Longitudinal Stability of Intellectual Functioning in Autism Spectrum Disorder: From Age 3 Through Mid-adulthood.

Intelligence (IQ) scores are used in educational and vocational planning for individuals with autism spectrum disorder (ASD) yet little is known about the stability of IQ throughout development. We examined longitudinal age-related IQ stability in 119 individuals with ASD (3-36 years of age at first visit) and 128 typically developing controls. Intelligence measures were collected over a 20-year period. In ASD, Full Scale (FSIQ) and Verbal (VIQ) Intelligence started lower in childhood and increased at a greater rate with age relative to the control group. By early adulthood, VIQ and working memory stabilized, whereas nonverbal and perceptual scores continued to change. Our results suggest that in individuals with ASD, IQ estimates may be dynamic in childhood and young adulthood.

Beery VMI and Brain Volumetric Relations in Autism Spectrum Disorder.

Although diminished proficiency on tasks that require visual-motor integration (VMI) has been reported in individuals with autism spectrum disorder (ASD), very few studies have examined the association between VMI performance and neuroanatomical regions of interest (ROI) involved in motor and perceptual functioning. To address these issues, the current study included an all-male sample of 41 ASD (ages 3-23 years) and 27 typically developing (TD) participants (ages 5-26 years) who completed the Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI) as part of a comprehensive neuropsychological battery. All participants underwent 3.0 T magnetic resonance imaging (MRI) with image quantification (FreeSurfer software v5.3). The groups were statistically matched on age, handedness, and intracranial volume (ICV). ASD participants performed significantly lower on VMI and IQ measures compared with the TD group. VMI performance was significantly correlated with FSIQ and PIQ in the TD group only. No pre-defined neuroanatomical ROIs were significantly different between groups. Significant correlations were observed in the TD group between VMI and total precentral gyrus gray matter volume (r = .51, p = .006) and total frontal lobe gray matter volume (r = .46, p = .017). There were no significant ROI correlations with Beery VMI performance in ASD participants. At the group level, despite ASD participants exhibiting reduced visuomotor abilities, no systematic relation with motor or sensory-perceptual ROIs was observed. In the TD group, results were consistent with the putative role of the precentral gyrus in motor control along with frontal involvement in planning, organization, and execution monitoring, all essential for VMI performance. Given that similar associations between VMI and ROIs were not observed in those with ASD, neurodevelopment in ASD group participants may not follow homogenous patterns making correlations in these brain regions unlikely to be observed.

Social Responsiveness Scale (SRS) in Relation to Longitudinal Cortical Thickness Changes in Autism Spectrum Disorder.

The relationship between brain development and clinical heterogeneity in autism (ASD) is unknown. This study examines the Social Responsiveness Scale (SRS) in relation to the longitudinal development of cortical thickness. Participants (N = 91 ASD, N = 56 TDC; 3-39 years at first scan) were scanned up to three times over a 7-year period. Mixed-effects models examined cortical thickness in relation to SRS score. ASD participants with higher SRS scores showed regionally increased age-related cortical thinning. Regional thickness differences and reduced age-related cortical thinning were found in predominantly right lateralized regions in ASD with decreasing SRS scores over time. Our findings emphasize the importance of examining clinical phenotypes in brain-based studies of ASD.

Auditory attention in autism spectrum disorder: An exploration of volumetric magnetic resonance imaging findings.

Studies have shown that individuals with autism spectrum disorder (ASD) tend to perform significantly below typically developing individuals on standardized measures of attention, even when controlling for IQ. The current study sought to examine within ASD whether anatomical correlates of attention performance differed between those with average to above-average IQ (AIQ group) and those with low-average to borderline ability (LIQ group) as well as in comparison to typically developing controls (TDC). Using automated volumetric analyses, we examined regional volume of classic attention areas including the superior frontal gyrus, anterior cingulate cortex, and precuneus in ASD AIQ (n = 38) and LIQ (n = 18) individuals along with 30 TDC. Auditory attention performance was assessed using subtests of the Test of Memory and Learning (TOMAL) compared among the groups and then correlated with regional brain volumes. Analyses revealed group differences in attention. The three groups did not differ significantly on any auditory attention-related brain volumes; however, trends toward significant size-attention function interactions were observed. Negative correlations were found between the volume of the precuneus and auditory attention performance for the AIQ ASD group, indicating larger volume related to poorer performance. Implications for general attention functioning and dysfunctional neural connectivity in ASD are discussed.

