PROJECT SUMMARY
Stroke-causing illness, disability, and early death is set to double worldwide within the next 15 years. Despite
physical therapy, about 50% of stroke survivors have impaired hand function, which strongly impacts activities
of daily living and independence; novel treatment methods are urgently required. While most pre-clinical research
addressing stroke recovery and rehabilitation focuses on restoring damaged descending movement pathways,
dexterous hand function is also reliant on the brain receiving ascending somatosensory input and being able to
use it to guide movements. Clinically and in animal models, deficits in somatosensory cortices predict worse
recovery of hand function following stroke, though the functional mechanisms by which somatosensory signals
support hand function remain poorly characterized. In this proposal, we aim to uncover how somatosensory
signals drive motor activity during the acquisition and performance of dexterous manipulation behaviors in intact
and post-stroke non-human primates.
The main experimental approach of this proposal includes simultaneous high-density, high channel-count
acute electrophysiological recordings from the somatosensory thalamus, primary somatosensory cortex, and
primary motor cortex in intact and post-stroke non-human primates performing complex manipulation tasks. The
main analytical approach includes modeling motor activity evolution as a combination of intrinsic motor cortical
dynamics and inputs from somatosensory thalamic and somatosensory cortex. The hypothesis of this proposal
is that somatosensory input signals guide the identification of effective motor activity trajectories that become
frequently used and less input-dependent with improved manipulation skill. Thus, somatosensory signals are
critical for improvement of manipulation skill and recovery of dexterity post-stroke. Completion of this proposal
will identify nodes and functional interactions within the sensorimotor system that could be targeted with novel
therapies for improving recovery of hand function following stroke.
I will complete these aims with the guidance of an exceptional mentoring team led by Dr. Karunesh
Ganguly and including Dr. Joni Wallis, Dr. Robert Morecraft, and Dr. Aaron Suminski. During the mentored phase
of the award at UCSF, I will develop a state-of-the-art high channel-count, multi-area electrophysiological
approach for monitoring the sensorimotor network. I will also conduct the proposed experiments in animals
performing object manipulation tasks, pilot a haptic brain-machine-interface task, and focus on professional
development in order to facilitate a successful transition into an independent faculty position at an academic
institution.
