Biology subjects

Dumas, G.

Publications and source records attributed to Dumas, G..

At least 19 recordsLinked to original sources

bioRxiv2026

Heterogeneity of Brain Dynamics in Genetic and Psychiatric Conditions

Whether the heterogeneity of psychiatric conditions converges on shared neurophysiological alterations or translates into distinct signatures remains unclear. We assembled high-density electroencephalogram (hd-EEG) resting-state recordings from 4,812 individuals aged 5 months to 66 years across 11 psychiatric conditions, a broad spectrum of rare genetic variants, and typically developing (TD) individuals. We established normative developmental trajectories of source-space EEG across spectral organization, connectivity, and signal complexity. Psychiatric conditions showed small deviations, revealing a shared transdiagnostic profile. In contrast, single rare variants showed substantially larger, distinct and sometimes mirror-opposite signatures that collapsed toward the psychiatric profile when pooled. Autism Spectrum Disorder showed some of the smallest group-level effects yet the largest individual deviations, indicating substantial but directionally inconsistent alterations. EEG deviations followed a cortical gradient, with larger effects in sensorimotor regions. We demonstrate that sample sizes in the hundreds are required for robust associations with psychiatric diagnoses. This interactive open resource provides normative scores to benchmark future results.

neuroscience↗

bioRxiv2026

Tuning in together: LSD enhances inter-brain synchrony and felt connectedness in romantic couples

Social connection is fundamental to human wellbeing. Serotonergic psychedelics such as lysergic acid diethylamide (LSD) acutely heighten subjective connectedness, yet their effects on real-time social connection remain poorly understood. Using EEG hyperscanning in a randomized, double-blind, placebo-controlled crossover study, we recorded neural activity simultaneously from both members of healthy romantic couples (N=25) who received LSD (50 g) or placebo together, across resting and interactive states. LSD increased subjective connectedness, including feelings of love, closeness, trust, and being "in sync," while reducing loneliness, compared to placebo. This affiliative shift dissociated from the drugs pharmacokinetic time-course, remaining elevated as subjective intensity and plasma concentration declined. In parallel, LSD increased inter-brain synchrony during shared rest, carried specifically by theta-band amplitude-envelope coupling. Importantly, this effect survived two complementary controls. First, it exceeded coupling between unrelated individuals and second the effects depended on contemporaneous neural alignment rather than shared drug-induced dynamics. Exploratory analyses showed that romantic partners with greater resting synchrony reported greater feelings of connectedness. These findings provide the first evidence that a psychedelic enhances brain-to-brain coupling between people, linking a pharmacologically induced state of felt connection to a measurable signature shared across interacting brains.

neuroscience↗

bioRxiv2026

Tetradic Dynamics of Dyadic Sensorimotor Coordination: A Multiscale EEG Hyperscanning Study

HighlightsO_LILeader-follower roles structure dyadic coordination mechanisms C_LIO_LIMirroring yields a robust Follower reaction time advantage C_LIO_LITonic-phasic analyses reveal scale-dependent condition asymmetry C_LIO_LIPhasic dynamics resolve into Leader anticipation and Follower post-response inhibition C_LIO_LIIntegrated information decomposition reveals a role-specific inter-brain predictive architecture C_LI How do leader and follower roles shape the brain mechanisms that support coordinated action between people? This question has direct therapeutic relevance for conditions such as schizophrenia and autism spectrum disorder, where the capacity for reciprocal social coordination is a defining vulnerability. Here, we propose a tetradic framework and examine sensorimotor coordination in 16 healthy adult pairs using simultaneous dual-brain EEG hyperscanning, a 2x2 within-subject design crossing Role (Leader/Follower) and Condition (Mirroring/Matching). Mirroring required resonance with a partners movement; Matching required its controlled transformation. This contrast was designed to dissociate automatic from controlled coordination processes across roles. Behaviourally, Mirroring produced a reaction-time advantage that was selective to Followers, a finding replicated in a combined cohort, and consistent with role-dependent attention-inhibition gating. At the neural level, sustained (tonic) activity was dominated by Matching-related frontoparietal engagement regardless of role, while time-resolved (phasic) activity revealed a Mirroring-dominant reorganization that differentiated into role-specific patterns: anticipatory gating in Leaders and post-response inhibitory rebound in Followers. Information-theoretic decomposition of inter-brain coupling identified a Leader-specific predictive signal in medial prefrontal and cingulate cortices, a Follower-specific adaptive signal across sensorimotor and temporal regions, and a shared redundancy scaffold in orbitofrontal and insular cortices. These findings characterize tetradic coordination within dyads as a multiscale, role-asymmetric architecture in which top-down predictive control and bottom-up adaptive regulation are functionally dissociable. The tetradic framework provides an organizing scaffold for this dissociation, and the role-specific signatures it reveals offer candidate biomarkers for clinical populations in whom interpersonal coordination is disrupted.

