Engineering neuroplasticity using volitional control of activity-dependent optogenetic stimulation in macaque sensorimotor cortex

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Principal Investigator: Azadeh  Yazdan Shahmorad
Organization: UNIVERSITY OF WASHINGTON
Fiscal Year: 2024
Award: $704,998
Funding agency: National Institute of Neurological Disorders and Stroke

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.

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