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Supplemental material, sj-docx-1-jop-10.1177_02698811221092509 for Differences in social brain function in autism spectrum disorder are linked to the serotonin transporter: A randomised placebo-controlled single-dose crossover trial by Nichol ML Wong, Ottavia Dipasquale, Federico Turkheimer, James L Findon, Robert H Wichers, Mihail Dimitrov, Clodagh M Murphy, Vladimira Stoencheva, Dene M Robertson, Declan G Murphy, Eileen Daly and Grainne M McAlonan in Journal of Psychopharmacology

Supplemental material, sj-docx-1-aut-10.1177_13623613221081343 for Adults with autism spectrum disorder and the criminal justice system: An investigation of prevalence of contact with the criminal justice system, risk factors and sex differences in a specialist assessment service by Charlotte E Blackmore, Emma L Woodhouse, Nicola Gillan, Ellie Wilson, Karen L Ashwood, Vladimira Stoencheva, Alexandra Nolan, Grainne M McAlonan, Dene M Robertson, Susannah Whitwell, Quinton Deeley, Michael C Craig, Janneke Zinkstok, Rob Wichers, Debbie Spain, Ged Roberts, Declan GM Murphy, Clodagh M Murphy and Eileen Daly in Autism

The original version of this Article contained an error in Fig. 1, in which the images shown in panel 1b were inadvertently duplicated from those in panel 1a. This error was introduced during the preparation of figures during the revision process. This has been corrected in both the PDF and HTML versions of the Article.

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10-6). Novel reciprocal case-control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present.

Additional file 1. Supplementary material.

[Importance] Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood., [Objective] To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia., [Design, Setting, and Participants] Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244., [Main Outcomes and Measures] Interregional profiles of group difference in cortical thickness between cases and controls., [Results] A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders., [Conclusions and Relevance] In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.

Excitation-inhibition (E:I) imbalance is theorized as an important pathophysiological mechanism in autism. Autism affects males more frequently than females and sex-related mechanisms (e.g., X-linked genes, androgen hormones) can influence E:I balance. This suggests that E:I imbalance may affect autism differently in males versus females. With a combination of in-silico modeling and in-vivo chemogenetic manipulations in mice, we first show that a time-series metric estimated from fMRI BOLD signal, the Hurst exponent (H), can be an index for underlying change in the synaptic E:I ratio. In autism we find that H is reduced, indicating increased excitation, in the medial prefrontal cortex (MPFC) of autistic males but not females. Increasingly intact MPFC H is also associated with heightened ability to behaviorally camouflage social-communicative difficulties, but only in autistic females. This work suggests that H in BOLD can index synaptic E:I ratio and that E:I imbalance affects autistic males and females differently.

Additional file 1: Supplementary Methods. 1. Participant Demographics and Exclusion Criteria. 2. Calculation of ADOS Calibrated Severity Score (CSS). 3. MRI Data Quality Assessment, Exclusion of Scans, and Manual Edits. 4. Canonical Correlation Analysis (CCA). 5. Robustness of the results across feature selection algorithms. Supplementary Tables S1. Post-hoc multiple comparisons of means. Supplementary Table S2. Sample demographics after matching for age and gender. Supplementary Table S3. Clusters with significantly increased and decreased cortical volume (CV), surface area (SA), and cortical thickness (CT) for the main effect of 22q11.2DS. Supplementary Table S4. Clusters with significantly increased and decreased cortical volume (CV), surface area (SA), and cortical thickness (CT) for the main effect of ASD. Supplementary Table S5. Clusters with a significant 22q11.2DS-by-ASD interaction effect in cortical volume (CV) and surface area (SA). Supplementary Figure S1. Between-group comparison for 22q11.2DS compared to typically developing Controls. Supplementary Figure S2. Between-group comparison for idiopathic ASD compared to typically developing Controls. Supplementary Figure S3. Un-thresholded Results for the Categorical Analyses. Supplementary Figure S4. Effect Sizes for Categorial results. Supplementary Figure S5. (In)Homogeneity of Variance between idiopathic ASD and 22q11.ASD individuals. Supplementary Figure S6. Categorical analyses corrected for age and gender. Supplementary Figure S7. Schematic Overview of the Methodology behind the Canonical Correlation Analysis (CCA). Supplementary Figure S8. Reliability of the results across feature selection algorithms. Supplementary Figure S9. Boxplots for the significant 22q11.2DS-by-ASD Interaction Clusters. Supplementary Figure S10. Categorical 22q11.2DS-by-ASD Interaction Effect when covarying for repetitive symptoms. Supplementary Figure S11. Distribution of SRS subdomain and total scores across groups

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) often co-occur and share neurocognitive deficits. One such shared impairment is in duration discrimination. However, no studies using functional magnetic resonance imaging (fMRI) have investigated whether these duration discrimination deficits are underpinned by the same or different underlying neurofunctional processes. In this study, we used fMRI to compare the neurofunctional correlates of duration discrimination between young adult males with ASD (n = 23), ADHD (n = 25), the comorbid condition of ASD+ADHD (n = 24), and typical development (TD, n = 26) using both region of interest (ROI) and whole brain analyses. Both the ROI and the whole-brain analyses showed that the comorbid ASD+ADHD group compared to controls, and for the ROI analysis relative to the other patient groups, had significant under-activation in right inferior frontal cortex (IFG) a key region for duration discrimination that is typically under-activated in boys with ADHD. The findings show that in young adult males with pure ASD, pure ADHD and comorbid ASD+ADHD with no intellectual disability, only the comorbid group demonstrates neurofunctional deficits in a typical duration discrimination region.

