Biology subjects

Smolka, M. N.

Publications and source records attributed to Smolka, M. N..

At least 19 recordsLinked to original sources

bioRxiv2026

Predicting alcohol consumption from resting-state functional connectivity: Feature relevance and the potential of meta-matching.

Alcohol use disorder (AUD) is among the most prevalent mental disorders. Associations between resting-state fMRI functional connectivity (FC) and AUD have been reported but rarely replicated. In this preregistered study, we investigated the extent to which FC predicts alcohol consumption, as measured by the AUDIT-C score, in a large sample of non-treatment-seeking alcohol consumers (N = 739), including 528 participants with varying degrees of AUD severity. To optimize performance, we compared kernel ridge regression (KRR) trained directly on this sample with transfer-learning models based on multilayer meta-matching embeddings, from which we derived data-driven relevance maps at the connection, region, and network levels. We tested split-half reliability, reproducibility across cohorts, and outcome specificity of the relevance maps. Both models predicted AUDIT-C scores moderately but significantly (r {approx} 0.15). Meta-matching did not outperform KRR in prediction. Relevance maps showed limited split-half reliability, consistent with the modest predictive performance, but reproduced moderately well across two independent cohorts. These maps indicate reduced connectivity among limbic regions, the anterior middle temporal gyrus, the dorsomedial prefrontal cortex, and dorsal attention network regions. In contrast, hypothesized hyperconnectivity patterns involving the striatum, anterior cingulate cortex, and precuneus were less reliable and mostly non-significant. Overall, our findings suggest that resting-state FC contains reproducible but weak signals related to alcohol consumption. Transfer learning improved relevance-map reliability but not prediction performance and reduced outcome specificity. These results support the utility of interpretable machine learning for identifying connectivity patterns related to drinking behavior, while also highlighting current limitations in its predictive power.

neuroscience↗

bioRxiv2026

Impaired Control Symptoms in Alcohol Use Disorder Show Convergent Associations Across Behavioral and Neural Markers of Inhibitory Control and Drinking Behavior

Background: Deficits in inhibitory control are considered a central feature of alcohol use disorder (AUD), yet behavioral and neuroimaging findings have been inconsistent. One potential explanation is the marked heterogeneity of AUD, which encompasses multiple symptom dimensions that may differ in their underlying neurocognitive mechanisms. In this study, we investigated whether behavioral and neural markers of inhibitory control are associated with specific DSM-5 AUD symptom domains. Methods: A total of 589 participants (432 with non-treatment seeking AUD, 157 controls) completed a Stop-Signal Task (SST) during fMRI. Associations between DSM-5 symptom domains (impaired control over alcohol use, risky use, social problems, physical dependence) and SST performance, inhibition-related brain activation, and alcohol consumption were examined. Real-life drinking behavior was additionally assessed over 12 months using ecological momentary assessment (EMA). Results: Greater impaired control symptom severity was associated with poorer performance on go trials and diminished post-error slowing during SST. At the neural level, higher impaired control symptom severity was associated with reduced activation across fronto-insular, parietal, cingulate, supplementary motor, and cerebellar regions. In contrast, other symptom domains showed little to no associations with inhibition-related behavioral or neural measures. Higher impaired control symptom severity was associated with greater alcohol consumption across questionnaire-based and EMA-based assessments. Conclusions: In this large cohort, altered behavioral performance and recruitment of inhibition-related brain regions in the SST was selectively linked to impaired control symptoms. These findings highlight the importance of symptom-based approaches for understanding heterogeneity in addiction and may inform the development of more targeted interventions.