Longitudinal development of thalamic and internal capsule microstructure in autism spectrum disorder.

The thalamus is a key sensorimotor relay area that is implicated in autism spectrum disorder (ASD). However, it is unknown how the thalamus and white-matter structures that contain thalamo-cortical fiber connections (e.g., the internal capsule) develop from childhood into adulthood and whether this microstructure relates to basic motor challenges in ASD. We used diffusion weighted imaging in a cohort-sequential design to assess longitudinal development of the thalamus, and posterior- and anterior-limbs of the internal capsule (PLIC and ALIC, respectively) in 89 males with ASD and 56 males with typical development (3-41 years; all verbal). Our results showed that the group with ASD exhibited different developmental trajectories of microstructure in all regions, demonstrating childhood group differences that appeared to approach and, in some cases, surpass the typically developing group in adolescence and adulthood. The PLIC (but not ALIC nor thalamus) mediated the relation between age and finger-tapping speed in both groups. Yet, the gap in finger-tapping speed appeared to widen at the same time that the between-group gap in the PLIC appeared to narrow. Overall, these results suggest that childhood group differences in microstructure of the thalamus and PLIC become less robust in adolescence and adulthood. Further, finger-tapping speed appears to be mediated by the PLIC in both groups, but group differences in motor speed that widen during adolescence and adulthood suggest that factors beyond the microstructure of the thalamus and internal capsule may contribute to atypical motor profiles in ASD. Autism Res 2018, 11: 450-462. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Microstructure of the thalamus, a key sensory and motor brain area, appears to develop differently in individuals with autism spectrum disorder (ASD). Microstructure is important because it informs us of the density and organization of different brain tissues. During childhood, thalamic microstructure was distinct in the ASD group compared to the typically developing group. However, these group differences appeared to narrow with age, suggesting that the thalamus continues to dynamically change in ASD into adulthood.

Longitudinal development of manual motor ability in autism spectrum disorder from childhood to mid-adulthood relates to adaptive daily living skills.

Many individuals with autism spectrum disorder (ASD) exhibit motor difficulties, but it is unknown whether manual motor skills improve, plateau, or decline in ASD in the transition from childhood into adulthood. Atypical development of manual motor skills could impact the ability to learn and perform daily activities across the life span. This study examined longitudinal grip strength and finger tapping development in individuals with ASD (n = 90) compared to individuals with typical development (n = 56), ages 5 to 40 years old. We further examined manual motor performance as a possible correlate of current and future daily living skills. The group with ASD demonstrated atypical motor development, characterized by similar performance during childhood but increasingly poorer performance from adolescence into adulthood. Grip strength was correlated with current adaptive daily living skills, and Time 1 grip strength predicted daily living skills eight years into the future. These results suggest that individuals with ASD may experience increasingly more pronounced motor difficulties from adolescence into adulthood and that manual motor performance in ASD is related to adaptive daily living skills.

Investigating the Microstructural Correlation of White Matter in Autism Spectrum Disorder.

White matter microstructure forms a complex and dynamical system that is critical for efficient and synchronized brain function. Neuroimaging findings in children with autism spectrum disorder (ASD) suggest this condition is associated with altered white matter microstructure, which may lead to atypical macroscale brain connectivity. In this study, we used diffusion tensor imaging measures to examine the extent that white matter tracts are interrelated within ASD and typical development. We assessed the strength of inter-regional white matter correlations between typically developing and ASD diagnosed individuals. Using hierarchical clustering analysis, clustering patterns of the pairwise white matter correlations were constructed and revealed to be different between the two groups. Additionally, we explored the use of graph theory analysis to examine the characteristics of the patterns formed by inter-regional white matter correlations and compared these properties between ASD and typical development. We demonstrate that the ASD sample has significantly less coherence in white matter microstructure across the brain compared to that in the typical development sample. The ASD group also presented altered topological characteristics, which may implicate less efficient brain networking in ASD. These findings highlight the potential of graph theory based network characteristics to describe the underlying networks as measured by diffusion magnetic resonance imaging and furthermore indicates that ASD may be associated with altered brain network characteristics. Our findings are consistent with those of a growing number of studies and hypotheses that have suggested disrupted brain connectivity in ASD.

Beery VMI performance in autism spectrum disorder.

