Mapping the neural and physiologic response to tonic pain with low-intensity focused ultrasound: a bridge towards therapeutic applications

PROJECT ABSTRACT The experience of pain involves a combination of brain, autonomic, and behavioral responses, and dysfunction in these neural and physiologic processes underlie several chronic pain conditions. How these systems interact to generate the experience of pain, though, is poorly understood. The posterior insula (PI) and dorsal anterior cingulate cortex (dACC) are core brain regions that serve critical functions in pain and autonomic processing, however their causal role in these functions remain uncertain. The PI and dACC are thus promising therapeutic targets for non-invasive neuromodulation, but unfortunately these regions are deep to the cortex, precluding access with existing non-invasive techniques like transcranial magnetic stimulation (TMS) or transcranial electrical stimulation (TES). Low-intensity focused ultrasound (LIFU) is an emerging non-invasive neuromodulation approach that focuses mechanical energy to selectively target brain regions at any depth to transiently and reversibly alter neural activity. The Legon lab was the first to demonstrate its potential for neuromodulation in humans and has performed several foundational studies to establish LIFU’s potential as a next-generation non-invasive technique. In this F30 proposal, we are mapping the neural and physiologic responses to pain and then causally manipulating the PI and dACC to identify their specific contributions in these processes in healthy participants. To accomplish this, we will leverage electroencephalogram and multimodal physiologic measures including electrocardiogram, electrodermal activity, and continuous blood pressure monitoring during a tonic, pain-inducing stimulus at various intensities. This work will help to determine key brain- body interactions that subserve fundamental roles in the human pain experience.