Associations between atypical intracortical myelin content and neuropsychological functions in middle to older aged adults with ASD.

INTRODUCTION: In vivo myeloarchitectonic mapping based on Magnetic Resonance Imaging (MRI) provides a unique view of gray matter myelin content and offers information complementary to other morphological indices commonly employed in studies of autism spectrum disorder (ASD). The current study sought to determine if intracortical myelin content (MC) and its age-related trajectories differ between middle aged to older adults with ASD and age-matched typical comparison participants. METHODS: Data from 30 individuals with ASD and 36 age-matched typical comparison participants aged 40-70 years were analyzed. Given substantial heterogeneity in both etiology and outcomes in ASD, we utilized both group-level and subject-level analysis approaches to test for signs of atypical intracortical MC as estimated by T1w/T2w ratio. RESULTS: Group-level analyses showed no significant differences in average T1w/T2w ratio or its associations with age between groups, but revealed significant positive main effects of age bilaterally, with T1w/T2w ratio increasing with age across much of the cortex. In subject-level analyses, participants were classified into subgroups based on presence or absence of clusters of aberrant T1w/T2w ratio, and lower neuropsychological function was observed in the ASD subgroup with atypically high T1w/T2w ratio in spatially heterogeneous cortical regions. These differences were observed across several neuropsychological domains, including overall intellectual functioning, processing speed, and aspects of executive function. CONCLUSIONS: The group-level and subject-level approaches employed here demonstrate the value of examining inter-individual variability and provide important preliminary insights into relationships between brain structure and cognition in the second half of the lifespan in ASD, suggesting shared factors contributing to atypical intracortical myelin content and poorer cognitive outcomes for a subset of middle aged to older autistic adults. These atypicalities likely reflect diverse histories of neurodevelopmental deficits, and possible compensatory changes, compounded by processes of aging, and may serve as useful markers of vulnerability to further cognitive decline in older adults with ASD.

Reduced asymmetry of the hand knob area and decreased sensorimotor u-fiber connectivity in middle-aged adults with autism.

Individuals with autism spectrum disorder (ASD) frequently present with impairments in motor skills (e.g., limb coordination, handwriting and balance), which are observed across the lifespan but remain largely untreated. Many adults with ASD may thus experience adverse motor outcomes in aging, when physical decline naturally occurs. The 'hand knob' of the sensorimotor cortex is an area that is critical for motor control of the fingers and hands. However, this region has received little attention in ASD research, especially in adults after midlife. The hand knob area of the precentral (PrChand) and postcentral (PoChand) gyri was semi-manually delineated in 49 right-handed adults (25 ASD, 24 typical comparison [TC] participants, aged 41-70 years). Using multimodal (T1-weighted, diffusion-weighted, and resting-state functional) MRI, we examined the morphology, ipsilateral connectivity and laterality of these regions. We also explored correlations between hand knob measures with motor skills and autism symptoms, and between structural and functional connectivity measures. Bayesian analyses indicated moderate evidence of group effects with greater right PrChand volume and reduced leftward laterality of PrChand and PoChand volume in the ASD relative to TC group. Furthermore, the right PoC-PrChand u-fibers showed increased mean diffusivity in the ASD group. In the ASD group, right u-fiber volume positively correlated with corresponding functional connectivity but did not survive multiple comparisons correction. Correlations of hand knob measures and behavior were observed in the ASD group but did not survive multiple comparisons correction. Our findings suggest that morphological laterality and u-fiber connectivity of the sensorimotor network, putatively involved in hand motor/premotor function, may be diminished in middle-aged adults with ASD, perhaps rendering them more vulnerable to motor decline in old age. The altered morphology may relate to atypical functional motor asymmetries found in ASD earlier in life, possibly reflecting altered functional asymmetries over time.

Functional connectivity within an anxiety network and associations with anxiety symptom severity in middle-aged adults with and without autism.