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bioRxiv2026

Reduced Control Over Pavlovian-to-Instrumental Transfer in Human Addiction: A Systematic Investigation Across Alcohol Use Disorder and Smoking Status

Pavlovian conditioned stimuli can compromise goal-directed behavior, particularly when they conflict with the required instrumental response. Previous research linked an increased impact of such Pavlovian-to-instrumental transfer (PIT) interference to risky drinking and alcohol dependence. However, it remained unclear whether the observed behavioral and neural alterations generalize to the substantially larger population of non-treatment-seeking individuals with predominantly mild-to-moderate alcohol use disorder (AUD) and to other substances like nicotine. We therefore studied 200 participants from the general population who were stratified by AUD and smoking status before completing a single-lever PIT task during functional imaging. PIT interference was measured as the difference in error rates between incongruent PIT trials, characterized by conflicts of Pavlovian and instrumental stimuli, and congruent trials. Associations with AUD and smoking status, as well as dimensional associations of behavioral PIT interference and neural responses to PIT conflicts with substance-related measures, were examined. As expected, participants with AUD showed greater PIT interference and reduced conflict-related activation in the lateral prefrontal, dorsomedial prefrontal, and anterior cingulate cortex than participants without AUD. The magnitude of these alterations also correlated with higher AUD severity and alcohol consumption, while being independent of smoking status and other smoking-related measures. These findings suggest that enhanced PIT interference generalizes to the broader AUD population but may not extend to other substances like nicotine. They further implicate a reduced recruitment of prefrontal control networks during PIT conflicts as a potential mechanism underlying enhanced PIT interference in AUD and its association with clinically relevant outcome measures.

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bioRxiv2026

Reduced planning depth and stronger probability discounting in alcohol and tobacco use disorder

Background: Substance use disorders (SUDs) are associated with impaired goal-directed decision-making, but the specific cognitive mechanisms underlying these deficits remain unclear. Forward planning, a key component of goal-directed control, requires strategies to contain computational demand and ensure feasibility through heuristics such as reducing planning depth, pruning unlikely options, and discounting probabilistic outcomes. This study investigated whether individuals with alcohol use disorder (AUD) and tobacco use disorder (TUD) differ from healthy controls in their use of these heuristics during sequential decision-making. Methods: We examined participants from the general population meeting criteria for at least moderate AUD (n = 45), TUD (n = 49), or both (n = 45), and compared them with matched healthy control groups. To assess forward planning, we used a previously published probabilistic three-step Markov decision task. Computational modeling was used to infer individual planning depths and compare model variants incorporating low-probability pruning, probability discounting, or both. Results: A combined model including both low-probability pruning and probability discounting best explained participants' behavior and was subsequently used for analysis. Compared to matched healthy controls, all groups with SUD exhibited significantly reduced planning depth. Moreover, individuals with SUD tended to show stronger probability discounting, with this effect reaching statistical significance in the comorbid group. Conclusion: Individuals with AUD and/or TUD engaged in forward planning using similar strategies as healthy controls but exhibited reduced planning depth and a tendency toward stronger probability discounting. These findings suggest the presence of altered planning processes in SUD, which could contribute to maladaptive decision-making. Future research is needed to clarify whether such differences reflect pre-existing cognitive traits, consequences of substance use, or both, and to explore their potential relevance for intervention.

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bioRxiv2026

Early life stress alters lifespan trajectories of amygdala development: a cross-species model of amygdala burnout

Early-life stress is associated with alterations in amygdala volume, but findings vary across studies and species. Rodent models typically report increased amygdala volume, whereas human studies often find reductions or mixed effects. We propose the amygdala burnout hypothesis, which suggests that early-life stress alters amygdala developmental trajectories, producing initial volumetric increases that are followed by reductions later in life. To test this hypothesis, we examined amygdala development across rodent and human cohorts spanning adolescence to older adulthood. In rodents, chronic stress was associated with increased amygdala nuclei volumes during adolescence. Comparable increases were observed in adolescents from the IMAGEN consortium, with evidence of a dose-dependent association between childhood stress and amygdala developmental trajectories. In contrast, analyses of older adults from the UK Biobank revealed reduced bilateral amygdala volume associated with early-life stress. Together, these findings support a developmental model that reconciles previously conflicting observations across species and age groups. Early-life stress is associated with alterations in amygdala volume, but findings vary across studies and species. Rodent models typically report increased amygdala volume, whereas human studies often find reductions or mixed effects. We propose the amygdala burnout hypothesis, which suggests that early-life stress alters amygdala developmental trajectories, producing initial volumetric increases that are followed by reductions later in life. To test this hypothesis, we examined amygdala development across rodent and human cohorts spanning adolescence to older adulthood. In rodents, chronic stress was associated with increased amygdala nuclei volumes during adolescence. Comparable increases were observed in adolescents from the IMAGEN consortium, with evidence of a dose-dependent association between childhood stress and amygdala developmental trajectories. In contrast, analyses of older adults from the UK Biobank revealed reduced bilateral amygdala volume associated with early-life stress. Together, these findings support a developmental model that reconciles previously conflicting observations across species and age groups.

