Ipsilesional anodal tDCS enhances the functional benefits of rehabilitation in patients after stroke

Abstract

Anodal transcranial direct current stimulation (tDCS) can boost the effects of motor training and facilitate plasticity in the healthy human brain. Motor rehabilitation depends on learning and plasticity, and motor learning can occur after stroke. We tested whether brain stimulation using anodal tDCS added to motor training could improve rehabilitation outcomes in patients after stroke. We performed a randomized, controlled trial in 24 patients at least 6 months after a first unilateral stroke not directly involving the primary motor cortex. Patients received either anodal tDCS (n= 11) or sham treatment (n= 13) paired with daily motor training for 9 days. We observed improvements that persisted for at least 3 months post-intervention after anodal tDCS compared to sham treatment on the Action Research Arm Test (ARAT) and Wolf Motor Function Test (WMFT) but not on the Upper Extremity Fugl-Meyer (UEFM) score. Functional magnetic resonance imaging (MRI) showed increased activity during movement of the affected hand in the ipsilesional motor and premotor cortex in the anodal tDCS group compared to the sham treatment group. Structural MRI revealed intervention-related increases in gray matter volume in cortical areas, including ipsilesional motor and premotor cortex after anodal tDCS but not sham treatment. The addition of ipsilesional anodal tDCS to a 9-day motor training program improved long-term clinical outcomes relative to sham treatment in patients after stroke.

Figure 1. Increased clinical scores in the anodal tDCS group compared to the sham treatment group.

We assessed UEFM, ARAT, and WMFT clinical scale ratings before and at multiple time points after rehabilitation and either anodal tDCS or sham treatment. Shown are changes in scores from baseline for UEFM (A), ARAT (B), and WMFT (C) for anodal tDCS (green, n=11) and sham treatment (blue, n=13) groups, for the four post-intervention timepoints, after regressing out the respective baselines. Error bars represent standard errors of the mean. Fisher’s combined probability tests showed greater scores in the anodal tDCS group compared to the sham treatment group combined across all tests and all timepoints (p=0.008). Considering each test separately, greater scores were found in the anodal tDCS group for both ARAT (p=0.031) and WMFT (p=0.037) but not for UEFM (p=0.329). For the timepoint of primary interest, the 3 month follow-up, Fisher’s combined probability test showed greater scores for the anodal tDCS group compared to the sham treatment group when combining across all tests (p=0.004). Considering each test separately, greater scores were found in the anodal tDCS group at the 3-month follow up for both ARAT (p=0.045) and WMFT (p=0.001), but not for UEFM (p=0.550). All p-values were corrected for multiple comparisons across measures/timepoints as appropriate. Changes in clinical scores from baseline in the anodal tDCS and sham treatment groups are shown separately in Figure S4.

Figure 2. Increased fMRI activity and gray matter volume in the anodal tDCS group compared to the sham treatment group.

Shown are changes in fMRI activation and gray matter volume before and after intervention in stroke patients receiving motor rehabilitation plus anodal tDCS or sham treatment (post>pre, anodal>sham, voxel-wise General Linear Model, p<0.05 corrected). Images are in radiological convention (R – right), and all lesions appear on the left, the target for tDCS (yellow flash). The X or Y coordinates for each brain slice are given below the slice. (A) Brain regions showing increases in fMRI activity during affected hand movement from baseline to immediately post-intervention for the anodal tDCS group versus the sham treatment group. (B) Regions showing greater increases in movement-related fMRI activity for anodal tDCS versus sham group from baseline to one month follow-up. See table S1 for the location and Z statistic of peak voxels from fMRI analysis. (C) Brain regions showing increases in gray matter density as assessed by voxel-based morphometry (VBM), from baseline to immediately post-intervention for the anodal tDCS group versus the sham treatment group.