neuroscience↗

bioRxiv2026

Theta Dual-Brain Stimulation of rTPJ Shapes Joint Agency

Joint agency, the shared feeling of "we are doing this together", has been linked to inter-brain synchrony, but its causal role in shaping this experience remains unclear. We applied dual transcranial alternating current stimulation (dual-tACS) over the right temporo-parietal junction (rTPJ) to 13 dyads performing an alternating tapping task (target ITI = 0.5 s; 180 deg. relative phase), manipulating in- and anti-phase coupling at theta (6 Hz), alpha (10 Hz), and beta (20 Hz). As a result, tapping in the theta anti-phase condition was significantly slower than the memorized reference tempo, whereas the other stimulation conditions did not influence the inter-tap interval. Meanwhile, the relative phase remained close to 180 deg. across all conditions. In the theta condition, anti-phase stimulation produced significantly lower joint agency than in-phase stimulation. Furthermore, mediation analysis suggested that the inter-tap interval may partially account for the effect of theta dual-brain stimulation on joint agency, although this indirect pathway did not reach statistical significance. These findings suggest that anti-phase theta stimulation over the rTPJ lowers joint agency, possibly by reducing coordination efficiency while preserving the overall 180 deg. alternation structure.

neuroscience↗

bioRxiv2025

Longitudinal intergenerational hyperscanning reveals indices of relationship formation and loneliness

Loneliness is globally acknowledged as a severe and burgeoning health risk, fuelling interest in helping people of all ages form meaningful social connections. One promising approach consists of intergenerational social programs. While behavioural and qualitative evidence derived from such programs promise health and wellbeing benefits, the physiological consequences of repeated intergenerational encounters remain unknown. Insight into physiological changes will shed light on the mechanisms of social connection. We charted longitudinal changes in interpersonal neural synchrony (INS) in 31 intergenerational (older/younger adult) and 30 same generation (younger adult) dyads across a six-session creative drawing program. At each session, dyads completed self-report measures, drew together and alone, and had their cortical activation recorded with fNIRS. In both groups, INS was greater while dyads drew together than alone. Across sessions, intergenerational dyads INS decreased and same generation dyads INS increased. INS in RIFG[~]RTPJ and RIFG[~]RIFG were predictive of loneliness levels and feelings of social closeness, respectively. This exploratory longitudinal research reinforces the multi-faceted nature of INS dynamics as social connections are forged.

neuroscience↗

bioRxiv2025

Aperiodic and Periodic EEG Component Lifespan Trajectories: Monotonic Decrease versus Growth-then-Decline

1.1Unraveling the lifespan trajectories of human brain development is critical for understanding brain health and disease. Recent research demonstrates that electroencephalography signals are composed of periodic and aperiodic components reflecting distinct physiological substrates. This dissociation raises the possibility that they follow different developmental tendencies. Here, we delineate the lifespan trajectories of aperiodic and periodic neural oscillations using a large international cohort (N=1,563, ages 5-95, resting state, eyes closed). We reveal two fundamental developmental patterns: a Monotonic decrease in aperiodic activity and a Growth-and-Decline pattern for periodic activity. Both components have inflections around age 20 and transition to a stable senescent phase around age 40. Spatially, anterior regions mainly exhibit aperiodic activity, while periodic activity concentrate on posterior regions and these patterns remain stable throughout life. Crucially, multimodal analysis shows these trajectories map onto distinct biological substrates. The periodic components Growth and Decline trajectory aligns with GABAergic function and myelination. In contrast, the monotonically decreasing trajectory of aperiodic activity mirrors fundamental biomarkers of biological aging, such as DNA methylation and telomere length. Transforming age to a logarithmic scale simplifies these nonlinear trajectories into a linear decreasing and a piecewise concave linear model for aperiodic and periodic components. This form provides a robust and parsimonious framework for quantifying maturation and identifying neurological deviations. HighlightsO_LIWe delineate distinct lifespan trajectories of aperiodic and periodic neural activity in a large-scale international cohort (N=1,563, ages 5-95). Aperiodic activity undergoes a Monotonic Decrease with age. In contrast, periodic activity follows a Growth-then-Decline trajectory, peaking in early adulthood. C_LIO_LIBoth trajectories feature a critical transition around age 20 and stabilize into a protracted senescent phase from approximately 40 onward. C_LIO_LIThese neural trajectories map onto distinct biological substrates: periodic activity tracks integrative functions (myelination, GABAergic, and aperiodic decline mirrors fundamental aging processes (DNA methylation). C_LIO_LIA stable pattern observed throughout the lifespan is the spatial segregation of neural activity, where aperiodic signals are dominant in anterior regions and periodic signals are concentrated in posterior ones. C_LIO_LILogarithmically transforming age linearized the developmental trajectories, yielding a monotonic decline for the aperiodic component and a concave piecewise for the periodic one. This process establishes robust linear norms for the personalized assessment of brain dysfunction. C_LI

