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 -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.

Public Health Relevance

Stroke is the leading cause of disability in the United States, leaving a substantial number of survivors with permanent weakness. It is critical to explore innovative directions of research to facilitate recovery of motor function. We anticipate that a greater understanding of the electrophysiology of brain networks after ischemic injury will allow for the development of new methods of rehabilitation.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Scientist Development Award - Research (K02)
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Neurological Sciences Training Initial Review Group (NST)
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Chen, Daofen
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Ramanathan, Dhakshin S; Guo, Ling; Gulati, Tanuj et al. (2018) Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke. Nat Med 24:1257-1267
Gulati, Tanuj; Guo, Ling; Ramanathan, Dhakshin S et al. (2017) Neural reactivations during sleep determine network credit assignment. Nat Neurosci 20:1277-1284