Background\ud The aim of the current paper was to provide the first comparison of computational mechanisms and neurofunctional substrates in adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD) and adolescents with Obsessive-Compulsive Disorder (OCD) during decision-making under ambiguity.\ud \ud Methods\ud Sixteen boys with ADHD, 20 boys with OCD and 20 matched controls (aged 12-18) completed a functional magnetic resonance imaging (fMRI) version of the Iowa gambling task. Brain activation was compared between groups using three-way ANCOVA. Hierarchical Bayesian analysis was used to compare computational modelling parameters between groups.\ud \ud Results\ud Patient groups shared reduced choice consistency and relied less on reinforcement learning during decision-making relative to controls, while adolescents with ADHD alone demonstrated increased reward sensitivity. During advantageous choices, both disorders shared underactivation in ventral striatum, while OCD patients showed disorder-specific underactivation in ventromedial orbitofrontal cortex (vmOFC). During outcome evaluation, shared underactivation to losses in patients relative to controls was found in medial prefrontal cortex (MPFC) and shared underactivation to wins was found in left putamen/caudate. ADHD boys showed disorder-specific dysfunction in right putamen/caudate, which was activated more to losses in patients with ADHD, but activated more to wins in controls.\ud \ud Conclusions\ud The findings suggest shared deficits in using learned reward expectancies to guide decision-making, as well as shared dysfunction in medial-fronto-striato-limbic brain regions. However, findings of unique dysfunction in vmOFC in OCD and in right putamen in ADHD indicate additional, disorder-specific abnormalities, and extend similar findings from inhibitory control tasks in the disorders to the domain of decision-making under ambiguity.

It is unknown whether sex influences the diagnostic evaluation of autism spectrum disorder, or whether male and female adults within the spectrum have different symptom profiles. This study reports sex differences in clinical outcomes for 1244 adults (935 males and 309 females) referred for autism spectrum disorder assessment. Significantly, more males (72%) than females (66%) were diagnosed with an autism spectrum disorder of any subtype (x2 = 4.09; p = 0.04). In high-functioning autism spectrum disorder adults (IQ > 70; N = 827), there were no significant sex differences in severity of socio-communicative domain symptoms. Males had significantly more repetitive behaviours/restricted interests than females (p = 0.001, d = 0.3). A multivariate analysis of variance indicated a significant interaction between autism spectrum disorder subtype (full-autism spectrum disorder/partial-autism spectrum disorder) and sex: in full-autism spectrum disorder, males had more severe socio-communicative symptoms than females; for partial-autism spectrum disorder, the reverse was true. There were no sex differences in prevalence of co-morbid psychopathologies. Sex influenced diagnostic evaluation in a clinical sample of adults with suspected autism spectrum disorder. The sexes may present with different manifestations of the autism spectrum disorder phenotype and differences vary by diagnostic subtype. Understanding and awareness of adult female repetitive behaviours/restricted interests warrant attention and sex-specific diagnostic assessment tools may need to be considered.

Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) often share phenotypes of repetitive behaviors, possibly underpinned by abnormal decision-making. To compare neural correlates underlying decision-making between these disorders, brain activation of boys with ASD (N = 24), OCD (N = 20) and typically developing controls (N = 20) during gambling was compared, and computational modeling compared performance. Patients were unimpaired on number of risky decisions, but modeling showed that both patient groups had lower choice consistency and relied less on reinforcement learning compared to controls. ASD individuals had disorder-specific choice perseverance abnormalities compared to OCD individuals. Neurofunctionally, ASD and OCD boys shared dorsolateral/inferior frontal underactivation compared to controls during decision-making. During outcome anticipation, patients shared underactivation compared to controls in lateral inferior/orbitofrontal cortex and ventral striatum. During reward receipt, ASD boys had disorder-specific enhanced activation in inferior frontal/insular regions relative to OCD boys and controls. Results showed that ASD and OCD individuals shared decision-making strategies that differed from controls to achieve comparable performance to controls. Patients showed shared abnormalities in lateral-(orbito)fronto-striatal reward circuitry, but ASD boys had disorder-specific lateral inferior frontal/insular overactivation, suggesting that shared and disorder-specific mechanisms underpin decision-making in these disorders. Findings provide evidence for shared neurobiological substrates that could serve as possible future biomarkers.

People with autism spectrum disorder (ASD) have poor decision-making and temporal foresight. This may adversely impact on their everyday life, mental health, and productivity. However, the neural substrates underlying poor choice behavior in people with ASD, or its' neurofunctional development from childhood to adulthood, are unknown. Despite evidence of atypical structural brain development in ASD, investigation of functional brain maturation in people with ASD is lacking. This cross-sectional developmental fMRI study investigated the neural substrates underlying performance on a temporal discounting (TD) task in 38 healthy (11-35 years old) male adolescents and adults with ASD and 40 age, sex, and IQ-matched typically developing healthy controls. Most importantly, we assessed group differences in the neurofunctional maturation of TD across childhood and adulthood. Males with ASD had significantly poorer task performance and significantly lower brain activation in typical regions that mediate TD for delayed choices, in predominantly right hemispheric regions of ventrolateral/dorsolateral prefrontal cortices, ventromedial prefrontal cortex, striatolimbic regions, and cerebellum. Importantly, differential activation in ventromedial frontal cortex and cerebellum was associated with abnormal functional brain maturation; controls, in contrast to people with ASD, showed progressively increasing activation with increasing age in these regions; which furthermore was associated with performance measures and clinical ASD measures (stereotyped/restricted interests). Findings provide first cross-sectional evidence that reduced activation of TD mediating brain regions in people with ASD during TD is associated with abnormal functional brain development in these regions between childhood and adulthood, and this is related to poor task performance and clinical measures of ASD. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

