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Background: Schizophrenia and autism share many behavioral and neurological similarities, including altered white matter tract structure. However, because schizophrenia and autism are rarely compared directly, it is difficult to establish whether white matter abnormalities are disorder-specific or are common across these disorders that share some symptomatology., Methods: In the current study, we compared white matter water diffusion using tensor imaging in 25 adults with autism, 15 adults with schizophrenia, all with IQ scores above 88, and 19 neurotypical adults., Results: Although the three groups evinced no statistically significant differences in measures of fractional anisotropy (FA), the schizophrenia group showed significantly greater mean diffusivity (MD; Cohen's d > 0.77), due to greater radial diffusivity (RD; Cohen's d > 0.92), compared to both the autism and control groups. This effect was evident across the brain rather than specific to a particular tract., Conclusions: The greater MD and RD in schizophrenia appears to be diagnosis-specific. The altered diffusion may reflect subtle abnormalities in myelination, which could be a potential mechanism underlying the widespread behavioral deficits associated with schizophrenia., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Autism spectrum disorder (ASD) and schizophrenia are neurodevelopmental conditions that are characterized by significant social impairment. Emerging genomic and neurobiological evidence has increasingly pointed to shared pathophysiologic mechanisms in the two disorders. Overlap in social impairment may reflect similar underlying neural dysfunction in social-cognitive brain networks, yet few studies have directly compared brain function and communication between those with ASD and schizophrenia., Methods: Outpatients with schizophrenia (n=36), ASD (n=33), and healthy volunteers (n=37) completed a visual perspective-taking task during functional neuroimaging at 3T to assess similarities and differences in fronto-temporal brain function and connectivity during social-cognitive processing. Analyses employed general linear models to examine differences in amplitude of BOLD-signal response between disorder groups, and computed functional connectivity coefficients to investigate differences in the connectivity profiles of networks implicated in social cognition., Results: Despite similar behavioral impairments, participants with ASD and schizophrenia evidenced distinct neural abnormalities during perspective-taking. Functional activation results indicated reduced temporo-parietal junction and medial prefrontal activity in ASD compared to schizophrenia (all P uncor <0.002). Functional connectivity analyses further revealed significantly greater local orbitofrontal connectivity in ASD than schizophrenia (all P FDR <0.028) during perspective-taking. Differences in brain activation and connectivity were unrelated to antipsychotic medication dose., Conclusions: Autism and schizophrenia are characterized by similar social-cognitive impairments that may stem from different underlying abnormalities in the functional organization and communication of the social brain., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Autism and schizophrenia share multiple phenotypic and genotypic markers, and there is ongoing debate regarding the relationship of these two disorders. To examine whether cortical dynamics are similar across these disorders, we directly compared fMRI responses to visual, somatosensory and auditory stimuli in adults with autism (N=15), with schizophrenia (N=15), and matched controls (N=15). All participants completed a one-back letter detection task presented at fixation (to control attention) while task-irrelevant sensory stimulation was delivered to the different modalities. We focused specifically on the response amplitudes and the variability in sensory fMRI responses of the two groups, given the evidence of greater trial-to-trial variability in adults with autism. Both autism and schizophrenia individuals showed weaker signal-to-noise ratios (SNR) in sensory-evoked responses compared to controls (d>0.42), but for different reasons. For the autism group, the fMRI response amplitudes were indistinguishable from controls but were more variable trial-to-trial (d=0.47). For the schizophrenia group, response amplitudes were smaller compared to autism (d=0.44) and control groups (d=0.74), but were not significantly more variable (d<0.29). These differential group profiles suggest (1) that greater trial-to-trial variability in cortical responses may be specific to autism and is not a defining characteristic of schizophrenia, and (2) that blunted response amplitudes may be characteristic of schizophrenia. The relationship between the amplitude and the variability of cortical activity might serve as a specific signature differentiating these neurodevelopmental disorders. Identifying the neural basis of these responses and their relationship to the underlying genetic bases may substantially enlighten the understanding of both disorders., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE)-a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 7-64 years) (http://fcon&#95;1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 male subjects with ASDs and 403 male age-matched TCs. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo- and hyperconnectivity in the ASD literature; both were detected, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid- and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies.

