Transcranial direct current stimulation (tDCS) paired with massed practice training to promote adaptive plasticity and motor recovery in chronic incomplete tetraplegia: A pilot study

Abstract

Objective: Our goal was to determine if pairing transcranial direct current stimulation (tDCS) with rehabilitation for two weeks could augment adaptive plasticity offered by these residual pathways to elicit longer-lasting improvements in motor function in incomplete spinal cord injury (iSCI).

Design: Longitudinal, randomized, controlled, double-blinded cohort study.

Setting: Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Participants: Eight male subjects with chronic incomplete motor tetraplegia.

Interventions: Massed practice (MP) training with or without tDCS for 2 hrs, 5 times a week.

Outcome measures: We assessed neurophysiologic and functional outcomes before, after and three months following intervention. Neurophysiologic measures were collected with transcranial magnetic stimulation (TMS). TMS measures included excitability, representational volume, area and distribution of a weaker and stronger muscle motor map. Functional assessments included a manual muscle test (MMT), upper extremity motor score (UEMS), action research arm test (ARAT) and nine hole peg test (NHPT).

Results: We observed that subjects receiving training paired with tDCS had more increased strength of weak proximal (15% vs 10%), wrist (22% vs 10%) and hand (39% vs. 16%) muscles immediately and three months after intervention compared to the sham group. Our observed changes in muscle strength were related to decreases in strong muscle map volume (r=0.851), reduced weak muscle excitability (r=0.808), a more focused weak muscle motor map (r=0.675) and movement of weak muscle motor map (r=0.935).

Conclusion: Overall, our results encourage the establishment of larger clinical trials to confirm the potential benefit of pairing tDCS with training to improve the effectiveness of rehabilitation interventions for individuals with SCI.

Trial registration: NCT01539109.

Keywords: Motor recovery; Plasticity; Spinal cord injury; Transcranial direct current stimulation; Transcranial magnetic stimulation.

Figures

Figure 1

Study design, CONSORT diagram and focus of massed practice training. (A) A CONSORT Diagram of the study demonstrates that 6 of the initial 8 enrolled subjects completed all elements of the study. (B) Subjects completed two baseline testing days (pre-test #1, pre-test #2) that occurred at least 2 weeks apart. Following baseline, subjects participated in massed practice training (MP) with active transcranial direct current stimulation (tDCS) or with sham tDCS. After the intervention, outcome measures were assessed immediately (post-test) and then three months after intervention completion (follow-up). Outcome measures were collected at all time points as indicated by the grey and white boxes. The outcome measures included both neurophysiologic with transcranial magnetic stimulation (TMS) and functional tests. (C) MP was tailored to each subject and focused on muscles within the shoulder, forearm and hand. The percent of exercises that focused on each region is shown for every participant. (D) tDCS anode electrode placement overlaid for all 10 training sessions. Darker areas denote more overlap in electrode placement between the 10 training sessions. The white dots denote the hot spot for the weaker muscle, while the red dots denote the hotspot for the stronger muscle.

Figure 2

(A) Upper extremity motor score (UEMS) scores following intervention in individuals with chronic incomplete tetraplegia. Most subjects demonstrated an increase in UEMS at post-test and demonstrated sustained or enhanced changes at follow-up. Similar trends were noted across participants for (B) Change in weak TMS muscle medical research council (MRC) grade and (C) change in total MMT for the weaker upper limb. The average change across the participants in each group is denoted in as a black line (tDCS+MP) or gray dashed line (sham+MP). MMT and UEMS was not completed at follow-up for S1-A. (D) Detailed MRC grade changes across the cervical myotomes examined in the UEMS score from pre-test to post-test. Myotomes that demonstrated >15% improvement are denoted in circles at post-test. Most participants demonstrated large improvements in MRC muscle grade for myotomes below the level of injury. (E) Average percent change in MRC grade for 24 muscles across the upper limb in each group. We noted that changes in MRC grade for the anterior deltoid, middle deltoid, posterior deltoid, biceps brachii, triceps brachii, wrist extensors, first dorsal interosseous (FDI), opponens and flexor pollsis brevis were more pronounced in the tDCS+MP group. All values are presented as a percent change from pre-test #1.

Figure 3

Change in (A) action research arm test (ARAT) and (B) nine hole peg test (NHPT) in individuals with chronic incomplete tetraplegia following intervention. Most subjects demonstrated minimal improvement in functional tasks at post-test and follow-up. S3-A demonstrated the most improvement in ARAT and NHPT. Values are presented as a percent change from pre-test #1. The average change across the participants in each group is denoted in as a black line (tDCS+MP) or gray dashed line (sham+MP).

Figure 4

Change in weak muscle excitability, or active motor threshold (AMT), in the tDCS+MP group and Sham+MP group. (Left) Individuals in the tDCS+MP group had a reduced excitability in their weaker muscles, as noted by an increase in AMT at post-test in comparison to Sham+MP. The average of each group is shown as a straight line symbol. (Inset) We noted that a reduction in excitability in the weaker muscle from pre-test #2 to post-test was related to more improvements in UEMS at post-test. (Right) Example motor evoked potentials at pre-test #2 and post-test demonstrating the reduction in excitability at post-test for the weak muscle in the tDCS+MP group.

Figure 5

(A) Change in volume for the representation of the stronger muscle in the tDCS+MP group and Sham+MP group. (A, upper) Example of volume changes of the stronger muscle in S3-A at pre-test #1, pre-test #2 and post-test. Example of volume changes of the stronger muscle in S8-S at pre-test #1, pre-test #2 and post-test. Example motor maps are shown as a 3-D contour plot normalized to the MEPMaxima for each respective map. Overall we noted that subjects in the tDCS+MP group showed a reduction in the volume of their strong muscle motor map at post-test in comparison to the sham+MP group. Participants with more decreases in the volume of their stronger muscle representation also were found to demonstrate more improvement in UEMS immediately after intervention. (B) We found that the tDCS+MP group also demonstrated a more focused representation of the weaker muscle following intervention than the sham+MP group. An example distribution change is shown for the representation of the weaker muscle in the tDCS+MP group and Sham+MP group. MEP amplitudes in distribution maps are presented as a %MEPMaxima (M-MEP), wherein red denotes sites that were ≥75% MEPMaxima, orange denotes sites that were ≤75% and ≥50% MEPMaxima, yellow denotes sites that were ≤50% and ≥25% MEPMaxima and blue represents sites that were ≤25% MEPMaxima. Individuals with a more focused weak muscle map, as denoted by a higher number of map sites demonstrating MEPs >75% the maximum MEP (M-MEP) had more improvement with UEMS at post-test. (C) Movement of the center of gravity (CoG) for the representation of the weaker muscle muscle for individuals with incomplete tetraplegia following intervention. Arrows denote movement of the CoG from pre-test #2 to post-test for each individual muscle. Yellow dashed line denotes the central sulcus in anatomical map. Here, E represents the extensor digitorum communis and D denotes the middle deltoid. Participants with more medial movement of their weaker muscle representation (center of gravity; CoG) demonstrated more gains in motor function at post-test for the UEMS.