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bioRxiv2026

Enhanced Alcohol-Specific but not General Pavlovian-to-Instrumental Transfer in Alcohol Use Disorder

Background: Pavlovian-to-instrumental transfer (PIT) paradigms assess how environmental cues influence instrumental behaviour. Our previous research linked PIT to alcohol use disorder (AUD) and high-risk drinking using monetary rewards during learning. To better capture alcohol-related cue effects, we developed a PIT paradigm delivering trial-by-trial alcohol and juice rewards alongside monetary rewards, to examine alcohol-specific and general PIT effects in parallel. Methods: Seventy-five participants with AUD and ninety-five controls completed the task during functional magnetic resonance imaging. Alcohol-specific PIT was defined as increased alcohol choices during presentation of alcohol-associated versus juice-associated cues. General PIT was defined as increased response vigor during gain- versus loss-associated cues. Behavioural and neural associations with AUD status and AUDIT scores from baseline through one-year follow-up were examined. Results: Participants with AUD showed stronger alcohol-specific PIT effect than controls. Alcohol-specific PIT was positively associated with baseline AUDIT scores and with AUDIT scores across the one-year follow-up. Alcohol cues elicited stronger anterior insula responses, and region-of-interest analysis showed greater left amygdala responses to alcohol versus juice cues in AUD compared with controls. In contrast, general PIT showed a negative association with AUDIT but no association with AUD status. In the general PIT, no AUD-related neural differences were observed. Conclusions: These findings suggest that alcohol-specific PIT captures a clinically meaningful mechanism of cue-driven alcohol seeking that is distinct from generalized motivational transfer, supporting its potential utility as a mechanistic marker in AUD.

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bioRxiv2026

Sex-specific associations of childhood adversity with frontostriatal network organization and anhedonia in young adulthood

IntroductionAnhedonia is a transdiagnostic psychiatric symptom linked to increased functional connectivity between the prefrontal cortex and striatum. Here, we examined how dimensions of early adversity contribute to this profile of connectivity. MethodsIn a European community sample of young adults (IMAGEN), we examined cross-sectional (n=613) and longitudinal (n=332) associations of adversity dimensions with resting-state fMRI-derived connectivity. We selected 10 ROIs from anhedonia literature, defined in the functional images as 4mm-radius spheres. We then used network-based regression models to identify clusters of ROI-ROI connections associated with threat and deprivation scores, using interaction terms to examine sex and age-specific associations. We also examined associations between adversity and anhedonia, operationalized using factor analysis of six items from self-report surveys. ResultsAt age 18-22, we identified sex-specific associations between deprivation and connectivity for a cluster of 9 ROI-ROI connections (p-FWE=0.038), primarily involving the nucleus accumbens. Specifically, we observed positive associations between deprivation and connectivity in males, and negative associations in females. In the longitudinal analysis, negative deprivation associations in females attenuated with age for a cluster of 14 connections (p-FWE=0.009). A cluster of 17 connections also had initial positive associations with threat in females that attenuated with age (p-FWE=0.008). No such longitudinal changes were observed in males. Higher deprivation was linked to increased later anhedonia in males but not females (p=0.026). ConclusionCompared to females, young adult males may be more vulnerable to developing anhedonia after experiencing deprivation in childhood. Dimensions of early adversity are linked to distinct pathways of frontostriatal development.