Comparison of brain function between children and adults with autism provides an understanding of the effects of the disorder and associated maturational differences on language processing. Functional imaging (functional magnetic resonance imaging) was used to examine brain activation and cortical synchronization during the processing of literal and ironic texts in 15 children with autism, 14 children with typical development, 13 adults with autism, and 12 adult controls. Both the children and adults with autism had lower functional connectivity (synchronization of brain activity among activated areas) than their age and ability comparison group in the left hemisphere language network during irony processing, and neither autism group had an increase in functional connectivity in response to increased task demands. Activation differences for the literal and irony conditions occurred in key language-processing regions (left middle temporal, left pars triangularis, left pars opercularis, left medial frontal, and right middle temporal). The children and adults with autism differed from each other in the use of some brain regions during the irony task, with the adults with autism having activation levels similar to those of the control groups. Overall, the children and adults with autism differed from the adult and child controls in (a) the degree of network coordination, (b) the distribution of the workload among member nodes, and (3) the dynamic recruitment of regions in response to text content. Moreover, the differences between the two autism age groups may be indicative of positive changes in the neural function related to language processing associated with maturation and/or educational experience., (© 2013 International Society for Autism Research, Wiley Periodicals, Inc.)

Individuals with autism often violate social rules and have lower accuracy in identifying and explaining inappropriate social behavior. Twelve children with autism (AD) and thirteen children with typical development (TD) participated in this fMRI study of the neurofunctional basis of social judgment. Participants indicated in which of two pictures a boy was being bad (Social condition) or which of two pictures was outdoors (Physical condition). In the within-group Social-Physical comparison, TD children used components of mentalizing and language networks [bilateral inferior frontal gyrus (IFG), bilateral medial prefrontal cortex (mPFC), and bilateral posterior superior temporal sulcus (pSTS)], whereas AD children used a network that was primarily right IFG and bilateral pSTS, suggesting reduced use of social and language networks during this social judgment task. A direct group comparison on the Social-Physical contrast showed that the TD group had greater mPFC, bilateral IFG, and left superior temporal pole activity than the AD group. No regions were more active in the AD group than in the group with TD in this comparison. Both groups successfully performed the task, which required minimal language. The groups also performed similarly on eyetracking measures, indicating that the activation results probably reflect the use of a more basic strategy by the autism group rather than performance disparities. Even though language was unnecessary, the children with TD recruited language areas during the social task, suggesting automatic encoding of their knowledge into language; however, this was not the case for the children with autism. These findings support behavioral research indicating that, whereas children with autism may recognize socially inappropriate behavior, they have difficulty using spoken language to explain why it is inappropriate. The fMRI results indicate that AD children may not automatically use language to encode their social understanding, making expression and generalization of this knowledge more difficult.

Prior studies have indicated brain abnormalities underlying social processing in autism, but no fMRI study has specifically addressed the differential processing of direct and averted gaze, a critical social cue. Fifteen adolescents and adults with autism and 14 typically developing comparison participants viewed dynamic virtual-reality videos depicting a simple but realistic social scenario, in which an approaching male figure maintained either direct or averted gaze. Significant group by condition interactions reflecting differential responses to direct versus averted gaze in people with autism relative to typically developing individuals were identified in the right temporoparietal junction, right anterior insula, left lateral occipital cortex, and left dorsolateral prefrontal cortex. Our results provide initial evidence regarding brain mechanisms underlying the processing of gaze direction during simple social encounters, providing new insight into the social deficits in individuals with autism.

Previous behavioral studies have shown that individuals with autism are less hindered by interference from global processing during the performance of lower-level perceptual tasks, such as finding embedded figures. The primary goal of this study was to examine the brain manifestation of such atypicality in high-functioning autism using fMRI. Fifteen participants with high-functioning autism and fifteen age- and IQ-matched typical controls were asked to perform a lower-level perceptual line-counting task in the presence of a distracting depiction of a 3-D object, in which participants counted whether there were more red or more green contours (In a contrasting 3-D task, participants judged whether the same 3-D stimulus objects (but without color in any contours) depicted a possible or impossible 3-D object). We hypothesized that individuals with autism would be less likely than controls to process the global 3-D information (and would hence show fewer neural signs of such interfering 3-D processing) during the lower-level line-counting task. The fMRI results revealed that in the line-counting task, the autism group did not show the increased medial frontal activity (relative to the possibility task), or the increased functional connectivity between the medial frontal region and posterior visual-spatial regions, demonstrated by the control group. Both findings are indices of lesser effort and difficulty in the line-counting task for the autism group than for the control group, attributed to less interference from the 3-D processing in the autism group. In addition, in the line-counting task, the control group showed a positive correlation between a measure of spatial ability (Vandenberg scores) and activation in the medial frontal region, suggesting that more spatially able control participants did more suppression of the irrelevant 3-D background information in order to focus on the line-counting task. The findings collectively indicate that the global 3-D structure of the figure had a smaller effect, if any, on local processing in the group with autism compared to the control group. The results from this study provide the first direct neural evidence of reduced global-to-local interference in autism., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Cortical and central white matter (WM) volumes were measured to assess short- and long-range connectivity in autism, respectively. Subjects included 23 boys with autism and 23 matched controls, all without intellectual disability. Magnetic resonance imaging data obtained at 1.5 T were analyzed using BRAINS2 software (University of Iowa, Iowa City, IA, USA). Central WM volume was quantified by subtracting cortical from supratentorial WM volumes. Reduced central WM volume was observed in the autism group. IQ was higher in controls with no observed correlations between WM volumes and IQ. This preliminary evidence of reduced central WM volume in autism suggests abnormal long-range connectivity., (© 2010 The Authors. Psychiatry and Clinical Neurosciences © 2010 Japanese Society of Psychiatry and Neurology.)