Few studies have examined the visuomotor integration (VMI) abilities of individuals with autism spectrum disorder (ASD). An all-male sample consisting of 56 ASD participants (ages 3-23 years) and 36 typically developing (TD) participants (ages 4-26 years) completed the Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI) as part of a larger neuropsychological battery. Participants were also administered standardized measures of intellectual functioning and the Social Responsiveness Scale (SRS), which assesses autism and autism-like traits. The ASD group performed significantly lower on the Beery VMI and on all IQ measures compared to the TD group. VMI performance was significantly correlated with full scale IQ (FSIQ), performance IQ (PIQ), and verbal IQ (VIQ) in the TD group only. However, when FSIQ was taken into account, no significant Beery VMI differences between groups were observed. Only one TD participant scored 1.5 standard deviations (SDs) below the Beery VMI normative sample mean, in comparison to 21% of the ASD sample. As expected, the ASD group was rated as having significantly higher levels of social impairment on the SRS compared to the TD group across all major domains. However, level of functioning on the SRS was not associated with Berry VMI performance. These findings demonstrate that a substantial number of individuals with ASD experience difficulties compared to TD in performing VMI-related tasks, and that VMI is likely affected by general cognitive ability. The fact that lowered Beery VMI performance occurred only within a subset of individuals with ASD and did not correlate with SRS would indicate that visuomotor deficits are not a core feature of ASD, even though they present at a higher rate of impairment than observed in TD participants.

Brainstem White Matter Predicts Individual Differences in Manual Motor Difficulties and Symptom Severity in Autism.

Mounting evidence suggests that poorer motor skills may be related to more severe autism symptoms. This study investigated if atypical white matter microstructure in the brain mediated the relationship between motor skills and ASD symptom severity. Sixty-seven males with ASD and 42 males with typical development (5-33 years old) completed a diffusion tensor imaging scan and measures of grip strength, finger tapping, and autism symptom severity. Within the ASD group, weaker grip strength predicted more severe autism symptoms. Fractional anisotropy of the brainstem's corticospinal tract predicted both grip strength and autism symptom severity and mediated the relationship between the two. These findings suggest that brainstem white matter may contribute to autism symptoms and grip strength in ASD.

WIDE RANGE ACHIEVEMENT TEST IN AUTISM SPECTRUM DISORDER: TEST-RETEST STABILITY.

The principal goal of this descriptive study was to establish the test-retest stability of the Reading, Spelling, and Arithmetic subtest scores of the Wide Range Achievement Test (WRAT-3) across two administrations in individuals with autism spectrum disorder. Participants (N = 31) were males ages 6-22 years (M = 15.2, SD = 4.0) who were part of a larger ongoing longitudinal study of brain development in children and adults with autism spectrum disorder (N = 185). Test-retest stability for all three subtests remained consistent across administration periods (M = 31.8 mo., SD = 4.1). Age at time of administration, time between administrations, and test form did not significantly influence test-retest stability. Results indicated that for research involving individuals with autism spectrum disorder with a full scale intelligence quotient above 75, the WRAT-3 Spelling and Arithmetic subtests have acceptable test-retest stability over time and the Reading subtest has moderate test-retest stability over time.

Mesial temporal lobe and memory function in autism spectrum disorder: an exploration of volumetric findings.

Studies have shown that individuals with autism spectrum disorder (ASD) tend to perform significantly below typical developing individuals on standardized measures of memory, even when not significantly different on measures of IQ. The current study sought to examine within ASD whether anatomical correlates of memory performance differed between those with average-to-above-average IQ (AIQ group) and those with low-average to borderline ability (LIQ group) as well as in relations to typically developing comparisons (TDC). Using automated volumetric analyses, we examined regional volume of classic memory areas including the hippocampus, parahippocampal gyrus, entorhinal cortex, and amygdala in an all-male sample AIQ (n = 38) and LIQ (n = 18) individuals with ASD along with 30 typically developing comparisons (TDC). Memory performance was assessed using the Test of Memory and Learning (TOMAL) compared among the groups and then correlated with regional brain volumes. Analyses revealed group differences on almost all facets of memory and learning as assessed by the various subtests of the TOMAL. The three groups did not differ on any region of interest (ROI) memory-related brain volumes. However, significant size-memory function interactions were observed. Negative correlations were found between the volume of the amygdala and composite, verbal, and delayed memory indices for the LIQ ASD group, indicating larger volume related to poorer performance. Implications for general memory functioning and dysfunctional neural connectivity in ASD are discussed.