IMPORTANCE: Autism spectrum disorder (ASD) is 2 to 5 times more common in male individuals than in female individuals. While the male preponderant prevalence of ASD might partially be explained by sex differences in clinical symptoms, etiological models suggest that the biological male phenotype carries a higher intrinsic risk for ASD than the female phenotype. To our knowledge, this hypothesis has never been tested directly, and the neurobiological mechanisms that modulate ASD risk in male individuals and female individuals remain elusive. OBJECTIVES: To examine the probability of ASD as a function of normative sex-related phenotypic diversity in brain structure and to identify the patterns of sex-related neuroanatomical variability associated with low or high probability of ASD. DESIGN, SETTING, AND PARTICIPANTS: This study examined a cross-sectional sample of 98 right-handed, high-functioning adults with ASD and 98 matched neurotypical control individuals aged 18 to 42 years. A multivariate probabilistic classification approach was used to develop a predictive model of biological sex based on cortical thickness measures assessed via magnetic resonance imaging in neurotypical controls. This normative model was subsequently applied to individuals with ASD. The study dates were June 2005 to October 2009, and this analysis was conducted between June 2015 and July 2016. MAIN OUTCOMES AND MEASURES: Sample and population ASD probability estimates as a function of normative sex-related diversity in brain structure, as well as neuroanatomical patterns associated with low or high ASD probability in male individuals and female individuals. RESULTS: Among the 98 individuals with ASD, 49 were male and 49 female, with a mean (SD) age of 26.88 (7.18) years. Among the 98 controls, 51 were male and 47 female, with a mean (SD) age of 27.39 (6.44) years. The sample probability of ASD increased significantly with predictive probabilities for the male neuroanatomical brain phenotype. For example, biological female individuals with a more male-typic pattern of brain anatomy were significantly (ie, 3 times) more likely to have ASD than biological female individuals with a characteristically female brain phenotype (P = .72 vs .24, respectively; χ21 = 20.26; P < .001; difference in P values, 0.48; 95% CI, 0.29-0.68). This finding translates to an estimated variability in population prevalence from 0.2% to 1.3%, respectively. Moreover, the patterns of neuroanatomical variability carrying low or high ASD probability were sex specific (eg, in inferior temporal regions, where ASD has different neurobiological underpinnings in male individuals and female individuals). CONCLUSIONS AND RELEVANCE: These findings highlight the need for considering normative sex-related phenotypic diversity when determining an individual's risk for ASD and provide important novel insights into the neurobiological mechanisms mediating sex differences in ASD prevalence.

Autism spectrum conditions (ASC) are more prevalent in males than females. The biological basis of this difference remains unclear. It has been postulated that one of the primary causes of ASC is a partial disconnection of the frontal lobe from higher-order association areas during development (that is, a frontal 'disconnection syndrome'). Therefore, in the current study we investigated whether frontal connectivity differs between males and females with ASC. We recruited 98 adults with a confirmed high-functioning ASC diagnosis (61 males: aged 18-41 years; 37 females: aged 18-37 years) and 115 neurotypical controls (61 males: aged 18-45 years; 54 females: aged 18-52 years). Current ASC symptoms were evaluated using the Autism Diagnostic Observation Schedule (ADOS). Diffusion tensor imaging was performed and fractional anisotropy (FA) maps were created. Mean FA values were determined for five frontal fiber bundles and two non-frontal fiber tracts. Between-group differences in mean tract FA, as well as sex-by-diagnosis interactions were assessed. Additional analyses including ADOS scores informed us on the influence of current ASC symptom severity on frontal connectivity. We found that males with ASC had higher scores of current symptom severity than females, and had significantly lower mean FA values for all but one tract compared to controls. No differences were found between females with or without ASC. Significant sex-by-diagnosis effects were limited to the frontal tracts. Taking current ASC symptom severity scores into account did not alter the findings, although the observed power for these analyses varied. We suggest these findings of frontal connectivity abnormalities in males with ASC, but not in females with ASC, have the potential to inform us on some of the sex differences reported in the behavioral phenotype of ASC.

IMPORTANCE Autism spectrum disorder (ASD) is 2 to 5 times more common in male individuals than in female individuals. While the male preponderant prevalence of ASD might partially be explained by sex differences in clinical symptoms, etiological models suggest that the biological male phenotype carries a higher intrinsic risk for ASD than the female phenotype. To our knowledge, this hypothesis has never been tested directly, and the neurobiological mechanisms that modulate ASD risk in male individuals and female individuals remain elusive. OBJECTIVES To examine the probability of ASD as a function of normative sex-related phenotypic diversity in brain structure and to identify the patterns of sex-related neuroanatomical variability associated with low or high probability of ASD. DESIGN, SETTING, AND PARTICIPANTS This study examined a cross-sectional sample of 98 right-handed, high-functioning adults with ASD and 98 matched neurotypical control individuals aged 18 to 42 years. A multivariate probabilistic classification approach was used to develop a predictive model of biological sex based on cortical thickness measures assessed via magnetic resonance imaging in neurotypical controls. This normative model was subsequently applied to individuals with ASD. The study dates were June 2005 to October 2009, and this analysis was conducted between June 2015 and July 2016. MAIN OUTCOMES AND MEASURES Sample and population ASD probability estimates as a function of normative sex-related diversity in brain structure, as well as neuroanatomical patterns associated with low or high ASD probability in male individuals and female individuals. RESULTS Among the 98 individuals with ASD, 49 were male and 49 female, with a mean (SD) age of 26.88 (7.18) years. Among the 98 controls, 51 were male and 47 female, with a mean (SD) age of 27.39 (6.44) years. The sample probability of ASD increased significantly with predictive probabilities for the male neuroanatomical brain phenotype. For example, biological female individuals with a more male-typic pattern of brain anatomy were significantly (ie, 3 times) more likely to have ASD than biological female individuals with a characteristically female brain phenotype (P =.72 vs.24, respectively; χ1 2= 20.26; P