Purpose of Review: Functional magnetic resonance imaging studies have had a profound impact on the delineation of the neurobiologic basis for autism. Advances in fMRI technology for investigating functional connectivity, resting state connectivity, and a default mode network have provided further detail about disturbances in brain organization and brain-behavior relationships in autism to be reviewed in this article., Recent Findings: Recent fMRI studies have provided evidence of enhanced activation and connectivity of posterior, or parietal-occipital, networks and enhanced reliance on visuospatial abilities for visual and verbal reasoning in high functioning individuals with autism. Evidence also indicates altered activation in frontostriatal networks for cognitive control, particularly involving anterior cingulate cortex, and altered connectivity in the resting state and the default mode network. The findings suggest that the specialization of many cortical networks of the human brain has failed to develop fully in high functioning individuals with autism., Summary: This research provides a growing specification of to the neurobiologic basis for this complex syndrome and for the co-occurrence of the signs and symptoms as a syndrome. With this knowledge has come new neurobiologically based opportunities for intervention.

Background: Autism is a developmental neurobiologic disorder associated with structural and functional abnormalities in several brain regions including the cerebral cortex. This longitudinal study examined developmental changes in brain volume and cortical thickness (CT) using magnetic resonance imaging (MRI) in children with autism., Methods: MRI scans and behavioral measures were obtained at baseline and after a 30-month interval in a sample of male subjects with autism (n = 18) and healthy age-, and sex-matched control subjects (n = 16) between ages 8 and 12 years at baseline., Results: No differences in brain volumes were observed between the autism and control subjects at baseline or follow-up. However, differences in total gray matter volumes were observed over time with significantly greater decreases in the autism group compared with control subjects. Differences in CT were observed over time with greater decreases in the autism group compared with control subjects in several brain regions including the frontal lobe. When accounting for multiple comparisons, differences between the two groups became nonsignificant except for changes in occipital CT. Furthermore, associations were observed between several clinical features and changes in CT with greater thinning of the cortex being correlated with more severe symptomatology., Conclusions: Findings from this study provide preliminary evidence for age-related changes in gray matter volume and CT in children with autism that are associated with symptoms severity. Future longitudinal studies of larger sample sizes are needed to evaluate developmental changes and examine the relationships between structural abnormalities and clinical expressions of the disorder.

The objective of this study was to examine the relationship between thalamic volume and brain size in individuals with Asperger's disorder (ASP). Volumetric measurements of the thalamus were performed on MRI scans obtained from 12 individuals with ASP (age range: 10-35 years) and 12 healthy controls (age range: 9-33 years). A positive correlation was found between total brain volume and thalamic size in controls, but not in ASP subjects. This occurred in the absence of differences in mean thalamic volumes between the study groups. Findings from this investigation point to an abnormal relationship between the thalamus and its projection areas in ASP and are consistent with similar studies in autism, supporting that these disorders are qualitatively similar and possibly quantitatively different.

Data sharing in autism neuroimaging presents scientific, technical, and social obstacles. We outline the desiderata for a data-sharing scheme that combines imaging with other measures of phenotype and with genetics, defines requirements for comparability of derived data and recommendations for raw data, outlines a core protocol including multispectral structural and diffusion-tensor imaging and optional extensions, provides for the collection of prospective, confound-free normative data, and extends sharing and collaborative development not only to data but to the analytical tools and methods applied to these data. A theme in these requirements is the need to preserve creative approaches and risk-taking within individual laboratories at the same time as common standards are provided for these laboratories to build on.

