Janine Reis

Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation

Motor skills can take weeks to months to acquire and can diminish over time in the absence of continued practice. Thus, strategies that enhance skill acquisition or retention are of great scientific and practical interest. Here we investigated the effect of noninvasive cortical stimulation on the extended time course of learning a novel and challenging motor skill task. A skill measure was chosen to reflect shifts in the tasks speed–accuracy tradeoff function (SAF), which prevented us from falsely interpreting variations in position along an unchanged SAF as a change in skill. Subjects practiced over 5 consecutive days while receiving transcranial direct current stimulation (tDCS) over the primary motor cortex (M1). Using the skill measure, we assessed the impact of anodal (relative to sham) tDCS on both within-day (online) and between-day (offline) effects and on the rate of forgetting during a 3-month follow-up (long-term retention). There was greater total (online plus offline) skill acquisition with anodal tDCS compared to sham, which was mediated through a selective enhancement of offline effects. Anodal tDCS did not change the rate of forgetting relative to sham across the 3-month follow-up period, and consequently the skill measure remained greater with anodal tDCS at 3 months. This prolonged enhancement may hold promise for the rehabilitation of brain injury. Furthermore, these findings support the existence of a consolidation mechanism, susceptible to anodal tDCS, which contributes to offline effects but not to online effects or long-term retention.

Direct Current Stimulation Promotes BDNF-Dependent Synaptic Plasticity: Potential Implications for Motor Learning

Despite its increasing use in experimental and clinical settings, the cellular and molecular mechanisms underlying transcranial direct current stimulation (tDCS) remain unknown. Anodal tDCS applied to the human motor cortex (M1) improves motor skill learning. Here, we demonstrate in mouse M1 slices that DCS induces a long-lasting synaptic potentiation (DCS-LTP), which is polarity specific, NMDA receptor dependent, and requires coupling of DCS with repetitive low-frequency synaptic activation (LFS). Combined DCS and LFS enhance BDNF-secretion and TrkB activation, and DCS-LTP is absent in BDNF and TrkB mutant mice, suggesting that BDNF is a key mediator of this phenomenon. Moreover, the BDNF val66met polymorphism known to partially affect activity-dependent BDNF secretion impairs motor skill acquisition in humans and mice. Motor learning is enhanced by anodal tDCS, as long as activity-dependent BDNF secretion is in place. We propose that tDCS may improve motor skill learning through augmentation of synaptic plasticity that requires BDNF secretion and TrkB activation within M1.

Contribution of transcranial magnetic stimulation to the understanding of cortical mechanisms involved in motor control.

Transcranial magnetic stimulation (TMS) was initially used to evaluate the integrity of the corticospinal tract in humans non‐invasively. Since these early studies, the development of paired‐pulse and repetitive TMS protocols allowed investigators to explore inhibitory and excitatory interactions of various motor and non‐motor cortical regions within and across cerebral hemispheres. These applications have provided insight into the intracortical physiological processes underlying the functional role of different brain regions in various cognitive processes, motor control in health and disease and neuroplastic changes during recovery of function after brain lesions. Used in combination with neuroimaging tools, TMS provides valuable information on functional connectivity between different brain regions, and on the relationship between physiological processes and the anatomical configuration of specific brain areas and connected pathways. More recently, there has been increasing interest in the extent to which these physiological processes are modulated depending on the behavioural setting. The purpose of this paper is (a) to present an up‐to‐date review of the available electrophysiological data and the impact on our understanding of human motor behaviour and (b) to discuss some of the gaps in our present knowledge as well as future directions of research in a format accessible to new students and/or investigators. Finally, areas of uncertainty and limitations in the interpretation of TMS studies are discussed in some detail.

Consensus: Can transcranial direct current stimulation and transcranial magnetic stimulation enhance motor learning and memory formation?

Noninvasive brain stimulation has developed as a promising tool for cognitive neuroscientists. Transcranial magnetic (TMS) and direct current (tDCS) stimulation allow researchers to purposefully enhance or decrease excitability in focal areas of the brain. The purpose of this article is to review information on the use of TMS and tDCS as research tools to facilitate motor memory formation, motor performance, and motor learning in healthy volunteers. Studies implemented so far have mostly focused on the ability of TMS and tDCS to elicit relatively short-lasting motor improvements and the mechanisms underlying these changes have been only partially investigated. Despite limitations, including the scarcity of data, work that has been already accomplished raises the exciting hypothesis that currently available noninvasive transcranial stimulation techniques could modulate motor learning and memory formation in healthy humans and potentially in patients with neurologic and psychiatric disorders.