Anxiety is highly prevalent in autism spectrum disorders (ASDs). However, few functional magnetic resonance imaging (fMRI) studies of ASDs have focused on anxiety (and fewer still on anxiety in middle-aged adults). Thus, relationships between atypical connectivity and anxiety in this population are poorly understood. The current study contrasted functional connectivity within anxiety network regions across adults (40-64 years) with and without autism, and tested for group by functional connectivity interactions on anxiety. Twenty-two adults with ASDs (16 males) and 26 typical control (TC) adults (22 males) completed the Beck Anxiety Inventory and a resting-state fMRI scan. An anxiety network consisting of 12 regions of interest was defined, based on a meta-analysis in TC individuals and two studies on anxiety in ASDs. We tested for main effects of group and group by anxiety interactions on connectivity within this anxiety network, controlling for head motion using ANCOVA. Results are reported at an FDR adjusted threshold of q < 0.1 (corrected) and p < 0.05 (uncorrected). Adults with ASDs showed higher anxiety and underconnectivity within the anxiety network, mostly involving bilateral insula. Connectivity within the anxiety network in the ASD group showed distinct relationships with anxiety symptoms that did not relate to ASD symptom severity. Functional connectivity involving the bilateral posterior insula was positively correlated with anxiety in the ASD (but not the TC) group. Increased anxiety in middle-aged adults with ASD is associated with atypical functional connectivity, predominantly involving bilateral insula. Results were not related to ASD symptom severity suggesting independence of anxiety-related effects. LAY SUMMARY: Anxiety is very common in adults with autism but the brain basis of this difference is not well understood. We compared functional connectivity between anxiety-related brain regions in middle-aged adults with and without autism. Adults with autism were more anxious and showed weaker functional connections between these regions. Some relationships between functional connectivity and higher anxiety were specific to the autism group. Results suggest that anxiety functions differently in autism.

Supplementary and Premotor Aspects of the Corticospinal Tract Show Links with Restricted and Repetitive Behaviors in Middle-Aged Adults with Autism Spectrum Disorder.

Individuals with autism spectrum disorder (ASD) show motor impairment into adulthood and risk decline during aging, but little is known about brain changes in aging adults with ASD. Few studies of ASD have directly examined the corticospinal tract (CST)-the major descending pathway in the brain responsible for voluntary motor behavior-outside its primary motor (M1) connections. In 26 middle-aged adults with ASD and 26 age-matched typical comparison participants, we used diffusion imaging to examine the microstructure and volume of CST projections from M1, dorsal premotor (PMd), supplementary motor area (SMA), and primary somatosensory (S1) cortices with respect to age. We also examined relationships between each CST sub-tract (-cst), motor skills, and autism symptoms. We detected no significant group or age-related differences in tracts extending from M1 or other areas. However, sub-tracts of the CST extending from secondary (but not primary) motor areas were associated with core autism traits. Increased microstructural integrity of left PMd-cst and SMA-cst were associated with less-severe restricted and repetitive behaviors (RRB) in the ASD group. These findings suggest that secondary motor cortical areas, known to be involved in selecting motor programs, may be implicated in cognitive motor processes underlying RRB in ASD.

Regionally decreased gyrification in middle-aged adults with autism spectrum disorders.

OBJECTIVE: To examine changing features of cortical morphology in middle-aged adults with autism spectrum disorders (ASDs) vs typical comparison (TC) participants, hypothesizing regionally decreased local gyrification index (lGI), given our previous findings of accelerated lGI decline during adolescence. METHODS: After quality assurance, T1-weighted MRI sequences from 20 participants with ASD and 21 TC participants (40-61 years) matched on age were analyzed. lGI, cortical thickness (CT), and surface area (SA) were measured with FreeSurfer version 5.3. Statistical analyses used a general linear model including age, nonverbal IQ, and total brain volume as covariates. Clusters of significant group effects were used as regions of interest for behavioral analyses. RESULTS: Clusters of decreased lGI were observed bilaterally in the ASD group with large effect sizes in insular and anterior cingulate (ACC), left postcentral, and middle frontal and right orbitofrontal and supramarginal regions. lGI was also shown to decline with age across groups in bilateral precentral and right supramarginal clusters. No significant group, age, or group-by-age interaction effects were observed for CT or SA in this age group. lGI showed a significant correlation with Social Responsiveness Scale total scores in a right caudal ACC cluster in the TC group only, while several correlations were found in the ASD group between executive function scores and clusters in the bilateral insula and right orbitofrontal cortex. CONCLUSION: The pattern of regionally decreased lGI observed here in middle-aged adults with ASDs is consistent with an abnormal trajectory of cortical folding changes across different stages of life in ASDs, as shown in previous studies.

