The combined use of transcranial direct current stimulation and robotic therapy as an add-on for conventional rehabilitation therapy may result in improved therapeutic outcomes due to modulation of brain plasticity. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.
Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of daily activities due to lower and upper limb impairments. Intensive physical and occupational therapy are still considered main treatments, but new adjunct therapies to standard rehabilitation that may optimize functional outcomes are being studied.
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that polarizes underlying brain regions through the application of weak direct currents through electrodes on the scalp, modulating cortical excitability. Increased interest in this technique can be attributed to its low cost, ease of use, and effects on human neural plasticity. Recent research has been performed to determine the clinical potential of tDCS in diverse conditions such as depression, Parkinson's disease, and motor rehabilitation after stroke. tDCS helps enhance brain plasticity and seems to be a promising technique in rehabilitation programs.
A number of robotic devices have been developed to assist in the rehabilitation of upper limb function after stroke. The rehabilitation of motor deficits is often a long process requiring multidisciplinary approaches for a patient to achieve maximum independence. These devices do not intend to replace manual rehabilitation therapy; instead, they were designed as an additional tool to rehabilitation programs, allowing immediate perception of results and tracking of improvements, thus helping patients to stay motivated.
Both tDSC and robot-assisted therapy are promising add-ons to stroke rehabilitation and target the modulation of brain plasticity, with several reports describing their use to be associated with conventional therapy and the improvement of therapeutic outcomes. However, more recently, some small clinical trials have been developed that describe the associated use of tDCS and robot-assisted therapy in stroke rehabilitation. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.
Neurological disorders such as stroke, cerebral palsy, and traumatic brain injury are leading causes of long-term disability, due to lesions and subsequent neurologic symptoms that can lead to severe incapacity and restriction of daily activities1. Movement disorders significantly reduce a patient’s quality of life. Motor recovery is fundamentally driven by neuroplasticity, the basic mechanism underlying the reacquisition of motor skills lost due to brain lesions2,3. Thus, rehabilitation therapies are strongly based on high-dose intensive training and intense repetition of movements to recover strength and range of motion. These repetitive activities are based on daily life movements, and patients may become less motivated due to the slow motor recovery and repetitive exercises, which can impair the success of neurorehabilitation4. Intensive physical and occupational therapy are still considered main treatments, but newer adjunct therapies to standard rehabilitation are being studied to optimize functional outcomes1.
The advent of robotic-assisted therapies has been shown to have great value in stroke rehabilitation, influencing processes of neuronal synaptic plasticity and reorganization. They have been investigated for the training of patients with damaged neurological functions and assisting people with disabilities5. One of the most important advantages of adding robot technology to rehabilitive interventions is its ability to deliver high-intensity and high-dosage training, which otherwise would be a very labor-intensive process6. The use of robotic therapies, along with virtual reality computer programs, allows for an immediate perception and evaluation of motor recovery and can change repetitive actions into meaningful, interactive functional tasks such as cleaning a stovetop7. This can elevate patients’ motivation and adherence to the long rehabilitation process and allows, through the possibility of measuring and quantifying movements, tracking of their progress5. Integration of robotic therapy into current practices may increase the efficacy and effectiveness of rehabilitation and enable the development of novel modes of exercise8.
Therapeutic rehabilitation robots provide task-specific training and can be divided into end-effector-type devices and exoskeleton-type devices9. The difference between these classifications is related to how movement is transferred from the device to the patient. End-effector devices have simpler structures, contacting the patient’s limb only at its most distal part, making it more difficult to isolate movement of one joint. Exoskeleton-based devices have more complex designs with a mechanical structure that mirrors the skeletal structure of the limb, so a movement of the device’s joint will produce the same movement on the patient’s limb7,9.
