Effects of non-invasive prefrontal neuromodulation on acute cortisol response to stress: A systematic review and meta-analysis.

Can a single session of noninvasive brain stimulation applied over the prefrontal cortex prevent stress-induced cortisol release?

Background: Non-invasive brain stimulation (NIBS) has been used as a probe to modulate cognitive functions in humans for the last 20 years. The two most commonly reported techniques are transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), which have both been used with different stimulation parameters to increase or decrease excitability in target cortical regions. Aims: In the present review, we highlight recent developments in TMS and tDCS in language research in healthy individuals. Main Contribution: We will first describe how tDCS and TMS have been employed to improve either performance of language tasks, or learning in the language domain (facilitatory brain stimulation). Then, we will show how these techniques were used as interference techniques (inhibitory brain stimulation) for understanding brain–behaviour interactions and to explore possible cause–effect links between altered activity in specific brain areas and particular behaviours. We will only review studies in healthy individuals, and first pilot trials in patient population with more general cognitive impairments (idiopathic Parkinson's Disease, Alzheimer's Disease). For tDCS studies in aphasia, see Holland and Crinion (2012); for TMS studies in aphasia, see Medina et al. (2012). Conclusions: In the healthy brain, NIBS can be used to delineate the functional significance of a particular brain region for the respective language task under study. Here, new possibilities of combining TMS or tDCS with functional imaging techniques offer unique opportunities to not only address the functional significance of a brain area underlying the coil or electrode, but in addition allow testing NIBS effects on an entire network. In this setting, TMS, both in its single-pulse and its repetitive form, allows the modulation of a specific function within milliseconds (single-pulse) or the order of seconds (particularly high-frequency rTMS trains), while tDCS has the disadvantage of requiring longer stimulation times. On the other hand, the relatively easy use of tDCS in the magnetic resonance scanner environment will render simultaneous recording of brain function and activation much more accessible, thus offering novel avenues in the study of network effects of NIBS. For proof-of principle studies to improve language learning in the healthy brain, tDCS may be the most fruitful approach due to its easy applicability and excellent safety profile. Subsequent use of this technique in parallel to training protocols to improve re-acquisition of language functions aphasic patients offers exciting possibilities in the realm of neurorehabilitation.

Home-based transcranial static magnetic field stimulation of the motor cortex for treating levodopa-induced dyskinesias in Parkinson's disease: A randomized controlled trial

Transcranial static magnetic field stimulation (tSMS) can induce functional recovery in patients with subacute stroke

Background: Schizophrenia is a mental disorder with significant social and economic burden. Although current pharmacological treatments are effective for controlling the positive symptoms, medications have small-to-no effect for the treatment of negative symptoms. Noninvasive Brain Stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and trigeminal nerve stimulation (TNS) are emerging as neuroplasticity enhancer, boosting treatment response for refractory symptoms in Schizophrenia. Objective: To assess the efficacy of non-invasive brain stimulation for negative symptoms in schizophrenia in randomized clinical trials (RCTs). Methods: A systematic review in the Medline and Cochrane Library databases was performed up to May 31, 2017. The primary outcome was the Hedges’ g for continuous scores in a random effects model. Heterogeneity was evaluated with the I 2 and the χ2 test. Publication bias was assessed using the Begg’s funnel plot. Meta-regression was performed usingthe random-effects model modified by Knapp and Hartung. Results: We included 31 RCTs (n=1272); most with small-to-modest sample sizes. Active stimulation was significantly superior over sham for negative symptoms (Hedges’ g = 0.23; 95% CI 0.11 – 0.34). The funnel plot and the Eggers test showed that heterogeneity and the risk of publication bias were low (I2 =2.3%, p=0.429 for the χ2 test; p=0.179 for the Egger’s test). Meta-regression showed no influence of any variable on the results found. Both transcranial magnetic stimulation and transcranial direct current stimulation were superior to sham. In a subgroup analysis, no trial was alone responsible for the positive results observed. Conclusion: NIBS active was superior to sham stimulation for the amelioration of negative symptoms in schizophrenia. We found no considerable heterogeneity or publication bias in our analysis, corroborating to the strength of our findings. Further RCTs with larger sample sizes are needed to clarify the precise impact of NIBS in negative symptoms in schizophrenia.

