Default mode network segregation and social deficits in autism spectrum disorder: Evidence from non-medicated children

Abstract

Functional pathology of the default mode network is posited to be central to social-cognitive impairment in autism spectrum disorders (ASD). Altered functional connectivity of the default mode network's midline core may be a potential endophenotype for social deficits in ASD. Generalizability from prior studies is limited by inclusion of medicated participants and by methods favoring restricted examination of network function. This study measured resting-state functional connectivity in 22 8–13 year-old non-medicated children with ASD and 22 typically developing controls using seed-based and network segregation functional connectivity methods. Relative to controls the ASD group showed both under- and over-functional connectivity within default mode and non-default mode regions, respectively. ASD symptoms correlated negatively with the connection strength of the default mode midline core—medial prefrontal cortex–posterior cingulate cortex. Network segregation analysis with the participation coefficient showed a higher area under the curve for the ASD group. Our findings demonstrate that the default mode network in ASD shows a pattern of poor segregation with both functional connectivity metrics. This study confirms the potential for the functional connection of the midline core as an endophenotype for social deficits. Poor segregation of the default mode network is consistent with an excitation/inhibition imbalance model of ASD.

Wavelet coherence-based classifier: A resting-state functional MRI study on neurodynamics in adolescents with high-functioning autism

“…For example by involving EXE and DMN, that are usually functionally anticorrelated, an insightful metric to test our classifier could be developed. In the study of Yerys et al (2015) [33] , the ASD groups demonstrated under-connectivity within the DMN, and a poorer network segregation of its midline core functional connectivity, as compared with controls. This midline core of the DMN encompassed the medial prefrontal cortex and posterior cingulate cortex.…”

The Social (Neural) Network: Towards a Unifying Endophenotype Between Genes and Behavior

“…Although previous research has associated ASD phenotypes with widespread hypoconnectivity 131,132,207,208,211,212 , we hypothesized that "noisy brains" were a more plausible explanation-rather than being disconnected, individuals expressing autistic-like traits would exhibit transient, dynamic connectivity that might otherwise deflate "static" estimates over the course of a scan. We proposed increased OXTR methylation as an underlying mechanism, such that decreased access to endogenous oxytocin would produce less-robust functional connections.…”

“…The dDMN largely corresponds to what others have termed the dorsal medial subsystem-these regions, primarily spanning the posterior cingulate and medial PFC, are frequently associated with empathetic processes such as mentalizing and perspective-taking 205,206 . Accordingly, connectivity across these regions is compromised in ASD 207,208 . The vDMN is relatively intact, by contrast-it comprises a medial temporal subsystem that is primarily associated with mental time-travel and other autobiographical memory-related functions 205,206 .…”

“…On a broader scale, the DMN and SN also interact. The decision to focus on subsystem connectivity was supported by previous work indicating specific deficits in ASD 207,208,211,212 , but it was also largely practical due to the computational complexity of dynamic connectivity analyses.…”

“…The explosion of network-based models of the brain has consequently led to powerful revelations about behavior and individual differences. Recent evidence has highlighted the notion that brain connectivity is a stable, intrinsic trait unique to an individual [175][176][177] , and psychopathological states such as autism 131,132,207,208,211,212,223 , schizophrenia 222 , and Alzheimer's dementia 172 (among others 173 ) are increasingly associated with abnormalities in functional and structural networks. Moreover, the integration of these methods with the philosophy of mind has generated a number of fascinating insights into the relationship between mental processes and the physical brain 224 .…”