;McAlonan et al 2009;Frazier et al 2012), adolescents (Waiter et al 2004(Waiter et al , 2005Alexander et al 2007) and adults (Keary et al 2009;Ecker et al 2010;Anderson et al 2011;Thomas et al 2011). On the other hand, the sparse literature on CC volume in low-functioning ASD (Riva et al 2011) prevents us from drawing inferences about the influence of IQ on CC volume and calls for further investigation.…”