neuroscience↗

bioRxiv2025

Inter-brain Synchronization in the Alpha Band during Minimal Tactile Interaction

Researchers have begun to examine the minimal conditions required for inter-brain coupling (IBC) in humans, and brain-to-brain synchrony can emerge during technology-mediated interactions, not only in shared physical spaces. Here, we present an exploratory electroencephalography (EEG) hyperscanning study investigating whether inter-brain synchronization (IBS) can emerge under conditions of both spatial isolation and minimal interaction. We used the Perceptual Crossing Experiment (PCE), a real-time task in which paired individuals search for one another in a one-dimensional virtual tactile environment using only minimal haptic cues. Dyad-shuffled surrogate analysis identified a small set of candidate inter-brain connections, with the strongest observed connections in the alpha bands. Unsupervised clustering identified four recurrent behavioral patterns and three inter-brain connectivity patterns. Descriptively, the two less common inter-brain configurations occurred more frequently during phases characterized by greater inter-avatar separation and reduced contact, although this association was not supported after accounting for the nested structure of the data. While preliminary, these findings provide a proof-of-concept framework for relating neural synchronization to interactive behavior in a highly constrained setting. The candidate connections were not individually significant, and whether inter-brain coupling arises under such conditions remains to be tested in hypothesis-driven designs.

animal behavior and cognition↗

bioRxiv2025

Online HD-tRNS over the right temporoparietal junction modulates social inference but not motor coordination

Social interactions are fundamental to human cognition, with the right temporoparietal junction (rTPJ) playing a key role in integrating motor coordination and social inference. Transcranial random noise stimulation (tRNS) is a promising technique for modulating cortical excitability, yet its effect on dynamic social processes remains unexplored. This study aimed to establish a causal link between rTPJ and real-time social interaction by applying high-definition transcranial random noise stimulation (HD-tRNS) during the Human Dynamic Clamp (HDC) paradigm. Specifically, we investigated whether online HD-tRNS modulates motor coordination and social inference when interacting with an adaptive virtual partner (VP). Eighty right-handed participants were assigned to one of two experiments: (Exp1) a block design with active HD-tRNS and sham blocks or (Exp2) a trial-by-trial design with intermixed active and sham conditions. Participants engaged in an interactive coordination task with a covert VP that could behave cooperatively or competitively. Kinematic data and self-reported measures of perceived cooperativeness and humanness were analyzed. HD-tRNS over the rTPJ did not influence motor coordination or task performance. However, in Exp1, participants receiving active stimulation progressively attributed lower cooperativeness and humanness to the competitive VP, suggesting improved detection of competitive intent. This effect was absent in Exp2, indicating that repeated stimulation was necessary for cumulative neuromodulatory effects. Online HD-tRNS over the rTPJ does not acutely impact motor coordination but progressively modulates social inference, particularly in competitive interactions. The findings highlight the rTPJs role in self-other distinction and suggest that repeated short neuromodulation sessions can shape social perception. Significant statementSocial interactions rely on distinguishing between cooperative and competitive behaviors, a process involving the right temporoparietal junction (rTPJ). Using high-definition transcranial random noise stimulation (HD-tRNS), we tested the rTPJs causal role in real-time social inference. While HD-tRNS did not affect motor coordination, repeated stimulation progressively reduced perceived cooperativeness and humanness of a competitive virtual partner, suggesting enhanced sensitivity to competitive intent. Our findings provide insights into social perception mechanisms and suggest HD-tRNS as a potential tool for studying and modulating social cognition, with implications for conditions affecting social inference, such as autism and schizophrenia.