The aim of this systematic review is to analyze the efficacy of noninvasive brain stimulation (NBS) in the treatment of central post-stroke pain (CPSP). We included randomized controlled trials testing the efficacy of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation versus placebo or other usual therapy in patients with CPSP. Articles in English, Portuguese, Spanish, Italian, and French were included. A bibliographic search was independently conducted on June 1, 2022, by two authors, using the databases MEDLINE (PubMed), Embase (Elsevier), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science Core Collection. The risk of bias was assessed using the second version of the Cochrane risk of bias (RoB 2) tool and the certainty of the evidence was evaluated through Grading of Recommendations Assessment, Development and Evaluation. A total of 2,674 records were identified after removing duplicates, of which 5 eligible studies were included, involving a total of 119 patients. All five studies evaluated repetitive TMS, four of which stimulated the primary motor cortex (M1) and one stimulated the premotor/dorsolateral prefrontal cortex. Only the former one reported a significant pain reduction in the short term, while the latter one was interrupted due to a consistent lack of analgesic effect. NBS in the M1 area seems to be effective in reducing short-term pain; however, more high-quality homogeneous studies, with long-term follow-up, are required to determine the efficacy of this treatment in CSPS.

Aim: To evaluate the effects of a single session of non-invasive brain stimulation (NIBS) on postural balance. Introduction: The NIBS has been used widely in improving balance. However, the effect of a single session of NIBS on balance in healthy individuals has not been systemically reviewed. Methods: A systematic literature review and best evidence synthesis were conducted, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, to determine the effects of different NIBS techniques on balance function in healthy individuals. The methodological quality of included articles was assessed by the risk of bias, and the Downs and Black tool. Data were analyzed by using the best evidence synthesis. Thirty-five articles were included that used the following NIBS techniques: anodal transcranial direct current stimulation (a-tDCS), cathodal transcranial direct current stimulation (c-tDCS), continuous theta burst stimulation (cTBS), and repetitive transcranial magnetic stimulation (rTMS) on primary motor cortex (M1), supplementary motor area (SMA), dorsolateral prefrontal cortex (DLPFC), and cerebellum on balance. Results: Strong evidence showed that a-tDCS of M1, SMA improve balance in healthy participants, and the a-tDCS of DLPFC induces improvement only in dual task balance indices. Also, the findings indicate that cerebellar a-tDCS might significantly improve balance, if at least 10 min cerebellar a-tDCS with an intensity of ≥1 mA, over or maximum 1.5 cm below the inion, is used. Strong evidence showed that c-tDCS, cTBS, and rTMS are not effective on the balance. Conclusion: According to the results, the a-tDCS may be a useful technique to improve balance in healthy adults. Impact statement The strong evidence found in this review indicates that single-session, stand-alone application of anodal transcranial direct current stimulation on the cerebellum, primary motor cortex (M1), and supplementary motor area can improve balance in healthy individuals. Moreover, strong evidence suggests that cathodal transcranial direct current stimulation has an adverse effect on balance and must be avoided as a technique for the treatment of balance. These results can be used to improve balance in patients with neurological disorders, and healthy older adults with balance dysfunctions.

The neuroethics of non-invasive brain stimulation

European reclassification of non-invasive brain stimulation as class III medical devices: A call to action

Non-invasive brain stimulation for negative symptoms in schizophrenia: An updated systematic review and meta-analysis

