Biology subjects

Holz, N.

Publications and source records attributed to Holz, N..

5 recordsLinked to original sources

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↗