neuroscience↗

bioRxiv2025

Towards Multi-Brain Decoding in Autism: A Self-Supervised Learning Approach

AbstractThis study introduces a self-supervised learning (SSL) approach to hyperscanning electroencephalography (EEG) data, targeting the identification of autism spectrum condition (ASC) during social interactions. Hyperscanning enables simultaneous recording of neural activity across interacting individuals, offering a novel path for studying brain-to-brain synchrony in ASC. Leveraging a large-scale, single-brain EEG dataset for SSL pretraining, we developed a multi-brain classification model fine-tuned with hyperscanning data from dyadic interactions involving ASC and neurotypical participants. The SSL model demonstrated superior performance (78.13% accuracy) compared to supervised baselines and logistic regression using spectral EEG biomarkers. These results underscore the efficacy of SSL in addressing the challenges of limited labeled data, enhancing EEG-based diagnostic tools for ASC, and advancing research in social neuroscience.

neuroscience↗

bioRxiv2025

Mirror effect of genomic deletions and duplications on cognitive ability across the human cerebral cortex

Cognitive deficits are common across many neurodevelopmental and psychiatric conditions, including those studied in the current set of PGC-CNV papers. How changes in regional gene expression across the cerebral cortex influence cognitive ability remains unknown. Population variation in gene dosage--which significantly impacts gene expression--represents a unique paradigm to address this question. We developed a cerebral-cortex gene-set burden analysis (CC-GSBA) to associate a trait with genomic deletions and duplications that disrupt genes with similar expression profiles across 180 cortical regions. We performed CC-GSBA across 180 cortical regions to test associations with cognitive ability in 260,000 individuals from general population cohorts. Most cortical gene sets were associated with a decrease in cognitive ability when deleted or duplicated, and this novel approach revealed opposing cortical patterns for the effect sizes of deletions and duplications. These cortical patterns of effect sizes followed the cortical gradient previously characterized at the molecular, cellular, and functional levels. We show that genes with preferential expression in sensorimotor regions demonstrated the largest effect on cognition when deleted. At the opposing end of the cortical gradient, genes with preferential expression in multimodal association regions affected cognition the most when duplicated. These two gene dosage cortical patterns could not be explained by particular cell types, developmental epochs, or genetic constraints, highlighting the fact that the macroscopic network organization of the cerebral cortex is key to understanding the effects of gene dosage on cognitive traits.

neuroscience↗

bioRxiv2024

Effects of gene dosage on cognitive ability: A function-based association study across brain and non-brain processes

Genomic Copy Number Variants (CNVs) that increase risk for neurodevelopmental disorders are also associated with lower cognitive ability in general population cohorts. Studies have focussed on a small set of recurrent CNVs, but burden analyses suggested that the vast majority of CNVs affecting cognitive ability are too rare to reach variant-level association. As a result, the full range of gene-dosage-sensitive biological processes linked to cognitive ability remains unknown. To investigate this issue, we identified all CNVs >50 kilobases in 258k individuals from 6 general population cohorts with assessments of general cognitive abilities. We performed a CNV-GWAS and functional burden analyses, which tested 6502 gene-sets defined by tissue and cell-type transcriptomics as well as gene ontology disrupted by all rare coding CNVs. CNV-GWAS identified a novel duplication at 2q12.3 associated with higher performance in cognitive ability. Among the 864 gene-sets associated with cognitive ability, only 11% showed significant effects for both deletions and duplication. Accordingly, we systematically observed negative correlations between deletion and duplication effect sizes across all levels of biological observations. We quantified the preferential effects of deletions versus duplication using tagDS, a new normalized metric. Cognitive ability was preferentially affected by cortical, presynaptic, and negative-regulation gene-sets when duplicated. In contrast, preferential effects of deletions were observed for subcortical, post-synaptic, and positive-regulation gene-sets. A large proportion of gene-sets assigned to non-brain organs were associated with cognitive ability due to low tissue specificity genes, which were associated with higher sensitive to haploinsufficiency. Overall, most biological functions associated with cognitive ability are divided into those sensitive to either deletion or duplications.

genetics↗

bioRxiv2023

Distinct Social Behavior and Inter-Brain Connectivity in Dyads with Autistic Individuals

