Short-term neuroplastic effects of brain-controlled and muscle-controlled electrical stimulation.

OBJECTIVES: Functional electrical stimulation (FES) has been shown to facilitate the recovery of grasping function in individuals with incomplete spinal cord injury. Neurophysiological theory suggests that this benefit may be further enhanced by a more consistent pairing of the voluntary commands sent from the user's brain down their spinal cord with the electrical stimuli applied to the user's periphery. The objective of the study was to compare brain-machine interfaces (BMIs)-controlled and electromyogram (EMG)-controlled FES therapy to three more well-researched therapies, namely, push button-controlled FES therapy, voluntary grasping (VOL), and BMI-guided voluntary grasping. MATERIALS AND METHODS: Ten able-bodied participants underwent one hour of each of five grasping training modalities, including BMI-controlled FES (BMI-FES), EMG-controlled FES (EMG-FES), conventional push button-controlled FES, VOL, and BMI-guided voluntary grasping. Assessments, including motor-evoked potential, grip force, and maximum voluntary contraction, were conducted immediately before and after each training period. RESULTS: Motor-evoked potential-based outcome measures were more upregulated following BMI-FES and especially EMG-FES than they were following VOL or FES. No significant changes were found in the more functional outcome measures. CONCLUSIONS: These results provide preliminary evidence suggesting the potential of BMI-FES and EMG-FES to induce greater neuroplastic changes than conventional therapies, although the precise mechanism behind these changes remains speculative. Further investigation will be required to elucidate the underlying mechanisms and to conclusively determine whether these effects can translate into better long-term functional outcomes and quality of life for individuals with spinal cord injury.

Failure of spinal paired associative stimulation to induce neuroplasticity in the human corticospinal tract.

CONTEXT/OBJECTIVE: Paired associative stimulation (PAS) involves paired-stimulation pulses at both the head (via transcranial magnetic stimulation) and the periphery (via peripheral nerve stimulation). The purpose of PAS, when applied to the spinal cord, is to induce neuroplasticity and upregulate the corticospinal tract leading to effector muscles. While limited research has suggested that it is possible to produce neuroplasticity through spinal PAS, all such studies have provided stimulation at a fixed frequency of 0.1 or 0.2 Hz. DESIGN/INTERVENTIONS: The present study therefore sought to compare the effectiveness of a typical 0.1 Hz paradigm with a 1 Hz paradigm, and a paradigm which provided stimulation in 5 Hz "bursts". Two inter-stimulus intervals were tested: one which was expected to produce synchronous pre- and post-synaptic activation at the spinal synapse, and one which was not. The peripheral stimulation was applied at the wrist, to induce thumb adduction. RESULTS: None of the paradigms were able to successfully induce neuroplasticity in a consistent manner. CONCLUSION: The high between-subject variability in this study suggests that responses to the spinal PAS treatment may have been highly individual. This serves to highlight a potential limitation of the spinal PAS treatment, which is that its effectiveness may not be universal, but rather dependent on each specific recipient. This may be a challenge faced by spinal PAS should it continue to be tested as a potential novel therapy.

Gauging recovery after hemorrhagic stroke in rats: implications for cytoprotection studies.

Successful clinical translation of prospective cytoprotectants will likely occur only with treatments that improve functional recovery in preclinical (rodent) studies. Despite this assumption, many rely solely on histopathologic end points or the use of one or two simple behavioral tests. Presently, we used a battery of tests to gauge recovery after a unilateral intracerebral hemorrhagic stroke (ICH) targeting the striatum. In total, 60 rats (N=15 per group) were stereotaxically infused with 0 (SHAM), 0.06 (MILD lesion), 0.12 (MODERATE lesion), or 0.18 U (SEVERE lesion) of bacterial collagenase. This created a range of injury akin to moderate (from SEVERE to MODERATE or MODERATE to MILD lesion size approximately 30% reduction) and substantial cytoprotection (SEVERE to MILD lesion size--51% reduction). Post-ICH functional testing occurred over 30 days. Tests included the horizontal ladder and elevated beam tests, swimming, limb-use asymmetry (cylinder) test, a Neurologic Deficit Scale, an adhesive tape removal test of sensory neglect, and the staircase and single pellet tests of skilled reaching. Most tests detected significant impairments (versus SHAM), but only a few (e.g., staircase) frequently distinguished among ICH groups and none consistently differentiated among all ICH groups. However, by using a battery of tests we could behaviorally distinguish groups. Thus, preclinical testing would benefit from using a battery of behavioral tests as anything less may miss treatment effects. Such testing must be based on factors including the type of lesion, the postoperative delay and the time required to complete testing.

17beta-Estradiol pretreatment reduces bleeding and brain injury after intracerebral hemorrhagic stroke in male rats.

17beta-estradiol reduces cell death after global and focal ischemia and subarachnoid hemorrhage in rodents. Presently, we tested whether estrogen improves outcome after intracerebral hemorrhage (ICH) in male rats. Rats were implanted subcutaneously with 0.05, 0.25, or 0.50 mg pellets of estrogen (21-day release) or subjected to a sham procedure. Two weeks after implantation, they were given a striatal ICH via an infusion of collagenase. The three estrogen groups had significantly smaller lesions at a 7-day survival. Some rats had core temperature measured with an implanted telemetry probe, which also measured whole-body movements. Estrogen did not affect temperature nor activity levels after ICH. A second study with 0.25 mg pellets, administered once or twice, showed persistent histologic protection (30 days) and some functional benefit (e.g., elevated beam). A spectrophotometric hemoglobin assay showed that the 0.25 mg dose significantly reduced hemorrhagic blood volume at 12 hours after ICH. Regardless, estrogen did not lessen cerebral edema at 2 days after ICH and functional benefits were not consistently found on all tests (e.g., cylinder task). In summary, estrogen pretreatment reduces injury after ICH, in part by reducing bleeding. Estrogen may thus lessen injury and improve outcome after ICH in humans.