The T-WREX is an exoskeleton-based robot that assists whole arm movements (shoulder, elbow, forearm, wrist, and finger movements). The adjustable mechanical arm allows variable levels of gravity support, enabling patients who have some residual upper limb function to achieve a larger active range of motion in a tridimensional spatial therapy7,9. The MIT-MANUS is an end-effector-type robot that works in a single plan (x- and y-axis) and allows a two-dimensional gravity compensated therapy, assisting shoulder and elbow movements by moving the patient’s hand in the horizontal or vertical plane9,10. Both robots have built-in position sensors that can quantify upper extremity motor control and recovery and an interface for computer integration that allows 1) the training of meaningful functional tasks simulated in a virtual learning environment and 2) therapeutic exercise games, which help the practice of motor planning, eye-hand coordination, attention, and visual field defects or neglects7,9. They also allow for the compensation of gravity effects on the upper limb and are capable of offering support and assistance to repetitive and stereotyped movements in severely impaired patients. This progressively reduces assistance as the subject improves and applies minimal assistance or resistance to movement for mildly impaired patients9,11.
Another new technique for neurorehabilitation is transcranial direct current stimulation (tDCS). tDCS is a non-invasive brain stimulation technique that induces cortical excitability changes through the use of low amplitude direct currents applied via scalp electrodes12,13. Depending on the polarity of the current flow, brain excitability can be increased by anodal stimulation or decreased by cathodal stimulation2.
Recently, there has been increased interest in tDCS, as it has been shown to have beneficial effects on a wide range of diseases such as stroke, epilepsy, Parkinson’s disease, Alzheimer’s disease, fibromyalgia, psychiatric disorders such as depression, affective disorders, and schizophrenia2. tDCS has some advantages, such as its relatively low cost, ease of use, safety, and rare side effects14. tDCS is also a painless method and can be reliably blinded in clinical trials, as it has a sham mode13. tDCS is likely not optimal for functional recovery on its own; however, it is showing increased promise as an associated therapy in rehabilitation, as it enhances brain plasticity15.
In this protocol, we demonstrate combined robot-assisted therapy (with two state-of-the-art robots) and non-invasive neuromodulation with tDCS as a method for improving rehabilitation outcomes, in addition to conventional physical therapy. Most studies involving robotic therapies or tDCS have used them as isolated techniques, and few have combined both, which may enhance the beneficial effects beyond each intervention alone. These smaller trials demonstrated a possible synergistic effect between the two procedures, with improved motor recovery and functional ability8,15,16,17,18,19. Therefore, novel multi-modal therapies may enhance movement recovery beyond the current possibilities.
This protocol follows the guidelines of our institution's human research ethics committee.
1. tDCS
2. Robotic Therapy with MIT-Manus
3. Training with MIT-Manus Arm
Note: This robotic arm allows training of elbow flexion and extension, shoulder protraction and retraction, and shoulder internal and external rotation on a horizontal plane.
4. Training with T-WREX
Non-invasive brain stimulation with tDCS has recently generated interest due to its potential neuroplastic effects, comparatively inexpensive equipment, ease of use, and few side effects22. Studies have shown that neuromodulation by tDCS has the potential to modulate cortical excitability and plasticity, thus promoting improvements in motor performance through synaptic plasticity by stimulating the primary motor cortex4. Anodal stimulation increases cortical excitability by facilitating the depolarization of neurons in the primary motor cortex area, whereas cathodal stimulation hyperpolarizes the resting membrane potential and reduces the neuronal firing, which reduces interhemispheric inhibition from the contralesional primary motor cortex. Dual tDCS combines these two montages by facilitating activity in the ipsilesional area and inhibiting the contralesional hemisphere12,23.
Previous studies have reported electrophysiological effects of tDCS lasting up to 90 min and behavioral effects lasting up to 30 min, after a single 20 min tDCS session (Figure 4)24,32. The evidence is still controversial, as these positive findings are not consistent. Lindenberg et al.25 found functional motor improvement after bihemispheric stimulation that outlasted the intervention period (Figure 5), and a meta-analysis published in 2012 suggested that the use of non-invasive brain stimulation such as TMS and repetitive TMS were associated with improvements in motor recovery, both individually and when compared to placebo stimulation2. An experimental trial by Fusco et al.26 found no functional improvement for cathodal tDCS in early phases of stroke; however, Fregni et al.13 found that both isolated cathodal or anodal (but not sham) stimulation improved motor function significantly. These controversial findings are probably due to heterogeneity of patient characteristics (i.e., acute vs. chronic stroke patients, mild vs. severe motor impairments) and stimulation characteristics (i.e., number of tDCS sessions, session duration, anodal vs. cathodal vs. dual stimulation).
