Effects of non-invasive brain stimulation in multiple sclerosis: systematic review and meta-analysis

Objective: The objective of this meta-analysis was to summarize evidence on the therapeutic effects of non-invasive brain stimulation (NIBS) on core symptoms of multiple sclerosis (MS). Specifically, findings from studies deploying transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) protocols were summarized in this review. Methods: We systematically searched articles published in four databases, until 31 May 2021, which compared the effects of active tDCS or rTMS with sham intervention in MS patients. We used a random-effects model for this meta-analysis. Meta-regression and subgroup meta-analysis were used to examine the effects of stimulation dose and different stimulation protocols, respectively. Results: Twenty-five randomized controlled trials (RCTs) were included in this review, consisting of 19 tDCS and 6 rTMS studies. tDCS led to a significant and immediate reduction of fatigue with a large effect size (Hedges’s g = −0.870, 95% confidence intervals (CI) = [−1.225 to −0.458], number needed to treat (NNT) = 2). Particularly, a subgroup analysis showed that applying tDCS over the left DLPFC and bilateral S1 led to fatigue reductions compared to sham stimulation. Furthermore, tDCS had favorable effects on fatigue in MS patients with low physical disability but not those with high physical disability, and additionally improved cognitive function. Finally, whereas rTMS was observed to reduce muscle spasticity, these NIBS protocols showed no further effect on MS-associated pain and mood symptoms. Conclusion: tDCS in MS alleviates fatigue and improves cognitive function whereas rTMS reduces muscle spasticity. More high-quality studies are needed to substantiate the therapeutic effects of different NIBS protocols in MS

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

[Commentary]: The serotonin transporter in depression: Meta-analysis of in vivo and post mortem findings and implications for understanding and treating depression

Meta-analyses are one of the cornerstones of evidence-based medicine. This is especially true as pertains to clinical molecular imaging studies by single photon computed tomography (SPECT) and positron emission tomography (PET), many of which are underpowered due to their inherent expense and technical difficulty. For example, a formal analysis of the statistical power of [18F]fluorodeoxyglucose PET oncology studies highlighted the relationship between precision of the endpoint and the necessary group size for obtaining sensitivity to a 20% treatment effect (Doot et al., 2012). And yet, if sufficiently powered, molecular imaging can be the only way to obtain information about disease pathophysiology without confounds arising from ante mortem treatment and post mortem changes in the biomarker. The recent meta-analysis by Kambeitz and Howes (2015) reporting on the availability of plasma membrane serotonin transporters (SERT) in brain of patients with depressive disorders is a case in point; the summary yielded a total of 27 PET and SPECT imaging studies, comprising 514 patients and 555 healthy controls (although the composite group sizes reported in Results and Abstract differ), and revealed significantly lower SERT availability in several brain regions of the depression group. While the overall effect size (Hedges´ g) of approximately −0.3 is hardly pathognomonic of depression, the finding in such a large population confirms a long posited deficit or down-regulation of this marker of serotonin innervations (Spies et al., 2015), which furthermore could not be discerned in their additional meta-analysis of post mortem studies. The authors interpreted their results to support the importance of SERT as a molecular target for treatment of depression (despite the implication that most depressive patients have entirely normal SERT levels)..

Neural processes underlying mirror-induced visual illusion: an activation likelihood estimation meta-analysis

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Journal of Neuroimaging / Cortical Thickness Estimations of FreeSurfer and the CAT12 Toolbox in Patients with Alzheimers Disease and Healthy Controls

BACKGROUND AND PURPOSE Automated cortical thickness (CT) measurements are often used to assess gray matter changes in the healthy and diseased human brain. The FreeSurfer software is frequently applied for this type of analysis. The computational anatomy toolbox (CAT12) for SPM, which offers a fast and easytouse alternative approach, was recently made available. METHODS In this study, we compared region of interest (ROI)wise CT estimations of the surfacebased FreeSurfer 6 (FS6) software and the volumebased CAT12 toolbox for SPM using 44 elderly healthy female control subjects (HC). In addition, these 44 HCs from the crosssectional analysis and 34 age and sexmatched patients with Alzheimer's disease (AD) were used to assess the potential of detecting group differences for each method. Finally, a testretest analysis was conducted using 19 HC subjects. All data were taken from the OASIS database and MRI scans were recorded at 1.5 Tesla. RESULTS A strong correlation was observed between both methods in terms of ROI mean CT estimates (R2 = .83). However, CAT12 delivered significantly higher CT estimations in 32 of the 34 ROIs, indicating a systematic difference between both approaches. Furthermore, both methods were able to reliably detect atrophic brain areas in AD subjects, with the highest decreases in temporal areas. Finally, FS6 as well as CAT12 showed excellent testretest variability scores. CONCLUSION Although CT estimations were systematically higher for CAT12, this study provides evidence that this new toolbox delivers accurate and robust CT estimates and can be considered a fast and reliable alternative to FreeSurfer.(VLID)342385

Increasing Adiponectin Signaling by Sub-Chronic AdipoRon Treatment Elicits Antidepressant- and Anxiolytic-Like Effects Independent of Changes in Hippocampal Plasticity

(1) Background: Adiponectin is an adipocyte-secreted hormone that has antidepressant- and anxiolytic-like effects in preclinical studies. Here, we investigated the antidepressant- and anxiolytic-like effects of sub-chronic treatment with AdipoRon, an adiponectin receptor agonist, and its potential linkage to changes in hippocampal adult neurogenesis and synaptic plasticity. (2) Methods: Different cohorts of wild-type C57BL/6J and CamKIIα-Cre male mice were treated with sub-chronic (7 days) AdipoRon, followed by behavioral, molecular, and electrophysiological experiments. (3) Results: 7-day AdipoRon treatment elicited antidepressant- and anxiolytic-like effects but did not affect hippocampal neurogenesis. AdipoRon treatment reduced hippocampal brain-derived neurotrophic factor (BDNF) levels, neuronal activation in the ventral dentate gyrus, and long-term potentiation of the perforant path. The knockdown of N-methyl-D-aspartate (NMDA) receptor subunits GluN2A and GluN2B in the ventral hippocampus did not affect the antidepressant- and anxiolytic-like effects of AdipoRon. (4) Conclusions: Increasing adiponectin signaling through sub-chronic AdipoRon treatment results in antidepressant- and anxiolytic-like effects independent of changes in hippocampal structural and synaptic function