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016.

This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3-13 A/m(2)) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 milliamperes, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations.

TMS and drugs revisited 2014

The combination of pharmacology and transcranial magnetic stimulation to study the effects of drugs on TMS-evoked EMG responses (pharmaco-TMS-EMG) has considerably improved our understanding of the effects of TMS on the human brain. Ten years have elapsed since an influential review on this topic has been published in this journal (Ziemann, 2004). Since then, several major developments have taken place: TMS has been combined with EEG to measure TMS evoked responses directly from brain activity rather than by motor evoked potentials in a muscle, and pharmacological characterization of the TMS-evoked EEG potentials, although still in its infancy, has started (pharmaco-TMS-EEG). Furthermore, the knowledge from pharmaco-TMS-EMG that has been primarily obtained in healthy subjects is now applied to clinical settings, for instance, to monitor or even predict clinical drug responses in neurological or psychiatric patients. Finally, pharmaco-TMS-EMG has been applied to understand the effects of CNS active drugs on non-invasive brain stimulation induced long-term potentiation-like and long-term depression-like plasticity. This is a new field that may help to develop rationales of pharmacological treatment for enhancement of recovery and re-learning after CNS lesions. This up-dated review will highlight important knowledge and recent advances in the contribution of pharmaco-TMS-EMG and pharmaco-TMS-EEG to our understanding of normal and dysfunctional excitability, connectivity and plasticity of the human brain.

Probing for hemispheric specialization for motor skill learning: a transcranial direct current stimulation study

Convergent findings point to a left-sided specialization for the representation of learned actions in right-handed humans, but it is unknown whether analogous hemispheric specialization exists for motor skill learning. In the present study, we explored this question by comparing the effects of anodal transcranial direct current stimulation (tDCS) over either left or right motor cortex (M1) on motor skill learning in either hand, using a tDCS montage to better isolate stimulation to one hemisphere. Results were compared with those previously found with a montage more commonly used in the field. Six groups trained for three sessions on a visually guided sequential pinch force modulation task with their right or left hand and received right M1, left M1, or sham tDCS. A linear mixed-model analysis for motor skill showed a significant main effect for stimulation group (left M1, right M1, sham) but not for hand (right, left) or their interaction. Left M1 tDCS induced significantly greater skill learning than sham when hand data were combined, a result consistent not only with the hypothesized left hemisphere specialization for motor skill learning but also with possible increased left M1 responsiveness to tDCS. The unihemispheric montage effect size was one-half that of the more common montage, and subsequent power analysis indicated that 75 subjects per group would be needed to detect differences seen with only 12 subjects with the customary bihemispheric montage.

Direct and indirect costs of refractory epilepsy in a tertiary epilepsy center in Germany

Summary:  Purpose: There are only few studies on the costs of epilepsy in Germany. Therefore, we performed a pilot study to estimate the direct and indirect costs of refractory epilepsy in a German epilepsy center.

Topiramate selectively decreases intracortical excitability in human motor cortex.

Summary:  Purpose: Topiramate (TPM) is a novel drug with broad antiepileptic effect in children and adults. In vitro studies suggest activity as sodium‐channel blocker, as γ‐aminobutyric acid type A (GABAA)‐receptor agonist and as non–N‐methyl‐D‐aspartate (NMDA)‐glutamate receptor antagonist.

Time- but Not Sleep-Dependent Consolidation of tDCS-Enhanced Visuomotor Skills

Consolidation of motor skills after training can occur in a time- or sleep-dependent fashion. Recent studies revealed time-dependent consolidation as a common feature of visuomotor tasks. We have previously shown that anodal transcranial direct current stimulation (tDCS) in combination with repeated motor training benefits consolidation by the induction of offline skill gains in a complex visuomotor task, preventing the regular occurrence of skill loss between days. Here, we asked 2 questions: What is the time course of consolidation between days for this task and do exogenously induced offline gains develop as a function of time or overnight sleep? We found that both the development of offline skill loss in sham-stimulated subjects and offline skill gains induced by anodal tDCS critically depend on the passage of time after training, but not on overnight sleep. These findings support the view that tDCS interacts directly with the physiological consolidation process. However, in a control experiment, anodal tDCS applied after the training did not induce skill gains, implying that coapplication of tDCS and training is required to induce offline skill gains, pointing to the initiation of consolidation already during training.