The evidence for robotic therapy in rehabilitation is more prominent, demonstrating clear incremental reductions of motor impairment27. However, due to the large number of manufacturers and several types of robotic devices, each machine has unique properties, qualities, and limitations. The American Heart Association suggests that robot-assisted therapy for upper extremities has achieved Class I level of evidence for stroke patients in outpatient settings and Class IIa in inpatient settings1. A review of 19 trials and 666 patients found that subjects who received robot-assisted arm training after stroke were more likely to show improvements in daily living activities and paretic arm function6. A single-blind trial found that children with cerebral paralysis improved significantly in measures of manual dexterity compared to the control group28, while Timmermans et al.29 found that chronic stroke patients showed significant improvements in task-oriented arm training that was maintained for 6 months post-intervention. Additionally, a multi-center randomized controlled trial found that chronic stroke patients with moderate to severe upper-limb impairments showed significant but modest improvements in arm function, movement, and quality of life measures after robotic training over the 36-week study period compared to the standard of care patients but not intensive physical therapy patients (Figure 6)5.
While trials of neurorehabilitation with either tDCS or robotic therapy have been performed, few have been conducted combining these therapies. Hesse et al.16 performed a preliminary pilot study and found that anodal tDCS to the affected hemisphere combined with robot-assisted arm training caused no significant improvements in motor function in sub-acute stroke patients. Another study by Ochi et al.19 showed that both anodal tDCS to the affected hemisphere and cathodal stimulation to the unaffected hemisphere could achieve a limited but similar magnitude motor improvement. Finally, Edwards et al.18 found that improvements in cortical excitability and reduced cortical inhibition in active groups of tDCS plus robot therapy resulted in larger gains on motor function.
Recent research suggests that the stimulation sequence is important to the improvement of function. Giacobbe et al.15 evaluated the dimension of timing in combined robotic therapy with tDCS for wrist rehabilitation in chronic stroke patients and found that wrist movement speed and smoothness (> 15%) were improved when tDCS was delivered prior to a 20 min session of robotic training but not when delivered during or after training (Figure 7). These results contrast with other studies that found that simultaneous occupational therapy and tDCS lead to significant motor improvements31. Finally, Nair et al.31 found that the use of simultaneous cathodal tDCS and occupational therapy resulted in significantly higher changes of motor recovery compared to therapy with sham stimulation (Figure 8).
Figure 1: Materials for tDCS. Please click here to view a larger version of this figure.
Figure 2: Vertex position. Cortical areas are marked according to the 10/20 system. Please click here to view a larger version of this figure.
Figure 3: Motor cortex position. Cortical areas are marked according to the 10/20 system. Please click here to view a larger version of this figure.
Figure 4: Electrophysiological effects of a single tDCS session. After a single tDCS session of 20 min, electrophysiological effects can last up to 90 min, and behavioral effects up to 30 min after stimulation. Reprinted from Nitsche et al.32, with permission from Springer Nature. Please click here to view a larger version of this figure.
Figure 5: Changes in primary and secondary outcomes during the 36-week study period as compared to baseline. Lo et al.5 found significant but modest improvements in arm function, movement, and quality of life after robot training. This figure is reprinted with permission from Massachusetts Medical Society5. Please click here to view a larger version of this figure.
Figure 6: Changes in motor impairment scores and fMRI laterality index. Lindenberg et al.25 found functional changes in motor impairment scores and improved function of the affected limbs after bihemispheric tDCS. Reprinted from Lindenberg et al. with permission from Lippincott Williams & Wilkins25. Please click here to view a larger version of this figure.
Figure 7: Effect of intervention type on motor performance kinematics. Giacobbe et al.15 found that tDCS delivered prior to robotic therapy improved wrist movements and smoothness. Reprinted from Giacobbe et al.15 with permission from IOS Press. The publication is available at IOS Press through 10.3233/NRE-130927 Please click here to view a larger version of this figure.
