NCS-FO: Closed-loop neuromodulation for chronic pain

New York University Medical Center, New York NY

Investigators

Abstract

Proposal Title: NSF-FO: Closed-loop neuromodulation for chronic pain Pain is a complex and multi-dimensional experience that nevertheless occurs commonly in people's daily lives. Chronic pain affects 1.5 billion people worldwide and has contributed to major healthcare costs. The treatment of chronic pain remains insufficient, highlighted by the current opioid epidemic. In the past few decades, neuroscience research has provided accumulating knowledge of pain processing in the central nervous system. However, effective analgesic options with limited side effects remain elusive, in large part because the neural mechanism for how chronic pain is perceived and modulated in the brain is poorly understood. This proposal tries to challenge the status quo using chronic pain-treated rodent models. The use of rodent models would allow researchers to examine the brain activity at specific localized neural circuits at a cellular resolution, and to further provide a guideline for neuromodulation-based pain treatment. The project has great translational potential to advance personalized pain medicine and provide therapy for the chronic pain associated with a wide range of neuropsychiatric disorders. This project will also promote education and diversity in training undergraduate/graduate students or postdoctoral fellows, and will be committed to data sharing and outreach activity in order to maximize the benefit to society. This research project will integrate behavior and electrophysiology studies to investigate the causal impact of neuromodulation on neocortical circuits in chronic pain conditions. The ultimate objective of this proposal is to develop a noninvasive brain machine interface system for detecting and relieving chronic pain in a rodent model. On the one hand, this project will investigate examine basic neuroscience questions regarding the neural variability underlying complex sensory and affective processes. On the other hand, this project will investigate a minimally invasive neuromodulation strategy for treating chronic pain. In Aim 1, in vivo extracellular neural activity (including the ensemble spike activity and local field potentials) will be recorded from the primary somatosensory cortex and anterior cingulate cortex of freely behaving chronic pain-treated rats. This will allow researchers to characterize nociceptive response variability under different chronic pain conditions. In Aim 2, a closed-loop rodent neuromodulation interface will be developed for chronic pain control, which combines the detection of pain signals (?detection arm?) and neuromodualtion (?treatment arm?). This aim will optimize neural signal processing using multi-region local field potentials and further leverage advances in neuromodulation techniques to employ epicranial current stimulation on the targeted brain region (such as the primary motor cortex). In Aim 3, the current stimulation parameters (e.g., intensity and duration) will be optimized using online neurofeedback to improve the efficacy of neuromodulation in light of reinforcement learning. In summary, the brain-machine interface system will tease apart the mechanism of cortical pain circuits, and characterize the nociceptive response variability under different (inflammatory vs. neuropathic) chronic pain conditions. Together, these results will reveal novel insights into circuit mechanisms of chronic pain. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.