Autism Spectrum Disorder (ASD) is defined by distinctive socio-cognitive behaviors that deviate from typical patterns. Notably, social imitation skills appear to be particularly impacted, manifesting early on in development. This paper compared the behavior and inter-brain dynamics of dyads made up of two typically developing (TD) participants with mixed dyads made up of ASD and TD participants during social imitation tasks. By combining kinematics and EEG-hyperscanning, we show that individuals with ASD exhibited a preference for the follower rather than the lead role in imitating scenarios. Moreover, the study revealed inter-brain synchrony differences, with low-alpha inter-brain synchrony differentiating control and mixed dyads. The studys findings suggest the importance of studying interpersonal phenomena in dynamic and ecological settings and using hyperscanning methods to capture inter-brain dynamics during actual social interactions.

neuroscience↗

bioRxiv2022

Technologically-Assisted Communication Attenuates Inter-Brain Synchrony

The transition to technologically-assisted communication has permeated all facets of human social life; yet, its impact on the social brain is still unknown and the effects may be most notable during key developmental transitions. Applying a two-brain perspective, the current pre-registered study measured mother-child brain-to-brain synchrony using hyperscanning EEG at the transition to adolescence during live face-to-face interaction versus technologically-assisted remote communication. The live interaction elicited 9 significant cross-brain links between densely inter-connected frontal and temporal areas in the beta range [14-30 Hz]. Mothers right frontal region connected with childs right and left frontal, temporal, and central regions, suggesting its regulatory role in organizing the two-brain dynamics. In contrast, the remote interaction elicited only 1 significant cross-brain-cross-hemisphere link, attenuating the robust right-to-right-brain connectivity during live social moments that communicates socio-affective signals. Furthermore, while the level of social behavior was comparable between the two interactions, brain-behavior links emerged only during the live exchange, suggesting that remote interactions yield a somewhat thinner biobehavioral experience. Mother-child right temporal-temporal synchrony linked with moments of shared gaze and the degree of child engagement and empathic behavior was associated with right frontal-frontal synchrony. Our findings indicate that human co-presence is underpinned by specific neurobiological processes, suggest potential reasons for "zoom fatigue", and open a much-needed discussion on the cost of social technology for brain maturation, particularly among youth. HighlightsO_LITechnologically-assisted communication is prevalent; yet, its impact on the social brain is unknown C_LIO_LIWe measured mother-child brain-to-brain synchrony during live and technologically-assisted remote interaction C_LIO_LIThe live interaction elicited 9 cross-brain links between densely inter-connected frontal and temporal areas in the beta range C_LIO_LIThe remote interaction yielded only 1 significant cross-brain cross-hemisphere link C_LIO_LIBrain-behavior linked emerged only during the live interaction C_LIO_LIFurther research should examine the cost of social technology to brain maturation, particularly among youth. C_LI

neuroscience↗

bioRxiv2022

A Neurodynamic Model of Inter-Brain Coupling in the Gamma Band

The use of EEG to simultaneously record multiple brains (i.e., hyperscanning) during social interactions has led to the discovery of inter-brain coupling (IBC). IBC is defined as the neural synchronization between people and is considered to be a marker of social interaction. IBC has previously been observed across different frequency bands, including Theta [4-7 Hz]. Given the proximity of this frequency range with behavioral rhythms, models have been able to combine IBC in Theta with sensorimotor coordination patterns. Interestingly, empirical EEG-hyperscanning results also report the emergence of IBC in the Gamma range [>30 Hz]. Gamma oscillations fast and transient nature makes a direct link between Gamma-IBC and other (much slower) interpersonal dynamics difficult, leaving Gamma-IBC without a plausible model. However, at the intra-brain level, Gamma activity is coupled with the dynamics of lower frequencies through cross-frequency coupling (CFC). This paper provides a biophysical explanation for the emergence of Gamma inter-brain coupling using a Kuramoto model of four oscillators divided into two separate (brain) units. By modulating both the degree of inter-brain coupling in the Theta band (i.e., between-units coupling) and CFC (i.e., intra-unit Theta-Gamma coupling), we provide a theoretical explanation of the observed Gamma-IBC phenomenon in the EEG-hyperscanning literature.

