UCSF

Chronic impairment of upper limb motor function is a common and debilitating consequence of stroke with limited treatment options. While past research has identified neuroplastic changes that are crucial for recovery, most studies focused on changes that are not directly related to movement and in single brain areas. A better understanding of how neural dynamics during movement, across multiple motor areas, are altered throughout recovery is necessary to develop targeted neuromodulatory treatments.

In both chapters 2 and 3, spiking and local field potential (LFP) activity were measured from motor areas of rodents undergoing upper limb rehabilitation after a motor cortical stroke. Chapter 2 studied the movement-related neural dynamics in the perilesional cortex (PLC), the primary site of plasticity post-stroke. Movement-related low frequency oscillations (LFOs), present in both spiking and LFP, in PLC was diminished after stroke and was associated with motor recovery. The amplitude of LFOs was also reduced in a human stroke patient compared to intact subjects. Epidural direct current stimulation applied during movement increased the amplitude of LFOs and improved motor function in rodents, even in the chronic phase post-stroke. These findings demonstrate that LFOs can be a stable and translatable biomarker for tracking of post-stroke motor function and a target for neuromodulation. Chapter 3 investigated the role of the dorsolateral striatum (DLS), a motor area one synapse downstream of cortex and crucial for both motor execution and learning, and the interaction between PLC and DLS during recovery. With recovery, neural activity in both PLC and DLS became more movement modulated, more reliable and contained more information about motor behavior. PLC and DLS reorganized simultaneously throughout rehabilitation and their spiking activity also became more coordinated. These results show that motor recovery involve concerted reorganization of neural activity patterns in both cortical and subcortical motor areas.

Overall, this thesis showed that synchronous and reliable neural patterns during movement, coordinated across motor areas, are important for motor recovery. Neuromodulatory methods, such as electrical stimulation, that increase the reliability and coordination of neural activity could be promising treatments to enhance motor function post-stroke.