Jiří Horáček

Purpose: We examine brain connectivity alterations in early‐stage schizophrenia, with a focus on patterns of hyper‐ and hypoconnectivity. Although altered functional connectivity (FC) is well documented in schizophrenia, substantial inconsistencies remain regarding the location and direction of specific dysconnections. We hypothesize that early FC changes in schizophrenia include both decreases and increases and are correlated with symptoms and medication levels, with insufficient preprocessing potentially masking out some of these effects. Method: Using a large sample of 100 first‐episode schizophrenia patients (42 females) and 90 healthy controls (50 females), we compared FC across 90 brain regions defined by the Automated Anatomical Labeling atlas. We assessed medication effects and examined associations between FC changes and duration of untreated psychosis, duration of antipsychotic (AP) treatment, and symptom severity. In addition, we performed a systematic comparison of four functional magnetic resonance imaging data denoising strategies. Finding: Relative to controls, patients showed increased FC in 150 region pairs and decreased FC in 15 pairs, when using a “stringent” data denoising scheme. Despite this numerical imbalance, the overall distribution of FC changes remained balanced: Median FC was not systematically shifted, indicating no global bias toward hyper‐ or hypoconnectivity. Importantly, several FC alterations were significantly associated with symptom severity and AP medication. Conclusion: These findings indicate localized dysconnections embedded within a globally balanced connectivity profile in early schizophrenia. This balance was disrupted by less stringent denoising, leading to results dominated by hypoconnectivity, highlighting preprocessing as a major source of variability across studies.

Music is a central component of psychedelic settings, yet little experimental work has examined how psilocybin and musical composition influence music-evoked emotional responses in healthy volunteers. This exploratory, double-blind, placebo-controlled study assessed these effects during the plateau phase of psilocybin and the corresponding time window in placebo sessions following oral administration of psilocybin (0.26 mg/kg) or placebo. The study consisted of two parts. In Part 1 (n = 19), a pilot stage, the first half of participants rated music-induced affective valence for eight compositions representing different genres/subgenres (Rock/Punk, Metal/Industrial Metal, Metal/Industrial Metal, Classical/Baroque, Electronic/Dub, Folk/Nordic Folk, Electronic/Techno, Electronic/Trance, Electronic/Psytrance) using a visual analogue scale (VAS). Based on Part 1, the classical composition with the highest overall affective valence and the psytrance composition with the largest psilocybin–placebo contrast (i.e., the composition most responsive to psilocybin) were selected for Part 2 (n = 17), in which the second half of participants assessed emotional responses to music using the Geneva Emotional Music Scale (GEMS-9). Psilocybin increased wonder, transcendence, and joyful activation across both contrasting compositions. Relative to each other, the classical composition elicited greater peacefulness, tenderness, and nostalgia, whereas the psytrance composition elicited greater tension across both psilocybin and placebo conditions. A composition × condition interaction was observed for sadness: under psilocybin, sadness increased during the classical composition and decreased during the psytrance composition. These findings suggest that psilocybin and contrasting musical compositions independently influence different aspects of music-evoked emotional responses, with limited interaction effects, and point to potential implications for protocol design and music selection in psychedelic settings.

Background: Ketamine is a rapid-acting antidepressant with robust evidence, but unclear predictors of therapeutic response. Objectives: Based on previous knowledge, hemodynamic parameters and acute altered state of consciousness have been hypothesized as potential correlates of subsequent antidepressant outcome. Design: A post hoc analysis was performed using the data from an open-label study, in which 39 patients with depression received a single intravenous infusion of ketamine (0.54 mg/kg). Antidepressant response was defined as ⩾50% reduction in the Montgomery–Åsberg Depression Rating Scale (MADRS) at day 7. Methods: Systolic and diastolic blood pressure (SBP and DBP), heart rate, Clinician-Administered Dissociative States Scale (CADSS) and Brief Psychiatric Rating Scale (BPRS) were assessed during the infusion, alongside plasma levels of ketamine and norketamine. Data were analyzed using mixed-effects models and correlation and regression techniques. Results: Responders exhibited significantly higher SBP and DBP during ketamine infusion compared with nonresponders. The degree of dissociation or psychotomimetic symptoms during the infusion did not differ significantly between responders and nonresponders. Antipsychotic (AP) augmentation was associated with worse antidepressant outcome as well as with lower infusion-related blood pressure values. CADSS and BPRS did not differ between AP users and nonusers. None of the parameters correlated with plasma levels of ketamine or norketamine. Conclusion: Higher blood pressure during ketamine administration was associated with better antidepressant outcome, supporting the hypothesis concerning sympathetic activation in treatment responders. Psychological parameters (as measured by CADSS and BPRS) were not linked to subsequent outcomes and did not resolve inconsistencies in previous studies. Concomitant antipsychotic medication attenuated ketamine’s antidepressant effects. Trial registration: EudraCT 2018-001539-39.

