Wednesday, February 5, 2025
2/5/2025
PROJECT SUMMARY Neurological injuries and diseases negatively affect quality of life for millions of people in the US. In particular, damage to the posterior parietal cortex (PPC) causes various visual and oculomotor pathologies, including optic ataxia, oculomotor apraxia, and simultagnosia. Nonhuman primate and human studies have elucidated how PPC integrates visual and motor information to plan and execute movement decisions. However, much still remains unknown about how and where PPC represents future decisions and actions. In this proposal, we will use two complementary techniques, functional ultrasound neuroimaging (fUS) and electrophysiology, to explore how PPC represents decision and motor variables. These variables include movement effector, target location, and action desirability. To date, neural recording techniques have sacrificed spatial and temporal resolution for field of view or vice-versa. Now, fUS is available as an innovative neuroimaging technique that measures cerebral hemodynamics with exceptional spatiotemporal resolution (<100 µm; ~100 ms) and a large field of view (several cm) – specifications ideally suited to recording detailed activity of entire cortical regions in parallel. In addition, we will use electrophysiology, the gold standard for neuronal recordings, to verify fUS findings at the single-neuron level. In Specific Aim 1, we will investigate the anatomical organization of movement location in PPC by recording fUS data as rhesus macaques complete eye and hand movements to visual targets. This will provide a detailed cortical map of response fields in PPC according to effector and movement location. In Specific Aim 2, we will identify how and where decision variables (effort and reward) are encoded in PPC. Like Specific Aim 1, we will record fUS data while animals perform eye and hand movements, but we will also vary reward and effort by independently changing the liquid reward amount and required accuracy (i.e. effort) for each movement. In Specific Aim 3, we will investigate the link between cerebral hemodynamics and the underlying neural activity through simultaneous fUS and broad-band electrophysiology (single-unit, multi-unit, and LFP). We will use these data to 1) validate our fUS findings and 2) explore interesting patches of activity at the single neuron level. If successful, this contribution will further validate fUS as a robust and accessible neuroimaging technique for future research and clinical applications where electrophysiology is difficult to attain and/or scale. Together, these Specific Aims will elucidate where motor and decision variables are encoded in PPC from the micro-scale (electrophysiology) to the meso-scale (fUS). By understanding the neuronal circuits influencing visual-motor decisions, we can better understand visual-motor disorders, e.g. optic ataxia and oculomotor apraxia. This project will be conducted through the UCLA-Caltech MSTP under the mentorship of Drs. Andersen and Shapiro. The described research will form the basis of my PhD thesis and instill the skills for me to become an accomplished physician scientist.
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