Low intensity transcranial electric stimulation: Safety,ethical, legal regulatory and application guidelines

Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAEs) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1–2 mA and during tACS at higher peak-to-peak intensities above 2 mA.The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues.Safety is established for low-intensity ‘conventional’ TES defined as <4 mA, up to 60 min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3–13 A/m² that are over an order of magnitude above those produced by tDCS in humans. Using AC stimulation fewer AEs were reported compared to DC. In specific paradigms with amplitudes of up to 10 mA, frequencies in the kHz range appear to be safe.In this paper we provide structured interviews and recommend their use in future controlled studies, in particular when trying to extend the parameters applied. We also discuss recent regulatory issues, reporting practices and ethical issues. These recommendations achieved consensus in a meeting, which took place in Göttingen, Germany, on September 6–7, 2016 and were refined thereafter by email correspondence.     

重复性经颅磁刺激对脑卒中患者运动功能的改善作用

目的探讨重复性经颅磁刺激(r TMS)对脑卒中患者运动功能的改善作用。方法收集2013-06~2015-07该院康复科住院治疗的脑卒中患者100例,随机将患者分为r TMS组和对照组各50例。对照组接受常规药物、针灸及运动等康复治疗。r TMS组在对照组基础上使用r TMS治疗。比较两组治疗前、治疗后的运动功能(Fugl-Meyer)评分、神经功能缺损(NIHSS)评分及日常生活能力(FIM)评分变化情况。结果治疗后,两组Fugl-Meyer、FIM评分比治疗前显著提高,NIHSS评分则显著降低(P0.05);治疗后,r TMS组FuglMeyer、FIM评分比对照组显著提高,NIHSS评分显著降低(P0.05)。两组治疗期间均无明显的不良反应发生。结论 r TMS对脑卒中患者的肢体运动功能有良好的改善作用,因此可作为一种无创性、新型的安全治疗手段。     

Rostral anterior cingulate cortex is a structural correlate of repetitive TMS treatment response in depression

Background

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for medication-refractory major depression, yet the mechanisms of action for this intervention are poorly understood. Here we investigate cerebral cortex thickness as a possible biomarker of rTMS treatment response.

Low-frequency rTMS targeting individual self-initiated finger-tapping task activation modulates the amplitude of local neural activity in the putamen

Repetitive transcranial magnetic stimulation (rTMS) has been used in the clinical treatment of Parkinson's disease (PD). Most of rTMS studies on PD used high-frequency stimulation; however, excessive nonvoluntary movement may represent abnormally cortical excitability, which is likely to be suppressed by low-frequency rTMS. Decreased neural activity in the basal ganglia on functional magnetic resonance imaging (fMRI) is a characteristic of PD. In the present study, we found that low-frequency (1 Hz) rTMS targeting individual finger-tapping activation elevated the amplitude of local neural activity (percentage amplitude fluctuation, PerAF) in the putamen as well as the functional connectivity (FC) of the stimulation target and basal ganglia in healthy participants. These results provide evidence for our hypothesis that low-frequency rTMS over the individual task activation site can modulate deep brain functions, and that FC might serve as a bridge transmitting the impact of rTMS to the deep brain regions. It suggested that a precisely localized individual task activation site can act as a target for low-frequency rTMS when it is used as a therapeutic tool for PD.     

rTMS ameliorates depressive-like behaviors and regulates the gut microbiome and medium- and long-chain fatty acids in mice exposed to chronic unpredictable mild stress

Introduction

Repetitive transcranial magnetic stimulation (rTMS) is a clinically useful therapy for depression. However, the effects of rTMS on the metabolism of fatty acids (FAs) and the composition of gut microbiota in depression are not well established.

Methods

Mice received rTMS (15 Hz, 1.26 T) for seven consecutive days after exposure to chronic unpredictable mild stress (CUMS). The subsequent depressive-like behaviors, the composition of gut microbiota of stool samples, as well as medium- and long-chain fatty acids (MLCFAs) in the plasma, prefrontal cortex (PFC), and hippocampus (HPC) were evaluated.

Results

CUMS induced remarkable changes in gut microbiotas and fatty acids, specifically in community diversity of gut microbiotas and PUFAs in the brain. 15 Hz rTMS treatment alleviates depressive-like behaviors and partially normalized CUMS induced alterations of microbiotas and MLCFAs, especially the abundance of Cyanobacteria, Actinobacteriota, and levels of polyunsaturated fatty acids (PUFAs) in the hippocampus and PFC.

Conclusion

These findings revealed that the modulation of gut microbiotas and PUFAs metabolism might partly contribute to the antidepressant effect of rTMS.     

Theta Burst Stimulation Is Not Inferior to High-Frequency Repetitive Transcranial Magnetic Stimulation in Reducing Symptoms of Posttraumatic Stress Disorder in Veterans With Depression: A Retrospective Case Series

ObjectivesTwo commonly used forms of repetitive transcranial magnetic stimulation (rTMS) were recently shown to be equivalent for the treatment of depression: high-frequency stimulation (10 Hz), a protocol that lasts between 19 and 38 minutes, and intermittent theta burst stimulation (iTBS), a protocol that can be delivered in just three minutes. However, it is unclear whether iTBS treatment offers the same benefits as those of standard 10-Hz rTMS for comorbid symptoms such as those seen in posttraumatic stress disorder (PTSD).Materials and MethodsIn this retrospective case series, we analyzed treatment outcomes in veterans from the Veterans Affairs San Diego Healthcare System who received 10-Hz (n = 47) or iTBS (n = 51)-rTMS treatments for treatment-resistant depression between February 2018 and June 2022. We compared outcomes between these two stimulation protocols in symptoms of depression (using changes in the Patient Health Questionnaire-9 [PHQ-9]) and PTSD (using changes in the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, or Patient Checklist [PCL]-5).ResultsThere was an imbalance of sex between groups (p < 0.05). After controlling for sex, we found no significant difference by stimulation protocol for depression (PHQ-9, F [1,94] = 0.16, p = 0.69, eta-squared = 0.002), confirming the original study previously noted. We also showed no difference by stimulation protocol of changes in PTSD symptoms (PCL-5, F [1,94] = 3.46, p = 0.067, eta-squared = 0.036). The iTBS group showed a decrease from 41.9 ± 4.4 to 25.1 ± 4.9 (a difference of 16.8 points) on the PCL-5 scale whereas the 10-Hz group showed a decrease from 43.6 ± 2.9 to 35.2 ± 3.2 on this scale (a difference of 8.4 points). Follow-up analyses restricting the sample in various ways did not meaningfully change these results (no follow-up analyses showed that there was a significant difference between stimulation protocols).ConclusionsAlthough limited by small sample size, nonblind, and pseudorandomized assignment, our data suggest that iTBS is similar to 10-Hz stimulation in inducing reductions in PTSD symptoms and depression in military veterans.     

Brain excitability and connectivity of neuronal assemblies in Alzheimer's disease: From animal models to human findings

The human brain contains about 100 billion neurons forming an intricate network of innumerable connections, which continuously adapt and rewire themselves following inputs from external and internal environments as well as the physiological synaptic, dendritic and axonal sculpture during brain maturation and throughout the life span.