Explore the vast range of titles available.

Changes in the frontostriatal system activity support individuals’ perseverance in distressful thoughts and rigid, repetitive behaviours that define obsessive-compulsive disorder (OCD). Converging evidence from preclinical and clinical work suggests that OCD maps onto a functional imbalance in the ventral and dorsal frontostriatal circuits. However, the neural mechanisms supporting these dysregulations remain elusive, their association with symptom severity is unclear, and therapeutic interventions are limited. To address these gaps, we combined neuroimaging and behavioural data from individuals with OCD and controls with computational modelling. We found that bidirectionally decreasing spontaneous neural coupling in the ventromedial circuit while concurrently increasing dorsolateral cortico-striatal coupling delivered the highest functional improvements in OCD. The analysis of longitudinal changes in obsessions and compulsions with respect to modelled neural interventions supported our predictions. By highlighting behaviourally meaningful neural mechanisms hidden from traditional neuroimaging analysis, this study advances knowledge on the neural basis of OCD and provides new therapeutic targets for obsessions and compulsions. This study presents a computational framework describing OCD frontostriatal dynamics, offering possible intervention targets to normalise functional brain activity and reduce symptom severity.

Relational reasoning is the ability to infer and understand the relations between multiple elements. In humans, this ability supports higher cognitive functions and is linked to fluid intelligence. Relational complexity (RC) is a cognitive framework that offers a generalisable method for classifying the complexity of reasoning problems. To date, increased RC has been linked to static patterns of brain activity supported by the frontoparietal system, but limited work has assessed the multivariate spatiotemporal dynamics that code for RC. To address this, we conducted representational similarity analysis in two independent neuroimaging datasets (Dataset 1 fMRI, n = 40; Dataset 2 EEG, n = 45), where brain activity was recorded while participants completed a visuospatial reasoning task that included different levels of RC (Latin Square Task). Our findings revealed that spatially, RC representations were widespread, peaking in brain networks associated with higher‐order cognition (frontoparietal, dorsal‐attention, and cingulo‐opercular). Temporally, RC was represented in the 2.5–4.1 s post‐stimuli window and emerged in the alpha and beta frequency range. Finally, multimodal fusion analysis demonstrated that shared variability within EEG‐fMRI signals within higher‐order cortical networks were better explained by the theorized RC model, relative to a model of cognitive effort (CE). Altogether, the results further our understanding of the neural representations supporting relational processing, highlight the spatially distributed coding of RC and CE across cortical networks, and emphasize the importance of late‐stage, frequency‐specific neural dynamics in resolving RC. Using multimodal whole‐brain imaging, we found brain activity patterns corresponded to relational complexity (RC) transitions in higher‐cortical networks, encoded in frequency‐specific bands during late‐stage processing. Compared to an alternative model of “cognitive effort”, brain representations demonstrated stronger correspondence to RC, with individual encoding linked to participant performance.

Current behavioural treatment of obsessive‐compulsive disorder (OCD) is informed by fear conditioning and involves iteratively re‐evaluating previously threatening stimuli as safe. However, there is limited research investigating the neurobiological response to conditioning and reversal of threatening stimuli in individuals with OCD. A clinical sample of individuals with OCD (N = 45) and matched healthy controls (N = 45) underwent functional magnetic resonance imaging. While in the scanner, participants completed a well‐validated fear reversal task and a resting‐state scan. We found no evidence for group differences in task‐evoked brain activation or functional connectivity in OCD. Multivariate analyses encompassing all participants in the clinical and control groups suggested that subjective appraisal of threatening and safe stimuli were associated with a larger difference in brain activity than the contribution of OCD symptoms. In particular, we observed a brain‐behaviour continuum whereby heightened affective appraisal was related to increased bilateral insula activation during the task (r = 0.39, pFWE = .001). These findings suggest that changes in conditioned threat‐related processes may not be a core neurobiological feature of OCD and encourage further research on the role of subjective experience in fear conditioning. Studying brain imaging of patients with obsessive‐compulsive disorder (OCD) during a fear reversal task showed no significant brain activation differences with healthy controls. Multivariate analysis revealed that subjective appraisal had a greater impact on brain activity than OCD symptoms.

