To date, electroconvulsive therapy (ECT) is the most potent treatment in severe depression. Although ECT has been successfully applied in clinical practice for over 70 years, the underlying mechanisms of action remain unclear. We used functional MRI and a unique data-driven analysis approach to examine functional connectivity in the brain before and after ECT treatment. Our results show that ECT has lasting effects on the functional architecture of the brain. A comparison of pre-and posttreatment functional connectivity data in a group of nine patients revealed a significant cluster of voxels in and around the left dorsolateral prefrontal cortical region (Brodmann areas 44, 45, and 46), where the average global functional connectivity was considerably decreased after ECT treatment (P < 0.05, family-wise error-corrected). This decrease in functional connectivity was accompanied by a significant improvement (P < 0.001) in depressive symptoms; the patients' mean scores on the Montgomery Asberg Depression Rating Scale pre-and posttreatment were 36.4 (SD = 4.9) and 10.7 (SD = 9.6), respectively. The findings reported here add weight to the emerging "hyperconnectivity hypothesis" in depression and support the proposal that increased connectivity may constitute both a biomarker for mood disorder and a potential therapeutic target. T he treatment of depressive disorder is one of the most pressing issues in contemporary medical practice: The illness is a leading cause of significant disability worldwide (1). Current therapeutic strategies are imperfect, and there is an urgent need to develop more consistently effective and rapidly acting treatment solutions. Unfortunately, our understanding of the etiopathology of mood disorder is incomplete. As a result, the elucidation of the mechanisms of action of effective treatment has necessarily been less than secure and advance has been slow. Available treatments (e.g., chemical antidepressant therapy) were discovered serendipitously rather than designed, and insight into the biology of depressive disorder by study of antidepressant actions has been limited. In particular, the effectiveness of electroconvulsive therapy (ECT), the most potent and rapidly acting of all antidepressant agents (2), has eluded a coherent explanatory framework despite its regular use for more than 70 years. However, if the effects of ECT could be reproduced in a less invasive way, and with a more benign side-effect profile, the treatment of severe depression would be significantly enhanced. To achieve this, we need first to understand better how ECT influences brain function. Here, we show that ECT alters the functional architecture of frontal systems by strongly down-regulating connectivity in key circuits implicated in mood disorder.Efforts to delineate the neural substrate of mood disorder using functional brain imaging technology have generally identified abnormal frontal cortical and limbic activity in depressed patients (3-9). Although such regional findings tend to correspond anatomically to tho...

A major challenge in the diagnosis of disorders of consciousness is the differential diagnosis between the vegetative state (VS) and the minimally conscious state (MCS). Clinically, VS is defined by complete unawareness, whereas MCS is defined by the presence of inconsistent but clearly discernible behavioural signs of consciousness. In healthy individuals, pain cries have been reported to elicit functional activation within the pain matrix of the brain, which may be interpreted as empathic reaction. In this study, pain cries were presented to six VS patients, six MCS patients, and 17 age-matched healthy controls. Conventional task-related functional magnetic resonance imaging (fMRI) showed no significant differences in functional activation between the VS and MCS groups. In contrast to this negative finding, the application of a novel data-driven technique for the analysis of the brain's global functional connectivity yielded a positive result. The weighted global connectivity (WGC) was significantly greater in the MCS group compared to the VS group (p < 0.05, family-wise error corrected). Using areas of significant WGC differences as 'seed regions' in a secondary connectivity analysis revealed extended functional networks in both MCS and healthy groups, whereas no such long-range functional connections were observed in the VS group. These results demonstrate the potential of functional connectivity MRI (fcMRI) as a clinical tool for differential diagnosis in disorders of consciousness.

The zebrafish has the capacity to regenerate its heart after severe injury. While the function of a few genes during this process has been studied, we are far from fully understanding how genes interact to coordinate heart regeneration. To enable systematic insights into this phenomenon, we generated and integrated a dynamic co-expression network of heart regeneration in the zebrafish and linked systems-level properties to the underlying molecular events. Across multiple post-injury time points, the network displays topological attributes of biological relevance. We show that regeneration steps are mediated by modules of transcriptionally coordinated genes, and by genes acting as network hubs. We also established direct associations between hubs and validated drivers of heart regeneration with murine and human orthologs. The resulting models and interactive analysis tools are available at http://infused.vital-it.ch. Using a worked example, we demonstrate the usefulness of this unique open resource for hypothesis generation and in silico screening for genes involved in heart regeneration.

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