James R. Carey

Invasive Cortical Stimulation to Promote Recovery of Function After Stroke A Critical Appraisal

BACKGROUND AND PURPOSE Residual motor deficits frequently linger after stroke. Search for newer effective strategies to promote functional recovery is ongoing. Brain stimulation, as a means of directing adaptive plasticity, is appealing. Animal studies and Phase I and II trials in humans have indicated safety, feasibility, and efficacy of combining rehabilitation and concurrent invasive cortical stimulation. However, a recent Phase III trial showed no advantage of the combination. We critically review results of various trials and discuss the factors that contributed to the distinctive result. SUMMARY OF REVIEW Regarding cortical stimulation, it is important to determine the (1) location of peri-infarct representations by integrating multiple neuroanatomical and physiological techniques; (2) role of other mechanisms of stroke recovery; (3) viability of peri-infarct tissue and descending pathways; (4) lesion geometry to ensure no alteration/displacement of current density; and (5) applicability of lessons generated from noninvasive brain stimulation studies in humans. In terms of combining stimulation with rehabilitation, we should understand (1) the principle of homeostatic plasticity; (2) the effect of ongoing cortical activity and phases of learning; and (3) that subject-specific intervention may be necessary. CONCLUSIONS Future cortical stimulation trials should consider the factors that may have contributed to the peculiar results of the Phase III trial and address those in future study designs.

Comparison of Finger Tracking Versus Simple Movement Training via Telerehabilitation to Alter Hand Function and Cortical Reorganization After Stroke

Objective. To compare 2 telerehabilitation training strategies, repetitive tracking movements versus repetitive simple movements, to promote brain reorganization and recovery of hand function. Methods. Twenty subjects with chronic stroke and 10 degrees of voluntary finger extension were randomly assigned to receive 1800 telerehabilitation trials over 2 weeks of either computerized tracking training (track group) with the affected finger and wrist involving temporospatial processing to achieve accuracy or movement training (move group) with no attention to accuracy. Following movement training, the move group crossed over to receive an additional 2 weeks of tracking training. Behavioral changes were measured with the Box and Block test, Jebsen Taylor test, and finger range of motion, along with a finger-tracking activation paradigm during fMRI. Results. The track group showed significant improvement in all 4 behavioral tests; the move group improved in the Box and Block and Jebsen Taylor tests. The improvement for the track group in the Box and Block and Jebsen Taylor tests did not surpass that for the move group. A consistent group pattern of brain reorganization was not evident. The move group, after crossing over, did not show further significant improvements. Conclusion . Telerehabilitation may be effective in improving performance in subjects with chronic stroke. Tracking training with reinforcement to enhance learning, however, did not produce a clear advantage over the same amount of practice of random movements. Two weeks of training may be insufficient to demonstrate a behavioral advantage and associated brain reorganization.

Neuromodulation for Brain Disorders: Challenges and Opportunities

The field of neuromodulation encompasses a wide spectrum of interventional technologies that modify pathological activity within the nervous system to achieve a therapeutic effect. Therapies including deep brain stimulation, intracranial cortical stimulation, transcranial direct current stimulation, and transcranial magnetic stimulation have all shown promising results across a range of neurological and neuropsychiatric disorders. While the mechanisms of therapeutic action are invariably different among these approaches, there are several fundamental neuroengineering challenges that are commonly applicable to improving neuromodulation efficacy. This paper reviews the state-of-the-art of neuromodulation for brain disorders and discusses the challenges and opportunities available for clinicians and researchers interested in advancing neuromodulation therapies.

New modalities of brain stimulation for stroke rehabilitation

Stroke is a leading cause of disability, and the number of stroke survivors continues to rise. Traditional neurorehabilitation strategies aimed at restoring function to weakened limbs provide only modest benefit. New brain stimulation techniques designed to augment traditional neurorehabilitation hold promise for reducing the burden of stroke-related disability. Investigators discovered that repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and epidural cortical stimulation (ECS) can enhance neural plasticity in the motor cortex post-stroke. Improved outcomes may be obtained with activity-dependent stimulation, in which brain stimulation is contingent on neural or muscular activity during normal behavior. We review the evidence for improved motor function in stroke patients treated with rTMS, tDCS, and ECS and discuss the mediating physiological mechanisms. We compare these techniques to activity-dependent stimulation, discuss the advantages of this newer strategy for stroke rehabilitation, and suggest future applications for activity-dependent brain stimulation.

Primed low-frequency repetitive transcranial magnetic stimulation and constraint-induced movement therapy in pediatric hemiparesis: a randomized controlled trial.

The aim of this study was to determine the feasibility and efficacy of five treatments of 6 Hz primed, low‐frequency, repetitive transcranial magnetic stimulation (rTMS) combined with constraint‐induced movement therapy (CIMT) to promote recovery of the paretic hand in children with congenital hemiparesis.

