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Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.

Background The default mode network (DMN), a brain system anchored in the posteromedial cortex, has been identified as under-connected in adults with autism spectrum disorder (ASD). However, to date there have been no attempts to characterize this network and its involvement in mediating social deficits in children with ASD. Furthermore, the functionally heterogeneous profile of the posteromedial cortex raises questions regarding how altered connectivity manifests in specific functional modules within this brain region in children with ASD. Methods Here we use resting-state fMRI and an anatomically informed approach to investigate the functional connectivity of the DMN in 20 children with ASD and 19 age-, gender-, and IQ-matched typically developing children. We utilize multivariate regression analyses to test whether altered patterns of connectivity are predictive of social impairment severity. Results Compared to TD children, children with ASD demonstrated hyper-connectivity of the posterior cingulate and retrosplenial cortices with predominately medial and anterolateral temporal cortex. In contrast, the precuneus in ASD children demonstrated hypo-connectivity with visual cortex, basal ganglia, and locally within the posteromedial cortex. Aberrant posterior cingulate cortex hyper-connectivity was linked with severity of social impairments in ASD, whereas precuneus hypo-connectivity was unrelated to social deficits. Consistent with previous work in healthy adults, we observe a functionally heterogeneous profile of connectivity within the posteromedial cortex in both TD and ASD children. Conclusions This work links hyper-connectivity of DMN-related circuits to the core social deficits in young children with ASD and highlights fundamental aspects of posteromedial cortex heterogeneity.

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. Here we review converging multimodal evidence for DMN dysfunction in the context of specific components of social cognitive dysfunction in ASD: ‘self-referential processing’ - the ability to process social information relative to oneself and ‘theory of mind’ or ‘mentalizing’ - 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 impairments in the ability to flexibly attend to socially relevant stimuli. We conclude by highlighting open questions for future research.

Individuals with autism spectrum disorders (ASDs) often show insensitivity to the human voice, a deficit that is thought to play a key role in communication deficits in this population. The social motivation theory of ASD predicts that impaired function of reward and emotional systems impedes children with ASD from actively engaging with speech. Here we explore this theory by investigating distributed brain systems underlying human voice perception in children with ASD. Using resting-state functional MRI data acquired from 20 children with ASD and 19 age-and intelligence quotientmatched typically developing children, we examined intrinsic functional connectivity of voice-selective bilateral posterior superior temporal sulcus (pSTS). Children with ASD showed a striking pattern of underconnectivity between left-hemisphere pSTS and distributed nodes of the dopaminergic reward pathway, including bilateral ventral tegmental areas and nucleus accumbens, left-hemisphere insula, orbitofrontal cortex, and ventromedial prefrontal cortex. Children with ASD also showed underconnectivity between righthemisphere pSTS, a region known for processing speech prosody, and the orbitofrontal cortex and amygdala, brain regions critical for emotion-related associative learning. The degree of underconnectivity between voice-selective cortex and reward pathways predicted symptom severity for communication deficits in children with ASD. Our results suggest that weak connectivity of voiceselective cortex and brain structures involved in reward and emotion may impair the ability of children with ASD to experience speech as a pleasurable stimulus, thereby impacting language and social skill development in this population. Our study provides support for the social motivation theory of ASD.auditory cortex | nucleus accumbens

SUMMARY Control over behavior is enabled by the brain’s control networks, which interact with lower-level sensory motor and default networks to regulate their functions. Such interactions are facilitated by specialized “connector hub” regions that interconnect discrete networks. Previous work has treated hubs as a single category of brain regions, although their unitary nature is dubious when examined in individual brains. Here we investigated the nature of hubs by using fMRI to characterize individual-specific hub regions in two independent datasets. We identified three separable sets of connector hubs that integrate information between specific brain networks. These three hub categories occupy different positions within the brain’s network structure; they affect networks differently when artificially lesioned, and they are differentially engaged during cognitive and motor task performance. This work suggests a model of brain organization in which different connector hubs integrate control functions and enable top-down control of separate processing streams.

Autism spectrum disorders (ASDs) are characterized by social impairments alongside cognitive and behavioral inflexibility. While social deficits in ASDs have extensively been characterized, the neurobiological basis of inflexibility and its relation to core clinical symptoms of the disorder are unknown. We acquired functional neuroimaging data from 2 cohorts, each consisting of 17 children with ASDs and 17 age- and IQ-matched typically developing (TD) children, during stimulus-evoked brain states involving performance of social attention and numerical problem solving tasks, as well as during intrinsic, resting brain states. Effective connectivity between key nodes of the salience network, default mode network, and central executive network was used to obtain indices of functional organization across evoked and intrinsic brain states. In both cohorts examined, a machine learning algorithm was able to discriminate intrinsic (resting) and evoked (task) functional brain network configurations more accurately in TD children than in children with ASD. Brain state discriminability was related to severity of restricted and repetitive behaviors, indicating that weak modulation of brain states may contribute to behavioral inflexibility in ASD. These findings provide novel evidence for a potential link between neurophysiological inflexibility and core symptoms of this complex neurodevelopmental disorder.

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