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Background: Transcranial direct current stimulation (tDCS) can enhance cognitive function in healthy individuals, with promising applications as a therapeutic intervention. Despite this potential, variability in the efficacy of tDCS has been a considerable concern., Objective: /Hypothesis: Given that tDCS is always applied at a set intensity, we examined whether individual differences in sensitivity to brain stimulation might be one variable that modulates the efficacy of tDCS in a motor learning task., Methods: In the first part of the experiment, single-pulse transcranial magnetic stimulation (TMS) over primary motor cortex (M1) was used to determine each participant's resting motor threshold (rMT). This measure was used as a proxy of individual sensitivity to brain stimulation. In an experimental group of 28 participants, 2 mA tDCS was then applied during a motor learning task with the anodal electrode positioned over left M1. Another 14 participants received sham stimulation., Results: M1-Anodal tDCS facilitated learning relative to participants who received sham stimulation. Of primary interest was a within-group analysis of the experimental group, showing that the rate of learning was positively correlated with rMT: Participants who were more sensitive to brain stimulation as operationalized by our TMS proxy (low rMT), showed faster adaptation., Conclusions: Methodologically, the results indicate that TMS sensitivity can predict tDCS efficacy in a behavioral task, providing insight into one source of variability that may contribute to replication problems with tDCS. Theoretically, the results provide further evidence of a role of sensorimotor cortex in adaptation, with the boost from tDCS observed during acquisition., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Transcutaneous spinal direct current stimulation (tsDCS) is a new non-invasive technique to modulate spinal cord activity. The pathophysiological concept of primary RLS proposes increased spinal excitability., Objective: This pilot study used tsDCS to reduce pathologically enhanced spinal excitability in RLS patients and to thereby ameliorate clinical symptoms., Methods: 20 patients with idiopathic RLS and 14 healthy subjects participated in this double-blinded, placebo-controlled study. All participants received one session of cathodal, anodal and sham stimulation of the thoracic spinal cord for 15 min (2.5 mA) each, in randomized order during their symptomatic phase in the evening. The soleus Hoffmann-reflex with Hmax/Mmax-ratio and seven different H2/H1-ratios (of two H-reflex responses to double stimuli) were measured. The RLS symptoms were assessed by a visual analogue scale (VAS). All parameters were measured before and twice after tsDCS., Results: RLS patients showed increased H2/H1-ratios during their symptomatic phase in the evening. Application of anodal stimulation led to a decreased H2/H1-ratio for 0.2 and 0.3 s interstimulus intervals in patients. Furthermore, application of anodal and cathodal stimulation led to a reduction in restless legs symptoms on the VAS, whereas application of sham stimulation had no effects on either the VAS or on the H2/H1-ratio in patients. VAS changes did not correlate with changes of H2/H1-ratios., Conclusions: This is the first tsDCS study in idiopathic RLS, which resulted in short-lasting clinical improvement. Furthermore, our results support the pathophysiological concept of spinal cord hyperexcitability in primary RLS and provide the basis for a new non-pharmacological treatment tool., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Anodal transcranial direct current stimulation (tDCS) of the prefrontal cortex has been proposed as therapeutic intervention in major depression. According to clinical needs, this study addresses the question whether tDCS is effective in treatment resistant major depressive episodes., Methods: Twenty-two patients with a major depressive episode were randomly assigned to a cross-over protocol comparing tDCS and placebo stimulation add-on to a stable antidepressant medication. The parameters of active tDCS were: 1 or 2 mA for 20 minutes/day, anode over the left dorsolateral prefrontal cortex, cathode over the contralateral supraorbital region. Active and placebo tDCS was applied for 2 weeks using indistinguishable DC stimulators. Patients, raters, and operators were blinded to treatment conditions., Results: There was no significant difference in depression scores after 2 weeks of real compared with 2 weeks of sham tDCS. Scores on the Hamilton Depression Rating Scale were reduced from baseline by 14.7% for active tDCS and 10% for placebo tDCS. In contrast, subjective mood ratings showed an increase in positive emotions after real tDCS compared with sham tDCS., Conclusions: Anodal tDCS, applied for 2 weeks, was not superior to placebo treatment in patients with treatment resistant depression. However, secondary outcome measures are pointing to a positive effect of tDCS on emotions. Therefore, modified and improved tDCS protocols should be carried out in controlled pilot trials to develop tDCS towards an efficacious antidepressant intervention in therapy-resistant depression., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Chronic pain resulting from injury of the peripheral or central nervous system may be associated with a significant dysfunction of extensive neural networks. Noninvasive stimulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) may be suitable to treat chronic pain as they can act on these networks by modulating neural activities not only in the stimulated area, but also in remote regions that are interconnected to the site of stimulation. Motor cortex was the first cortical target that was proved to be efficacious in chronic pain treatment. At present, significant analgesic effects were also shown to occur after the stimulation of other cortical targets (including prefrontal and parietal areas) in acute provoked pain, chronic neuropathic pain, fibromyalgia, or visceral pain. Therapeutic applications of rTMS in pain syndromes are limited by the short duration of the induced effects, but prolonged pain relief can be obtained by repeating rTMS sessions every day for several weeks. Recent tDCS studies also showed some effects on various types of chronic pain. We review the evidence to date of these two techniques of noninvasive brain stimulation for the treatment of pain.

The combination of brain stimulation techniques like transcranial magnetic stimulation (TMS) with CNS active drugs in humans now offers a unique opportunity to explore the physiologic effects of these substances in vivo in the human brain. Motor threshold, motor evoked potential size, motor evoked potential intensity curves, cortical silent period, short-interval intracortical inhibition, intracortical facilitation, short-interval intracortical facilitation, long-interval intracortical inhibition and short latency afferent inhibition represent the repertoire for investigating drug effects on motor cortical excitability by TMS. Here we present an updated overview on the pharmacophysiologic mechanisms with special emphasis on methodologic pitfalls and possible future developments or requirements.