Evidence of Motor Skill Learning in Acute Stroke Patients Without Lesions to the Thalamus and Internal Capsule.

BACKGROUND: It is currently unknown whether motor skill learning (MSkL) with the paretic upper limb is possible during the acute phase after stroke and whether lesion localization impacts MSkL. Here, we investigated MSkL in acute (1-7 days post) stroke patients compared with healthy individuals (HIs) and in relation to voxel-based lesion symptom mapping. METHODS: Twenty patients with acute stroke and 35 HIs were trained over 3 consecutive days on a neurorehabilitation robot measuring speed, accuracy, and movement smoothness variables. Patients used their paretic upper limb and HI used their nondominant upper limb on an MSkL task involving a speed/accuracy trade-off. Generalization was evaluated on day 3. All patients underwent a 3-dimensional magnetic resonance imaging used for VSLM. RESULTS: Most patients achieved MSkL demonstrated by day-to-day retention and generalization of the newly learned skill on day 3. When comparing raw speed/accuracy trade-off values, HI achieved larger MSkL than patients. However, relative speed/accuracy trade-off values showed no significant differences in MSkL between patients and HI on day 3. In patients, MSkL progression correlated with acute motor and cognitive impairments. The voxel-based lesion symptom mapping showed that acute vascular damage to the thalamus or the posterior limb of the internal capsule reduced MSkL. CONCLUSIONS: Despite worse motor performance for acute stroke patients compared with HI, most patients were able to achieve MSkL with their paretic upper limb. Damage to the thalamus and posterior limb of the internal capsule, however, reduced MSkL. These data show that MSkL could be implemented into neurorehabilitation during the acute phase of stroke, particularly for patients without lesions to the thalamus and posterior limb of the internal capsule. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01519843.

Effect of a single dose of retigabine in cortical excitability parameters: A cross-over, double-blind placebo-controlled TMS study.

BACKGROUND: Antiepileptic drugs (AEDs) decrease the occurrence of epileptic seizures and modulate cortical excitability through several mechanisms that likely interact. The modulation of brain excitability by AEDs is believed to reflect their antiepileptic action(s) and could be used as a surrogate marker of their efficacy. Transcranial magnetic stimulation (TMS) is one of the best noninvasive methods to study cortical excitability in human subjects. Specific TMS parameters can be used to quantify the various mechanisms of action of AEDs. A new AED called retigabine increases potassium efflux by changing the conformation of KCNQ 2-5 potassium channels, which leads to neuronal hyperpolarisation and a decrease in excitability. HYPOTHESIS: The purpose of this study is to investigate the effect of retigabine on cortical excitability. Based on the known mechanisms of action of retigabine, we hypothesized that the oral intake of retigabine would increase the resting motor threshold (RMT). METHODS: Fifteen healthy individuals participated in a placebo-controlled, double-blind, randomised, clinical trial (RCT). The primary outcome measure was the RMT quantified before and after oral intake of retigabine. Several secondary TMS outcome measures were acquired. RESULTS: The mean RMT, active motor threshold (AMT) and intensity to obtain a 1mV peak-to-peak amplitude potential (SI1mV) were significantly increased after retigabine intake compared to placebo (RMT: P=0.039; AMT: P=0.014; SI1mV: P=0.019). No significant differences were found for short-interval intracortical inhibition/intracortical facilitation (SICI/ICF), long-interval intracortical inhibition (LICI) or short-interval intracortical facilitation (SICF). CONCLUSION: A single dose of retigabine increased the RMT, AMT and S1mV in healthy individuals. No modulating intracortical facilitation or inhibition was observed. This study provides the first in vivo demonstration of the modulating effects of retigabine on the excitability of the human brain, and the results are consistent with the data showing that retigabine hyperpolarizes neurons mainly by increasing potassium conductance.

Postoperative analgesic effect of transcranial direct current stimulation in lumbar spine surgery: a randomized control trial.

BACKGROUND: Ultimately, the experience of pain derives from changes in brain excitability. Therefore, modulating the excitability of cortical areas involved in pain processing may become an attractive option in the context of multimodal analgesia during the postoperative period. Repetitive transcranial magnetic stimulation (rTMS) can reduce morphine consumption during the postoperative period after gastric bypass surgery. We tested the potential of another method of noninvasive brain stimulation, transcranial direct current stimulation (tDCS), to reduce morphine consumption or pain perception during the postoperative period. METHODS: Fifty-nine ASA I to II patients undergoing lumbar spine surgery were randomized to receive anodal (n=20), cathodal (n=20), or sham (n=19) tDCS in the recovery room in a double-blind manner. Morphine consumption administrated through patient-controlled analgesia (PCA) was the primary outcome; pain perception as measured by visual analog scale was the secondary outcome. RESULTS: There were no statistically significant differences between the 3 groups of patients, either for PCA morphine consumption or for pain scores. CONCLUSIONS: Several factors may explain the observed lack of impact of tDCS on PCA morphine consumption and pain perception: the method of brain stimulation (tDCS/rTMS), potential interactions with anesthetic drugs, differences in patients population (gastric bypass surgery/lumbar spine surgery), and the previous experience of pain and chronic consumption of analgesic drugs. Further studies with tDCS should be performed before concluding that tDCS is inefficient for postoperative pain control, because noninvasive brain stimulation methods, such as rTMS and tDCS, may become attractive in the setting of multimodal analgesia.

Effects of combined peripheral nerve stimulation and brain polarization on performance of a motor sequence task after chronic stroke.

BACKGROUND AND PURPOSE: Recent work demonstrated that application of peripheral nerve and cortical stimulation independently can induce modest improvements in motor performance in patients with stroke. The purpose of this study was to test the hypothesis that combining peripheral nerve stimulation (PNS) to the paretic hand with anodal direct current stimulation (tDCS) to the ipsilesional primary motor cortex (M1) would facilitate beneficial effects of motor training more than each intervention alone or sham (tDCS(Sham) and PNS(Sham)). METHODS: Nine chronic stroke patients completed a blinded crossover designed study. In separate sessions, we investigated the effects of single applications of PNS+tDCS, PNS+tDCS(Sham), tDCS+PNS(Sham), and PNS(Sham)+tDCS(Sham) before motor training on the ability to perform finger motor sequences with the paretic hand. RESULTS: PNS+tDCS resulted in a 41.3% improvement in the number of correct key presses relative to PNS(Sham)+tDCS(Sham), 15.4% relative to PNS+tDCS(Sham), and 22.7% relative to tDCS+PNS(Sham). These performance differences were maintained 1 and 6 days after the end of the training. CONCLUSIONS: These results indicate that combining PNS with tDCS can facilitate the beneficial effects of training on motor performance beyond levels reached with each intervention alone, a finding of relevance for the neurorehabilitation of motor impairments after stroke.