Biology subjects

Holz, N.

Publications and source records attributed to Holz, N..

10 recordsLinked to original sources

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.

neuroscience↗

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.

neuroscience↗

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.

neuroscience↗

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.

neuroscience↗

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.

neuroscience↗

bioRxiv2024

Reward processing in children with Affective Dysregulation

IntroductionAffective dysregulation (AD) in children is characterized by irritability, anger, and frequent intense temper outbursts. Considerable evidence implies altered processing of frustration about missed rewards, but few studies investigated the preceding and thus potentially predictive reward anticipation and initial delivery processing in children with AD. MethodsA total of 103 children aged 8 to 12 years (50 with AD and 53 without AD) were examined during a monetary reward anticipation task with event-related potential (ERP) components resolving reward anticipation (cue-CNV [Contingent Negative Variation]) and reward delivery phases (Reward Positivity and Feedback-Related Negativity). All components were analyzed by repeated measures ANOVA. Regression analyses also evaluated the associations between those ERP components and dimensional AD symptoms. ResultsChildren with AD showed attenuated anticipatory reward processing compared to No-ADs. The CNV at fronto-central site (FCz) showed a significant group effect (No-AD>AD, p=0.017). Post-hoc test showed that this group difference was stronger for the cue monetary condition (monetary cue: p=.007, d=0.56, verbal cue: p=.901, d=0.16), and that only the No-AD group showed a significant difference between conditions (p<0.001). No significant effects were obtained for the delivery phase. Regression analysis showed that a reduced anticipatory CNV at FCz significantly explained AD symptoms, and that anger/irritability and anxiety/depressive symptoms predicted a reduced anticipatory CNV at FCz. ConclusionThis neurophysiological characterization of reward anticipation and delivery in children with AD demonstrates altered neural activity in AD during anticipation of reward rather than following the delivery (or omission) of the reward itself. Our results highlight that altered reward anticipation in AD can occur outside frustration-prone tasks or settings, and underline the important role of both anger/irritability and anxiety/depressive symptoms in the pathophysiology of AD for atypical reward anticipation.

neuroscience↗

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.

neuroscience↗

bioRxiv2024

Variation in moment-to-moment brain state engagement changes across development and contributes to individual differences in executive function

Neural variability, or variation in brain signals, facilitates dynamic brain responses to ongoing demands. This flexibility is important during development from childhood to young adulthood, a period characterized by rapid changes in experience. However, little is known about how variability in the engagement of recurring brain states changes during development. Such investigations would require the continuous assessment of multiple brain states concurrently. Here, we leverage a new computational framework to study state engagement variability (SEV) during development. A consistent pattern of SEV changing with age was identified across cross-sectional and longitudinal datasets (N>3000). SEV developmental trajectories stabilize around mid-adolescence, with timing varying by sex and brain state. SEV successfully predicts executive function (EF) in youths from an independent dataset. Worse EF is further linked to alterations in SEV development. These converging findings suggest SEV changes over development, allowing individuals to flexibly recruit various brain states to meet evolving needs.

neuroscience↗

bioRxiv2024

Adolescent maturation of cortical excitation-inhibition balance based on individualized biophysical network modeling

The balance of excitation and inhibition is a key functional property of cortical microcircuits which changes through the lifespan. Adolescence is considered a crucial period for the maturation of excitation-inhibition balance. This has been primarily observed in animal studies, yet human in vivo evidence on adolescent maturation of the excitation-inhibition balance at the individual level is limited. Here, we developed an individualized in vivo marker of regional excitation-inhibition balance in human adolescents, estimated using large-scale simulations of biophysical network models fitted to resting-state functional magnetic resonance imaging data from two independent cross-sectional (N = 752) and longitudinal (N = 149) cohorts. We found a widespread relative increase of inhibition in association cortices paralleled by a relative age-related increase of excitation, or lack of change, in sensorimotor areas across both datasets. This developmental pattern co-aligned with multiscale markers of sensorimotor-association differentiation. The spatial pattern of excitation-inhibition development in adolescence was robust to inter-individual variability of structural connectomes and modeling configurations. Notably, we found that alternative simulation-based markers of excitation-inhibition balance show a variable sensitivity to maturational change. Taken together, our study highlights an increase of inhibition during adolescence in association areas using cross sectional and longitudinal data, and provides a robust computational framework to estimate microcircuit maturation in vivo at the individual level.

neuroscience↗

bioRxiv2023

Early life adversities affect expected value signaling in the adult brain

BackgroundEarly adverse experiences are assumed to affect fundamental processes of reward learning and decision-making. However, computational neuroimaging studies investigating these circuits are sparse and limited to studies that investigated adversities retrospectively in adolescent samples. MethodsWe used prospective data from a longitudinal birth cohort study (n=156, 87 females, mean age=32.2) to investigate neurocomputational components underlying reinforcement learning in an fMRI-based passive avoidance task. We applied a principal component analysis to capture common variation across seven prenatal and postnatal adversity measures. The resulting adversity factors (factor 1: postnatal psychosocial adversities and prenatal maternal smoking, factor 2: prenatal maternal stress and obstetric adversity, and factor 3: lower maternal stimulation) and single adversity measures were then linked to computational markers of reward learning (i.e. expected value, prediction errors) in the core reward network. ResultsUsing the adversity factors, we found that adversities were linked to lower expected value representation in striatum, ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex (ACC). Expected value encoding in vmPFC further mediated the relationship between adversities and psychopathology. In terms of specific adversity effects, we found that obstetric adversity was associated with lower prediction error signaling in the vmPFC and ACC, whereas lower maternal stimulation was related to lower expected value encoding in the striatum, vmPFC, and ACC. ConclusionsOur results suggested that adverse experiences have a long-term disruptive effect on reward learning in several important reward-related brain regions, which can be associated with non-optimal decision-making and thereby increase the vulnerability of developing psychopathology.

neuroscience↗