A Review of Default Mode Network Connectivity and Its Association With Social Cognition in Adolescents With Autism Spectrum Disorder and Early-Onset Psychosis

Abstract

Recent studies have demonstrated substantial phenotypic overlap, notably social impairment, between autism spectrum disorder (ASD) and schizophrenia. However, the neural mechanisms underlying the pathogenesis of social impairments across these distinct neuropsychiatric disorders has not yet been fully examined. Most neuroimaging studies to date have focused on adults with these disorders, with little known about the neural underpinnings of social impairments in younger populations. Here, we present a narrative review of the literature available through April 2020 on imaging studies of adolescents with either ASD or early-onset psychosis (EOP), to better understand the shared and unique neural mechanisms of social difficulties across diagnosis from a developmental framework. We specifically focus on functional connectivity studies of the default mode network (DMN), as the most extensively studied brain network relevant to social cognition across both groups. Our review included 29 studies of DMN connectivity in adolescents with ASD (Mean age range = 11.2-21.6 years), and 14 studies in adolescents with EOP (Mean age range = 14.2-24.3 years). Of these, 15 of 29 studies in ASD adolescents found predominant underconnectivity when examining DMN connectivity. In contrast, findings were mixed in adolescents with EOP, with five of 14 studies reporting DMN underconnectivity, and an additional six of 14 studies reporting both under-and over-connectivity of the DMN. Specifically, intra-DMN networks were more frequently underconnected in ASD, but overconnected in EOP. On the other hand, inter-DMN connectivity patterns were mixed (both under-and over-connected) for each group, especially DMN connectivity with frontal, sensorimotor, and temporoparietal regions in ASD, and with frontal, temporal, subcortical, and cerebellar regions in EOP. Finally, disrupted DMN connectivity appeared to be associated with social impairments in both groups, less so with other features distinct to each condition, such as repetitive behaviors/restricted interests in ASD and hallucinations/delusions in EOP. Further studies on demographically well-matched groups of adolescents with each of these conditions

Changes of Entropy Connectivity of the Default Mode and Central Executive Networks in ASD

“…Abnormal functional connectivity in the DMN have been reported in autism-related studies [34,45], and weaker intrinsic connectivity in the DMN is associated with poorer social skills of ASD [14,23].The present study also observed weakened entropy connectivity between VPCC (BA 23) and VACC (BA 24) in the DMN of ASD. This under-connectivity might induce abnormal emotional processing and self-awareness disorders of patients with ASD.…”

“…It's similar to the theory of weak central coherence [33] The under-connectivity theory has been supported by subsequent studies. These investigations nd that the weakened functional connection between the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) results in a decrease in the level of social cognition [22,34] and the lack of functional connections between the frontal and posterior cortex (i.e., the parietal, occipital, and temporal lobes) in individuals with ASD contributes to poor performance for complex cognitive tasks such as language comprehension, social interaction, and working memory [35][36][37]. In addition, under-connectivity of the brain structural network such as abnormalities of white matter tracts (corpus callosum, arcuate fasciculus, inferior frontal-occipital fasciculus, etc.)…”

Thalamocortical connectivity is associated with autism symptoms in high-functioning adults with autism and typically developing adults

“…The lack of group differences for seeded regions in the DMN and CEN is surprising given the widespread evidence for altered connectivity in these networks across age groups 31,33,35,37,57 . One study of male highfunctioning ASD adults found hypoconnectivity between core DMN regions that negatively correlated with AQ 36 .…”

“…We additionally used a cortical seed-based approach for analyzing thalamocortical FC 18 and included seeds from the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and left dorsolateral prefrontal cortex (dlPFC). These seeds allowed us to examine FC in the two most commonly studied resting state networks in ASD, default mode (DMN) [35][36][37] and central executive (CEN) [38][39][40][41][42] . These networks have shown altered connectivity with sensorimotor regions in previous studies of adolescents with ASD 37 and are known to engage the thalamus as a key functional region 27,43 .…”

Social Cognition in a Research Domain Criteria Perspective: A Bridge Between Schizophrenia and Autism Spectra Disorders

“…Other neural networks described as possible protagonists in the SC process in ASD and SSD are the Default Mode Network (DMN) and the Salience Network (SN). The DMN is a major network encompassing the medial PFC, PCC, precuneus and bilateral inferior parietal lobules, which is activated when there is no engagement in any specific task and deactivated in the context of effortful cognitive tasks and SC tasks ( 115 – 118 ). The SN is a task activated brain network and comprises the anterior insula, dorsal ACC, the anterior PFC and the thalamus ( 119 ).…”