Functional Connectivities Are More Informative Than Anatomical Variables in Diagnostic Classification of Autism.

Machine learning techniques have been implemented to reveal brain features that distinguish people with autism spectrum disorders (ASDs) from typically developing (TD) peers. However, it remains unknown whether different neuroimaging modalities are equally informative for diagnostic classification. We combined anatomical magnetic resonance imaging (aMRI), diffusion weighted imaging (DWI), and functional connectivity MRI (fcMRI) using conditional random forest (CRF) for supervised learning to compare how informative each modality was in diagnostic classification. In-house data (N = 93) included 47 TD and 46 ASD participants, matched on age, motion, and nonverbal IQ. Four main analyses consistently indicated that fcMRI variables were significantly more informative than anatomical variables from aMRI and DWI. This was found (1) when the top 100 variables from CRF (run separately in each modality) were combined for multimodal CRF; (2) when only 19 top variables reaching >67% accuracy in each modality were combined in multimodal CRF; and (3) when the large number of initial variables (before dimension reduction) potentially biasing comparisons in favor of fcMRI was reduced using a less granular region of interest scheme. Consistent superiority of fcMRI was even found (4) when 100 variables per modality were randomly selected, removing any such potential bias. Greater informative value of functional than anatomical modalities may relate to the nature of fcMRI data, reflecting more closely behavioral condition, which is also the basis of diagnosis, whereas brain anatomy may be more reflective of neurodevelopmental history.

The cingulum and cingulate U-fibers in children and adolescents with autism spectrum disorders.

The cingulum is the major fiber system connecting the cingulate and surrounding medial cortex and medial temporal lobe internally and with other brain areas. It is important for social and emotional functions related to core symptomatology in autism spectrum disorders (ASDs). While the cingulum has been examined in autism, the extensive system of cingulate U-fibers has not been studied. Using probabilistic tractography, we investigated white matter fibers of the cingulate cortex by distinguishing its deep intra-cingulate bundle (cingulum proper) and short rostral anterior, caudal anterior, posterior, and isthmus cingulate U-fibers in 61 ASD and 54 typically developing children and adolescents. Increased mean and radial diffusivity of the left cingulum proper was observed in the ASD group, replicating previous findings on the cingulum. For cingulate U-fibers, an atypical age-related decline in right posterior cingulate U-fiber volume was found in the ASD group, which appeared to be driven by an abnormally large volume in younger children. History of repetitive and restrictive behavior was negatively associated with right caudal anterior cingulate U-fiber volume, linking cingulate motor areas with neighboring gyri. Aberrant development in U-fiber volume of the right posterior cingulate gyrus may underlie functional abnormalities found in this region, such as in the default mode network.

Local Cortical Gyrification is Increased in Children With Autism Spectrum Disorders, but Decreases Rapidly in Adolescents.

Extensive MRI evidence indicates early brain overgrowth in autism spectrum disorders (ASDs). Local gyrification may reflect the distribution and timing of aberrant cortical expansion in ASDs. We examined MRI data from (Study 1) 64 individuals with ASD and 64 typically developing (TD) controls (7-19 years), and from (Study 2) an independent sample from the Autism Brain Imaging Data Exchange (n = 31/group). Local Gyrification Index (lGI), cortical thickness (CT), and surface area (SA) were measured. In Study 1, differences in lGI (ASD > TD) were found in left parietal and temporal and right frontal and temporal regions. lGI decreased bilaterally with age, but more steeply in ASD in left precentral, right lateral occipital, and middle frontal clusters. CT differed between groups in right perisylvian cortex (TD > ASD), but no differences were found for SA. Partial correlations between lGI and CT were generally negative, but associations were weaker in ASD in several clusters. Study 2 results were consistent, though less extensive. Altered gyrification may reflect unique information about the trajectory of cortical development in ASDs. While early overgrowth tends to be undetectable in later childhood in ASDs, findings may indicate that a trace of this developmental abnormality could remain in a disorder-specific pattern of gyrification.

Atypical Functional Connectivity of Amygdala Related to Reduced Symptom Severity in Children With Autism.

OBJECTIVE: Converging evidence indicates that brain abnormalities in autism spectrum disorders (ASDs) involve atypical network connectivity. Given the central role of social deficits in the ASD phenotype, this investigation examined functional connectivity of the amygdala-a brain structure critically involved in processing of social information-in children and adolescents with ASDs, as well as age-dependent changes and links with clinical symptoms. METHOD: Resting-state functional magnetic resonance imaging (rs-fMRI) data from 55 participants with ASDs and 50 typically developing (TD) controls, aged 7 to 17 years, were included. Groups were matched for age, gender, IQ, and head motion. Functional connectivity MRI (fcMRI) analysis was applied to examine intrinsic functional connectivity (iFC) of the amygdala, including cross-sectional tests of age-related changes. RESULTS: Direct between-group comparisons revealed reduced functional connectivity between bilateral amygdalae and left inferior occipital cortex, accompanied by greater connectivity between right amygdala and right sensorimotor cortex in the ASD group. This atypical pattern of amygdala connectivity was associated with decreased symptom severity and better overall functioning, as specifically seen in an ASD subgroup with the most atypical amygdala iFC but the least impaired social functioning. Age-related strengthening of amygdala-prefrontal connectivity, as observed in the TD group, was not detected in children with ASDs. CONCLUSION: Findings support aberrant network sculpting in ASDs, specifically atypical integration between amygdala and primary sensorimotor circuits. Paradoxical links between atypical iFC and behavioral measures suggest that abnormal amygdala functional connections may be compensatory in some individuals with ASDs.

White matter compromise in autism? Differentiating motion confounds from true differences in diffusion tensor imaging.

Common findings from diffusion tensor imaging (DTI) in autism spectrum disorder (ASD) include reduced fractional anisotropy (FA), and increased mean and radial diffusivity (MD, RD) of white matter tracts. However, findings may be confounded by head motion. We examined how group-level motion matching affects DTI comparisons between ASD and typically developing (TD) groups. We included 57 ASD and 50 TD participants, comparing three subsets at increasing levels of motion-matching stringency: full sample (FS); quality-controlled (QC); and quantitatively-matched (QM). Groups were compared on diffusivity measures using Tract-Based Spatial Statistics (TBSS) and probabilistic tractography. Two methods for estimating diffusivity were compared: dti-fit and restore. TBSS: In set FS, FA was reduced in the ASD compared to the TD group throughout the right hemisphere. This effect was less extensive in set QC and absent in set QM. However, effect sizes remained stable or increased with better quality-control in some regions. Tractography: In set QM, MD was significantly higher in ASD overall and RD was higher in bilateral ILF. Effects were more robust in QM than in FS or QC sets. Effect sizes in several tracts increased with stringent quality matching. Restore improved tensor estimates, with some increases in effect sizes, but did not fully compensate for reduced quality. Findings suggest that some previously reported DTI findings for ASD may have been confounded by motion. However, effects in the tightly matched subset indicate that tract-specific anomalies probably do exist in ASD. Our results highlight the need for careful quality-control and motion-matching. Autism Res 2017, 10: 1606-1620. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Reduced Hemispheric Asymmetry of White Matter Microstructure in Autism Spectrum Disorder.

OBJECTIVE: Many past studies have suggested atypical functional and anatomical hemispheric asymmetries in autism spectrum disorder (ASD). However, almost all of these have examined only language-related asymmetries. Here, we conduct a comprehensive investigation of microstructural asymmetries across a large number of fiber tracts in ASD. METHOD: We used diffusion tensor imaging for a comprehensive investigation of anatomical white matter asymmetries across the entire white matter skeleton, using tract-based spatial statistics in 41 children and adolescents with ASD and a matched group of 44 typically developing (TD) participants. RESULTS: We found significant asymmetries in the TD group, being rightward for fractional anisotropy and leftward for mean diffusivity (with concordant asymmetries for radial and axial diffusivity). These asymmetries were significantly reduced in the group with ASD: in whole brain analysis for fractional anisotropy, and in a region where several major association and projection tracts travel in close proximity within occipital white matter for mean diffusivity, axial diffusivity, and radial diffusivity. No correlations between global white matter asymmetry and age or socio-communicative abilities were detected. CONCLUSION: Our findings in TD children and adolescents can be interpreted as reflecting different processing modes (more integrative in the right and more specialized in the left hemisphere). These asymmetries and the "division of labor" between hemispheres implied by them appear to be diminished in autism spectrum disorder.

Restriction Spectrum Imaging As a Potential Measure of Cortical Neurite Density in Autism.

Autism postmortem studies have shown various cytoarchitectural anomalies in cortical and limbic areas including increased cell packing density, laminar disorganization, and narrowed minicolumns. However, there is little evidence on dendritic and axonal organization in ASD. Recent imaging techniques have the potential for non-invasive, in vivo studies of small-scale structure in the human brain, including gray matter. Here, Restriction Spectrum Imaging (RSI), a multi-shell diffusion-weighted imaging technique, was used to examine gray matter microstructure in 24 children with ASD (5 female) and 20 matched typically developing (TD) participants (2 female), ages 7-17 years. RSI extends the spherical deconvolution model to multiple length scales to characterize neurite density (ND) and organization. Measures were examined in 48 cortical regions of interest per hemisphere. To our knowledge, this is the first time that a multi-compartmental diffusion model has been applied to cortical gray matter in ASD. The ND measure detected robust age effects showing a significant positive relationship to age in all lobes except left temporal when groups were combined. Results were also suggestive of group differences (ASDTD) in bilateral parietal regions as well as widespread age effects were detected. Our findings support the value of multi-shell diffusion imaging for assays of cortical gray matter. This approach has the potential to add to postmortem literature, examining intracortical organization, intracortical axonal content, myelination, or caliber. Robust age effects further support the validity of the ND metric for in vivo examination of gray matter microstructure in ASD and across development. While diffusion MRI does not approach the precision of histological studies, in vivo imaging measures of microstructure can complement postmortem studies, by allowing access to large sample sizes, a whole-brain field of view, longitudinal designs, and combination with behavioral and functional assays. This makes multi-shell diffusion imaging a promising technique for understanding the underlying cytoarchitecture of the disorder.

Regional specificity of aberrant thalamocortical connectivity in autism.

Preliminary evidence suggests aberrant (mostly reduced) thalamocortical (TC) connectivity in autism spectrum disorder (ASD), but despite the crucial role of thalamus in sensorimotor functions and its extensive connectivity with cerebral cortex, relevant evidence remains limited. We performed a comprehensive investigation of region-specific TC connectivity in ASD. Resting-state functional MRI and diffusion tensor imaging (DTI) data were acquired for 60 children and adolescents with ASD (ages 7-17 years) and 45 age, sex, and IQ-matched typically developing (TD) participants. We examined intrinsic functional connectivity (iFC) and anatomical connectivity (probabilistic tractography) with thalamus, using 68 unilateral cerebral cortical regions of interest (ROIs). For frontal and parietal lobes, iFC was atypically reduced in the ASD group for supramodal association cortices, but was increased for cingulate gyri and motor cortex. Temporal iFC was characterized by overconnectivity for auditory cortices, but underconnectivity for amygdalae. Occipital iFC was broadly reduced in the ASD group. DTI indices (such as increased radial diffusion) for regions with group differences in iFC further indicated compromised anatomical connectivity, especially for frontal ROIs, in the ASD group. Our findings highlight the regional specificity of aberrant TC connectivity in ASD. Their overall pattern can be largely accounted for by functional overconnectivity with limbic and sensorimotor regions, but underconnectivity with supramodal association cortices. This could be related to comparatively early maturation of limbic and sensorimotor regions in the context of early overgrowth in ASD, at the expense of TC connectivity with later maturing cortical regions.

Reduced integration and differentiation of the imitation network in autism: A combined functional connectivity magnetic resonance imaging and diffusion-weighted imaging study.

OBJECTIVE: Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but few studies have integrated functional with structural connectivity measures. This multimodal investigation examined functional and structural connectivity of the imitation network in children and adolescents with ASD, and its links with clinical symptoms. METHODS: Resting state functional magnetic resonance imaging and diffusion-weighted imaging were performed in 35 participants with ASD and 35 typically developing controls, aged 8 to 17 years, matched for age, gender, intelligence quotient, and head motion. RESULTS: Within-network analyses revealed overall reduced functional connectivity (FC) between distributed imitation regions in the ASD group. Whole brain analyses showed that underconnectivity in ASD occurred exclusively in regions belonging to the imitation network, whereas overconnectivity was observed between imitation nodes and extraneous regions. Structurally, reduced fractional anisotropy and increased mean diffusivity were found in white matter tracts directly connecting key imitation regions with atypical FC in ASD. These differences in microstructural organization of white matter correlated with weaker FC and greater ASD symptomatology. INTERPRETATION: Findings demonstrate atypical connectivity of the brain network supporting imitation in ASD, characterized by a highly specific pattern. This pattern of underconnectivity within, but overconnectivity outside the functional network is in contrast with typical development and suggests reduced network integration and differentiation in ASD. Our findings also indicate that atypical connectivity of the imitation network may contribute to ASD clinical symptoms, highlighting the role of this fundamental social cognition ability in the pathophysiology of ASD.

Corticospinal tract anatomy and functional connectivity of primary motor cortex in autism.

OBJECTIVE: Growing evidence indicates that autism spectrum disorder (ASD) stems from abnormal structural and functional connectivity of neural networks. Although diagnostic symptoms are sociocommunicative, motor-related functions (beyond repetitive mannerisms) are also impaired. However, evidence on connectivity at the level of basic motor execution is limited, which we address here. METHOD: We compared right-handed children and adolescents (aged 7-18 years) with ASD (n = 44) to matched typically developing participants (TD, n = 36) using magnetic resonance imaging (MRI). Diffusion-weighted imaging and probabilistic tractography measured microstructure of the corticospinal tract (CST). Intrinsic functional connectivity MRI examined whole-brain voxelwise correlations, both with identical precentral gyrus (PCG) seeds. RESULTS: In the group with ASD, radial and mean diffusivity were increased bilaterally in the CST, particularly in superior segments, and a leftward asymmetry of CST volume detected in the TD group was reversed. Functionally, overconnectivity was found for both left and right PCG with prefrontal, parietal, medial occipital, and cingulate cortices. The group with ASD also showed significantly reduced asymmetry of functional connectivity for both left and right PCG seeds. Finally, in the group with ASD, significant correlations were found for functional overconnectivity of the right PCG seed with anisotropy and mean diffusivity in the right CST. CONCLUSION: The findings, implicating both functional and anatomical connectivity of the primary motor cortex, suggest that network anomalies in ASD go well beyond sociocommunicative domains, affecting basic motor execution. They also suggest that even in right-handed adolescents with ASD, typical left hemisphere dominance is reduced, both anatomically and functionally, with an unusual degree of right hemisphere motor participation.

Longitudinal magnetic resonance imaging study of cortical development through early childhood in autism.

