Biology subjects

Wessa, M.

Publications and source records attributed to Wessa, M..

4 recordsLinked to original sources

bioRxiv2026

Structural Brain Network Alterations in Relation to Treatment and Illness Severity in Bipolar Disorder

BackgroundLarge-scale T1-weighted MRI studies have established grey-matter abnormalities in bipolar disorder (BD), with our group contributing to consensus findings. However, structural connectivity, particularly within emotion- and reward-related circuits, remains poorly understood. Diffusion-weighted MRI (dMRI) enables investigation of white-matter pathways, yet prior work is constrained by small samples, methodological heterogeneity, and unclear medication effects. We conducted the largest dMRI network analysis in BD, relating symptom burden and polypharmacy to tractography-derived connectivity and graph-theoretic metrics. MethodsCross-sectional structural and diffusion MRI scans from 449 individuals with BD (35.7{+/-}12.6 years) and 510 controls (33.3{+/-}12.6 years), aged 18-65, were analyzed across 16 ENIGMA-BD sites. Standardized segmentation/parcellation and constrained spherical deconvolution tractography generated individual structural connectivity matrices. Graph-theoretic metrics of global and subnetwork organization were related to symptom severity and medications. ResultsBD showed widespread network alterations (lower density and efficiency, longer path length, and higher betweenness centrality), altered microstructural organization in a limbic-basal ganglia circuit, and abnormal streamline counts in a default-mode/salience/fronto-limbic-basal ganglia network. Longer illness duration, later onset, and psychosis history were associated with greater abnormalities in network architecture, whereas more manic episodes were associated with greater fronto-limbic connectivity. Antidepressant (particularly SSRI), anticonvulsant, and antipsychotic use related to poorer global and fronto-limbic connectivity; no clear lithium effects emerged. ConclusionsAs the largest structural connectivity study in BD, we reveal widespread disruption in reward and emotion-regulation networks influenced by illness severity and medication use. Results show that multisite harmonization is feasible and highlight ENIGMA-BD as a scalable framework for identifying reproducible neurobiological markers.

neuroscience↗

bioRxiv2025

The elusive neural signature of emotion regulation capabilities: evidence from a large-scale consortium

Cognitive reappraisal is a fundamental emotion regulation strategy for mental and physical well-being, but how its neural mechanisms relate to individual differences remains poorly understood. In a consortium effort analyzing 40 fMRI datasets (N=2,175), we examined the relationship between neural activation during reappraisal tasks and three core individual difference indices of reappraisal capabilities: (1) trait questionnaires, (2) task-based affective ratings, and (3) amygdala down-regulation. Strikingly, there was no shared overlap across these three common indices. Only a very weak correlation emerged between amygdala down-regulation and task-based affective ratings. Whole-brain analyses revealed no reliable neural associations with trait questionnaires, and associations with task-based affective ratings fell outside canonical emotion regulation networks (e.g., prefrontal circuitry). Moreover, amygdala down-regulation, often interpreted as a stable individual marker, was confounded by person-specific whole-brain responses -- a limitation extending to fMRI research beyond the emotion regulation domain. These findings challenge the assumption that an individuals prefrontal activity is a valid indicator of their reappraisal capabilities and suggest that common trait, behavioral, and neural measures might capture distinct facets of emotion regulation. More broadly, our results highlight concrete methodological challenges for fMRI research on individual differences, with implications extending beyond emotion regulation to the neuroscience of personality, psychopathology, and general well-being.

neuroscience↗

bioRxiv2021

Don't Stress, It's Under Control: Neural Correlates of Stressor Controllability in Humans

Animal research has repeatedly shown that experience of control over an aversive event can protect against the negative consequences of later uncontrollable stress. Neurobiologically, this effect is assumed to correspond to persistent changes in the pathway linking the ventromedial prefrontal cortex (vmPFC) and the dorsal raphe nucleus. However, it remains unclear to what extent these findings translate to humans. During functional magnetic resonance imaging, we subjected participants to controllable and uncontrollable aversive but non-painful electric stimuli, as well as to a control condition without aversive stimulation. In each trial, a symbol signalled whether participants could terminate the stressor through correct performance in a button-matching task or whether the stressor would be randomly terminated, i.e., uncontrollable. Along with neural responses, we assessed participants accuracy, reaction times, and heart rate. To relate neural activations and subjective experience, we asked participants to rate perceived control, helplessness, and stress. Results were largely in line with our hypotheses. The vmPFC was generally deactivated by stress, but this effect was attenuated when participants could terminate the stressor compared to when their responses had no effect. Furthermore, activation in stress-responsive regions, including the bilateral insula, was reduced during controllable trials. Under uncontrollable stress, greater vmPFC recruitment was linked to reduced feelings of helplessness. An investigation of condition-dependent differences in vmPFC connectivity yielded no significant results. Our findings further corroborate animal research and emphasise the role of the vmPFC in controllability-dependent regulation of stress responses. Based on the results, we discuss future directions in the context of resilience research and mental health promotion.

neuroscience↗

bioRxiv2018

A Combined Behavioral and Neuroimaging Battery to Test Positive Appraisal Style Theory of Resilience in Longitudinal Studies

Resilience is the maintenance or rapid recovery of mental health during and after stressor exposure. It is becoming increasingly clear that resilience results from a complex and dynamic process of adaptation to stressors involving the biological, psychological and social levels. Positive appraisal style theory of resilience (PASTOR) claims that the common final pathway to maintained mental health lies in the non-negative (non-catastrophizing, non-pessimistic) appraisal of potential stressors, permitting the organism to fine-tune stress responses to optimal levels, thus avoiding unnecessary stress, inefficient deployment of resources and concomitant deleterious allostatic load effects. Successful adaptation consists in developing or strengthening a positive appraisal style. Another key element of PASTOR is that a positive appraisal style is strongly determined by the efficacy and efficiency of the neural and cognitive processes that underlie positive stressor appraisal. We here present a combined behavioral and functional magnetic resonance imaging (fMRI) battery designed to assess such processes repeatedly in longitudinal settings. The battery includes tests of stress reactivity and recovery, reward sensitivity, safety learning and memory in the context of fear conditioning and extinction, volitional situation-focused reappraisal, volitional self-focused reappraisal, and emotional interference inhibition, along with structural MRI and resting-state MRI scans. A detailed description of the battery methods is provided. The feasibility of the battery was successfully tested in N=55 healthy subjects; group results of the individual tasks largely replicate existing literature.

neuroscience↗