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bioRxiv2026

Protracted Maturation of Proactive and Reactive Systems Predicts Cognitive Stability and Psychopathology : A longitudinal multi-cohort study

Inhibitory control matures progressively from childhood to early adulthood, yet the neural mechanisms driving this development and their relevance to psychiatric risk remain poorly understood. Guided by the Dual Cognitive Control model, we leveraged longitudinal fMRI from two independent cohorts in the US (ABCD, ages 9-12) and Europe (IMAGEN, ages 14-22) to map the spatiotemporal dynamics of reactive and proactive control using novel single-trial modeling and representational similarity analysis. We found both reactive and proactive stopping networks stabilize after mid-adolescence, tracking the developmental patterns of inhibitory control and behavioral stability. By decoding trial-by-trial fluctuations along a speed-caution continuum, we demonstrate that brain-behavior coupling to a proactive "Safe state" tightens progressively with age. Furthermore, network-level representational coherence of this Safe state emerged as a scanner-invariant, trait-like biomarker that robustly predicted inhibitory control, behavioral stability, and transdiagnostic psychopathology across multiple developmental windows, providing a validated neural phenotype for precision psychiatry.

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bioRxiv2026

Adversity and adolescent brain development: differential associations with grey and white matter across two longitudinal cohorts

Globally, 60% of the population has experienced at least one type of adversity (e.g., emotional abuse, bullying) across infancy, childhood, and adolescence. Such experiences have been linked to an increased risk for mental health disorders. Changes in brain structure following experiences of childhood adversity have been hypothesised to be a mechanistic pathway explaining later mental health issues. However, to understand how changes in brain structure might mediate the effects of adversity, it is essential to identify which underlying neuronal processes may be affected by different types of adverse experiences. A key open question is whether grey or white matter is more vulnerable to adversity, as these two structures reflect distinct neurobiological mechanisms. This study investigated whether differences in trajectories of grey and white matter development during adolescence can be explained by exposure to different types of adversity. We applied the Adverse Adolescent Experiences Framework (Pollmann et al., 2025) categorising adversity into four levels: Intrapersonal (e.g., accidents), Caregiver (e.g., emotional neglect), Peer (e.g., bullying), and Community (e.g., neighbourhood safety). Exposure to each of the four factors was estimated through principal components analyses. We analysed two large longitudinal datasets: the Adolescent Brain Cognitive Development study ([~]12,000 adolescents measured at ages 10, 12, and 14) and the IMAGEN study ([~]1,400 adolescents measured at ages 14, 19, and 22). Using latent growth curve models, we captured individual differences in brain development by estimating baseline levels (intercepts) and rates of change (slopes) for total grey matter volume and mean white matter fractional anisotropy. In both cohorts, we found significant interindividual variability in baseline levels and rates of change for both grey matter volume and fractional anisotropy. Caregiver, Peer, and Community adversities were negatively associated only with the intercepts of grey matter volume and white matter fractional anisotropy. Importantly, associations differed between grey and white matter. In ABCD, Peer and Community adversities were more strongly associated with grey matter volume intercepts. In contrast, in IMAGEN, Caregiver, Peer and Community adversities were more strongly linked to white matter fractional anisotropy intercepts. This suggests that adversity has unique associations with grey and white matter, rather than exerting a uniform influence on brain structure. By demonstrating that different environments generate distinct biological associations with brain maturation, this work underscores the need to consider both grey and white matter when assessing the neurodevelopmental pathways to outcomes across the lifespan.

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bioRxiv2026

Trajectories of brain organisation transition from predicting externalising to internalising symptoms across adolescence

