Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
ReviewThe Default Mode Network in Autism
Section snippets
Autism Spectrum Disorder, Social Deficits, and Default Mode Network
Autism, derived from the Greek word “auto” meaning “self,” describes a lack of interest in social interactions with the “other.” The term autism was first used by Eugen Bleuler to describe adolescents and adults with schizophrenia (1), and it became the cornerstone for Leo Kanner’s characterization of infants and young children who showed a lack of interest in communicating with others and appeared to be “lost in their own narrow worlds” (2). Although these early descriptions have been
Functional Neuroanatomy of DMN and Its Role in Social Cognition
Over the past 3 decades, a number of influential studies have consistently demonstrated that a strongly intrinsically interconnected network of brain structures 11, 12, including the posterior cingulate cortex (PCC), precuneus, medial prefrontal cortex (mPFC), temporoparietal junction (TPJ), and hippocampus 13, 14 (Figure 1), is attenuated during a wide range of cognitive tasks 13, 15. In parallel, several investigations have also uncovered that these structures, collectively named the default
Task-Based Functional Magnetic Resonance Imaging Studies of Atypical DMN Function
A prominent cognitive deficit of ASD is impairment in the ability to decode the mental states of self and others, and DMN dysfunction may be a critical neural signature of these deficits 31, 32, 33. The majority of task-based functional magnetic resonance imaging (fMRI) studies of ASD have been conducted with adults, or mixed groups of adolescents and adults, with ASD relative to age-matched neurotypical individuals. Task-related fMRI studies also focus primarily on activation in specific nodes
Intrinsic Functional Connectivity Evidence for Aberrant DMN
Intrinsic functional connectivity as measured by resting-state fMRI has been widely used to investigate the functional architecture of the DMN (16). Resting-state fMRI has been used more extensively in studies of ASD than task-related fMRI owing to the relative ease of acquiring the data, especially in developmental cohorts (50). There is strong evidence that the DMN is among the most disrupted functional networks in ASD 10, 51. Importantly, a number of studies report that disrupted intrinsic
Structural MRI Evidence for Atypical DMN in ASD
Prominent structural aberrations in the DMN across several morphological metrics have been reported in ASD, including cortical thickness and volume and gray matter density. One study using voxel-based morphometry reported altered PCC gray matter organization in children and adolescents with ASD, which was associated with symptom severity (77). Furthermore, there is also evidence of increased cortical thickness in the PCC (78) and ventral mPFC (79) (Figure 5C) in children, adolescents, and
Atypical White Matter Pathways Associated With DMN in ASD
A number of diffusion tensor imaging studies report atypical white matter connectivity in ASD (88). White matter tracts along the cingulum bundle connect the mPFC and PCC (Figure 1C), and the majority of studies report decreased fractional anisotropy, a metric of white matter integrity, in the cingulum in children and adolescents with ASD 89, 90, 91, 92, 93, although some studies report increases 94, 95. Tracts connecting the PCC and TPJ have been challenging to measure with conventional
Atypical Cellular Organization of DMN in ASD: Evidence From Postmortem Studies
Although MRI studies provide critical information regarding aberrant brain function and structure at macroscopic levels, histological analysis of human postmortem brain tissue is necessary to elucidate the cellular processes that may go awry in ASD (105). Neuronal migration deficits in early brain development may be a critical component of the pathophysiology of ASD 106, 107. Recent postmortem studies of brain tissue demonstrate altered laminar patterns and increased density of white matter
Neurophysiological Basis of DMN Dysfunction in ASD
A prominent neurobiological theory postulates that ASD is characterized by an excitation/inhibition (E/I) imbalance in local neural circuits that subserve sensory, social, and affective processes 109, 110, 111, 112, 113. E/I imbalance in ASD is thought to alter local and global brain signaling and contribute to atypical fluctuations in regional fMRI signals 67, 114, leading to difficulties with modulating flexible and goal-directed behaviors. Thus, the DMN has emerged as a key target for E/I
DMN Dysfunction in the Context of Salience Network Aberrations in ASD
Complex social behaviors involve cognitive and perceptual processes that are supported by interactions between large-scale brain systems, including the DMN (131). Notably, the DMN interfaces with two other major networks in the brain, the salience network (SN) and the central executive network (131). Thus, the consequences of DMN dysfunction likely manifest also in interactions of the DMN with other brain systems 10, 131.
A triple network model of psychopathology (131) posits that atypical
Conclusions
We have sought to provide a comprehensive review of evidence pointing to aberrant DMN function in the context of mental processes that contribute to social deficits in ASD. These processes most prominently include mentalizing, theory of mind, and self-referential processing, which have consistently been shown to activate the core nodes of the DMN in neurotypical individuals. We have linked neural models of DMN function with specific phenotypic features of social dysfunction in ASD. We used this
Acknowledgments and Disclosures
This work was supported by the National Institutes of Health (Grant Nos. HD059205, MH084164, and NS086085 to VM), Singer Foundation (to VM), Simons Foundation (to VM), Stanford Child Health Research Initiative and the Autism Science Foundation Post Doctoral Fellowships (to AP), and Swiss National Science Foundation Fellowship Grant No. 158831 (to MS).
The authors report no biomedical financial interests or potential conflicts of interest.
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AP and CJL contributed equally to this work.