Structural imaging studies of autism have documented increased total brain volume and early acceleration in brain growth. Functional MR imaging (fMRI) studies in autism have also led to the view of autism as a disorder of cortical functioning in which functional connectivity or synchronization of brain regions and cortical activity are disturbed with atypical cortical specialization.

Background: Inhibiting prepotent responses is critical to optimal cognitive and behavioral function across many domains. Several behavioral studies have investigated response inhibition in autism, and the findings varied according to the components involved in inhibition. There has been only one published functional magnetic resonance imaging (fMRI) study so far on inhibition in autism, which found greater activation in participants with autism than control participants., Methods: This study investigated the neural basis of response inhibition in 12 high-functioning adults with autism and 12 age- and intelligence quotient (IQ)-matched control participants during a simple response inhibition task and an inhibition task involving working memory., Results: In both inhibition tasks, the participants with autism showed less brain activation than control participants in areas often found to be active in response inhibition tasks, namely the anterior cingulate cortex. In the more demanding inhibition condition, involving working memory, the participants with autism showed more activation than control participants in the premotor areas. In addition to the activation differences, the participants with autism showed lower levels of synchronization between the inhibition network (anterior cingulate gyrus, middle cingulate gyrus, and insula) and the right middle and inferior frontal and right inferior parietal regions., Conclusions: The results indicate that the inhibition circuitry in the autism group is activated atypically and is less synchronized, leaving inhibition to be accomplished by strategic control rather than automatically. At the behavioral level, there was no difference between the groups.

This study was conducted to examine the volume of the thalamus in autism and to investigate the effect of brain size on this structure in an attempt to replicate, in a larger sample, findings from a previous study reporting the existence of a relationship between brain volume and thalamus in healthy controls but not in individuals with autism. Additionally, the relationships between thalamic volumes and clinical features were examined. Volumetric measurements of the right and left thalamic nuclei were performed on MRI scans obtained from 40 high-functioning individuals with autism (age range: 8-45 years) and 41 healthy controls (age range: 9-43 years). No differences were observed between the two groups for unadjusted thalamic volumes. However, the expected linear relationship between TBV and thalamic volume was not observed in individuals with autism. Furthermore, no correlations were observed between thalamic volumes and clinical features. Findings from this larger study are consistent with the previous report of an abnormal brain size effect on the thalamus in autism and support the possibility of abnormal connections between cortical and subcortical structures in this disorder.

The objective of this investigation was to examine the existence of minor physical anomalies (MPA) in autism. The interorbital and interlens distances were measured on MRI scans obtained from a sample of 40 non-mentally retarded individuals with autism and 41 healthy controls. No differences were observed between the two groups on any measurements. However, when the analysis was conducted using a split median procedure, individuals with autism and either low FSIQ, PIQ, or VIQ had shorter interorbital distances when compared to controls. Hypotelorism is a MPA that may be present in a subgroup of individuals with autism. Additional research is warranted using large sample sizes with a wide range of intellectual functioning.

Disturbances in lateral preference in autism are of interest because of their potential to shed light on brain maturational processes in this disorder. Forty-seven autistic individuals with a history of disordered early language development and 22 autistic individuals with normal early language acquisition were matched with 112 healthy individuals and compared on a standardized measure of lateral preference, the Edinburgh Handedness Inventory. Autistic individuals with a history of early language disturbance showed more atypical cerebral dominance than both healthy participants and autistic individuals with normal early language skills. The data indicated maturational disturbances in establishing lateral preference rather than increased rates of left handedness. Atypical establishment of cerebral dominance may be one cause of disordered language development in autism.

Objective: To determine whether brain volume, as assessed on MRI scans, differs between individuals with autism and control subjects, and whether such differences are affected by age., Background: Previous studies have found increased brain weight, head circumference, and MRI brain volume in children with autism. However, studies of brain size in adults with autism have yielded conflicting results. The authors hypothesize that enlargement of the brain may be a feature of brain development during early childhood in autism that normalizes with maturational processes., Methods: The authors measured total brain volumes from 1.5-mm coronal MRI scans in 67 non-mentally retarded children and adults with autism and 83 healthy community volunteers, ranging in age from 8 to 46 years. Head circumference was also measured. Groups did not differ on age, sex, verbal IQ, or socioeconomic status., Results: Brain volumes were significantly larger for children with autism 12 years old and younger compared with normally developing children, when controlling for height. Brain volumes for individuals older than age 12 did not differ between the autism and control groups. Head circumference was increased in both younger and older groups of subjects with autism, suggesting that those subjects older than age 12 had increased brain volumes as children., Conclusions: Brain development in autism follows an abnormal pattern, with accelerated growth in early life that results in brain enlargement in childhood. Brain volume in adolescents and adults with autism is, however, normal, and appears to be due to a slight decrease in brain volume for these individuals at the same time that normal children are experiencing a slight increase.

