Abstract
Introduction: Transcranial direct current stimulation (tDCS) has been shown to modulate cortical plasticity, enhance motor learning and post-stroke upper extremity motor recovery. It has also been demonstrated to facilitate activation of brain-computer interface (BCI) in stroke patients. We had previously demonstrated that BCI-assisted motor imagery (MI-BCI) can improve upper extremity impairment in chronic stroke participants. This study was carried out to investigate the effects of priming with tDCS prior to MI-BCI training in chronic stroke patients with moderate to severe upper extremity paresis and to investigate the cortical activity changes associated with training.
Methods: This is a double-blinded randomized clinical trial. Participants were randomized to receive 10 sessions of 20-min 1 mA tDCS or sham-tDCS before MI-BCI, with the anode applied to the ipsilesional, and the cathode to the contralesional primary motor cortex (M1). Upper extremity sub-scale of the Fugl-Meyer Assessment (UE-FM) and corticospinal excitability measured by transcranial magnetic stimulation (TMS) were assessed before, after and 4 weeks after intervention.
Results: Ten participants received real tDCS and nine received sham tDCS. UE-FM improved significantly in both groups after intervention. Of those with unrecordable motor evoked potential (MEP-) to the ipsilesional M1, significant improvement in UE-FM was found in the real-tDCS group, but not in the sham group. Resting motor threshold (RMT) of ipsilesional M1 decreased significantly after intervention in the real-tDCS group. Short intra-cortical inhibition (SICI) in the contralesional M1 was reduced significantly following intervention in the sham group. Correlation was found between baseline UE-FM score and changes in the contralesional SICI for all, as well as between changes in UE-FM and changes in contralesional RMT in the MEP- group.
Conclusion: MI-BCI improved the motor function of the stroke-affected arm in chronic stroke patients with moderate to severe impairment. tDCS did not confer overall additional benefit although there was a trend toward greater benefit. Cortical activity changes in the contralesional M1 associated with functional improvement suggests a possible role for the contralesional M1 in stroke recovery in more severely affected patients. This has important implications in designing neuromodulatory interventions for future studies and tailoring treatment.
Introduction
Post-stroke recovery of upper extremity (UE) function remains a challenge. Less than 15% of stroke survivors with severe impairment experience complete motor recovery (1, 2). Intensive and repetitive practice is effective for motor recovery (3), but is labor-intensive and costly. More effective rehabilitation strategies that will deliver better functional outcomes without increasing cost of care are needed.
Motor imagery (MI), or mental practice is a mental rehearsal process of a specific movement without physical performance to enhance post-stroke upper extremity motor recovery (4–10). It has been demonstrated to be a safe, self-paced method to improve motor performance in athletes (6) and is effective in augmenting the effects of motor practice in stroke patients (7–9).
MI shares similar neural substrates with motor execution (11, 12). Functional neural changes induced by MI is similar to that of short-term motor learning (5) with corresponding changes in corticospinal excitability and reorganization of motor representation have been demonstrated with MI (4, 13).
Robot-assisted training is typically applied to deliver intensive, task-specific training in rehabilitation of motor function, but has also been used to provide appropriate sensorimotor integration through guidance of movement along a trajectory (14–18). The coupling of MI and robot-assisted arm movement through brain computer interface (MI-BCI) has been postulated to enhance sensorimotor integration by bridging the motor intent and providing appropriate somatosensory feedback through passive manipulation of the paretic arm, thereby guiding activity-dependent cortical plasticity through feedback on brain activity (19). Our previous studies of MI-BCI in chronic stroke demonstrated better improvement in motor function with fewer repetitions in the same time of training (20, 21). Others have found similar benefit using BCI-driven orthoses for rehabilitation of severe UE paresis (22).
Transcranial direct current stimulation (tDCS) is a non-invasive method of modulating corticospinal excitability by changing the firing threshold of neuronal membrane and modifying spontaneous activity according to the direction of current, such that cathodal tDCS decreases cortical excitability while anodal tDCS increases it (23–25). Good functional recovery has frequently been associated with a rebalancing of interhemispheric inhibition (17, 26). Based on this, cathodal tDCS is applied to the contralesional primary motor cortex (M1) and anodal tDCS to the ipsilesional M1 to enhance corticospinal excitability. This is the paradigm most frequently studied to enhance motor recovery after stroke (27–31), and has thus far yielded mixed results (32).
Additionally, tDCS has also been explored as a priming tool to improve the accuracy of BCI, both in healthy subjects (33, 34) and in stroke patients with mixed results (35, 36). We had previously reported the preliminary results of the first ever study to investigate the effect of a course of training with BCI-assisted motor imagery (MI-BCI) with tDCS priming (simultaneous anodal stimulation to the ipsilesional M1 and cathodal stimulation to the contralesional M1) prior to each session, compared to MI-BCI with sham tDCS, on recovery of chronic stroke patients with moderate to severe impairment (37). This population was chosen as they have the most difficulty engaging in active motor task training. The stimulation protocol was selected based on the intent to rebalance transcallosal inhibition, as suggested by previous studies (28, 30, 38). Clinical improvement was observed post-training, with online BCI accuracies being significantly better in the tDCS group, compared to the sham group.
The neurobiological principles that govern post-stroke recovery of motor function are incompletely understood. While task-specific training, and MI as an extension, is applied based on principles of activity-dependent cortical plasticity, and non-invasive brain stimulation is applied based on rebalancing of interhemispheric inhibitions, a more detailed understanding of the cortical reorganization associated with the combination of therapeutic modalities, and indeed of the recovery process itself, is required in order to tailor therapeutic approaches. TMS may be used to probe these changes in cortical excitability. Here we report the changes in cortical activity associated with this training protocol, which will inform the design of future studies.[…]