Understanding the dynamics of brain-behaviour relationships during adolescence is critical for elucidating the neurodevelopmental basis of mental health. Leveraging two large-scale longitudinal cohorts--the Adolescent Brain Cognitive Development (ABCD) and IMAGEN studies, comprising over 10,000 participants aged 10 to 22 years with six waves of multimodal neuroimaging and behavioural data, we applied multi-view sparse canonical correlation analysis to investigate evolving associations between structural MRI, resting-state functional connectivity, and multi-domain behavioural measures. Our findings reveal four fundamental patterns of developmental reorganisation in brain-psychopathology relationships. First, symptom profiles evolved from predominantly externalising features (aggression, attention problems) at ages 10-12 toward global psychopathology by age 14, then transitioned toward internalising features (e.g., anxiety, depression) by ages 19-22, reflecting fundamental shifts in vulnerability from behavioural dysregulation to affective disturbance. Second, cortical thickness exhibited negative associations with externalising symptom profiles throughout development. During early adolescence (ages 10-14) this was driven by broadly distributed decreases across sensorimotor, temporal, visual, and cingulate regions alongside overall mean cortical thickness. After 14, this diffuse pattern shifted towards late maturing association cortices, notably the dorsolateral prefrontal and lateral temporal cortices. Third, this was accompanied by subcortical effects that exhibited greater age-specificity: whilst cerebellar volume contributions were evident at most timepoints, basal ganglia volume influence was principally evident in early development (ages 10-12), with thalamic structures and global subcortical grey matter volume becoming dominant at age 14, marking a transition in which subcortical structures mediate psychopathology associations. Fourth, functional connectivity showed a more dynamic developmental trajectory. During early adolescence, symptom associations were driven by positive connectivity between cognitive control and sensorimotor networks, whereas late adolescence exhibited predominantly positive connectivity patterns, transitioning from dense sensorimotor-frontoparietal configurations to more specific patterns involving the central executive and default-mode networks. These findings fundamentally challenge static biomarker models, demonstrating that adolescent psychopathology reflects developmentally contingent brain-behaviour relationships rather than static neural markers. Age 14 emerges as a critical inflection point marked by convergent thalamic reconfiguration, global subcortical grey matter dominance, and symptom profile transitions. This work provides an empirical foundation for precision mental health strategies tailored to specific developmental windows, with implications for reducing psychiatric burden in youth.

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bioRxiv2026

Reproducible Human Reward Imaging Phenotypes Exhibit Differential Sensitivity to Dopamine D2 Receptor Antagonism

Human reward processing varies along cue-centric and outcome-centric axes, but a reproducible mechanistic account of individual variation in incentive salience attribution has been lacking. Using fMRI across five cohorts (N-total=1,251; N1=890; N2=245; N3=34; N4=48; N5=34), we identified two robust imaging phenotypes mirroring sign- and goal-tracking (ST-like, GT-like). ST-like individuals showed dominant ventral striatal responses to reward-anticipation cues and sustained incentive salience attribution; GT-like individuals showed heightened responses to reward outcomes. This distinction was replicable across sites and independent samples. Single-dose and repeated-dose D2/D3 antagonism (risperidone, haloperidol, amisulpride) selectively reduced anticipatory ventral striatal activity in ST, with single-dose antagonism additionally producing a parallel drop in self-reported energy. Instead, D2/D3 partial agonism (aripiprazole) increased anticipatory and reduced outcome-phase responses in GT. In a psychosis cohort, antipsychotic D2 affinity was associated with blunted anticipatory signals and higher negative symptom burden, offering a neuroimaging-driven basis for stratifying patients and predicting response to dopaminergic agents.

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bioRxiv2026

Nonparametric Bayesian Contextual Control: Integrating Automatisation and Prior Knowledge for Stable Adaptive Behaviour

