Stéphanie Lefebvre

Dual-tDCS Enhances Online Motor Skill Learning and Long-Term Retention in Chronic Stroke Patients.

Background: Since motor learning is a key component for stroke recovery, enhancing motor skill learning is a crucial challenge for neurorehabilitation. Transcranial direct current stimulation (tDCS) is a promising approach for improving motor learning. The aim of this trial was to test the hypothesis that dual-tDCS applied bilaterally over the primary motor cortices (M1) improves online motor skill learning with the paretic hand and its long-term retention. Methods: Eighteen chronic stroke patients participated in a randomized, cross-over, placebo-controlled, double bind trial. During separate sessions, dual-tDCS or sham dual-tDCS was applied over 30 min while stroke patients learned a complex visuomotor skill with the paretic hand: using a computer mouse to move a pointer along a complex circuit as quickly and accurately as possible. A learning index involving the evolution of the speed/accuracy trade-off was calculated. Performance of the motor skill was measured at baseline, after intervention and 1 week later. Results: After sham dual-tDCS, eight patients showed performance worsening. In contrast, dual-tDCS enhanced the amount and speed of online motor skill learning compared to sham (p < 0.001) in all patients; this superiority was maintained throughout the hour following. The speed/accuracy trade-off was shifted more consistently after dual-tDCS (n = 10) than after sham (n = 3). More importantly, 1 week later, online enhancement under dual-tDCS had translated into superior long-term retention (+44%) compared to sham (+4%). The improvement generalized to a new untrained circuit and to digital dexterity. Conclusion: A single-session of dual-tDCS, applied while stroke patients trained with the paretic hand significantly enhanced online motor skill learning both quantitatively and qualitatively, leading to successful long-term retention and generalization. The combination of motor skill learning and dual-tDCS is promising for improving post-stroke neurorehabilitation.

Single session of dual-tDCS transiently improves precision grip and dexterity of the paretic hand after stroke

Background. After stroke, deregulated interhemispheric interactions influence residual paretic hand function. Anodal or cathodal transcranial direct current stimulation (tDCS) can rebalance these abnormal interhemispheric interactions and improve motor function. Objective. We explored whether dual-hemisphere tDCS (dual-tDCS) in participants with chronic stroke can improve fine hand motor function in 2 important aspects: precision grip and dexterity. Methods. In all, 19 chronic hemiparetic individuals with mild to moderate impairment participated in a double-blind, randomized trial. During 2 separate cross-over sessions (real/sham), they performed 10 precision grip movements with a manipulandum and the Purdue Pegboard Test (PPT) before, during, immediately after, and 20 minutes after dual-tDCS applied simultaneously over the ipsilesional (anodal) and contralateral (cathodal) primary motor cortices. Results. The precision grip performed with the paretic hand improved significantly 20 minutes after dual-tDCS, with reduction of the grip force/load force ratio by 7% and in the preloading phase duration by 18% when compared with sham. The dexterity of the paretic hand started improving during dual-tDCS and culminated 20 minutes after the end of dual-tDCS (PPT score +38% vs +5% after sham). The maximal improvements in precision grip and dexterity were observed 20 minutes after dual-tDCS. These improvements correlated negatively with residual hand function quantified with ABILHAND. Conclusions. One bout of dual-tDCS improved the motor control of precision grip and digital dexterity beyond the time of stimulation. These results suggest that dual-tDCS should be tested in longer protocols for neurorehabilitation and with moderate to severely impaired patients. The precise timing of stimulation after stroke onset and associated training should be defined.

Could dual-hemisphere transcranial direct current stimulation (tDCS) reduce spasticity after stroke?

After providing informed consent, a 61-year-old chronic stroke female patient participated in a double-blind, randomised, placebo-controlled trial to test the potential of transcranial direct current stimulation (tDCS) to improve motor skill learning with the paretic hand. Two years before, she suffered from an ischaemic stroke in the territory of the deep right middle cerebral artery (Fig. 1), leading to left-sided hemiplegia (NIH Stroke Scale: 9). After discharge (modified Rankin Score: 4), she benefited from long-term neurorehabilitation. She recovered walking and partial control of the proximal left upper limb but she had no voluntary finger movements (mRS=3). She developed a severe left-sided spasticity, requiring the daily intake of baclofen 75 mg and tizanidine 4 mg. She was chronically on venlafaxin 75 mg, lorazepam 0.5 mg, aspirin, atorvastatin and ranitidine. The treatment was not modified during the whole experiment. She participated in two experimental sessions separated by 2 weeks, each composed of two distinct parts. During the first part (Intervention session), she performed training on the circuit with dual-tDCS application (real or sham). Two versions (similar difficulty) of the circuit were used for the two Intervention sessions. During the second part (Recall session), which took place 1 week apart, the patient performed the same circuit as during the previous ‘‘Intervention session’’ to test the retention of the motor skill. The Recall session consisted of two evaluations (5 min apart) of the motor skill (duration: 5 min, alternating 30-s blocks of testing and rest). She sat in front of a computer screen; the computer mouse was taped in her left hand. A circuit was displayed on the screen, she was instructed to move the cursor as fast as possible over the circuit, and as precisely as possible by keeping the cursor within the boundaries of the track [1]. During the Intervention session, training was provided during 30 min, alternating blocks of 30 s of practice and rest. Performance was evaluated before (Baseline), during, and up to 60 min after, and 1 week later (Recall). Velocity and accuracy were extracted to compute a performance index (PI) involving a speed/accuracy trade-off. The evolution of the PI from Baseline was expressed as a learning index (LI): LI = [(PI PI baseline)/PI baseline] 9 100. An increment of LI reflects a performance improvement relative to ‘‘Baseline’’ [1]. LI was computed on each circuit block. Before training, she received a short familiarisation with a simple square circuit. During training, dual-tDCS was applied over both primary motor cortices (M1), with anodal stimulation over the ipsilesional M1 and cathodal stimulation over the contralesional M1. The M1 were located using the C3 and C4 positions of the 10-20 EEG system. Real (30 min) and sham (45 s) dual-tDCS were applied with an Eldith DC-Stimulator (NeuroConn, Ilmenau, Germany) in a randomised, double-blind fashion. DualtDCS was delivered via two soaked (NaCl 0.9 %) electrodes (35 cm) at an intensity of 1 mA (fade in/out 8 s). During the first experimental session, she was allocated to receive real dual-tDCS; motor performance and longterm retention of the motor skill markedly improved Y. Vandermeeren (&) S. Lefebvre P. Laloux Department of Neurology, CHU UCL Mont-Godinne, Universite catholique de Louvain (UCL), Avenue Dr G. Therasse, 5530 Yvoir, Belgium e-mail: yves.vandermeeren@uclouvain.be