Atypical cortical organization and reduced integrity of the gray-white matter boundary have been reported by postmortem studies in individuals with autism spectrum disorder (ASD). However, there are no in vivo studies that examine these particular features of cortical organization in ASD. Hence, we used structural magnetic resonance imaging to examine differences in tissue contrast between gray and white matter in 98 adults with ASD and 98 typically developing controls, to test the hypothesis that individuals with ASD have significantly reduced tissue contrast. More specifically, we examined contrast as a percentage between gray and white matter tissue signal intensities (GWPC) sampled at the gray-white matter boundary, and across different cortical layers. We found that individuals with ASD had significantly reduced GWPC in several clusters throughout the cortex (cluster, P < 0.05). As expected, these reductions were greatest when tissue intensities were sampled close to gray-white matter interface, which indicates a less distinct gray-white matter boundary in ASD. Our in vivo findings of reduced GWPC in ASD are therefore consistent with prior postmortem findings of a less well-defined gray-white matter boundary in ASD. Taken together, these results indicate that GWPC might be utilized as an in vivo proxy measure of atypical cortical microstructural organization in future studies. 27 2 877 887 PT: J

Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) often share phenotypes of repetitive behaviors, possibly underpinned by abnormal decision-making. To compare neural correlates underlying decision-making between these disorders, brain activation of boys with ASD (N = 24), OCD (N = 20) and typically developing controls (N = 20) during gambling was compared, and computational modeling compared performance. Patients were unimpaired on number of risky decisions, but modeling showed that both patient groups had lower choice consistency and relied less on reinforcement learning compared to controls. ASD individuals had disorder-specific choice perseverance abnormalities compared to OCD individuals. Neurofunctionally, ASD and OCD boys shared dorsolateral/inferior frontal underactivation compared to controls during decision-making. During outcome anticipation, patients shared underactivation compared to controls in lateral inferior/orbitofrontal cortex and ventral striatum. During reward receipt, ASD boys had disorder-specific enhanced activation in inferior frontal/insular regions relative to OCD boys and controls. Results showed that ASD and OCD individuals shared decision-making strategies that differed from controls to achieve comparable performance to controls. Patients showed shared abnormalities in lateral-(orbito)fronto-striatal reward circuitry, but ASD boys had disorder-specific lateral inferior frontal/insular overactivation, suggesting that shared and disorder-specific mechanisms underpin decision-making in these disorders. Findings provide evidence for shared neurobiological substrates that could serve as possible future biomarkers.

Neuroimaging studies have reported structural and physiological differences that could help understand the causes and development of Autism Spectrum Disorder (ASD). Many of them rely on multisite designs, with the recruitment of larger samples increasing statistical power. However, recent large-scale studies have put some findings into question, considering the results to be strongly dependent on the database used, and demonstrating the substantial heterogeneity within this clinically defined category. One major source of variance may be the acquisition of the data in multiple centres. In this work we analysed the differences found in the multisite, multi-modal neuroimaging database from the UK Medical Research Council Autism Imaging Multicentre Study (MRC AIMS) in terms of both diagnosis and acquisition sites. Since the dissimilarities between sites were higher than between diagnostic groups, we developed a technique called Significance Weighted Principal Component Analysis (SWPCA) to reduce the undesired intensity variance due to acquisition site and to increase the statistical power in detecting group differences. After eliminating site-related variance, statistically significant group differences were found, including Broca's area and the temporo-parietal junction. However, discriminative power was not sufficient to classify diagnostic groups, yielding accuracies results close to random. Our work supports recent claims that ASD is a highly heterogeneous condition that is difficult to globally characterize by neuroimaging, and therefore different (and more homogenous) subgroups should be defined to obtain a deeper understanding of ASD. Hum Brain Mapp 38:1208–1223, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc. 38 3 1208 1223 Export Date: 17 July 2017

Background Fine motor skill impairments are common in autism spectrum disorder (ASD), significantly affecting quality of life. Sensory inputs reaching the primary motor cortex (M1) from the somatosensory cortex (S1) are likely involved in fine motor skill and specifically motor learning. However, the role of these connections has not been directly investigated in humans. This study aimed to investigate, for the first time, the role of the S1-M1 connections in healthy subjects in vivo and whether microstructural alterations are associated with motor impairment in ASD. Methods Sixty right-handed neurotypical adult men aged 18 to 45 years, and 60 right-handed age- and sex-matched subjects diagnosed with ASD underwent fine motor skill assessment and scanning with diffusion tensor imaging (DTI). The streamlines of the hand region connecting S1-M1 of the motor-sensory homunculus were virtually dissected using TrackVis, and diffusion properties were extracted. The face/tongue region connections were used as control tracts. Results The ASD group displayed lower motor performances and altered DTI measurements of the hand-region connection. Behavioral performance correlated with hand-region DTI measures in both groups, but not with the face/tongue connections, indicating anatomical specificity. There was a left-hemisphere association of motor ability in the control group and an atypical rightward shift in the ASD group. Conclusions These findings suggest that direct interaction between S1 and M1 may contribute to the human ability to precisely interact with and manipulate the environment. Because electrophysiological evidence indicates that these connections may underpin long-term potentiation in M1, our findings may lead to novel therapeutic treatments for motor skill disorders. © 2016 Society of Biological Psychiatry 81 3 211 219 Export Date: 17 July 2017

Neuroimaging studies have reported structural and physiological differences that could help understand the causes and development of Autism Spectrum Disorder (ASD). Many of them rely on multisite designs, with the recruitment of larger samples increasing statistical power. However, recent large-scale studies have put some findings into question, considering the results to be strongly dependent on the database used, and demonstrating the substantial heterogeneity within this clinically defined category. One major source of variance may be the acquisition of the data in multiple centres. In this work we analysed the differences found in the multisite, multi-modal neuroimaging database from the UK Medical Research Council Autism Imaging Multicentre Study (MRC AIMS) in terms of both diagnosis and acquisition sites. Since the dissimilarities between sites were higher than between diagnostic groups, we developed a technique called Significance Weighted Principal Component Analysis (SWPCA) to reduce the undesired intensity variance due to acquisition site and to increase the statistical power in detecting group differences. After eliminating site-related variance, statistically significant group differences were found, including Broca's area and the temporo-parietal junction. However, discriminative power was not sufficient to classify diagnostic groups, yielding accuracies results close to random. Our work supports recent claims that ASD is a highly heterogeneous condition that is difficult to globally characterize by neuroimaging, and therefore different (and more homogenous) subgroups should be defined to obtain a deeper understanding of ASD. Hum Brain Mapp 38:1208–1223, 2017.

