Autistic traits, resting-state connectivity, and absolute pitch in professional musicians: shared and distinct neural features.

BACKGROUND: Recent studies indicate increased autistic traits in musicians with absolute pitch and a higher proportion of absolute pitch in people with autism. Theoretical accounts connect both of these with shared neural principles of local hyper- and global hypoconnectivity, enhanced perceptual functioning, and a detail-focused cognitive style. This is the first study to investigate absolute pitch proficiency, autistic traits, and brain correlates in the same study. SAMPLE AND METHODS: Graph theoretical analysis was conducted on resting-state (eyes closed and eyes open) EEG connectivity (wPLI, weighted phase lag index) matrices obtained from 31 absolute pitch (AP) and 33 relative pitch (RP) professional musicians. Small-worldness, global clustering coefficient, and average path length were related to autistic traits, passive (tone identification) and active (pitch adjustment) absolute pitch proficiency, and onset of musical training using Welch two-sample tests, correlations, and general linear models. RESULTS: Analyses revealed increased path length (delta 2-4 Hz), reduced clustering (beta 13-18 Hz), reduced small-worldness (gamma 30-60 Hz), and increased autistic traits for AP compared to RP. Only clustering values (beta 13-18 Hz) were predicted by both AP proficiency and autistic traits. Post hoc single connection permutation tests among raw wPLI matrices in the beta band (13-18 Hz) revealed widely reduced interhemispheric connectivity between bilateral auditory-related electrode positions along with higher connectivity between F7-F8 and F8-P9 for AP. Pitch-naming ability and pitch adjustment ability were predicted by path length, clustering, autistic traits, and onset of musical training (for pitch adjustment) explaining 44% and 38% of variance, respectively. CONCLUSIONS: Results show both shared and distinct neural features between AP and autistic traits. Differences in the beta range were associated with higher autistic traits in the same population. In general, AP musicians exhibit a widely underconnected brain with reduced functional integration and reduced small-world property during resting state. This might be partly related to autism-specific brain connectivity, while differences in path length and small-worldness reflect other ability-specific influences. This is further evidenced for different pathways in the acquisition and development of absolute pitch, likely influenced by both genetic and environmental factors and their interaction

Structural covariance networks in children with autism or ADHD

Abstract While autism and attention-deficit/hyperactivity disorder (ADHD) are considered distinct conditions from a diagnostic perspective, they share some phenotypic features and have high comorbidity. Taking a dual-condition approach might help elucidate shared and distinct neural characteristics. Graph theory was used to analyse properties of cortical thickness structural covariance networks across both conditions and relative to a neurotypical (NT; n=87) group using data from the ABIDE (autism; n=62) and ADHD-200 datasets (ADHD; n=69). This was analysed in a theoretical framework examining potential differences in long and short range connectivity. We found convergence between autism and ADHD, where both conditions show an overall decrease in CT covariance with increased Euclidean distance compared to a neurotypical population. The two conditions also show divergence: less modular overlap between the two conditions than there is between each condition and the neurotypical group. Lastly, the ADHD group also showed reduced wiring costs compared to the autism groups. Our results indicate a need for taking an integrated approach when considering highly comorbid conditions such as autism and ADHD. Both groups show a distance-covariance relation that more strongly favours short-range over long-range. Thus, on some network features the groups seem to converge, yet on others there is divergence

Transcriptomic and connectomic correlates of differential spatial patterning among gliomas.

