Shaping Motor Recovery After Stroke Using Activity-Dependent Stimulation

Background and/or Objectives: Stroke is a leading cause of disability with over 800,000 annual cases reported in the United States alone. The number of stroke survivors with persistent motor deficits is expanding as a result of improved acute treatment options and an aging population. There is a clear need to develop novel strategies for post-stroke motor recovery.

Design: Activity-dependent stimulation (ADS) is a technique to artificially couple the activity of distant populations of neurons. Applying ADS to spared cortical areas in the sensorimotor network may restore sensorimotor integration and facilitate behavioral recovery after ischemic injury. A longitudinal, within-subject design in a rat model of endothelin-1 (ET-1) induced stroke was used. Microelectrode arrays (MEAs) were implanted in spared somatosensory areas prior to injury to correlate neural activity and behavioral performance on a skilled reaching task.

Setting : Preclinical neuroscience research laboratory.

Participants : Rats were randomly assigned to one of three groups: ADS, random open-loop stimulation (OLS), and an unstimulated control group.

Interventions: ADS was used to link neural activity in spared post-lesion premotor (PM) and primary somatosensory (S1) cortices. All groups underwent combined stimulation and rehabilitative training sessions three times a week for eight weeks following lesion.

Main Outcome Measures: Mean firing rate, interspike intervals, and task-related motor dynamics were calculated from MEA-recorded neural activity. Behavioral performance was quantified via success rate on pellet retrieval attempts.

Results: All experimental groups showed significant reduction in post-lesion behavioral performance that gradually improved during rehabilitation. Rats treated with ADS, compared with both OLS and control conditions, had higher success rates on the reaching task during periods of stimulation, nearly reestablishing levels of pre-lesion motor performance. Although no differences in overall neural activity were observed between groups, task-related neural dynamics were significantly modulated by injury and respective stimulation conditions.

Conclusions: ADS enhances motor recovery after stroke, possibly by reestablishing functional motor networks between spared ipsilesional sensorimotor regions.