Costa, R. M. | bioRxiv Science

bioRxiv2018

Right-sided brain lesions predominate among patients with lesional mania: evidence from a systematic review and pooled lesion analysis

BackgroundDespite claims that lesional mania is associated with right-hemisphere lesions, supporting evidence is scarce, and association with specific brain areas has not been demonstrated.\n\nAimsTo test whether focal brain lesions in lesional mania are more often right-than left-sided, and if lesions converge on areas relevant to mood regulation.\n\nMethodsWe performed a systematic literature search (PROSPERO registration CRD42016053675) on PubMed and Web-Of-Science, using terms that reflected diagnoses and structures of interest, and lesional mechanisms. Two researchers reviewed the articles separately according to PRISMA Guidelines, to select reports of adult-onset hypomania, mania or mixed state following a focal brain lesion. When available, eligible lesion images were manually traced onto the corresponding slices of MNI space, and lesion topography analyzed using standard brain atlases. Pooled-analyses of individual patient data were performed.\n\nResultsData from 207 lesional mania patients was extracted from 110 reports. Among patients with focal lesions (N=197) more patients had lesions involving the right (84.3%) than the left (34.5%) hemisphere. Among 54 lesion images that were available, right-sided predominance of lesions was confirmed, and found to be was conserved across multiple brain regions, including the temporal lobe, fusiform gyrus and thalamus. These, in addition to several frontal lobe areas, were also identified as preferential lesion sites in comparisons with control lesions.\n\nConclusionsPooled-analyses, based on the most comprehensive dataset of lesional mania available to date, confirm a preferential association with right-hemisphere lesions, while suggesting that several brain areas/circuits, relevant to mood regulation, are most frequently affected.

neuroscience↗

bioRxiv2017

Single-Trial Inhibition of Anterior Cingulate Disrupts Model-based Reinforcement Learning in a Two-step Decision Task.

The anterior cingulate cortex (ACC) is implicated in learning the value of actions, but it remains poorly understood whether and how it contributes to model-based mechanisms that use action-state predictions and afford behavioural flexibility. To isolate these mechanisms, we developed a multi-step decision task for mice in which both action-state transition probabilities and reward probabilities changed over time. Calcium imaging revealed ramps of choice-selective neuronal activity, followed by an evolving representation of the state reached and trial outcome, with different neuronal populations representing reward in different states. ACC neurons represented the current action-state transition structure, whether state transitions were expected or surprising, and the predicted state given chosen action. Optogenetic inhibition of ACC blocked the influence of action-state transitions on subsequent choice, without affecting the influence of rewards. These data support a role for ACC in model-based reinforcement learning, specifically in using action-state transitions to guide subsequent choice. HighlightsO_LIA novel two-step task disambiguates model-based and model-free RL in mice. C_LIO_LIACC represents all trial events, reward representation is contextualised by state. C_LIO_LIACC represents action-state transition structure, predicted states, and surprise. C_LIO_LIInhibiting ACC impedes action-state transitions from influencing subsequent choice. C_LI

neuroscience↗