Unravelling the complex events driving grade-specific spatial distribution of brain tumour occurrence requires rich datasets from both healthy individuals and patients. Here, we combined open-access data from The Cancer Genome Atlas, the UKBiobank and the Allen Brain Human Atlas to disentangle how the different spatial occurrences of Glioblastoma Multiforme (GBM) and Low-Grade Gliomas (LGG) are linked to brain network features and the normative transcriptional profiles of brain regions. From MRI of brain tumour patients we first constructed a grade-related frequency map of the regional occurrence of LGG and the more aggressive GBM. Using associated mRNA transcription data, we derived a set of differential gene expressions from GBM and LGG tissues of the same patients. By combining the resulting values with normative gene expressions from postmortem brain tissue, we constructed a grade-related expression map indicating which brain regions express genes dysregulated in aggressive gliomas. Additionally, we derived an expression map of genes previously associated with tumour subtypes in a GWAS study (tumour-related genes). There were significant associations between grade-related frequency, grade-related expression, and tumour-related expression maps, as well as functional brain network features (specifically, nodal strength and participation coefficient) that are implicated in neurological and psychiatric disorders. These findings identify brain network dynamics and transcriptomic signatures as key factors in regional vulnerability for GBM and LGG occurrence, placing primary brain tumours within a well-established framework of neurological and psychiatric cortical alterations

Oxytocin increases eye contact during a real-time, naturalistic social interaction in males with and without autism.

Autism spectrum conditions (autism) affect ~1% of the population and are characterized by deficits in social communication. Oxytocin has been widely reported to affect social-communicative function and its neural underpinnings. Here we report the first evidence that intranasal oxytocin administration improves a core problem that individuals with autism have in using eye contact appropriately in real-world social settings. A randomized double-blind, placebo-controlled, within-subjects design is used to examine how intranasal administration of 24 IU of oxytocin affects gaze behavior for 32 adult males with autism and 34 controls in a real-time interaction with a researcher. This interactive paradigm bypasses many of the limitations encountered with conventional static or computer-based stimuli. Eye movements are recorded using eye tracking, providing an objective measurement of looking patterns. The measure is shown to be sensitive to the reduced eye contact commonly reported in autism, with the autism group spending less time looking to the eye region of the face than controls. Oxytocin administration selectively enhanced gaze to the eyes in both the autism and control groups (transformed mean eye-fixation difference per second=0.082; 95% CI:0.025-0.14, P=0.006). Within the autism group, oxytocin has the most effect on fixation duration in individuals with impaired levels of eye contact at baseline (Cohen's d=0.86). These findings demonstrate that the potential benefits of oxytocin in autism extend to a real-time interaction, providing evidence of a therapeutic effect in a key aspect of social communication.We are grateful to the Autism Research Trust (ART) for funding the consumable costs of this study. BA was supported by the Wellcome Trust. SBC and BC were supported by the MRC during the period of this work. This study was conducted in association with the NIHR CLAHRC-EoE, and the EU-AIMS IMI. MVL was supported by a postdoctoral fellowship from the British Academy. MH was supported by the Deutsche Forschungsgemeinschaft (DFG, HE 5310/1-1) and the European Neuroscience Network NEUREX.This is the final published version. It first appeared at http://www.nature.com/tp/journal/v5/n2/full/tp2014146a.html

Examining the relationship between altered brain functional connectome and disinhibition across 33 impulsive and compulsive behaviours

Impulsive and compulsive problem behaviours are associated with a variety of mental disorders. Latent phenotyping indicates the expression of impulsive and compulsive problem behaviours is predominantly governed by a transdiagnostic 'disinhibition' phenotype. In a cohort of 117 individuals, recruited as part of the Neuroscience in Psychiatry Network (NSPN), we examined how brain functional connectome and network properties relate to disinhibition. Reduced functional connectivity within a subnetwork of frontal (especially right inferior frontal gyrus), occipital and parietal regions was linked to disinhibition. Findings provide insights into neurobiological pathways underlying the emergence of impulsive and compulsive disorders

Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women

Oxytocin may influence various human behaviors and the connectivity across subcortical and cortical networks. Previous oxytocin studies are male biased and often constrained by task-based inferences. Here, we investigate the impact of oxytocin on resting-state connectivity between subcortical and cortical networks in women. We collected resting-state functional magnetic resonance imaging (fMRI) data on 26 typically developing women 40 min following intranasal oxytocin administration using a double-blind placebo-controlled crossover design. Independent components analysis (ICA) was applied to examine connectivity between networks. An independent analysis of oxytocin receptor (OXTR) gene expression in human subcortical and cortical areas was carried out to determine plausibility of direct oxytocin effects on OXTR. In women, OXTR was highly expressed in striatal and other subcortical regions, but showed modest expression in cortical areas. Oxytocin increased connectivity between corticostriatal circuitry typically involved in reward, emotion, social communication, language and pain processing. This effect was 1.39 standard deviations above the null effect of no difference between oxytocin and placebo. This oxytocin-related effect on corticostriatal connectivity covaried with autistic traits, such that oxytocin-related increase in connectivity was stronger in individuals with higher autistic traits. In sum, oxytocin strengthened corticostriatal connectivity in women, particularly with cortical networks that are involved in social-communicative, motivational and affective processes. This effect may be important for future work on neurological and psychiatric conditions (for example, autism), particularly through highlighting how oxytocin may operate differently for subsets of individuals.During this research RB was funded by the MRC UK, the Pinsent Darwin Trust and the Cambridge Trust. M-CL is supported by the William Binks Autism Neuroscience Fellowship, Cambridge and the O’Brien Scholars Program within the Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health and The Hospital for Sick Children, Toronto. SB-C is supported by the MRC UK, the Wellcome Trust and the Autism Research Trust. The research was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East of England at Cambridgeshire and Peterborough NHS Foundation Trust

Synaptic and transcriptionally downregulated genes are associated with cortical thickness differences in autism.

Differences in cortical morphology-in particular, cortical volume, thickness and surface area-have been reported in individuals with autism. However, it is unclear what aspects of genetic and transcriptomic variation are associated with these differences. Here we investigate the genetic correlates of global cortical thickness differences (ΔCT) in children with autism. We used Partial Least Squares Regression (PLSR) on structural MRI data from 548 children (166 with autism, 295 neurotypical children and 87 children with ADHD) and cortical gene expression data from the Allen Institute for Brain Science to identify genetic correlates of ΔCT in autism. We identify that these genes are enriched for synaptic transmission pathways and explain significant variation in ΔCT. These genes are also significantly enriched for genes dysregulated in the autism post-mortem cortex (Odd Ratio (OR) = 1.11, Pcorrected  10-14), driven entirely by downregulated genes (OR = 1.87, Pcorrected  10-15). We validated the enrichment for downregulated genes in two independent data sets: Validation 1 (OR = 1.44, Pcorrected = 0.004) and Validation 2 (OR = 1.30; Pcorrected = 0.001). We conclude that transcriptionally downregulated genes implicated in autism are robustly associated with global changes in cortical thickness variability in children with autism

Brain charts for the human lifespan

10.1038/s41586-022-04554-yNature6047906525-53

Coordinated cortical thickness alterations across six neurodevelopmental and psychiatric disorders.

Funder: Max-Planck-GesellschaftFunder: Bundesministerium für Bildung und ForschungNeuropsychiatric disorders are increasingly conceptualized as overlapping spectra sharing multi-level neurobiological alterations. However, whether transdiagnostic cortical alterations covary in a biologically meaningful way is currently unknown. Here, we studied co-alteration networks across six neurodevelopmental and psychiatric disorders, reflecting pathological structural covariance. In 12,024 patients and 18,969 controls from the ENIGMA consortium, we observed that co-alteration patterns followed normative connectome organization and were anchored to prefrontal and temporal disease epicenters. Manifold learning revealed frontal-to-temporal and sensory/limbic-to-occipitoparietal transdiagnostic gradients, differentiating shared illness effects on cortical thickness along these axes. The principal gradient aligned with a normative cortical thickness covariance gradient and established a transcriptomic link to cortico-cerebello-thalamic circuits. Moreover, transdiagnostic gradients segregated functional networks involved in basic sensory, attentional/perceptual, and domain-general cognitive processes, and distinguished between regional cytoarchitectonic profiles. Together, our findings indicate that shared illness effects occur in a synchronized fashion and along multiple levels of hierarchical cortical organization