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Background: Bipolar disorder I (BD-I) is a heterogeneous disorder with a high prevalence of comorbid anxiety. The aim of this study was to investigate whether anxiety and mania symptoms define distinct subgroups within BD-I and to explore potential differences in functional network characteristics between these subgroups. Methods: Subgroups were identified using scores from clinical anxiety and mania scales. After dimension reduction of these scores, data-driven clustering analysis with cross-validation was employed to reveal the existence of subgroups. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were pre-processed using fMRIPrep. After parcellation and network construction, global and regional graph theoretical measures were calculated per subgroup. Results: Clustering results revealed that, based on anxiety symptomatology, subjects fell into two distinct subgroups, whereas mania symptoms divided subjects into four unique subgroups. These subgroups varied notably on several symptom scales. Network assortativity was significantly associated with anxiety subgroups. Post-hoc pairwise comparisons did not reveal significant global functional network differences between the anxiety subgroups or between mania subgroups. Regional network differences between clinical subgroups were especially apparent for strength and degree in the temporal and frontal lobes. Limitations: Small sample size of some subgroups is a limitation of this study as is the categorical rather than continuous representation of anxiety and mania symptoms. Conclusions: BD-I populations may be stratified into robust subgroups based on anxiety and mania symptoms, showing differences in functional network connectivity. Our findings highlight new avenues of research for investigating heterogeneity in psychiatric populations.

The cerebellum generates internal prediction models and actively compares anticipated and actual outcomes in order to reach a desired end state. In this process, reward can serve as a reinforcer that shapes internal prediction models, enabling context-appropriate behavior. While the involvement of the cerebellum in reward processing has been established in animals, there is no detailed account of which cerebellar regions are involved in reward anticipation and outcome processing in humans. To this end, an activation likelihood estimation meta-analysis of functional neuroimaging studies was performed to investigate cerebellar functional activity patterns associated with reward anticipation and outcome processing in healthy adults. Results showed that reward anticipation (k = 31) was associated with regional activity in the bilateral anterior lobe, bilateral lobule VI, left Crus I and the posterior vermis, while reward outcome (k = 16) was associated with regional activity in the declive and left lobule VI. These findings demonstrate distinct involvement of the cerebellum in reward anticipation and outcome processing as part of a predictive coding routine.

The original version of this article unfortunately contained an error. In the Methods section in the original version of the article, “five-point scale" should read “seven-point scale”.This typographical mistake has been amended in the corrected version of the article.

Objectives: Top-down stress regulation, important for military operational performance and mental health, involves emotional working memory and the dorsolateral prefrontal cortex (DLPFC). Multisession transcranial direct current stimulation (tDCS) applied over the DLPFC during working memory training has been shown to improve working memory performance. This study tested the hypothesis that combined tDCS with working memory training also improves top-down stress regulation. However, tDCS response differs between individuals. Resting-state electrophysiological brain activity was post hoc explored as a possible predictor of tDCS response. The predictive value of the ratio between slow-wave theta oscillations and fast-wave beta oscillations (theta/beta ratio) was examined, together with the previously identified tDCS response predictors age, education, and baseline working memory performance. Materials and Methods: Healthy military service members (n = 79) underwent three sessions of real or sham tDCS over the right DLPFC (anode: F4, cathode: behind C2) at 2 mA for 20 minutes during emotional working memory training (N-back task). At baseline and within a week after the tDCS training sessions, stress regulation was assessed by fear-potentiated startle responses and subjective fear in a threat-of-shock paradigm with instructed emotional downregulation. Results were analyzed in generalized linear mixed-effects models. Results: Threat-of-shock responses and emotional working memory performance showed no significant group-level effects of the real vs sham tDCS training intervention (p > 0.07). In contrast, when considering baseline theta/beta ratios or the other tDCS response predictors, exploratory results showed a trait-dependent beneficial effect of tDCS on emotional working memory training performance during the first session (p < 0.01). Conclusions: No evidence was found for effectivity of the tDCS training intervention to improve stress regulation in healthy