Development of circuit-based therapies for motor recovery after stroke

University Of California, San Francisco, San Francisco CA

Investigators

Linked publications & trials

Abstract

? DESCRIPTION (provided by applicant): Stroke is a major cause of disability. Despite significant advances in stroke rehabilitation methods there continue to be substantial long-term disability. Additional research is required to further our understanding and to develop new methods to facilitate recovery. Over the past decade, there have been impressive advances in electrophysiological recording technology and computational approaches. Studies using these methods in healthy animals support a conceptual framework for highly dynamic interactions between neurons and the broader motor networks. For motor recovery after stroke, the precise spatiotemporal dynamics at the single neuron, ensemble and network oscillation level remain unclear. Such knowledge can lead to the development of more targeted modulation of recovering circuits and the enhancement of motor recovery (e.g. physiological electrical stimulation or pharmacological activation of specific neural subtypes). We propose to use an in vivo electrophysiological framework to model the long-term network dynamics of the recovery process. We specifically aim to conduct multi-scale chronic monitoring in awake- behaving rodents recovering from a motor cortex stroke. Our preliminary data indicates that synchronous activity driven by oscillations in the ß-band (i.e. 12-30 Hz band in the local field potential) is important for the recovery process and that modulation of it can enhance recovery. The underlying hypothesis of this proposal is that synchronous spike-field interactions in the perilesional cortex is essential for motor recovery. We will pursue the following aims. 1) Determine the spike-field interactions in the perilesional cortex that predict motor recovery after stroke. 2). Assess if state-dependent stimulation during periods of elevated spike-field synchrony is more effective than constant direct current stimulation for motor recovery. 3). Determine the neuronal cell-types that drive the perilesional oscillatory dynamics. Completion of these aims will provide new directions for stroke rehabilitation as well as provide important career development. These lines of investigation have the possibility of discovering important knowledge about the network and the neurophysiological basis of motor recovery and can offer novel approaches to cortical neuromodulation and the enhancement of motor recovery.