Individuals affected by autism spectrum conditions (ASC) are considerably heterogeneous. Novel approaches are needed to parse this heterogeneity to enhance precision in clinical and translational research. Applying a clustering approach taken from genomics and systems biology on two large independent cognitive datasets of adults with and without ASC (n = 694; n = 249), we find replicable evidence for 5 discrete ASC subgroups that are highly differentiated in item-level performance on an explicit mentalizing task tapping ability to read complex emotion and mental states from the eye region of the face (Reading the Mind in the Eyes Test; RMET). Three subgroups comprising 45–62% of ASC adults show evidence for large impairments (Cohen’s d = −1.03 to −11.21), while other subgroups are effectively unimpaired. These findings delineate robust natural subdivisions within the ASC population that may allow for more individualized inferences and accelerate research towards precision medicine goals.

It has been postulated that autism spectrum disorder is underpinned by an 'atypical connectivity' involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a 'whole brain' non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate - predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these results suggest that autism spectrum disorder is a condition linked to aberrant developmental trajectories of the frontal networks that persist in adult life.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, which is accompanied by differences in gray matter neuroanatomy and white matter connectivity. However, it is unknown whether these differences are linked or reflect independent aetiologies. Using a multimodal neuroimaging approach, we therefore examined 51 male adults with ASD and 48 neurotypical controls to investigate the relationship between gray matter local gyrification (lGI) and white matter diffusivity in associated fiber tracts. First, ASD individuals had a significant increase in gyrification around the left pre-and post-central gyrus. Second, white matter fiber tracts originating and/or terminating in the cluster of increased lGI had a significant increase in axial diffusivity. This increase in diffusivity was predominantly observed in tracts in close proximity to the cortical sheet. Last, we demonstrate that the increase in lGI was significantly correlated with increased diffusivity of short tracts. This relationship was not significantly modulated by a main effect of group (i.e., ASD), which was more closely associated with gray matter gyrification than white matter diffusivity. Our findings suggest that differences in gray matter neuroanatomy and white matter connectivity are closely linked, and may reflect common rather than distinct aetiological pathways. © The Author 2016. 26 7 3297 3309 Cited By :2; Export Date: 17 July 2017

It has been postulated that autism spectrum disorder is underpinned by an 'atypical connectivity' involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a 'whole brain' non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate - predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these results suggest that autism spectrum disorder is a condition linked to aberrant developmental trajectories of the frontal networks that persist in adult life. © 2016 The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. 139 2 616 630 Cited By :7; Export Date: 17 July 2017

It has been postulated that autism spectrum disorder is underpinned by an 'atypical connectivity' involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a 'whole brain' non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate - predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these results suggest that autism spectrum disorder is a condition linked to aberrant developmental trajectories of the frontal networks that persist in adult life.

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions characterized by atypical structural and functional brain connectivity. Complex network analysis has been mainly used to describe altered network-level organization for functional systems and white matter tracts in ASD. However, atypical functional and structural connectivity are likely to be also linked to abnormal development of the correlated structure of cortical gray matter. Such covariations of gray matter are particularly well suited to the investigation of the complex cortical pathology of ASD, which is not confined to isolated brain regions but instead acts at the systems level. In this study, we examined network centrality properties of gray matter networks in adults with ASD (n = 84) and neurotypical controls (n = 84) using graph theoretical analysis. We derived a structural covariance network for each group using interregional correlation matrices of cortical volumes extracted from a surface-based parcellation scheme containing 68 cortical regions. Differences between groups in closeness network centrality measures were evaluated using permutation testing. We identified several brain regions in the medial frontal, parietal and temporo-occipital cortices with reductions in closeness centrality in ASD compared to controls. We also found an association between an increased number of autistic traits and reduced centrality of visual nodes in neurotypicals. Our study shows that ASD are accompanied by atypical organization of structural covariance networks by means of a decreased centrality of regions relevant for social and sensorimotor processing. These findings provide further evidence for the altered network-level connectivity model of ASD. © 2015 Elsevier Ltd. 69 142 149 Cited By :2; Export Date: 17 July 2017

BackgroundIncreasing evidence suggests that autism is associated with abnormal white-matter (WM) anatomy and impaired brain ‘connectivity’. While myelin plays a critical role in synchronized brain communication, its aetiological role in autistic symptoms has only been indirectly addressed by WM volumetric, relaxometry and diffusion tensor imaging studies. A potentially more specific measure of myelin content, termed myelin water fraction (MWF), could provide improved sensitivity to myelin alteration in autism.MethodWe performed a cross-sectional imaging study that compared 14 individuals with autism and 14 age- and IQ-matched controls. T1 relaxation times (T1), T2 relaxation times (T2) and MWF values were compared between autistic subjects, diagnosed using the Autism Diagnostic Interview – Revised (ADI-R), with current symptoms assessed using the Autism Diagnostic Observation Schedule (ADOS) and typical healthy controls. Correlations between T1, T2 and MWF values with clinical measures [ADI-R, ADOS, and the Autism Quotient (AQ)] were also assessed.ResultsIndividuals with autism showed widespread WM T1 and MWF differences compared to typical controls. Within autistic individuals, worse current social interaction skill as measured by the ADOS was related to reduced MWF although not T1. No significant differences or correlations with symptoms were observed with respect to T2.ConclusionsAutistic individuals have significantly lower global MWF and higher T1, suggesting widespread alteration in tissue microstructure and biochemistry. Areas of difference, including thalamic projections, cerebellum and cingulum, have previously been implicated in the disorder; however, this is the first study to specifically indicate myelin alteration in these regions.

