Klára Boros

Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients.

Cortical excitability changes induced by tDCS and revealed by TMS, are increasingly being used as an index of neuronal plasticity in the human cortex. The aim of this paper is to summarize the partially adverse effects of 567 tDCS sessions over motor and non-motor cortical areas (occipital, temporal, parietal) from the last 2 years, on work performed in our laboratories. One-hundred and two of our subjects who participated in our tDCS studies completed a questionnaire. The questionnaire contained rating scales regarding the presence and severity of headache, difficulties in concentrating, acute mood changes, visual perceptual changes and any discomforting sensation like pain, tingling, itching or burning under the electrodes, during and after tDCS. Participants were healthy subjects (75.5%), migraine patients (8.8%), post-stroke patients (5.9%) and tinnitus patients (9.8%). During tDCS a mild tingling sensation was the most common reported adverse effect (70.6%), moderate fatigue was felt by 35.3% of the subjects, whereas a light itching sensation under the stimulation electrodes occurred in 30.4% of cases. After tDCS headache (11.8%), nausea (2.9%) and insomnia (0.98%) were reported, but fairly infrequently. In addition, the incidence of the itching sensation (p=0.02) and the intensity of tingling sensation (p=0.02) were significantly higher during tDCS in the group of the healthy subjects, in comparison to patients; whereas the occurrence of headache was significantly higher in the patient group (p=0.03) after the stimulation. Our results suggest that tDCS applied to motor and non-motor areas according to the present tDCS safety guidelines, is associated with relatively minor adverse effects in healthy humans and patients with varying neurological disorders.

Comparatively weak after-effects of transcranial alternating current stimulation (tACS) on cortical excitability in humans

OBJECTIVE Interference with brain rhythms by noninvasive transcranial stimulation that uses weak transcranial alternating current may reveal itself to be a new tool for investigating cortical mechanisms currently unresolved. Here, we aim to extend transcranial direct current stimulation (tDCS) techniques to transcranial alternating current stimulation (tACS). BACKGROUND Parameters such as electrode size and position were taken from those used in previous tDCS studies. METHODS Motor evoked potentials (MEPs) revealed by transcranial magnetic stimulation (TMS), electroencephalogram (EEG)-power, and reaction times measured in a motor implicit learning task, were analyzed to detect changes in cortical excitability after 2-10 minutes of AC stimulation and sinusoidal DC stimulation (tSDCS) by using 1, 10, 15, 30, and 45 Hz and sham stimulation over the primary motor cortex in 50 healthy subjects (eight-16 subjects in each study). RESULTS A significantly improved implicit motor learning was observed after 10 Hz AC stimulation only. No significant changes were observed in any of the analyzed frequency bands of EEG and with regard to the MEP amplitudes after AC or tSDCS stimulation. Similarly, if the anodal or cathodal DC stimulation was superimposed on 5, 10, and 15 Hz AC stimulation, the MEP amplitudes did not change significantly. CONCLUSIONS Transcranial application of weak AC current may appear to be a tool for basic and clinical research in diseases with altered EEG activity. However, its effect seems to be weaker than tDCS stimulation, at least in the present context of stimulus intensity and duration. Further studies are required to extend cautiously the safety range and uncover its influence on neuronal circuitries.

Premotor transcranial direct current stimulation (tDCS) affects primary motor excitability in humans.

Recent studies have shown that repetitive transcranial magnetic stimulation (rTMS) over the premotor cortex (PM) modifies the excitability of the ipsilateral primary motor cortex (M1). Transcranial direct current stimulation (tDCS) is a new method to induce neuroplasticity in humans non‐invasively. tDCS generates neuroplasticity directly in the cortical area under the electrode, but might also induce effects in distant brain areas, caused by activity modulation of interconnected areas. However, this has not yet been tested electrophysiologically. We aimed to study whether premotor tDCS can modify the excitability of the ipsilateral M1 via cortico‐cortical connectivity. Sixteen subjects received cathodal and anodal tDCS of the PM and eight subjects of the dorsolateral prefrontal cortex. Premotor anodal, but not premotor cathodal or prefrontal tDCS, modified selectively short intracortical inhibition/intracortical facilitation (SICI/ICF), while motor thresholds, single test‐pulse motor‐evoked potential and input–output curves were stable throughout the experiments. Specifically, anodal tDCS decreased intracortical inhibition and increased paired‐pulse excitability. The selective influence of premotor tDCS on intracortical excitability of the ipsilateral M1 suggests a connectivity‐driven effect of tDCS on remote cortical areas. Moreover, this finding indirectly substantiates the efficacy of tDCS to modulate premotor excitability, which might be of interest for applications in diseases accompanied by pathological premotor activity.

