Review
The Default Mode Network in Autism

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Abstract

Autism spectrum disorder (ASD) is characterized by deficits in social communication and interaction. Since its discovery as a major functional brain system, the default mode network (DMN) has been implicated in a number of psychiatric disorders, including ASD. We review converging multimodal evidence for DMN dysfunction in the context of specific components of social cognitive dysfunction in ASD—self-referential processing, which is the ability to process social information relative to oneself; and theory of mind or mentalizing, which is the ability to infer the mental states, such as beliefs, intentions, and emotions, of others. We show that altered functional and structural organization of the DMN and its atypical developmental trajectory are prominent neurobiological features of ASD. We integrate findings on atypical cytoarchitectonic organization and imbalance in excitatory-inhibitory circuits, which alter local and global brain signaling, to scrutinize putative mechanisms underlying DMN dysfunction in ASD. Our synthesis of the extant literature suggests that aberrancies in key nodes of the DMN and their dynamic functional interactions contribute to atypical integration of information about the self in relation to “other” as well as to impairments in the ability to flexibly attend to socially relevant stimuli. We conclude by highlighting open questions for future research.

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.

References (141)

  • H. Chen et al.

    Multivariate classification of autism spectrum disorder using frequency-specific resting-state functional connectivity-A multi-center study

    Prog Neuropsychopharmacol Biol Psychiatry

    (2016)
  • R.J. Ypma et al.

    Default mode hypoconnectivity underlies a sex-related autism spectrum

    Biol Psychiatry Cogn Neurosci Neuroimaging

    (2016)
  • C.J. Lynch et al.

    Default mode network in childhood autism: Posteromedial cortex heterogeneity and relationship with social deficits

    Biol Psychiatry

    (2013)
  • D.P. Kennedy et al.

    The intrinsic functional organization of the brain is altered in autism

    Neuroimage

    (2008)
  • C.S. Monk et al.

    Abnormalities of intrinsic functional connectivity in autism spectrum disorders

    Neuroimage

    (2009)
  • S.J. Weng et al.

    Alterations of resting state functional connectivity in the default network in adolescents with autism spectrum disorders

    Brain Res

    (2010)
  • J.L. Wiggins et al.

    Using a self-organizing map algorithm to detect age-related changes in functional connectivity during rest in autism spectrum disorders

    Brain Res

    (2011)
  • M. Assaf et al.

    Abnormal functional connectivity of default mode sub-networks in autism spectrum disorder patients

    Neuroimage

    (2010)
  • C.J. Lynch et al.

    Default mode network in childhood autism: Posteromedial cortex heterogeneity and relationship with social deficits

    Biol Psychiatry

    (2013)
  • K. Supekar et al.

    Brain hyperconnectivity in children with autism and its links to social deficits

    Cell Rep

    (2013)
  • K. Supekar et al.

    Development of functional and structural connectivity within the default mode network in young children

    Neuroimage

    (2010)
  • J.D. Power et al.

    The development of human functional brain networks

    Neuron

    (2010)
  • L.Q. Uddin et al.

    Multivariate searchlight classification of structural magnetic resonance imaging in children and adolescents with autism

    Biol Psychiatry

    (2011)
  • A. Raznahan et al.

    Patterns of coordinated anatomical change in human cortical development: A longitudinal neuroimaging study of maturational coupling

    Neuron

    (2011)
  • K.A. Doyle-Thomas et al.

    Effects of age and symptomatology on cortical thickness in autism spectrum disorders

    Res Autism Spectr Disord

    (2013)
  • H.Y. Lin et al.

    Regional brain volume differences between males with and without autism spectrum disorder are highly age-dependent

    Mol Autism

    (2015)
  • L. Walker et al.

    Diffusion tensor imaging in young children with autism: Biological effects and potential confounds

    Biol Psychiatry

    (2012)
  • M. Noriuchi et al.

    Altered white matter fractional anisotropy and social impairment in children with autism spectrum disorder

    Brain Res

    (2010)
  • N. Barnea-Goraly et al.

    White matter structure in autism: preliminary evidence from diffusion tensor imaging

    Biol Psychiatry

    (2004)
  • D.J. Simmonds et al.

    Developmental stages and sex differences of white matter and behavioral development through adolescence: A longitudinal diffusion tensor imaging (DTI) study

    Neuroimage

    (2014)
  • C. Lebel et al.

    Diffusion tensor imaging of white matter tract evolution over the lifespan

    Neuroimage

    (2012)
  • S.H. Ameis et al.

    Altered white matter connectivity as a neural substrate for social impairment in autism spectrum disorder

    Cortex

    (2015)
  • E. Bleuler

    Autistic thinking

  • L. Kanner

    Autistic disturbances of affective contact

    Nervous Child

    (1943)
  • L.Q. Uddin

    The self in autism: An emerging view from neuroimaging

    Neurocase

    (2011)
  • M.R. Banaji et al.

    The self in social contexts

    Annu Rev Psychol

    (1994)
  • R.B. Mars et al.

    On the relationship between the “default mode network” and the “social brain”

    Front Hum Neurosci

    (2012)
  • I. Molnar-Szakacs et al.

    Self-processing and the default mode network: Interactions with the mirror neuron system

    Front Hum Neurosci

    (2013)
  • W. Li et al.

    The default mode network and social understanding of others: What do brain connectivity studies tell us

    Front Hum Neurosci

    (2014)
  • L.Q. Uddin et al.

    Reconceptualizing functional brain connectivity in autism from a developmental perspective

    Front Hum Neurosci

    (2013)
  • P. Hagmann et al.

    Mapping the structural core of human cerebral cortex

    PLoS Biol

    (2008)
  • R.L. Buckner et al.

    Cortical hubs revealed by intrinsic functional connectivity: Mapping, assessment of stability, and relation to Alzheimer’s disease

    J Neurosci

    (2009)
  • R.L. Buckner et al.

    The brain’s default network: Anatomy, function, and relevance to disease

    Ann N Y Acad Sci

    (2008)
  • M.E. Raichle et al.

    A default mode of brain function

    Proc Natl Acad Sci U S A

    (2001)
  • M.D. Greicius et al.

    Default-mode activity during a passive sensory task: Uncoupled from deactivation but impacting activation

    J Cogn Neurosci

    (2004)
  • D.A. Gusnard et al.

    Searching for a baseline: Functional imaging and the resting human brain

    Nat Rev Neurosci

    (2001)
  • J.R. Andrews-Hanna et al.

    Evidence for the default network’s role in spontaneous cognition

    J Neurophysiol

    (2010)
  • M.Y. Acikalin et al.

    A coordinate-based meta-analysis of overlaps in regional specialization and functional connectivity across subjective value and default mode networks

    Front Neurosci

    (2017)
  • R.N. Spreng et al.

    The common neural basis of autobiographical memory, prospection, navigation, theory of mind, and the default mode: A quantitative meta-analysis

    J Cogn Neurosci

    (2009)
  • A.R. Laird et al.

    Behavioral interpretations of intrinsic connectivity networks

    J Cogn Neurosci

    (2011)
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    AP and CJL contributed equally to this work.

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