Relational reasoning is the ability to infer and understand the relations between multiple elements. In humans, this ability supports higher cognitive functions and is linked to fluid intelligence. Relational complexity (RC) is a cognitive framework that offers a generalisable method for classifying the complexity of reasoning problems. To date, increased RC has been linked to static patterns of brain activity supported by the frontoparietal system, but limited work has assessed the multivariate spatiotemporal dynamics that code for RC. To address this, we conducted representational similarity analysis in two independent neuroimaging datasets (Dataset 1 fMRI, n=40; Dataset 2 EEG, n=45), where brain activity was recorded while participants completed a visuospatial reasoning task that included different levels of RC (Latin Square Task). Our findings revealed that, spatially, RC representations were widespread, peaking in brain networks associated with higher-order cognition (frontoparietal, dorsal-attention, and cingulo-opercular). Temporally, RC was represented in the 2.5 - 4.1 seconds post-stimuli window and emerged in the alpha and beta frequency range. Finally, multimodal fusion analysis demonstrated that shared variability within EEG-fMRI signals within higher-order cortical networks were better explained by the theorised RC model, relative to a model of cognitive effort (CE). Altogether, the results further our understanding of the neural representations supporting relational processing, highlight the spatially distributed coding of RC and CE across cortical networks, and emphasise the importance of late-stage, frequency-specific neural dynamics in resolving RC.Competing Interest StatementC.R., L.C., and L.J.H. are involved in a not-for-profit clinical neuromodulation centre (Queensland Neurostimulation Centre). This centre had no role in the present study.Footnotes* Updated figures 1 and 3, provided additional supplementary material in response to reviewer feedback

New interventions are needed for obsessive-compulsive disorder. Here we present a randomized single-blinded, two-arm, parallel-group, sham-controlled clinical trial assessing the efficacy of prefrontal cortex stimulation in reducing obsessive-compulsive disorder symptoms and frontostriatal connectivity (ACTRN12616001687482). Conducted at a single academic center, the trial enrolled participants diagnosed with obsessive-compulsive disorder who underwent baseline clinical assessments and neuroimaging. The intervention comprised 20 weekday sessions of neuronavigated continuous theta burst stimulation of the frontal pole or sham. Participants and all staff assessing intervention outcomes were blind to the conditions. We enrolled a sample of 50 individuals (26 active continuous theta burst stimulation) who completed the neuroimaging and clinical assessments at the primary 4 week endpoint. Clinical data at the secondary 6 month endpoint were obtained from 46 participants (23 active). Symptoms of obsessive-compulsive disorder (primary outcome) decreased in both groups (active −4.35, P < 0.001; sham −5.92, P < 0.001), but there was no significant difference between groups (P = 0.33, ηp2 = 0.02). Likewise, there was no significant difference between groups in changes of frontal pole connectivity with the striatum (P = 0.09, ηp2 = 0.06). Changes in secondary outcomes (symptoms of anxiety and depression and localized frontal pole activity) did not differ between groups. Dropout rates did not vary between groups and the most common treatment-related adverse event in both groups was headache. Our findings suggest that frontal pole continuous theta burst stimulation is no different to sham in reducing obsessive-compulsive disorder symptoms. The absence of changes in brain activity prompts further evaluation of alternative stimulation protocols.Cocchi and coauthors report that continuous theta burst stimulation of the frontal pole shows no difference from sham in reducing symptoms of obsessive-compulsive disorder or frontostriatal connectivity.

Relational reasoning—the capacity to understand how elements relate to one another—is a defining feature of human intelligence, yet its computational basis remains unclear. Here, we combined human neuroimaging (7T fMRI) with artificial neural network modeling to identify circuit-level analogues of human reasoning computations. Using the Latin Square Task, we found that humans and transformers were able to generalize the task reliably, while standard architectures used in cognitive neuroscience could not. Analysing the transformer components revealed distinct computational roles: positional encoding captured the spatial structure of the task and aligned with representations in visual cortex, whereas attention encoded relational structure and mapped onto frontoparietal and default-mode networks. Attention weights tracked the relational complexity of the task, providing a computational analogue of working-memory demands. These results advance knowledge on the core computations supporting complex reasoning, highlighting attention-based architectures as powerful models for investigating the neural basis of higher cognition.