neuroscience↗

bioRxiv2022

Multilevel Development of Cognitive Abilities in an Artificial Neural Network

Several neuronal mechanisms have been proposed to account for the formation of cognitive abilities through postnatal interactions with the physical and socio-cultural environment. Here, we introduce a three-level computational model of information processing and acquisition of cognitive abilities. We propose minimal architectural requirements to build these levels and how the parameters affect their performance and relationships. The first sensorimotor level handles local nonconscious processing, here during a visual classification task. The second level or cognitive level globally integrates the information from multiple local processors via long-ranged connections and synthesizes it in a global, but still nonconscious manner. The third and cognitively highest level handles the information globally and consciously. It is based on the Global Neuronal Workspace (GNW) theory and is referred to as conscious level. We use trace and delay conditioning tasks to, respectively, challenge the second and third levels. Results first highlight the necessity of epigenesis through selection and stabilization of synapses at both local and global scales to allow the network to solve the first two tasks. At the global scale, dopamine appears necessary to properly provide credit assignment despite the temporal delay between perception and reward. At the third level, the presence of interneurons becomes necessary to maintain a self-sustained representation within the GNW in the absence of sensory input. Finally, while balanced spontaneous intrinsic activity facilitates epigenesis at both local and global scales, the balanced excitatory-inhibitory ratio increases performance. Finally, we discuss the plausibility of the model in both neurodevelopmental and artificial intelligence terms.

neuroscience↗

bioRxiv2020

Attenuated Anticipation of Social and Monetary Rewards in Autism Spectrum Disorders

BackgroundReward processing has been proposed to underpin atypical social behavior, a core feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social rewards in ASD. Utilizing a large sample, we aimed to assess altered reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD. MethodsFunctional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.5 years) and 181 typically developing (TD) participants (7.6-30.8 years). ResultsAcross social and monetary reward anticipation, whole-brain analyses (p<0.05, family-wise error-corrected) showed hypoactivation of the right ventral striatum (VS) in ASD. Further, region of interest (ROI) analysis across both reward types yielded hypoactivation in ASD in both the left and right VS. Across delivery of social and monetary reward, hyperactivation of the VS in individuals with ASD did not survive correction for multiple comparisons. Reward type by diagnostic group interactions, and a dimensional analysis of autism trait scores were not significant during anticipation or delivery. Levels of attention-deficit/hyperactivity disorder (ADHD) symptoms did not affect reward processing in ASD. ConclusionsOur results do not support current theories linking atypical social interaction in ASD to specific alterations in processing of social rewards. Instead, they point towards a generalized hypoactivity of VS in ASD during anticipation of both social and monetary rewards. We suggest that this indicates attenuated subjective reward value in ASD independent of social content and ADHD symptoms.

neuroscience↗

bioRxiv2020

Towards robust and replicable sex differences in the intrinsic brain function of autism

BackgroundMarked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data. MethodsWe addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7-18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z > 3.1, cluster-level P < 0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research (GENDAAR). ResultsDiscovery analyses in ABIDE revealed significant main effects across the intrinsic functional connectivity (iFC) of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples - EU-AIMS LEAP. LimitationsGiven the lack of a priori harmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability. ConclusionsAtypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies.

neuroscience↗

bioRxiv2020

Differential functional neural circuitry behind autism subtypes with marked imbalance between social-communicative and restricted repetitive behavior symptom domains

Social-communication (SC) and restricted repetitive behaviors (RRB) are autism diagnostic symptom domains. SC and RRB severity can markedly differ within and between individuals and may be underpinned by different neural circuitry and genetic mechanisms. Modeling SC-RRB balance could help identify how neural circuitry and genetic mechanisms map onto such phenotypic heterogeneity. Here we developed a phenotypic stratification model that makes highly accurate (97-99%) out-of-sample SC=RRB, SC>RRB, and RRB>SC subtype predictions. Applying this model to resting state fMRI data from the EU-AIMS LEAP dataset (n=509), we find that while the phenotypic subtypes share many commonalities in terms of intrinsic functional connectivity, they also show replicable differences within some networks compared to a typically-developing group (TD). Specifically, the somatomotor network is hypoconnected with perisylvian circuitry in SC>RRB and visual association circuitry in SC=RRB. The SC=RRB subtype show hyperconnectivity between medial motor and anterior salience circuitry. Genes that are highly expressed within these networks show a differential enrichment pattern with known autism-associated genes, indicating that such circuits are affected by differing autism-associated genomic mechanisms. These results suggest that SC-RRB imbalance subtypes share many commonalities, but also express subtle differences in functional neural circuitry and the genomic underpinnings behind such circuitry.

neuroscience↗