Humans have a remarkable ability to act efficiently and accurately in familiar situations while remaining flexible in novel circumstances. Nonparametric contextual inference has been proposed as a computational principle that can model how agents achieve flexible yet stable behaviour in dynamic and possibly unknown environments. However, it remains an open question how humans learn, deploy and reuse stable contextual task representations so efficiently. To address this question, we propose the nonparametric Bayesian Contextual Control (NP-BCC) model, which integrates nonparametric contextual learning with two well-established cognitive mechanisms: repetition-based automatisation and schema-like prior knowledge. These two mechanisms are assumed to support behavioural stability and facilitate novel task acquisition. Simulations in dynamic multi-armed bandit tasks of increasing difficulty illustrate how the NP-BCC can acquire and reuse contextual task representations, with the proposed mechanisms operating in the intended, functionally meaningful manner. Specifically, we show via simulations that automatisation not only enhances task performance but also stabilizes contextual inference and structure learning, while structured prior knowledge accelerates the acquisition of novel contexts. We discuss the implications of our findings for computational accounts of adaptive behaviour and contextual learning, and outline directions for future empirical work, including investigations of context-dependent behavioural dysregulation relevant to conditions such as substance use disorders. Author summaryPeople are very good at repeating well-learned actions in familiar situations, but they can also quickly adjust their behaviour when circumstances change. How the brain balances stability and flexibility is still not fully understood. There is growing evidence that the brain organizes experience into different "contexts", which are mental representations of encountered situations. Computational models based on this idea can in principle reproduce flexible behaviour, but they often become unstable in complex environments. To improve stability, we borrow two simple strategies from everyday human behaviour. First, people tend to repeat actions that have worked well before. Second, when facing something new, they often reuse strategies from similar past situations. Using simulations, we show that combining these strategies with context-based learning produces more reliable behaviour in the model. Prior experience helps the model understand new situations more quickly, while repeated actions help stabilise behaviour once a situation becomes familiar. Taken together, our findings show how such mechanisms can give rise to both flexible and stable behaviour in the model.

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bioRxiv2025

Chronic pain is linked to a resting-state neural archetype that optimizes learning from punishments

Chronic pain is a leading cause of disability, yet its underlying susceptibility traits remain unclear. Disorders like chronic pain may stem from extreme neural types, or archetypes, optimized for specific cognitive strategies and reflected in patterns of resting-state networks. Here, we examined a sample from the general population (n = 892) and three clinical samples with subacute back pain (n = 76), chronic back pain (n = 30), and treatment-resistant depression (n = 24). Using the sample from the general population, we found three neural archetypes that prioritize different cognitive strategies. Clinical pain samples, compared to the sample from the general population, mapped close to an archetype optimized for punishment learning (Archetype P). We replicated these results by recomputing the archetypes starting from the clinical pain samples, additionally revealing an association between Archetype P and pain severity. These findings suggest a neural-cognitive trait underlying susceptibility to chronic pain.

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bioRxiv2025

Brain Diffusion Transformer for Personalized Neuroscience and Psychiatry

Task-fMRI analyses typically focus on localized activation contrasts between stimuli, neglecting the brains dynamic hierarchy. We introduce Brain Diffusion Transformer (Brain-DiT), a deep generative model capturing recurrent processing underlying individualized neurocognitive state transitions via functional networks. Without prior assumptions, Brain-DiT identifies canonical cognitive regions in the brain and reveals replicable subgroups with distinct neural circuits in large cohorts, offering critical clinical insights overlooked by traditional methods: individuals exhibiting negative emotion bias, linked to language-related regions, had a 12-fold higher likelihood of major depression, and those with maladaptive inhibition strategies, associated with overactive medial frontal regions, showed a 9-fold increased risk of alcohol abuse. By bridging cognitive theory and psychiatric applications, Brain-DiT provides a unified analytical paradigm, paving the way for operational personalized medicine in psychiatry.

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bioRxiv2025

Mapping the coupling between tract reachability and cortical geometry of the human brain

The study of cortical geometry and connectivity is prevalent in research on the human brain. However, these two aspects of brain structure are usually examined separately, leaving the essential connections between the brains folding patterns and white matter connectivity unexplored. In this study, we aimed to elucidate fundamental links between cortical geometry and white matter tract connectivity. We developed the concept of tract-geometry coupling (TGC) by optimizing the alignment between tract connectivity to the cortex and multiscale cortical geometry. Specifically, spectral analyses of the cortical surface yielded a set of geometrical eigenmodes, which were then used to explain the locations on the cortical surface reached by specific white matter tracts, referred to as tract reachability. In two independent datasets, we confirmed that tract reachability was well characterized by cortical geometry. We further observed that TGC had high test-retest ability and was specific to each individual. Interestingly, low-frequency TGC was found to be heritable and more informative than the high-frequency components in behavior prediction. Finally, we found that TGC could reproduce task-evoked cortical activation patterns. Collectively, our study provides a new approach to mapping coupling between cortical geometry and connectivity, highlighting how these two aspects jointly shape the connected brain.