Increased brain size has been observed in individuals with autism with a wide range of cognitive functioning. The purpose of this investigation was to obtain measurements of the brain volume in a sample of nonmentally retarded autistic individuals. Magnetic resonance imaging scans from 16 nonmentally retarded individuals with autism and 19 male volunteer comparison subjects were obtained and the following structures were measured: third, fourth, and lateral ventricles and intracranial and cerebral volumes. Mean cerebral and third ventricle volumes in the autistic subjects were significantly greater than in the controls when adjusted for intracranial volume. No other significant results were found. Our finding of increased brain volume in autism is consistent with previous reports in the literature. Additional longitudinal neuroimaging and, more importantly, neuropathologic studies are warranted to provide a better understanding of the complexities underlying increased brain size in autism.

Cognitive and brain maturational changes continue throughout late childhood and adolescence. During this time, increasing cognitive control over behavior enhances the voluntary suppression of reflexive/impulsive response tendencies. Recently, with the advent of functional MRI, it has become possible to characterize changes in brain activity during cognitive development. In order to investigate the cognitive and brain maturation subserving the ability to voluntarily suppress context-inappropriate behavior, we tested 8-30 year olds in an oculomotor response-suppression task. Behavioral results indicated that adult-like ability to inhibit prepotent responses matured gradually through childhood and adolescence. Functional MRI results indicated that brain activation in frontal, parietal, striatal, and thalamic regions increased progressively from childhood to adulthood. Prefrontal cortex was more active in adolescents than in children or adults; adults demonstrated greater activation in the lateral cerebellum than younger subjects. These results suggest that efficient top-down modulation of reflexive acts may not be fully developed until adulthood and provide evidence that maturation of function across widely distributed brain regions lays the groundwork for enhanced voluntary control of behavior during cognitive development., (Copyright 2001 Academic Press.)

In this pilot study, brain high energy phosphate and membrane phospholipid metabolism were investigated in the dorsal prefrontal cortex of 11 high-functioning autistic adolescent and young adult men (the age range is 12-36 years) and 11 age-, gender-, IQ, race- and socioeconomic status-matched normal controls using in vivo 31P nuclear magnetic resonance spectroscopy (MRS). The autistic group had decreased levels of phosphocreatine and esterified ends (alpha ATP + alpha ADP + dinucleotides + diphosphosugars) compared to the controls. When the metabolite levels were compared within each subject group with neuropsychologic and language test scores, a common pattern of correlations was observed across measures in the autistic group, but not in the control group. As test performance declined in the autistic subjects, levels of the most labile high energy phosphate compound and of membrane building blocks decreased, and levels of membrane breakdown products increased. No significant correlations were present with age in either group or with IQ in the control group, suggesting that these findings were not the consequence of age or IQ effects. This pilot study provides tentative evidence of alterations in brain energy and phospholipid metabolism in autism that correlate with the neuropsychologic and language deficits. The findings are consistent with a hypermetabolic energy state and undersynthesis of brain membranes and may relate to the neurophysiologic and neuropathologic abnormalities in autism.

A number of studies have demonstrated alterations in the structure and function of the frontolimbic system in some schizophrenic patients. Recent in vivo phosphorus-31 nuclear magnetic resonance studies of the dorsal prefrontal cortex in neuroleptic-naive, first-episode schizophrenic patients and matched controls have shown evidence of alterations in membrane phospholipid and energy metabolism. The membrane alterations observed in the schizophrenic patients are compatible with either premature aging or altered timing and exaggeration of regressive events occurring during normal brain development. These molecular changes may precede onset of clinical symptoms and brain structural changes in schizophrenia and suggest fresh approaches to the pathogenesis and treatment of this illness.

31P nuclear magnetic resonance (NMR) studies were conducted on perchloric acid extracts of the brain of one control, two Huntington's disease (HD), one probable Alzheimer's disease (AD), and one AD patient. These studies demonstrated significant elevations (over control) in the levels of phosphomonoesters in all brain areas of the patients with HD and AD even in areas devoid of neuropathological findings. Elevations of phosphodiesters were also observed, but they tended to reflect the degree of neuropathological change. We postulate that the 31P NMR findings represent molecular alterations with corresponding metabolic correlates which either antedate or occur in the absence of changes in cellular morphology or structure. As such the 31P NMR findings may reflect a subcellular "molecular neuropathology."