Atypical development of white matter microstructure of the corpus callosum in males with autism: a longitudinal investigation.

BACKGROUND: The corpus callosum is the largest white matter structure in the brain, and it is the most consistently reported to be atypical in diffusion tensor imaging studies of autism spectrum disorder. In individuals with typical development, the corpus callosum is known to undergo a protracted development from childhood through young adulthood. However, no study has longitudinally examined the developmental trajectory of corpus callosum in autism past early childhood. METHODS: The present study used a cohort sequential design over 9 years to examine age-related changes of the corpus callosum in 100 males with autism and 56 age-matched males with typical development from early childhood (when autism can first be reliably diagnosed) to mid-adulthood (after development of the corpus callosum has been completed) (3 to 41 years of age). RESULTS: The group with autism demonstrated a different developmental trajectory of white matter microstructure in the anterior corpus callosum's (genu and body) fractional anisotropy, which suggests atypical brain maturation in these regions in autism. When analyses were broken down by age group, atypical developmental trajectories were present only in the youngest participants (10 years of age and younger). Significant main effects for group were found in terms of decreased fractional anisotropy across all three subregions of the corpus callosum (genu, body, and splenium) and increased mean diffusivity, radial diffusivity, and axial diffusivity in the posterior corpus callosum. CONCLUSIONS: These longitudinal results suggest atypical early childhood development of the corpus callosum microstructure in autism that transitions into sustained group differences in adolescence and adulthood. This pattern of results provides longitudinal evidence consistent with a growing number of published studies and hypotheses regarding abnormal brain connectivity across the life span in autism.

Longitudinal volumetric brain changes in autism spectrum disorder ages 6-35 years.

Since the impairments associated with autism spectrum disorder (ASD) tend to persist or worsen from childhood into adulthood, it is of critical importance to examine how the brain develops over this growth epoch. We report initial findings on whole and regional longitudinal brain development in 100 male participants with ASD (226 high-quality magnetic resonance imaging [MRI] scans; mean inter-scan interval 2.7 years) compared to 56 typically developing controls (TDCs) (117 high-quality scans; mean inter-scan interval 2.6 years) from childhood into adulthood, for a total of 156 participants scanned over an 8-year period. This initial analysis includes between one and three high-quality scans per participant that have been processed and segmented to date, with 21% having one scan, 27% with two scans, and 52% with three scans in the ASD sample; corresponding percentages for the TDC sample are 30%, 30%, and 40%. The proportion of participants with multiple scans (79% of ASDs and 68% of TDCs) was high in comparison to that of large longitudinal neuroimaging studies of typical development. We provide volumetric growth curves for the entire brain, total gray matter (GM), frontal GM, temporal GM, parietal GM, occipital GM, total cortical white matter (WM), corpus callosum, caudate, thalamus, total cerebellum, and total ventricles. Mean volume of cortical WM was reduced significantly. Mean ventricular volume was increased in the ASD sample relative to the TDCs across the broad age range studied. Decreases in regional mean volumes in the ASD sample most often were due to decreases during late adolescence and adulthood. The growth curve of whole brain volume over time showed increased volumes in young children with autism, and subsequently decreased during adolescence to meet the TDC curve between 10 and 15 years of age. The volume of many structures continued to decline atypically into adulthood in the ASD sample. The data suggest that ASD is a dynamic disorder with complex changes in whole and regional brain volumes that change over time from childhood into adulthood.

Longitudinal changes in cortical thickness in autism and typical development.

