Patterns of Atypical Functional Connectivity and Behavioral Links in Autism Differ Between Default, Salience, and Executive Networks

Abstract

Autism spectrum disorder (ASD) is characterized by atypical brain network organization, but findings have been inconsistent. While methodological and maturational factors have been considered, the network specificity of connectivity abnormalities remains incompletely understood. We investigated intrinsic functional connectivity (iFC) for four "core" functional networks-default-mode (DMN), salience (SN), and left (lECN) and right executive control (rECN). Resting-state functional MRI data from 75 children and adolescents (37 ASD, 38 typically developing [TD]) were included. Functional connectivity within and between networks was analyzed for regions of interest (ROIs) and whole brain, compared between groups, and correlated with behavioral scores. ROI analyses showed overconnectivity (ASD > TD), especially between DMN and ECN. Whole-brain results were mixed. While predominant overconnectivity was found for DMN (posterior cingulate seed) and rECN (right inferior parietal seed), predominant underconnectivity was found for SN (right anterior insula seed) and lECN (left inferior parietal seed). In the ASD group, reduced SN integrity was associated with sensory and sociocommunicative symptoms. In conclusion, atypical connectivity in ASD is network-specific, ranging from extensive overconnectivity (DMN, rECN) to extensive underconnectivity (SN, lECN). Links between iFC and behavior differed between groups. Core symptomatology in the ASD group was predominantly related to connectivity within the salience network.

Autism and cerebellar dysfunction: Evidence from animal models

“…Tracing studies e mostly in non-human primates e revealed extensive connections between the cerebellum and cortical areas beyond cortical areas involved in motor functions. These findings have been corroborated by more recent functional imaging studies in human patients, demonstrating that cerebellar domains are part of whole brain networks such as the default mode network, salience network, and executive control network [7,19], networks which are important for social function and disrupted in functional connectivity studies in autism [20,27].…”

“…Consistent with this model, cerebellar connectivity with these areas has been demonstrated [17,18]. Furthermore, in studies of ASD patients, connectivity and function have been demonstrated to be abnormal in these areas, raising the possibility that cerebellar disruption might be involved in aberrant function of these distributed circuits [27].…”

Alterations in resting state connectivity along the autism trait continuum: a twin study

“…19,[22][23][24]26,27 The latter findings originated predominantly from adult samples or samples spanning large age ranges. When stratifying our sample by age, the positive correlation between autistic traits and within-SN connectivity was strongest in children, consistent with the observation that hyperconnectivity in ASD is more commonly reported in younger individuals.…”

“…Reduced connectivity of DMN-hubs has commonly been reported in individuals with ASD at different ages. [13][14][15][16][17][18][19][20]22 The DMN has been shown to be recruited during tasks requiring self-referential imagination and therefore been suggested to have a key role in self-relevant mentalizing. 61 This hypothesis is consistent with the DMN's overlap with networks essential for social cognition.…”

“…[17][18][19][20] In contrast, some studies have reported increased DMN RS connectivity. 13,[20][21][22] Reduced SN RS connectivity has been found in children, adolescents and adults with ASD, affecting connectivity within the SN as well as connectivity between SN key nodes and sensory, prefrontal, and emotion processing regions. 19,[22][23][24][25][26][27] Moreover, increased connectivity within the SN and between the insula and striatal/retrosplenial regions has been reported in children with ASD.…”