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bioRxiv2024

Context-Dependent Interaction Between Goal-Directed and Habitual Control Under Time Pressure

Habits are an important aspect of human behaviour. Habits are reflexive, inflexible, and fast, in contrast to goal-directed behaviour which is reflective, flexible, and slow. Current theories assume that habits and goal-directed actions are controlled by two separate but interacting systems. However, it is not clear how these two systems interact when actions must be made under time pressure. Here we use a task which induces habitual behaviour in the form of action sequences, while concurrently requiring participants to perform goal-directed actions that are either congruent or incongruent with the habit. This task thus allows for concurrent measurement of both goal-directed and habitual behaviour, thereby permitting a nuanced analysis of the interaction between these two control modes. Using computational modelling, we find that models where the influence of the habit depends on the number of repetitions, explain participant behaviour better than models that assume the habit to be constant. We further show that roughly half of the participants modulate their use of the habit depending on the context, i.e. they selectively inhibit the habits influence when it is incongruent to their explicit goals, but not when both are congruent and the influence of the habit is adaptive. Additional drift-diffusion modelling of choice and reaction time data shows that proactive control is mobilized in the congruent task context whereas reactive control is mobilized in the incongruent task context. The present study thus indicates that habitual control is context-dependent and can be adaptively deployed via proactive and reactive control, rather than being a fixed or isolated mechanism.

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bioRxiv2024

Genetic-Dependent Brain Signatures of Resilience: Interactions among Childhood Abuse, Genetic Risks and Brain Function

Resilience to emotional disorders is critical for adolescent mental health, especially following childhood abuse. Yet, brain signatures of resilience remain undetermined due to the differential susceptibility of the brains emotion processing system to environmental stresses. Analyzing brains responses to angry faces in a longitudinally large-scale adolescent cohort (IMAGEN), we identified two functional networks related to the orbitofrontal and occipital regions as candidate brain signatures of resilience. In girls, but not boys, higher activation in the orbitofrontal-related network was associated with fewer emotional symptoms following childhood abuse, but only when the polygenic burden for depression was high. This finding defined a genetic-dependent brain (GDB) signature of resilience. Notably, this GDB signature predicted subsequent emotional disorders in late adolescence, extending into early adulthood and generalizable to another independent prospective cohort (ABCD). Our findings underscore the genetic modulation of resilience-brain connections, laying the foundation for enhancing adolescent mental health through resilience promotion.

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bioRxiv2024

Bullying and Early Brain Development: A Longitudinal Structural Magnetic Resonance Imaging Study from Adolescence to Early Adulthood

This study investigated associations between bullying victimization and brain development using longitudinal structural MRI data from the IMAGEN cohort (n = 2,094; 1,009 females) across three time points ([~]14, [~]19, and [~]22 years). A data-driven analysis revealed that higher bullying victimization was significantly associated with accelerated volumetric growth in subcortical and limbic regions, including the putamen ({beta} = 0.12, 95% CI: 0.10-0.15), amygdala ({beta} = 0.07, 95% CI: 0.05-0.09), hippocampus ({beta} = 0.06, 95% CI: 0.04- 0.08), and anterior cingulate cortex (caudal: {beta} = 0.05, 95% CI: 0.03-0.07; rostral: {beta} = 0.06, 95% CI: 0.04-0.08). In contrast, bullying victimization was also significantly associated with reduced volumetric growth in the cerebellum ({beta} = -0.09, 95% CI: -0.11 to -0.07), entorhinal cortex ({beta} = -0.10, 95% CI: -0.13 to -0.07), and insula ({beta} = -0.08, 95% CI: -0.11 to -0.06).Exploratory analyses indicated that females exhibited more pronounced changes in emotional processing regions, while males showed greater changes in motor and sensory areas. Overall, the findings indicate that bullying victimization is associated with widespread structural differences in brain development from adolescence to early adulthood, with sex-specific trajectories.

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