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

Abstract

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.

Keywords: interhemispheric rivalry; motor skill learning; neurorehabilitation; stroke; transcranial direct current stimulation.

Figures

Figure 1

Brain imaging. Magnetic resonance imaging (MRI) or computed tomography (CT) scans at the level of the stroke for each patient. Patients 10 and 16 had CT scans, patient 4 had a T1-weighted MRI, patients 12 and 18 had Diffusion-Weighted Imaging (DWI), and all others had FLAIR T2-weighted MRI. Patients 4 and 5 had an intracerebral hemorrhage. Patients 8 and 9 had a slight secondary hemorrhagic transformation. Patients 1, 15, and 17 had at least one other lesion compatible with a previous, minor stroke. Patient 6 had associated leukoaraiosis and small chronic subcortical infarcts. Patient 4 had small chronic subcortical lacunar infarcts. For patient 13, the MRI scans were not retained in the patient’s medical folder, but a detailed neuroradiological report permitted localization of the lesion (Table 1).

Figure 2

Study design. (A) Study design: Patients participated in two intervention sessions, each of which was followed by a Delayed Recall session. Intervention sessions comprised 6 periods: Familiarization (F), Baseline (B), Training (T) and Immediate (A1), 30 min (A2), and 60 min (A3) tests. Delayed Recall sessions comprised 3 periods: Recall 1 (R1), Recall 2 (R2), and New Circuit Game (NG) tests. During F, patients performed an easy circuit over 1 min. During B, A1, A2, A3, R1, and R2, patients performed the Purdue pegboard test (PPT), Maximal hand grip force (MaxHF), and the “circuit game” with the specific circuit assigned to that session. During T, patients performed five blocks of six trials of the “circuit game” (with the specific circuit assigned to that session). During these Training, patients received 30 min of dual-tDCS or sham, based on their randomization order. During NG, patients performed a New Circuit Game of the same length and difficulty. (B) Left, square circuit used for Familiarization; Right, the four circuits of identical length and complexity used for motor skill learning, and New Circuit Game.

Figure 3

Differential evolution of motor skill learning under sham and dual-tDCS. Evolution of the Learning Index (LI), expressed as a percentage change from Baseline during the Intervention session [Baseline, Training, Immediate (After), 30, and 60 min] and Delayed Recall session (Recall 1 and Recall 2). LI is plotted as the mean ± SD of five consecutive blocks of the “circuit game.” LI was significantly improved under dual-tDCS compared to sham from the third block of Training until the end of testing. Numbers on the X-axis refer to blocks of the “circuit game.” White triangles, sham; black squares, dual-tDCS. *p < 0.05, **p < 0.005, ***p < 0.001 [all p values corrected for multiples comparisons (Bonferroni)].

Figure 4

Trade-off between error and velocity under sham and dual-tDCS. Matlab® (The MathWorks) was used to generate the scatter plots and ellipses. Scatter plot of the trade-off between error (X-axis) and velocity (Y-axis), expressed as percentage change from Baseline, for each patient after dual-tDCS (black squares) or sham (white triangles) at the end of Training (upper panel) and at Recall 1 (lower panel). The ellipses [contain 90% of the values, outliers (arrows)] show that both error and velocity improved more after dual-tDCS than sham, demonstrating a shift of the speed/accuracy trade-off, as expected in efficient motor skill learning. Moreover, whereas the ellipse for sham is roughly centered over the equilibrium point, the ellipse for dual-tDCS is clearly shifted from this point, in line with a shift of the speed-accuracy trade-off.

Figure A1

CONSORT flow diagram. Method of randomization: An experimenter established an inclusion list, attributing the Eldith® codes for dual-tDCS and sham to the first and second session in pseudo-randomized, balanced order for each successive patient. A second experimenter applied these codes blindly, and patients were not aware of their treatment, such that dual-tDCS was delivered in a double-blind fashion. Since it was the first time that this paradigm was used in stroke patients to induce long-term retention after motor skill learning, no power analysis was performed.

Figure A2

Split groups analysis. The left panel displays the first session (Intervention and Recall) separately for the nine stroke patients randomly allocated to real-dual-tDCS as the first intervention (black squares) and for the nine others allocated to sham (white triangle); i.e., as if the study had assumed a parallel-group design. The LI was significantly improved under dual-tDCS compared to sham from the fifth block of Training (see Appendix 2). The right panel displays the second session (Intervention and Recall) for the two groups of stroke patients [sham (white squares) or dual-tDCS (black triangle) as the second intervention]. Evolution of the Learning Index (LI) is expressed as a percentage change from Baseline during the Intervention session [Baseline, Training, Immediate (After), 30, and 60 min] and Delayed Recall session (Recall 1 and Recall 2). LI is plotted as the mean ± SD of five consecutive blocks of the “circuit game.” *p < 0.05 [all p values corrected for multiples comparisons (Bonferroni)]. Numbers on the X-axis refer to blocks of the “circuit game.”