Tracking control in the nonparetic hand of subjects with stroke

OBJECTIVE To examine in subjects with stroke using their nonparetic side how different levels of stimulus-response (S-R) compatibility, which require different levels of information processing, affect manual tracking control. DESIGN Descriptive study comparing finger movement tracking performance under S-R-compatible and S-R-incompatible conditions between subjects with stroke and healthy controls. Four two-factor analysis of variance tests with one independent factor (group, gender, laterality, or order) and one repeated measures factor (position) comprised the data analysis. SETTING University-based research setting. PATIENTS Forty subjects with chronic stroke: 20 right hemiplegia (average age, 65.2+/-2.3 yrs); 20 left hemiplegia (average age, 68.6+/-2.3 yrs). Fifty-one healthy controls: 24 using nondominant hand (average age, 68.6+/-2.1 yrs); 27 using dominant hand (average age, 68.7+/-2.0 yrs). All were right-handed. MAIN OUTCOME MEASURE Tracking accuracy index (AI), based on root-mean-square error normalized to scale of each subjects tracking target. RESULTS In S-R-incompatible condition, AI of subjects with stroke was not significantly different from controls (F[1, 89]=1.73, p=.19). In S-R-compatible condition, AI of control subjects was significantly better than subjects with stroke (F[1, 89]=14.3, p=.0003). CONCLUSION Manual tracking is impaired in nonparetic hand of subjects with stroke, suggesting that information processing, distinctly separate from motor weakness, may be an underestimated problem impairing controlled movements in individuals with stroke.

Noninvasive brain stimulation and motor recovery after stroke.

PURPOSE Upper limb function is the best predictor of long-term disability after stroke. Despite extensive rehabilitation, recovery of upper limb motor function is frequently incomplete after stroke. METHODS We review the pertinent literature on functional reorganization within the cerebral motor network after stroke and noninvasive techniques to modulate brain function towards beneficial plasticity. RESULTS Direct current stimulation and repetitive transcranial magnetic stimulation are powerful tools to (i) modulate cortical excitability, (ii) induce remote changes within the cortical motor system and (iii) thereby improve upper limb motor function after stroke. Today no relevant side effects have been reported. CONCLUSIONS Neuromodulation, by means of noninvasive brain stimulation techniques, has been shown to be a safe, feasible and effective method to promote recovery of motor function after stroke. However, several methodological and theoretical issues remain to be addressed in future work.

Safety of 6-Hz Primed Low-Frequency rTMS in Stroke

Background. Suppression of activity in the contralesional motor cortex may promote recovery of function after stroke. Furthermore, the known depressant effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) can be increased and prolonged by preceding it with 6-Hz priming stimulation. Objective. The authors explored the safety of 6-Hz primed low-frequency rTMS in 10 patients with ischemic stroke. Methods. Priming consisted of 10 minutes of 6-Hz rTMS applied to the contralesional hemisphere at 90% of resting motor threshold delivered in 2 trains/min with 5 s/train and 25-second intervals between trains. Low-frequency rTMS consisted of an additional 10 minutes of 1-Hz rTMS at 90% of resting motor threshold without interruption. Possible adverse effects were assessed with the National Institutes of Health Stroke Scale (NIHSS), the Wechsler Adult Intelligence Scale—Third Edition (WAIS-III), the Hopkins Verbal Learning Test—Revised (HVLT-R), the Beck Depression Inventory—Second Edition (BDI-II), a finger movement tracking test, and individual self-assessments. Pretest, treatment, and posttest occurred on the first day with follow-up tests on the next 5 weekdays. Results. There were no seizures and no impairment of NIHSS, WAIS-III, or BDI-II scores. Transient impairment occurred on the HVLT-R. Transient tiredness was common. Occasional reports of headache, neck pain, increased sleep, reduced sleep, nausea, and anxiety occurred. Conclusion. Because there were no major adverse effects, the authors concluded that the treatment was safe for the individuals in this study and that further investigation is now warranted to examine efficacy and safety of serial treatments of 6-Hz primed low-frequency rTMS.

Primary Motor Area Activation during Precision-Demanding versus Simple Finger Movement

The authors used functional magnetic resonance imaging to explore whether the primary motor area (M1) serves a processing role in a finger-movement tracking task, emphasizing attention to accuracy, beyond its execution role of simple movements, with no attention to accuracy. Twenty healthy subjects performed alternating conditions: Rest, involving no finger movement; Track, involving careful control of a cursor along a target pathway with finger extension/flexion movements; and Move, involving finger extension/flexion movements without careful control. The authors compared volume of activated voxels in the M1, blood-oxygen-level-dependent (BOLD) signal intensity of activated voxels in the M1, and BOLD signal intensity of all voxels in the M1 between the Track and Move conditions. The results showed greater volume and signal intensity in both the contralateral and ipsilateral M1 during Track than during Move. Overall, the results suggest that the M1 is engaged not only in the execution of movements but also in spatial and temporal processing to produce accurately controlled movements. These findings invite further work exploring whether precision-demanding movements, such as tracking, form a more potent stimulus for promoting helpful brain reorganization in the M1 during the recovery from stroke than simple repetitive movements.

Design and implementation of a home stroke telerehabilitation system

Motor retraining following stroke can occur through intensive, repetitive motion tasks that require concentration to promote new connections in the brain. Conducting intensive, repetitive therapy in the clinic is time consuming for both patient and therapist. A home-based, clinician-directed tracking training system for rehabilitation is presented. Two biofeedback motion training systems have been developed, one for hand and wrist motor relearning and the other for the ankle. The systems include a potentiometer joint sensor, a smart box interface and a laptop host computer. An internet connection allowed for periodic video teleconferencing between patient and therapist. The hand/wrist system was evaluated in a pilot project with 24 subjects. The results demonstrated technical feasibility for the technology. The ankle system is currently undergoing evaluation.