Gut inflammation is thought to modify brain activity and behaviour via modulation of the gut-brain axis. However, how relapsing and remitting exposure to peripheral inflammation over the natural history of inflammatory bowel disease (IBD) contributes to altered brain dynamics is poorly understood. Here, we used electroencephalography (EEG) to characterise changes in spontaneous spatiotemporal brain states in Crohns Disease (CD) (n = 40) and Ulcerative Colitis (UC) (n = 30), compared to healthy individuals (n = 28). We first provide evidence of a significantly perturbed and heterogeneous microbial profile in CD, consistent with previous work showing enduring and long-standing dysbiosis in clinical remission. Results from our brain state assessment show that CD and UC exhibit alterations in the temporal properties of states implicating default-mode network, parietal, and visual regions, reflecting a shift in the predominance from externally to internally-oriented attentional modes. We investigated these dynamics at a finer sub-network resolution, showing a CD-specific and highly selective enhancement of connectivity between the insula and mPFC, regions implicated in cognitive-interoceptive appraisal mechanisms. Alongside overall higher anxiety scores in CD, we also provide preliminary support to suggest that the strength of chronic interoceptive hyper-signalling in the brain co-occurs with disease duration. Together, our results demonstrate that a long-standing diagnosis of CD is, in itself, a key factor in determining the risk of developing altered brain network signatures. Competing Interest Statement The authors have declared no competing interest.

Human decision making is modified by emotional state. Rodents exhibit similar biases during interpretation of ambiguous cues that can be altered by affective state manipulations. In this study, the impact of negative affective state on judgement bias in rats was measured using an ambiguous-cue interpretation task. Acute treatment with an anxiogenic drug (FG7142), and chronic restraint stress and social isolation both induced a bias towards more negative interpretation of the ambiguous cue. The diffusion model was fit to behavioural data to allow further analysis of the underlying decision making processes. To uncover the way in which parameters vary together in relation to affective state manipulations, independent component analysis was conducted on rate of information accumulation and distances to decision threshold parameters for control data. Results from this analysis were applied to parameters from negative affective state manipulations. These projected components were compared to control components to reveal the changes in decision making processes that are due to affective state manipulations. Negative affective bias in rodents induced by either FG7142 or chronic stress is due to a combination of more negative interpretation of the ambiguous cue, reduced anticipation of the high reward and increased anticipation of the low reward.

Anhedonia - a diminished interest or pleasure in activities - is a core self-reported symptom of depression which is poorly understood and often resistant to conventional antidepressants. This symptom may occur due to dysfunction in one or more sub-components of reward processing: motivation, consummatory experience and/or learning. However, the precise impairments remain elusive. Dissociating these components (ideally, using cross-species measures) and relating them to the subjective experience of anhedonia is critical as it may benefit fundamental biology research and novel drug development. Using a battery of behavioural tasks based on rodent assays, we examined reward motivation (Joystick-Operated Runway Task, JORT; and Effort-Expenditure for Rewards Task, EEfRT) and reward sensitivity (Sweet Taste Test) in a non-clinical population who scored high (N = 32) or low (N = 34) on an anhedonia questionnaire (Snaith-Hamilton Pleasure Scale). Compared to the low anhedonia group, the high anhedonia group displayed marginal impairments in effort-based decision-making (EEfRT) and reduced reward sensitivity (Sweet Taste Test). However, we found no evidence of a difference between groups in physical effort exerted for reward (JORT). Interestingly, whilst the EEfRT and Sweet Taste Test correlated with anhedonia measures, they did not correlate with each other. This poses the question of whether there are subgroups within anhedonia; however, further work is required to directly test this hypothesis. Our findings suggest that anhedonia is a heterogeneous symptom associated with impairments in reward sensitivity and effort-based decision-making.

Isoprene is a key trace component of the atmosphere emitted by vegetation and other organisms. It is highly reactive and can impact atmospheric composition and climate by affecting the greenhouse gases ozone and methane and secondary organic aerosol formation. Marine fluxes are poorly constrained due to the paucity of long-term measurements; this in turn limits our understanding of isoprene cycling in the ocean. Here we present the analysis of isoprene concentrations in the atmosphere measured across the Southern Ocean over 4 months in the summertime. Some of the highest concentrations ( >500 ppt) originated from the marginal ice zone in the Ross and Amundsen seas, indicating the marginal ice zone is a significant source of isoprene at high latitudes. Using the United Kingdom Earth System Model we show that current estimates of sea-to-air isoprene fluxes underestimate observed isoprene by a factor >20. A daytime source of isoprene is required to reconcile models with observations. The model presented here suggests such an increase in isoprene emissions would lead to >8% decrease in the hydroxyl radical in regions of the Southern Ocean, with implications for our understanding of atmospheric oxidation and composition in remote environments, often used as proxies for the pre-industrial atmosphere. High atmospheric concentrations of isoprene have been observed in the Southern Ocean. The authors investigate their potential marine sources and show how these emissions impact the modelling of atmospheric processes and composition in remote environments.