Project summary The brain shows marked plasticity across a variety of learning and memory tasks as well as during recovery after injury. Many have proposed to leverage this innate plasticity using brain stimulation to treat neural disorders. Implementing such treatments requires advanced engineering tools as well as a solid understanding of how stimulation-induced plasticity drives changes in network dynamics and connectivity at a large scale and across multiple brain areas. Here, I propose to use our novel engineering tools to precisely manipulate neural activity in macaque sensorimotor cortex to investigate and induce targeted cortical reorganization. I hypothesize that a closed-loop optogenetic stimulation of somatosensory cortex based on the natural functional connectivity of the sensorimotor system can drive cortical plasticity and induce functional recovery. The functional connectivity maps of the somatosensory and motor cortical areas will be estimated as a guide for targeted stimulation. In Aim 1 the effectiveness of volitional control of activity- dependent stimulation will be investigated to both strengthen the natural existing connections and to induce new connections. In Aim 2 the volitional control of activity-dependent stimulation will be evaluated to induce new connections in the presence of an ischemic lesion. These aims are designed to provide us with both behavioral and electrophysiological measures to assess the targeted cortical reorganization. The combination of these measures can shed light on different aspects of brain plasticity and functional recovery mechanisms. The results of these aims will be a proof of concept for the power of refined stimulation patterns for targeted rehabilitation and rewiring of the brain that not only can be used for neurorehabilitation but also can help understand the circuits and connectivity in these cortical areas.

Project Narrative Relevance: The brain shows marked plasticity across a variety of learning and memory tasks as well as during recovery after injury. This proposal aims to investigate targeted stimulation of cortex to drive cortical plasticity and induce functional recovery via state-of-the-art electrophysiology and optogenetics to simultaneously record and manipulate activity of sensorimotor neurons in awake behaving macaques. Understanding the role of these basic physiological phenomena will shed light on underlying mechanisms of brain plasticity that leads to functional reorganization in the brain and can provide us with vital insight to develop stimulation-based therapies for a broad range of neurological disorders such as stroke.