The natural history of brain growth in autism spectrum disorders remains unclear. Cross-sectional studies have identified regional abnormalities in brain volume and cortical thickness in autism, although substantial discrepancies have been reported. Preliminary longitudinal studies using two time points and small samples have identified specific regional differences in cortical thickness in the disorder. To clarify age-related trajectories of cortical development, we examined longitudinal changes in cortical thickness within a large mixed cross-sectional and longitudinal sample of autistic subjects and age- and gender-matched typically developing controls. Three hundred and forty-five magnetic resonance imaging scans were examined from 97 males with autism (mean age = 16.8 years; range 3-36 years) and 60 males with typical development (mean age = 18 years; range 4-39 years), with an average interscan interval of 2.6 years. FreeSurfer image analysis software was used to parcellate the cortex into 34 regions of interest per hemisphere and to calculate mean cortical thickness for each region. Longitudinal linear mixed effects models were used to further characterize these findings and identify regions with between-group differences in longitudinal age-related trajectories. Using mean age at time of first scan as a reference (15 years), differences were observed in bilateral inferior frontal gyrus, pars opercularis and pars triangularis, right caudal middle frontal and left rostral middle frontal regions, and left frontal pole. However, group differences in cortical thickness varied by developmental stage, and were influenced by IQ. Differences in age-related trajectories emerged in bilateral parietal and occipital regions (postcentral gyrus, cuneus, lingual gyrus, pericalcarine cortex), left frontal regions (pars opercularis, rostral middle frontal and frontal pole), left supramarginal gyrus, and right transverse temporal gyrus, superior parietal lobule, and paracentral, lateral orbitofrontal, and lateral occipital regions. We suggest that abnormal cortical development in autism spectrum disorders undergoes three distinct phases: accelerated expansion in early childhood, accelerated thinning in later childhood and adolescence, and decelerated thinning in early adulthood. Moreover, cortical thickness abnormalities in autism spectrum disorders are region-specific, vary with age, and may remain dynamic well into adulthood.

Longitudinal processing speed impairments in males with autism and the effects of white matter microstructure.

The present study used an accelerated longitudinal design to examine group differences and age-related changes in processing speed in 81 individuals with autism spectrum disorder (ASD) compared to 56 age-matched individuals with typical development (ages 6-39 years). Processing speed was assessed using the Wechsler Intelligence Scale for Children-3rd edition (WISC-III) and the Wechsler Adult Intelligence Scale-3rd edition (WAIS-III). Follow-up analyses examined processing speed subtest performance and relations between processing speed and white matter microstructure (as measured with diffusion tensor imaging [DTI] in a subset of these participants). After controlling for full scale IQ, the present results show that processing speed index standard scores were on average 12 points lower in the group with ASD compared to the group with typical development. There were, however, no significant group differences in standard score age-related changes within this age range. For subtest raw scores, the group with ASD demonstrated robustly slower processing speeds in the adult versions of the IQ test (i.e., WAIS-III) but not in the child versions (WISC-III), even though age-related changes were similar in both the ASD and typically developing groups. This pattern of results may reflect difficulties that become increasingly evident in ASD on more complex measures of processing speed. Finally, DTI measures of whole-brain white matter microstructure suggested that fractional anisotropy (but not mean diffusivity, radial diffusivity, or axial diffusivity) made significant but small-sized contributions to processing speed standard scores across our entire sample. Taken together, the present findings suggest that robust decreases in processing speed may be present in ASD, more pronounced in adulthood, and partially attributable to white matter microstructural integrity.

Neuropsychological investigation of motor impairments in autism.

It is unclear how standardized neuropsychological measures of motor function relate to brain volumes of motor regions in autism spectrum disorder (ASD). An all-male sample composed of 59 ASD and 30 controls (ages 5-33 years) completed three measures of motor function: strength of grip (SOG), finger tapping test (FTT), and grooved pegboard test (GPT). Likewise, all participants underwent magnetic resonance imaging with region of interest (ROI) volumes obtained to include the following regions: motor cortex (precentral gyrus), somatosensory cortex (postcentral gyrus), thalamus, basal ganglia, cerebellum, and caudal middle frontal gyrus. These traditional neuropsychological measures of motor function are assumed to differ in motor complexity, with GPT requiring the most followed by FTT and SOG. Performance by ASD participants on the GPT and FTT differed significantly from that of controls, with the largest effect size differences observed on the more complex GPT task. Differences on the SOG task between the two groups were nonsignificant. Since more complex motor tasks tap more complex networks, poorer GPT performance by those with ASD may reflect less efficient motor networks. There was no gross pathology observed in classic motor areas of the brain in ASD, as ROI volumes did not differ, but FTT was negatively related to motor cortex volume in ASD. The results suggest a hierarchical motor disruption in ASD, with difficulties evident only in more complex tasks as well as a potential anomalous size-function relation in motor cortex in ASD.

Longitudinal Heschl's gyrus growth during childhood and adolescence in typical development and autism.