Increased functional connectivity one week after motor learning and tDCS in stroke patients

Recent studies using resting-state functional magnetic resonance imaging (rs-fMRI) demonstrated that changes in functional connectivity (FC) after stroke correlate with recovery. The aim of this study was to explore whether combining motor learning to dual transcranial direct current stimulation (dual-tDCS, applied over both primary motor cortices (M1)) modulated FC in stroke patients. Twenty-two chronic hemiparetic stroke patients participated in a baseline rs-fMRI session. One week later, dual-tDCS/sham was applied during motor skill learning (intervention session); one week later, the retention session started with the acquisition of a run of rs-fMRI imaging. The intervention+retention sessions were performed once with dual-tDCS and once with sham in a randomized, cross-over, placebo-controlled, double-blind design. A whole-brain independent component analysis based analysis of variance (ANOVA) demonstrated no changes between baseline and sham sessions in the somatomotor network, whereas a FC increase was observed one week after dual-tDCS compared to baseline (qFDR <0.05, t63=4.15). A seed-based analysis confirmed specific stimulation-driven changes within a network of motor and premotor regions in both hemispheres. At baseline and one week after sham, the strongest FC was observed between the M1 and dorsal premotor cortex (PMd) of the undamaged hemisphere. In contrast, one week after dual-tDCS, the strongest FC was found between the M1 and PMd of the damaged hemisphere. Thus, a single session of dual-tDCS combined with motor skill learning increases FC in the somatomotor network of chronic stroke patients for one week.

Neural substrates underlying motor skill learning in chronic hemiparetic stroke patients

Motor skill learning is critical in post-stroke motor recovery, but little is known about its underlying neural substrates. Recently, using a new visuomotor skill learning paradigm involving a speed/accuracy trade-off in healthy individuals we identified three subpopulations based on their behavioral trajectories: fitters (in whom improvement in speed or accuracy coincided with deterioration in the other parameter), shifters (in whom speed and/or accuracy improved without degradation of the other parameter), and non-learners. We aimed to identify the neural substrates underlying the first stages of motor skill learning in chronic hemiparetic stroke patients and to determine whether specific neural substrates were recruited in shifters versus fitters. During functional magnetic resonance imaging (fMRI), 23 patients learned the visuomotor skill with their paretic upper limb. In the whole-group analysis, correlation between activation and motor skill learning was restricted to the dorsal prefrontal cortex of the damaged hemisphere (DLPFCdamh: r = −0.82) and the dorsal premotor cortex (PMddamh: r = 0.70); the correlations was much lesser (−0.16 < r > 0.25) in the other regions of interest. In a subgroup analysis, significant activation was restricted to bilateral posterior parietal cortices of the fitters and did not correlate with motor skill learning. Conversely, in shifters significant activation occurred in the primary sensorimotor cortexdamh and supplementary motor areadamh and in bilateral PMd where activation changes correlated significantly with motor skill learning (r = 0.91). Finally, resting-state activity acquired before learning showed a higher functional connectivity in the salience network of shifters compared with fitters (qFDR < 0.05). These data suggest a neuroplastic compensatory reorganization of brain activity underlying the first stages of motor skill learning with the paretic upper limb in chronic hemiparetic stroke patients, with a key role of bilateral PMd.

Combining motor learning and brain stimulation to enhance post-stroke neurorehabilitation

Worldwide, stroke is a leading cause of life-long disability resulting in dramatic restrictions in patients independence and in a growing economic burden for the community. The majority of stroke survivors suffers from chronic sequels among which hemiparesis is one of the most debilitating. Despite quick progresses over the last 20 years, the impact of neurorehabilitation on post-stroke recovery remains unsatisfactory. Developing new ways to enhance neurorehabilitation could thus benefit to millions of patients. A better insight into the physiology of the normal motor system and the mechanisms driving post-stroke recovery and neural plasticity should permit to develop a new science of neurorehabilitation.