BACKGROUND.Although mania is characteristic of bipolar disorder, it can also occur following focal brain damage. Such cases may provide unique insight into brain regions responsible for mania symptoms and identify therapeutic targets. METHODS.Lesion locations associated with mania were identified using a systematic literature search (n = 41) and mapped onto a common brain atlas. The network of brain regions functionally connected to each lesion location was computed using normative human connectome data (resting-state functional MRI, n = 1000) and contrasted with those obtained from lesion locations not associated with mania (n = 79). Reproducibility was assessed using independent cohorts of mania lesions derived from clinical chart review (n = 15) and of control lesions (n = 490). Results were compared with brain stimulation sites previously reported to induce or relieve mania symptoms. RESULTS.Lesion locations associated with mania were heterogeneous and no single brain region was lesioned in all, or even most, cases. However, these lesion locations showed a unique pattern of functional connectivity to the right orbitofrontal cortex, right inferior temporal gyrus, and right frontal pole. This connectivity profile was reproducible across independent lesion cohorts and aligned with the effects of therapeutic brain stimulation on mania symptoms. CONCLUSION.Brain lesions associated with mania are characterized by a specific pattern of brain connectivity that lends insight into localization of mania symptoms and potential therapeutic targets.

No abstract

Background Major Depressive Disorder (MDD) in older adults is a serious public health concern. Repetitive transcranial magnetic stimulation (rTMS) is a non-pharmacological intervention approved for Major Depressive Disorder (MDD) treatment in adults, but its value in older adults remains unknown. The present study aims to systematically review and meta-analyze evidence of rTMS efficacy in MDD treatment among older adults. Methods We systematically reviewed the literature for randomized controlled trials (RCTs) and open-label studies assessing rTMS for the treatment of MDD in patients older than 50 years-old, published until June 2020. Random-effects meta-analyses using standardized mean differences (SMD) were conducted to assess change in depression severity score (primary outcome), while odds-ratios (OR) were used to assess secondary categorical outcomes (response and remission). Additionally, univariate meta-regression analyses were performed to identify potential predictors of change in depression severity scores. Results Fourteen RCTs were included in meta-analyses and 26 studies (10 RCTs and 16 open-label studies) in meta-regression. Active rTMS was significantly superior to sham-treatment for reduction of severity (SMD=0.36; 95%CI=0.13-0.60), as well as response (OR=3.26; 95%CI=2.11-5.04) and remission (OR=4.63; 95%CI=2.24-9.55). Studies were of moderate to high quality, with funnel plots and Egger’s regression test not suggestive of publication bias. In meta-regressions, higher mean age and number of sessions were significantly associated to greater improvement. Conclusions Our results support that rTMS is an effective, safe and well-tolerated treatment for MDD in older adults, and that it should be considered in the treatment of this vulnerable population.