Transcranial Direct Current Stimulation Over Somatosensory Cortex Decreases Experimentally Induced Acute Pain Perception

Objective Multiple cortical areas including the primary somatosensory cortex are known to be involved in nociception. The aim of this study was to investigate the effect of transcranial direct current stimulation (tDCS) that modulates the cortical excitability painlessly and noninvasively, over somatosensory cortex on acute pain perception induced with a Tm:YAG laser. Methods Subjective pain rating scores and amplitude changes of the N1, N2, and P2 components of laser-evoked potentials of 10 healthy participants were analyzed before and after anodal, cathodal, and sham tDCS. Results Our results demonstrate that cathodal tDCS significantly diminished pain perception and the amplitude of the N2 component when the contralateral hand to the side of tDCS was laser-stimulated, whereas anodal and sham stimulation conditions had no significant effect. Discussion Our study highlights the antinociceptive effect of this technique and may contribute to the understanding of the mechanisms underlying pain relief. The pharmacologic prolongation of the excitability-diminishing after-effects would render the method applicable to different patient populations with chronic pain.

Cathodal transcranial direct current stimulation of the visual cortex in the prophylactic treatment of migraine

Background: The purpose of this study was to determine whether transcranial direct current stimulation (tDCS) can be an effective prophylactic therapy for migraine and migraine-associated pain. Method: This painless and non-invasive method was applied for 6 weeks over the visual cortex (V1), delivered three times per week. Thirty patients were assigned to cathodal or to sham stimulation, and 26 patients participated in the final analyses (cathodal: n = 13, sham: n = 13). During the first 3 weeks both groups received only placebo stimulation. Measures of attack frequency and duration, intensity of pain and number of migraine-related days were recorded 2 months before, during and 2 months post-treatment. Results: Patients treated by cathodal tDCS showed a significant reduction in the duration of attacks, the intensity of pain and the number of migraine-related days post-treatment as compared to the baseline period, but not in the frequency of the attacks. However, compared to the sham group, only the intensity of the pain was significantly reduced post-stimulation. No patients experienced severe adverse effects. Conclusion: Our results suggest that the application of cathodal stimulation over the V1 might be an effective prophylactic therapy in migraine, at least with regard to pain control.

Homeostatic Metaplasticity of the Motor Cortex is Altered during Headache-Free Intervals in Migraine with Aura

Preconditioning of the human primary motor cortex (M1) with transcranial direct current stimulation (tDCS) can shape the magnitude and direction of excitability changes induced by a subsequent session of repetitive transcranial magnetic stimulation (rTMS). Here, we examined this form of metaplasticity in migraine patients with visual aura and healthy controls. In both groups, facilitatory preconditioning of left M1 with anodal tDCS increased the mean amplitudes of motor-evoked potentials (MEPs) elicited in the contralateral hand, whereas inhibitory preconditioning with cathodal tDCS produced a decrease in amplitude. Following cathodal tDCS, a short train of low-intensity 5-Hz rTMS antagonized the suppression of the mean MEP amplitude in both groups. In contrast, the homeostatic effects of 5-Hz rTMS differed between groups when rTMS was given after anodal tDCS. In controls 5-Hz rTMS induced a marked decrease in MEP amplitudes, whereas in migraineurs rTMS induced only a modest decrease in MEP amplitudes, which were still facilitated after rTMS when compared with baseline amplitudes. These findings indicate that short-term homeostatic plasticity is altered in patients with visual aura between the attacks.

Pergolide increases the efficacy of cathodal direct current stimulation to reduce the amplitude of laser-evoked potentials in humans.

Transcranial direct current stimulation (tDCS) was recently reintroduced as a tool for inducing relatively long-lasting changes in cortical excitability in focal brain regions. Anodal stimulation over the primary motor cortex enhances cortical excitability, whereas cathodal stimulation decreases it. Prior studies have shown that enhancement of D2 receptor activity by pergolide consolidates tDCS-generated excitability diminution for up to 24 hours and that cathodal stimulation of the primary motor cortex diminishes experimentally induced pain sensation and reduces the N2-P2 amplitude of laser-evoked potentials immediately poststimulation. In the present study, we investigated the effect of pergolide and cathodal tDCS over the primary motor cortex on laser-evoked potentials and acute pain perception induced with a Tm:YAG laser in a double-blind, randomized, placebo-controlled, crossover study. The amplitude changes of laser-evoked potentials and subjective pain rating scores of 12 healthy subjects were analyzed prior to and following 15 minutes cathodal tDCS combined with pergolide or placebo intake at five different time points. Our results indicate that the amplitude of the N2 component was significantly reduced following cathodal tDCS for up to two hours. Additionally, pergolide prolonged the effect of the cathodal tDCS for up to 24 hours, and a significantly lowered pain sensation was observed for up to 40 minutes. Our study is a further step toward clinical application of cathodal tDCS over the primary motor cortex using pharmacological intervention to prolong the excitability-diminishing effect on pain perception for up to 24 hours poststimulation. Furthermore, it demonstrates the potential for repetitive daily stimulation therapy for pain patients.

Does the menstrual cycle influence the motor and phosphene thresholds in migraine

Background and purpose:  The excitability of the visual and motor cortical areas is altered in migraineurs. Controversial results of previous studies on cortical excitability may depend on the hormonal status of female subjects. The present study aimed to determine whether the different phases of the menstrual cycle influence the phosphene thresholds (PT) and resting motor thresholds (RMT) in migraineurs.