Autism spectrum disorders (ASD) are a group of conditions that show abnormalities in the neuroanatomy of multiple brain regions. The variability in the development of intelligence and language among individuals on the autism spectrum has long been acknowledged, but it remains unknown whether these differences impact on the neuropathology of ASD. In this study, we aimed to compare associations between surface-based regional brain measures and general intelligence (IQ) scores in ASD individuals with and without a history of language delay. We included 64 ASD adults of normal intelligence (37 without a history of language delay and 27 with a history of language delay and 80 neurotypicals). Regions with a significant association between verbal and nonverbal IQ and measures of cortical thickness (CT), surface area, and cortical volume were first identified in the combined sample of individuals with ASD and controls. Thicker dorsal frontal and temporal cortices, and thinner lateral orbital frontal and parieto-occipital cortices were associated with greater and lower verbal IQ scores, respectively. Correlations between cortical volume and verbal IQ were observed in similar regions as revealed by the CT analysis. A significant difference between ASD individuals with and without a history of language delay in the association between CT and verbal IQ was evident in the parieto-occipital region. These results indicate that ASD subgroups defined on the basis of differential language trajectories in childhood can have different associations between verbal IQ and brain measures in adulthood despite achieving similar levels of cognitive performance. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. 8 5 556 566 Cited By :2; Export Date: 17 July 2017

Autism spectrum disorders (ASD) are a group of conditions that show abnormalities in the neuroanatomy of multiple brain regions. The variability in the development of ntelligence and language among individuals on the autism spectrum has long been acknowledged, but it remains unknown whether these differences impact on the neuropathology of ASD. In this study, we aimed to compare associations between surface-based regional brain measures and general intelligence (IQ) scores in ASD individuals with and without a history of language delay. We included 64 ASD adults of normal intelligence (37 without a history of language delay and 27 with a history of language delay and 80 neurotypicals). Regions with a significant association between verbal and nonverbal IQ and measures of cortical thickness (CT), surface area, and cortical volume were first identified in the combined sample of individuals with ASD and controls. Thicker dorsal frontal and temporal cortices, and thinner lateral orbital frontal and parieto-occipital cortices were associated with greater and lower verbal IQ scores, respectively. Correlations between cortical volume and verbal IQ were observed in similar regions as revealed by the CT analysis. A significant difference between ASD individuals with and without a history of language delay in the association between CT and verbal IQ was evident in the parietooccipital region. These results indicate that ASD subgroups defined on the basis of differential language trajectories in childhood can have different associations between verbal IQ and brain measures in adulthood despite achieving similar levels of cognitive performance.

Little is known about the symptom profile of obsessive-compulsive disorder (OCD) in individuals who have autism spectrum disorders (ASD). It is also unknown whether self-report questionnaires are useful in measuring OCD in ASD. We sought to describe the symptom profiles of adults with ASD, OCD, and ASD+OCD using the Obsessive Compulsive Inventory-Revised (OCI-R), and to assess the utility of the OCI-R as a screening measure in a high-functioning adult ASD sample. Individuals with ASD (n=171), OCD (n=108), ASD+OCD (n=54) and control participants (n=92) completed the OCI-R. Individuals with ASD+OCD reported significantly higher levels of obsessive-compulsive symptoms than those with ASD alone. OCD symptoms were not significantly correlated with core ASD repetitive behaviors as measured on the ADI-R or ADOS-G. The OCI-R showed good psychometric properties and corresponded well with clinician diagnosis of OCD. Receiver operating characteristic analysis suggested cut-offs for OCI-R Total and Checking scores that discriminated well between ASD+versus -OCD, and fairly well between ASD-alone and OCD-alone. OCD manifests separately from ASD and is characterized by a different profile of repetitive thoughts and behaviors. The OCI-R appears to be useful as a screening tool in the ASD adult population. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. 8 5 477 485 Cited By :9; Export Date: 17 July 2017

Autism Spectrum Disorder (ASD) is diagnosed on the basis of behavioral symptoms, but cognitive abilities may also be useful in characterizing individuals with ASD. One hundred seventy-eight high-functioning male adults, half with ASD and half without, completed tasks assessing IQ, a broad range of cognitive skills, and autistic and comorbid symptomatology. The aims of the study were, first, to determine whether significant differences existed between cases and controls on cognitive tasks, and whether cognitive profiles, derived using a multivariate classification method with data from multiple cognitive tasks, could distinguish between the two groups. Second, to establish whether cognitive skill level was correlated with degree of autistic symptom severity, and third, whether cognitive skill level was correlated with degree of comorbid psychopathology. Fourth, cognitive characteristics of individuals with Asperger Syndrome (AS) and high-functioning autism (HFA) were compared. After controlling for IQ, ASD and control groups scored significantly differently on tasks of social cognition, motor performance, and executive function (P's < 0.05). To investigate cognitive profiles, 12 variables were entered into a support vector machine (SVM), which achieved good classification accuracy (81%) at a level significantly better than chance (P < 0.0001). After correcting for multiple correlations, there were no significant associations between cognitive performance and severity of either autistic or comorbid symptomatology. There were no significant differences between AS and HFA groups on the cognitive tasks. Cognitive classification models could be a useful aid to the diagnostic process when used in conjunction with other data sources-including clinical history.