An increasing number of studies are currently focusing on ‘personality neuroscience’, a term denoting the research aimed at neuroimaging correlates of inter-individual temperament and character variability. Among other methods, a graph theoretical analysis of the functional connectivity in resting-state functional magnetic resonance imaging data was applied in a study by Gao et al. (2013), reporting novel functional connectivity correlates of personality traits. The current paper presents a conceptual replication of the results of this study and discusses the related challenges, including an extension of the original statistical methods in order to illustrate the effect of the multiple comparison problem. Five personality dimensions were obtained using the revised ‘Big Five’ Personality Inventory, including scores of Extraversion and Neuroticism covered in the original paper. Using a larger sample (84 subjects) with adequate statistical power (ranging from 0.75 to 0.95 across analyses), we failed to replicate any of the nine specific neuroimaging correlates of personality presented by Gao et al. While acknowledging differences in the experimental procedures, we discuss that the lack of replication might be caused by the relatively liberal control of false positives in the original study. Indeed, the original testing scheme leads to an expected count of about 10 false positive observations among all tests; applying this scheme to our data we observed a similar number of positive tests, albeit for different relations. No significant correlations were found in our data when standard family-wise error control was applied. These results illustrate the importance of combining exploration with independent validation, use of large datasets, as well as appropriate control of multiple comparison problem in order to prevent false alarms in research into neural substrates of personality differences. Importantly, our findings do not disprove the existence of a link between personality and the brain’s intrinsic functional architecture; but rather suggest that such a link might be even more subtle and elusive than previously reported.

The relationship between personality and brain activity has been an increasingly popular topic of neuroscientific research. Naturalistic viewing has been shown to enhance individual differences and might, therefore, be particularly useful for exploring this relationship. Here, we thus examine neural signatures of personality using naturalistic fMRI of 82 healthy subjects. We implemented a simple dimensionality reduction method to characterize brain activity by its “typicality,” assessed a range of personality traits using widely‐used personality inventories, and tested the relationship between the two. We found that there is, indeed, a relationship between personality and the typicality of brain activity, which appears to be most consistently manifested by lower typicality in subjects with higher Neuroticism/Harm Avoidance. Our results highlight the usefulness of naturalistic viewing data for exploring the relationship between individual differences in personality and brain activity.

While schizophrenia diagnosis relies on clinical interviews, there is growing interest in neuroimaging-based computational tools to aid classification. In particular, resting-state fMRI-derived functional connectivity has been explored as a potential biomarker, with applications not only in supporting clinical assessment but also in research contexts such as patient stratification and probing disease mechanisms. Here, we compare two common approaches to computing functional connectivity - region of interest (ROI)-level and brain network-level - and evaluate their predictive power for classifying first-episode schizophrenia patients, in contrast to most prior work focusing on chronic patients. We show that ROI-level features consistently outperform network-level features. Despite the simplicity of our classification models, we achieved accuracies up to 83.15% using the AAL90 atlas. We also found that non-lagged functional connectivity generally outperforms lagged variants, suggesting that added temporal complexity may introduce noise rather than improve predictive power. Overall, our findings highlight region-based connectivity from a medium-resolution atlas as a promising representation for early-stage schizophrenia classification, while emphasising the need for validation on independent datasets to confirm generalisability.

People worldwide are confronted with environmental and sociopolitical stressors that act as potent sources of subjective uncertainty. The uncertainty arising in response to the volatility and unpredictability of adversities is amplified by their representation or misrepresentation in media news. While the causal effect of media news on vicarious traumatization has been well established, we argue that the impact of negative media news is principally related to distress and anxiety stemming from the uncertainty-inducing effect of media representations of the state of the world. As a growing body of research suggests, minimizing uncertainty related to global stressors is a significant driver of media news use. However, extensive media exposure perpetuates stress and is associated with symptoms of psychopathology. The self-perpetuating vicious circle of worry and excessive media consumption has been amply confirmed by new research related to the COVID-19 pandemic. Furthermore, attempts to alleviate stress and anxiety stemming from uncertainties often result in maladaptive strategies. In particular, the adoption of rigid behavioral patterns may prompt various forms of socially detrimental behavior. Critical factors in prevention and remediation include limiting media overexposure and implementing therapeutic interventions that focus on increasing tolerance to uncertainty.

In animal models, ketamine, a non-competitive N-methyl-D-aspartate (NMDA) antagonist, induces schizophrenia-like symptoms, such as positive and negative symptoms, as well as cognitive deficits. In the present study, we evaluated the behavioral responses and the number of EODs (electric organ discharges) of the weakly electric fish Gnathonemus petersii using the novel object recognition task (NORT). We aimed to investigate whether pharmacological modulation of the glutamatergic system would impair cognitive functions by administering the NMDA receptor antagonist ketamine, and whether these impairments could be suppressed by the administration of typical (first-generation) and atypical (second-generation) antipsychotics—clozapine and haloperidol, respectively. G. petersii preferred the familiar object over the novel object in the NORT paradigm. Although no significant differences were observed when exploring the two identical objects during the training session, the fish spent less time, moved a shorter distance, and emitted fewer EODs in the testing phase with the novel object. No direct relationship was detected between the EODs and behavioral responses to the administration of ketamine and typical antipsychotics. Ketamine administered with atypical antipsychotic clozapine disrupted the perception of the original object, where one of the objects was preferred. In the novel object trial, the time spent on the original and new objects was attenuated to the same level.