Heightened auditory sensitivity and atypical auditory processing are common in autism. Functional studies suggest abnormal neural response and hemispheric activation to auditory stimuli, yet the neurodevelopment underlying atypical auditory function in autism is unknown. In this study, we model longitudinal volumetric growth of Heschl's gyrus gray matter and white matter during childhood and adolescence in 40 individuals with autism and 17 typically developing participants. Up to three time points of magnetic resonance imaging data, collected on average every 2.5 years, were examined from individuals 3-12 years of age at the time of their first scan. Consistent with previous cross-sectional studies, no group differences were found in Heschl's gyrus gray matter volume or asymmetry. However, reduced longitudinal gray matter volumetric growth was found in the right Heschl's gyrus in autism. Reduced longitudinal white matter growth in the left hemisphere was found in the right-handed autism participants. Atypical Heschl's gyrus white matter volumetric growth was found bilaterally in the autism individuals with a history of delayed onset of spoken language. Heightened auditory sensitivity, obtained from the Sensory Profile, was associated with reduced volumetric gray matter growth in the right hemisphere. Our longitudinal analyses revealed dynamic gray and white matter changes in Heschl's gyrus throughout childhood and adolescence in both typical development and autism.

Fusiform correlates of facial memory in autism.

Prior studies have shown that performance on standardized measures of memory in children with autism spectrum disorder (ASD) is substantially reduced in comparison to matched typically developing controls (TDC). Given reported deficits in face processing in autism, the current study compared performance on an immediate and delayed facial memory task for individuals with ASD and TDC. In addition, we examined volumetric differences in classic facial memory regions of interest (ROI) between the two groups, including the fusiform, amygdala, and hippocampus. We then explored the relationship between ROI volume and facial memory performance. We found larger volumes in the autism group in the left amygdala and left hippocampus compared to TDC. In contrast, TDC had larger left fusiform gyrus volumes when compared with ASD. Interestingly, we also found significant negative correlations between delayed facial memory performance and volume of the left and right fusiform and the left hippocampus for the ASD group but not for TDC. The possibility of larger fusiform volume as a marker of abnormal connectivity and decreased facial memory is discussed.

Corpus Callosum Area in Children and Adults with Autism.

Despite repeated findings of abnormal corpus callosum structure in autism, the developmental trajectories of corpus callosum growth in the disorder have not yet been reported. In this study, we examined corpus callosum size from a developmental perspective across a 30-year age range in a large cross-sectional sample of individuals with autism compared to a typically developing sample. Midsagittal corpus callosum area and the 7 Witelson subregions were examined in 68 males with autism (mean age 14.1 years; range 3-36 years) and 47 males with typical development (mean age 15.3 years; range 4-29 years). Controlling for total brain volume, increased variability in total corpus callosum area was found in autism. In autism, increased midsagittal areas were associated with reduced severity of autism behaviors, higher intelligence, and faster speed of processing (p=0.003, p=0.011, p=0.013, respectively). A trend toward group differences in isthmus development was found (p=0.029, uncorrected). These results suggest that individuals with autism benefit functionally from increased corpus callosum area. Our cross-sectional examination also shows potential maturational abnormalities in autism, a finding that should be examined further with longitudinal datasets.

scMRI reveals large-scale brain network abnormalities in autism.

Autism is a complex neurological condition characterized by childhood onset of dysfunction in multiple cognitive domains including socio-emotional function, speech and language, and processing of internally versus externally directed stimuli. Although gross brain anatomic differences in autism are well established, recent studies investigating regional differences in brain structure and function have yielded divergent and seemingly contradictory results. How regional abnormalities relate to the autistic phenotype remains unclear. We hypothesized that autism exhibits distinct perturbations in network-level brain architecture, and that cognitive dysfunction may be reflected by abnormal network structure. Network-level anatomic abnormalities in autism have not been previously described. We used structural covariance MRI to investigate network-level differences in gray matter structure within two large-scale networks strongly implicated in autism, the salience network and the default mode network, in autistic subjects and age-, gender-, and IQ-matched controls. We report specific perturbations in brain network architecture in the salience and default-mode networks consistent with clinical manifestations of autism. Extent and distribution of the salience network, involved in social-emotional regulation of environmental stimuli, is restricted in autism. In contrast, posterior elements of the default mode network have increased spatial distribution, suggesting a 'posteriorization' of this network. These findings are consistent with a network-based model of autism, and suggest a unifying interpretation of previous work. Moreover, we provide evidence of specific abnormalities in brain network architecture underlying autism that are quantifiable using standard clinical MRI.