Autism Spectrum Disorder (ASD) is diagnosed on the basis of behavioral symptoms, but cognitive abilities may also be useful in characterizing individuals with ASD. One hundred seventy‐eight high‐functioning male adults, half with ASD and half without, completed tasks assessing IQ, a broad range of cognitive skills, and autistic and comorbid symptomatology. The aims of the study were, first, to determine whether significant differences existed between cases and controls on cognitive tasks, and whether cognitive profiles, derived using a multivariate classification method with data from multiple cognitive tasks, could distinguish between the two groups. Second, to establish whether cognitive skill level was correlated with degree of autistic symptom severity, and third, whether cognitive skill level was correlated with degree of comorbid psychopathology. Fourth, cognitive characteristics of individuals with Asperger Syndrome (AS) and high‐functioning autism (HFA) were compared. After controlling for IQ, ASD and control groups scored significantly differently on tasks of social cognition, motor performance, and executive function (P's

Autism Spectrum Disorder (ASD) is diagnosed on the basis of behavioral symptoms, but cognitive abilities may also be useful in characterizing individuals with ASD. One hundred seventy-eight high-functioning male adults, half with ASD and half without, completed tasks assessing IQ, a broad range of cognitive skills, and autistic and comorbid symptomatology. The aims of the study were, first, to determine whether significant differences existed between cases and controls on cognitive tasks, and whether cognitive profiles, derived using a multivariate classification method with data from multiple cognitive tasks, could distinguish between the two groups. Second, to establish whether cognitive skill level was correlated with degree of autistic symptom severity, and third, whether cognitive skill level was correlated with degree of comorbid psychopathology. Fourth, cognitive characteristics of individuals with Asperger Syndrome (AS) and high-functioning autism (HFA) were compared. After controlling for IQ, ASD and control groups scored significantly differently on tasks of social cognition, motor performance, and executive function (P's

Context: Neuroimaging studies of brain anatomy in autism spectrum disorder (ASD) have mostly been based on measures of cortical volume (CV). However, CV is a product of 2 distinct parameters, cortical thickness (CT) and surface area (SA), that in turn have distinct genetic and developmental origins. Objective: To investigate regional differences in CV, SA, and CT as well as their relationship in a large and well-characterized sample of men with ASD and matched controls. Design: Multicenter case-control design using quantitative magnetic resonance imaging. Setting: Medical Research Council UK Autism Imaging Multicentre Study. Participants: A total of 168 men, 84 diagnosed as having ASD and 84 controls who did not differ significantly in mean (SD) age (26 7] years vs 28 6] years, respectively) or full-scale IQ (110 14] vs 114 12], respectively). Main Outcome Measures : Between-group differences in CV, SA, and CT investigated using a spatially unbiased vertex-based approach; the degree of spatial overlap between the differences in CT and SA; and their relative contribution to differences in regional CV. Results: Individuals with ASD differed from controls in all 3 parameters. These mainly consisted of significantly increased CT within frontal lobe regions and reduced SA in the orbitofrontal cortex and posterior cingulum. These differences in CT and SA were paralleled by commensurate differences in CV. The spatially distributed patterns for CT and SA were largely nonoverlapping and shared only about 3% of all significantly different locations on the cerebral surface. Conclusions: Individuals with ASD have significant differences in CV, but these may be underpinned by (separable) variations in its 2 components, CT and SA. This is of importance because both measures result from distinct developmental pathways that are likely modulated by different neurobiological mechanisms. This finding may provide novel targets for future studies into the etiology of the condition and a new way to fractionate the disorder. ©2013 American Medical Association. All rights reserved. 70 1 59 70 Cited By :76; Export Date: 17 July 2017

Antisocial personality disorder (ASPD) and psychopathy involve significant interpersonal and behavioural impairments. However, little is known about their underlying neurobiology and in particular, abnormalities in white matter (WM) microstructure. Apreliminary diffusion tensor magnetic resonance imaging (DT-MRI) study of adult psychopaths employing tractography revealed abnormalities in the right uncinate fasciculus (UF) (Craig et al., 2009), indicating fronto-limbic disconnectivity. However, it is not clear whether WM abnormalities are restricted to this tract or are or more widespread, including other tracts which are involved in connectivity with the frontal lobe.We performed whole brain voxel-based analyses on WM fractional anisotropy (FA) and mean diffusivity (MD) maps acquired with DT-MRI to compare 15 adults with ASPD and healthy age, handedness and IQ-matched controls. Also, within ASPD subjects we related differences in FA and MD to measures of psychopathy.Significant WM FA reduction and MD increases were found respectively in ASPD subjects relative to controls. FA was bilaterally reduced in the genu of corpus callosum while in the right frontal lobe FA reduction was found in the UF, inferior fronto-occipital fasciculus (IFOF), anterior corona radiata and anterior limb and genu of the internal capsule. These differences negatively correlated with measures of psychopathy. Also in the right frontal lobe, increased MD was found in the IFOF and UF, and the corpus callosum and anterior corona radiata. There was a significant positive correlation between MD and psychopathy scores. Conclusions: The present study confirms a previous report of reduced FA in the UF. Additionally, we report for the first time, FA deficits in tracts involved in interhemispheric as well as frontal lobe connectivity in conjunction with MD increases in the frontal lobe. Hence, we provide evidence of significant WM microstructural abnormalities in frontal brain regions in ASPD and psychopathy. © 2011 Elsevier Srl. 48 2 216 229 Cited By :51; Export Date: 17 July 2017

Individual differences in cognitive style can be characterized along two dimensions: ‘systemizing’ (S, the drive to analyze or build ‘rule-based’ systems) and ‘empathizing’ (E, the drive to identify another's mental state and respond to this with an appropriate emotion). Discrepancies between these two dimensions in one direction (S > E) or the other (E > S) are associated with sex differences in cognition: on average more males show an S > E cognitive style, while on average more females show an E > S profile. The neurobiological basis of these different profiles remains unknown. Since individuals may be typical or atypical for their sex, it is important to move away from the study of sex differences and towards the study of differences in cognitive style. Using structural magnetic resonance imaging we examined how neuroanatomy varies as a function of the discrepancy between E and S in 88 adult males from the general population. Selecting just males allows us to study discrepant E-S profiles in a pure way, unconfounded by other factors related to sex and gender. An increasing S > E profile was associated with increased gray matter volume in cingulate and dorsal medial prefrontal areas which have been implicated in processes related to cognitive control, monitoring, error detection, and probabilistic inference. An increasing E > S profile was associated with larger hypothalamic and ventral basal ganglia regions which have been implicated in neuroendocrine control, motivation and reward. These results suggest an underlying neuroanatomical basis linked to the discrepancy between these two important dimensions of individual differences in cognitive style., Highlights ► Empathizing (E)–Systemizing (S) discrepancy differentiates human cognitive styles. ► We investigate the brain structural basis for ‘E–S discrepancy’ in adult males. ► S > E profile is related to larger cingulate and dorsal medial prefrontal structures. ► E > S profile is related to larger hypothalamus and ventral basal ganglia. ► E–S discrepancy is reflected by distinct individual differences in brain structure.

Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder that frequently persists into adulthood. However, in the UK, there is a paucity of adult services available for the increasing number of young people with ADHD who are now graduating from child services. Furthermore, there is limited research investigating the transition of young people with ADHD from child to adult services and a lack of guidance on how to achieve this effectively. This paper reviews the difficulties of young people with ADHD and their families who are transitioning between services; we review transition from the child and adult health teams' perspectives and identify barriers to the transition process. We conclude with recommendations on how to develop transition services for young people with ADHD.

Although many examples exist for shared neural representations of self and other, it is unknown how such shared representations interact with the rest of the brain. Furthermore, do high-level inference-based shared mentalizing representations interact with lower level embodied/simulation-based shared representations? We used functional neuroimaging (fMRI) and a functional connectivity approach to assess these questions during high-level inference-based mentalizing. Shared mentalizing representations in ventromedial prefrontal cortex, posterior cingulate/precuneus, and temporo-parietal junction (TPJ) all exhibited identical functional connectivity patterns during mentalizing of both self and other. Connectivity patterns were distributed across low-level embodied neural systems such as the frontal operculum/ventral premotor cortex, the anterior insula, the primary sensorimotor cortex, and the presupplementary motor area. These results demonstrate that identical neural circuits are implementing processes involved in mentalizing of both self and other and that the nature of such processes may be the integration of low-level embodied processes within higher level inference-based mentalizing. ■ © 2009 Massachusetts Institute of Technology. 22 7 1623 1635 Cited By :135; Export Date: 17 July 2017

The male bias in autism spectrum conditions (ASC) has led to females with ASC being under-researched. This lack of attention to females could hide variability due to sex that may explain some of the heterogeneity within ASC. In this study we investigate four key cognitive domains (mentalizing and emotion perception, executive function, perceptual attention to detail, and motor function) in ASC, to test for similarities and differences between males and females with and without ASC (n = 128 adults; n = 32 per group). In the mentalizing and facial emotion perception domain, males and females with ASC showed similar deficits compared to neurotypical controls. However, in attention to detail and dexterity involving executive function, although males with ASC showed poorer performance relative to neurotypical males, females with ASC performed comparably to neurotypical females. We conclude that performance in the social-cognitive domain is equally impaired in male and female adults with ASC. However, in specific non-social cognitive domains, performance within ASC depends on sex. This suggests that in specific domains, cognitive profiles in ASC are modulated by sex. © 2012 Lai et al. 7 10 Cited By :57; Export Date: 17 July 2017

Autism Spectrum Disorder (ASD) is diagnosed on the basis of behavioral symptoms, but cognitive abilities may also be useful in characterizing individuals with ASD. One hundred seventy-eight high-functioning male adults, half with ASD and half without, completed tasks assessing IQ, a broad range of cognitive skills, and autistic and comorbid symptomatology. The aims of the study were, first, to determine whether significant differences existed between cases and controls on cognitive tasks, and whether cognitive profiles, derived using a multivariate classification method with data from multiple cognitive tasks, could distinguish between the two groups. Second, to establish whether cognitive skill level was correlated with degree of autistic symptom severity, and third, whether cognitive skill level was correlated with degree of comorbid psychopathology. Fourth, cognitive characteristics of individuals with Asperger Syndrome (AS) and high-functioning autism (HFA) were compared. After controlling for IQ, ASD and control groups scored significantly differently on tasks of social cognition, motor performance, and executive function (P's < 0.05). To investigate cognitive profiles, 12 variables were entered into a support vector machine (SVM), which achieved good classification accuracy (81%) at a level significantly better than chance (P < 0.0001). After correcting for multiple correlations, there were no significant associations between cognitive performance and severity of either autistic or comorbid symptomatology. There were no significant differences between AS and HFA groups on the cognitive tasks. Cognitive classification models could be a useful aid to the diagnostic process when used in conjunction with other data sources-including clinical history.

The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Any views expressed are those of the author(s) and not necessarily those of the funders.

Background\ud \ud Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) are often comorbid and share similarities across some cognitive phenotypes, including certain aspects of attention. However, no functional magnetic resonance imaging (fMRI) studies have compared the underlying neural mechanisms contributing to these shared phenotypes.\ud \ud Methods\ud \ud Age and IQ-matched boys between 11 and 17 years old with ASD (N=20), OCD (N=20) and healthy controls (N = 20) performed a parametrically modulated psychomotor vigilance fMRI task. Brain activation and performance were compared between adolescents with OCD, ASD and controls.\ud \ud Results\ud \ud While boys with ASD and OCD were not impaired on task performance, there was a significant group by attention load interaction in several brain regions. With increasing attention load, left inferior frontal cortex/insula as well as left inferior parietal lobe/pre/post-central gyrus were progressively less activated in OCD boys relative to the other two groups. In addition, OCD boys showed progressively increased activation with increasing attention load in rostromedial prefrontal/anterior cingulate cortex relative to ASD and control boys. Shared neurofunctional abnormalities between ASD and OCD boys included increased activation with increasing attention load in cerebellum and occipital regions, possibly reflecting increased default mode network activation.\ud \ud Conclusions\ud \ud This first fMRI study to compare boys with ASD and OCD showed shared abnormalities in posterior cerebellar-occipital brain regions. However, OCD boys showed a disorder-specific pattern of reduced activation in left inferior frontal and temporo-parietal regions but increased activation of medial frontal regions which may potentially be related to neurobiological mechanisms underlying cognitive and clinical phenotypes of OCD.

ObjectiveAttention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders.MethodsStructural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures).ResultsWe found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed.ConclusionOur findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders.