Deficits in mesolimbic reward pathway underlie social interaction impairments in children with autism

Abstract

Lack of interest in social interaction is a hallmark of autism spectrum disorder. Animal studies have implicated the mesolimbic reward pathway in driving and reinforcing social behaviour, but little is known about the integrity of this pathway and its behavioural consequences in children with autism spectrum disorder. Here we test the hypothesis that the structural and functional integrity of the mesolimbic reward pathway is aberrant in children with autism spectrum disorder, and these aberrancies contribute to the social interaction impairments. We examine structural and functional connectivity of the mesolimbic reward pathway in two independent cohorts totalling 82 children aged 7-13 years with autism spectrum disorder and age-, gender-, and intelligence quotient-matched typically developing children (primary cohort: children with autism spectrum disorder n = 24, typically developing children n = 24; replication cohort: children with autism spectrum disorder n = 17, typically developing children n = 17), using high angular resolution diffusion-weighted imaging and functional MRI data. We reliably identify white matter tracts linking-the nucleus accumbens and the ventral tegmental area-key subcortical nodes of the mesolimbic reward pathway, and provide reproducible evidence for structural aberrations in these tracts in children with autism spectrum disorder. Further, we show that structural aberrations are accompanied by aberrant functional interactions between nucleus accumbens and ventral tegmental area in response to social stimuli. Crucially, we demonstrate that both structural and functional circuit aberrations in the mesolimbic reward pathway are related to parent-report measures of social interaction impairments in affected children. Our findings, replicated across two independent cohorts, reveal that deficits in the mesolimbic reward pathway contribute to impaired social skills in childhood autism, and provide fundamental insights into neurobiological mechanisms underlying reduced social interest in humans.

Deviation from normative brain development is associated with symptom severity in autism spectrum disorder

“…One aspect of brain development that needs to be further investigated is the interaction between brain anatomy and other neurobiological features related to brain connectivity (e.g., white matter tissue characteristics). In the last decade, brain connectivity alterations (e.g., disruption in diffusion metrics) have emerged as candidate biomarkers in [26][27][28][29][30][31][32][33][34], owing to recent advances in diffusion MRI (dMRI) [35,36]. While there exist many neurobiological findings on diffusion-related alterations in ASD, their developmental characteristics remain unclear.…”

Insular Cortex Projections to Nucleus Accumbens Core Mediate Social Approach to Stressed Juvenile Rats

“…This parallel may facilitate translation of the current findings to people. Abnormalities in social processes like emotion recognition are symptoms of several psychiatric conditions including autism spectrum disorders (Tracy et al, 2011;Lozier et al, 2014;Sato et al, 2017;Griffiths et al, 2017) and it is important to note that functional neuroimaging studies of individuals with autism find reduced insular activation to emotional stimuli (Di Martino et al, 2009;Hall et al, 2013;Morita et al, 2012), reduced striatal activation to social rewards (Schmitz et al, 2008;Scott-Van Zeeland et al, 2010;Supekar et al, 2018), and reduced functional connectivity between insular regions and ventral striatum (Fuccillo, 2016). The current experimental results provide important mechanistic support for this axis as a key to normative social cognition.…”

Hochfunktionaler Autismus bei Erwachsenen

“…Diese Modellvorstellung basiert auf verschiedenen empirischen Befunden zur funktionellen und strukturellen Konnektivität bei Autismus [22], [23], [24], [29] und ist deshalb auch klinisch von Bedeutung, weil sie betroffenen Patienten auch veranschaulichen kann, wieso sie in manchen Leistungsbereichen besser sein können als nichtautistische Menschen.…”