Cross-sectional magnetic resonance imaging (MRI) studies have long hypothesized that the brain in children with autism undergoes an abnormal growth trajectory that includes a period of early overgrowth; however, this has never been confirmed by a longitudinal study. We performed the first longitudinal study of brain growth in toddlers at the time symptoms of autism are becoming clinically apparent using structural MRI scans at multiple time points beginning at 1.5 years up to 5 years of age. We collected 193 scans on 41 toddlers who received a confirmed diagnosis of autistic disorder at approximately 48 months of age and 44 typically developing controls. By 2.5 years of age, both cerebral gray and white matter were significantly enlarged in toddlers with autistic disorder, with the most severe enlargement occurring in frontal, temporal, and cingulate cortices. In the longitudinal analyses, which we accounted for age and gender effect, we found that all regions (cerebral gray, cerebral white, frontal gray, temporal gray, cingulate gray, and parietal gray) except occipital gray developed at an abnormal growth rate in toddlers with autistic disorder that was mainly characterized by a quadratic age effect. Females with autistic disorder displayed a more pronounced abnormal growth profile in more brain regions than males with the disorder. Given that overgrowth clearly begins before 2 years of age, future longitudinal studies would benefit from inclusion of even younger populations as well as further characterization of genetic and other biomarkers to determine the underlying neuropathological processes causing the onset of autistic symptoms.

Monozygotic twins with Asperger syndrome: differences in behaviour reflect variations in brain structure and function.

A pair of monozygotic twins discordant for symptoms of Asperger syndrome was evaluated at the age of 13.45 years using psychometric, morphometric, behavioural, and functional imaging methods. The lower-functioning twin had a smaller brain overall, a smaller right cerebellum, and a disproportionately large left frontal lobe, and manifested almost no differential activation between distractors of high and low-congruence with target visual stimuli. The higher-functioning twin manifested a typically autistic pattern of anterior deactivation and posterior hyperactivation in response to incongruent distractors, overlaid with a typically normal pattern of activation of superior frontal cortex. The morphometric results are consistent with known correlations between brain structure and behaviour in autism, and the physiological results suggest correspondences between structure and function.

Localized enlargement of the frontal cortex in early autism.

BACKGROUND: Evidence from behavioral, imaging, and postmortem studies indicates that the frontal lobe, as well as other brain regions such as the cerebellum and limbic system, develops abnormally in children with autism. It is not yet clear to what extent the frontal lobe is affected; that is, whether all regions of frontal cortex show the same signs of structural maldevelopment. METHODS: In the present study, we measured cortical volume in four subregions of the frontal cortex in 2-year-old to 9-year-old boys with autism and normal control boys. RESULTS: The dorsolateral region showed a reduced age effect in patients when compared with control subjects, with a predicted 10% increase in volume from 2 years of age to 9 years of age compared with a predicted 48% increase for control subjects. In a separate analysis, dorsolateral and medial frontal regions were significantly enlarged in patients aged 2 to 5 years compared with control subjects of the same age, but the precentral gyrus and orbital cortex were not. CONCLUSIONS: These data indicate regional variation in the degree of frontocortical overgrowth with a possible bias toward later developing or association areas. Possible mechanisms for these regional differences are discussed.

Outcome classification of preschool children with autism spectrum disorders using MRI brain measures.

OBJECTIVE: To test the hypothesis that a combination of magnetic resonance imaging (MRI) brain measures obtained during early childhood distinguish children with autism spectrum disorders (ASD) from typically developing children and is associated with functional outcome. METHOD: Quantitative MRI technology was used to measure gray and white matter volumes (cerebrum and cerebellum), total brain volume, and the area of the cerebellar vermis in 52 boys with a provisional diagnosis of autism (aged 1.9-5.2 years) and 15 typically developing young children (aged 1.7-5.2 years). Diagnostic confirmation and cognitive outcome data were obtained after the children reached 5 years of age. RESULTS: A discriminant function analysis of the MRI brain measures correctly classified 95.8% of the ASD cases and 92.3% of the control cases. This set of variables also correctly classified 85% of the ASD cases as lower functioning and 68% of the ASD cases as higher functioning. CONCLUSIONS: These results indicate that variability in cerebellar and cerebral size is correlated with diagnostic and functional outcome in very young children with ASD.