Chapter 56 - Transcranial stimulation and cognition

Excessive emotional responses to stressful events can detrimentally affect psychological functioning and mental health. Recent studies have provided evidence that non-invasive brain stimulation (NBS) targeting the prefrontal cortex (PFC) can affect the regulation of stress-related emotional responses. However, the reliability and effect sizes have not been systematically analyzed. In the present study, we reviewed and meta-analyzed the effects of repetitive transcranial magnetic (rTMS) and transcranial direct current stimulation (tDCS) over the PFC on acute emotional stress reactivity in healthy individuals. Forty sham-controlled single-session rTMS and tDCS studies were included. Separate random effects models were performed to estimate the mean effect sizes of emotional reactivity. Twelve rTMS studies together showed no evidence that rTMS over the PFC influenced emotional reactivity. Twenty-six anodal tDCS studies yielded a weak beneficial effect on stress-related emotional reactivity (Hedges’ g = −0.16, CI95% = [−0.33, 0.00]). These findings suggest that a single session of NBS is insufficient to induce reliable, clinically significant effects but also provide preliminary evidence that specific NBS methods can affect emotional reactivity. This may motivate further research into augmenting the efficacy of NBS protocols on stress-related processes.

Spasticity is associated with various diseases of the nervous system. Current treatments such as drug therapy, botulinum toxin injections, kinesitherapy, and physiotherapy are not sufficiently effective in a large number of patients. Transcranial magnetic stimulation (TMS) can be considered as an alternative method of treatment. The purpose of this article was to conduct a systematic review and meta-analysis of all available publications assessing the efficacy of repetitive TMS in treatment of spasticity. Search for articles was conducted in databases PubMed, Willey, and Google. Keywords included "TMS", "spasticity", "TMS and spasticity", "non-invasive brain stimulation", and "non-invasive spinal cord stimulation". The difference in scores according to the Modified Ashworth Scale (MAS) for one joint before and after treatment was taken as the effect size. We found 26 articles that examined the TMS efficacy in treatment of spasticity. Meta-analysis included 6 trials comprising 149 patients who underwent real stimulation or simulation. No statistically significant difference in the effect of real and simulated stimulation was found in stroke patients. In patients with spinal cord injury and spasticity, the mean effect size value and the 95% confidence interval were -0.80 and (-1.12, -0.49), respectively, in a group of real stimulation; in the case of simulated stimulation, these parameters were 0.15 and (-0.30, -0.00), respectively. Statistically significant differences between groups of real stimulation and simulation were demonstrated for using high-frequency repetitive TMS or iTBS mode for the M1 area of the spastic leg (P=0.0002). According to the meta-analysis, the statistically significant effect of TMS in the form of reduced spasticity was demonstrated only for the developed due to lesions at the brain stem and spinal cord level. To clarify the amount of the antispasmodic effect of repetitive TMS at other lesion levels, in particular in patients with hemispheric stroke, further research is required.

P113 Modulation of food and body weight implicit attitudes with non-invasive brain stimulation techniques

Major depressive disorder (MDD) and cardiovascular diseases are intimately associated. Depression is an independent risk factor for mortality in cardiovascular samples. Neuroendocrine dysfunctions in MDD are related to an overactive hypothalamus-pituitary-adrenal (HPA) axis and increased sympathetic activity. Novel intervention strategies for MDD include the non-invasive brain stimulation (NIBS) techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). In fact, although these techniques have being increasingly used as a treatment for MDD, their cardiovascular effects were not sufficiently investigated, which would be important considering the dyad MDD/cardiovascular disorders. We investigated this issue through a systematic review for published articles from the first date available to May 2012 in MEDLINE and other databases, looking for main risk factors and surrogate markers for cardiovascular disease such as: cortisol, heart rate variability (HRV), alcohol, smoking, obesity, hypertension, glucose. We identified 37 articles (981 subjects) according to our eligibility criteria. Our main findings were that NIBS techniques might be effective strategies for down-regulating HPA activity and regulating food, alcohol, and cigarette consumption. NIBS’s effects on HRV and blood pressure presented mixed findings, with studies suggesting that HRV values can decrease or remain unchanged after NIBS, while one study found that rTMS increased blood pressure levels. Also, a single study showed that glucose levels decrease after tDCS. However, most studies tested the acute effects after one single session of rTMS/tDCS; therefore further studies are necessary to investigate whether NIBS modifies cardiovascular risk factors in the long-term. In fact, considering the burden of cardiac disease, further trials in cardiovascular, depressed, and non-depressed samples using NIBS should be performed.