Figure 8: Effect of cathodal tDCS plus occupational therapy31. Simultaneous tDCS and occupational therapy resulted in significantly (*) higher changes of motor improvement. Reprinted fromNair et al.31 with permission from IOS Press. The publication is available at IOS Press through 10.3233/RNN-2011-0612 Please click here to view a larger version of this figure.
In this protocol, we describe a standard therapy protocol for combined tDCS stimulation associated and robotic therapy, used as a complement to conventional rehabilitation programs in patients with arm impairments. The protocol's goal is to improve motor function and mobility. It is important to observe the ramping-on and ramping-off of the tDCS machine to avoid any risk of adverse effects. tDCS is a safe technique with few side effects described in the literature2.
The protocol may be modified in minor ways. Previous reports in the literature describe tDCS being applied before, during, or after motor training (either with robots or human assistance). In our protocol, we described a 20 min session of tDCS followed immediately by robotic therapy. Some studies have found better outcomes for simultaneous tDCS and robotic training.
After a stroke, based on the interhemispheric competition model, motor deficits are suggested to be in part due to reduced output from the primary motor cortex (M1) of the damaged hemisphere and to increased inhibitory influence from the contralesional M1 hemisphere. In this protocol, we opted for anodal stimulation of the lesional M1 and described the possibility of bihemispheric stimulation. Anodal tDCS stimulation increases cortical excitability of the damaged M1, while cathodal stimulation decreases cortical excitability in the intact M1; however, dual application of tDCS would target these both areas simultaneously. Other protocols also opt for a bihemispheric stimulation, as some studies have reported larger motor function gains18,25.
Previous studies have evaluated single-dose or few sessions of tDCS for neurorehabilitation, with short-term after-effects lasting up to 90 min after a 20-30 min stimulation session. Repeated sessions may have a greater duration and magnitude of effects by inducing a more significant manipulation in synaptic efficacy and greater magnitude of effects, as physical rehabilitation for movement disorders is usually a long process. There is a consensus, however, that for lasting motor improvements, tDCS should preferentially be performed in conjunction with training30.
Robotic therapy associated with non-invasive brain stimulation is still not yet widely accessible, due to the high costs of robotic therapy. Most robots, however, are still cost-prohibitive to many rehabilitation services, resulting in limited use. The cost of robotic technology may decrease in the future as opposed to the cost of human labor, and cost-effectiveness as an advantage of robotic therapy is possible7. This protocol is interesting because physical rehabilitation with robotic therapies has shown great promise in being an adjunct to conventional therapy, allowing both inpatients and outpatients to perform more repetitive tasks with higher intensities and for longer periods, resulting in an optimal rehabilitation program. Other advantages include instant feedback and objective measurements of the kinematics and dynamics of movement performance that is possible after each training session, helping to maintain patient motivation for active participation.
The combination of tDCS and physical rehabilitation assisted by robots may enhance the effects of either intervention used alone, resulting in additional motor gains for patients. The combination of robot-training peripheral sensorimotor activities that provide increased sensory feedback to the cortex along with the modulation of cortical excitability due to tDCS may result in a more positive outcome, due to synaptic plasticity. The evidence for this combinatorial approach is promising, though still limited and inconclusive, when compared to the therapies when they are individually applied. More studies are needed to further investigate the synergism and possible additional effects of the combined therapy, such as the optimal number of sessions and timing of each therapy and whether tDCS should be applied before, during, or after rehabilitation activities to effect functional outcomes.
The authors have nothing to disclose.
The authors would like to thank the Spaulding Laboratory of Neuromodulation and Instituto de Reabilitação Lucy Montoro for their generous support on this project.
tDCS device | Soterix Medical | Soterix Medical 1×1 | |
9V Battery (2x) | |||
Two rubber head bands | |||
Two conductive rubber electrodes | |||
Two sponge electrodes | |||
Cables | |||
NaCl solution | |||
Measurement tape | |||
Armeo Spring Robot | Hocoma | ||
inMotion ARM | Interactive Motion Technologies |