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The functional role of the basal ganglia (BG) in the gating of suitable motor responses to the cortex is well established. Growing evidence supports an analogous role of the BG during working memory encoding, a task phase in which the “input-gating” of relevant materials (or filtering of irrelevant information) is an important mechanism supporting cognitive capacity and the updating of working memory buffers. One important aspect of stimulus relevance is the novelty of working memory items, a quality that is understudied with respect to its effects on corticostriatal function and connectivity. To this end, we used functional magnetic resonance imaging (fMRI) in 74 healthy volunteers performing an established Sternberg working memory task with different task phases (encoding vs. retrieval) and degrees of stimulus familiarity (novel vs. previously trained). Activation analyses demonstrated a highly significant engagement of the anterior striatum, in particular during the encoding of novel working memory items. Dynamic causal modeling (DCM) of corticostriatal circuit connectivity identified a selective positive modulatory influence of novelty encoding on the connection from the dorsolateral prefrontal cortex (DLPFC) to the anterior striatum. These data extend prior research by further underscoring the relevance of the BG for human cognitive function and provide a mechanistic account of the DLPFC as a plausible top-down regulatory element of striatal function that may facilitate the “input-gating” of novel working memory materials. [ABSTRACT FROM AUTHOR]

The debilitating effects of social dysfunction in many psychiatric disorders prompt the need for systems-level biomarkers of social abilities that can be applied in clinical populations and longitudinal studies. A promising neuroimaging approach is the animated shapes paradigm based on so-called Frith-Happé animations (FHAs) which trigger spontaneous mentalizing with minimal cognitive demands. Here, we presented FHAs during functional magnetic resonance imaging to 46 subjects and examined the specificity and sensitivity of the elicited social brain responses. Test–retest reliability was additionally assessed in 28 subjects within a two-week interval. Specific responses to spontaneous mentalizing were observed in key areas of the social brain with high sensitivity and independently from the variant low-level kinematics of the FHAs. Mentalizing-specific responses were well replicable on the group level, suggesting good-to-excellent cross-sectional reliability [intraclass correlation coefficients (ICCs): 0.40–0.99; dice overlap at Puncorr<0.001: 0.26–1.0]. Longitudinal reliability on the single-subject level was more heterogeneous (ICCs of 0.40–0.79; dice overlap at Puncorr<0.001: 0.05–0.43). Posterior temporal sulcus activation was most reliable, including a robust differentiation between subjects across sessions (72% of voxels with ICC>0.40). These findings encourage the use of FHAs in neuroimaging research across developmental stages and psychiatric conditions, including the identification of biomarkers and pharmacological interventions. [ABSTRACT FROM AUTHOR]

Pharmacotherapy is effective in helping many patients suffering from psychiatric and neurological disorders, and both psychotherapeutic and stimulation-based techniques likewise have important roles to play in their treatment. However, therapeutic progress has recently been slow. Future success for improving the control and prevention of brain disorders will depend upon deeper insights into their causes and pathophysiological substrates. It will also necessitate new and more rigorous methods for identifying, validating, developing and clinically deploying new treatments. A field of Research and Development (R and D) that remains critical to this endeavour is Neuropsychopharmacology which transformed the lives of patients by introducing pharmacological treatments for psychiatric disorder some 60 years ago. For about half of this time, the European College of Neuropsychopharmacology (ECNP) has fostered efforts to enhance our understanding of the brain, and to improve the management of psychiatric disorders. Further, together with partners in academia and industry, and in discussions with regulators and patients, the ECNP is implicated in new initiatives to achieve this goal. This is then an opportune moment to survey the field, to analyse what we have learned from the achievements and failures of the past, and to identify major challenges for the future. It is also important to highlight strategies that are being put in place in the quest for more effective treatment of brain disorders: from experimental research and drug discovery to clinical development and collaborative ventures for reinforcing “R and D”. The present article sets the scene, then introduces and interlinks the eight articles that comprise this Special Volume of European Neuropsychopharmacology. A broad-based suite of themes is covered embracing: the past, present and future of “R and D” for psychiatric disorders; complementary contributions of genetics and epigenetics; efforts to improve the treatment of depression, neurodevelopmental and neurodegenerative disorders; and advances in the analysis and neuroimaging of cellular and cerebral circuits. [ABSTRACT FROM AUTHOR]

Abstract: The investigation of the brain connectome with functional magnetic resonance imaging (fMRI) and graph theory analyses has recently gained much popularity, but little is known about the robustness of these properties, in particular those derived from active fMRI tasks. Here, we studied the test–retest reliability of brain graphs calculated from 26 healthy participants with three established fMRI experiments (n-back working memory, emotional face-matching, resting state) and two parcellation schemes for node definition (AAL atlas, functional atlas proposed by Power et al.). We compared the intra-class correlation coefficients (ICCs) of five different data processing strategies and demonstrated a superior reliability of task-regression methods with condition-specific regressors. The between-task comparison revealed significantly higher ICCs for resting state relative to the active tasks, and a superiority of the n-back task relative to the face-matching task for global and local network properties. While the mean ICCs were typically lower for the active tasks, overall fair to good reliabilities were detected for global and local connectivity properties, and for the n-back task with both atlases, smallworldness. For all three tasks and atlases, low mean ICCs were seen for the local network properties. However, node-specific good reliabilities were detected for node degree in regions known to be critical for the challenged functions (resting-state: default-mode network nodes, n-back: fronto-parietal nodes, face-matching: limbic nodes). Between-atlas comparison demonstrated significantly higher reliabilities for the functional parcellations for global and local network properties. Our findings can inform the choice of processing strategies, brain atlases and outcome properties for fMRI studies using active tasks, graph theory methods, and within-subject designs, in particular future pharmaco-fMRI studies. [Copyright &y& Elsevier]