Effects of transcranial focused ultrasound of the human amygdala on episodic memory

About This Grant

PROJECT SUMMARY. The strength and persistence of emotional memories is believed to depend on the amygdala. Animal models demonstrate a central role of the amygdala on enhancing long-term retention of different forms of learning and memory. However, except for small studies in clinical populations with rare lesions or intracranial recordings, human neuroscience research on emotional memory processes is correlative in nearly all cases. The long-standing premise that the human amygdala is central to the enhancement of emotional memory has received limited causal support. It is possible that the human amygdala plays a more dispensable or nuanced role in the enhancement of emotional memory than assumed from animal neuroscience. Importantly, the amygdala remains a major target for translational neuroscience research focused on mental health disorders characterized by abnormalities in emotional learning, memory, and behavior. There are increasing efforts to directly target the amygdala using neurostimulation protocols as a cutting-edge treatment modality for psychiatric conditions such as posttraumatic stress disorder, with early reports of implanted deep-brain stimulating electrodes in PTSD patients. Yet, basic research using causal neurostimulation to directly target the amygdala is extremely limited. This project investigates the causal role of the amygdala in explicit emotional memory processes using a cutting-edge direct neuromodulation technique in combination with a validated emotional memory paradigm during functional MRI in healthy adult volunteers. Specifically, we directly test whether directly modulating amygdala activity with low-intensity transcranial focused ultrasound (tFUS) affects explicit memory processes using a within-subjects sham-controlled double-blinded crossover design. To date, there are no studies testing whether modulating amygdala function using tFUS affects episodic memory. For this R21 proposal, tFUS sonication (or sham) is administered to MRI-targeted left amygdala immediately prior to memory encoding, and memory retrieval is tested 24-hours later. The hypotheses and design of this proposal is supported by two separate lines of preliminary evidence from our laboratories at the University of Texas at Austin. First, we have demonstrated that focused ultrasound parameters designed to down-modulate amygdala function acutely inhibits amygdala blood oxygenation-level dependent (BOLD) signal during fMRI, providing proof-of-concept for non-invasive amygdala neuromodulation capability. Second, provocative preliminary behavioral data indicates that tFUS delivered to the left amygdala using these parameters, designed for down-modulating amygdala function, counterintuitively enhances the encoding of long-term episodic memories. The goal of this R21 is to help illuminate this finding by administering tFUS concurrent with fMRI followed immediately by emotional memory encoding also during fMRI. These findings could be of broad significance toward translational research efforts translating animal neuroscience models of learning and memory to humans, and ultimately determine how the amygdala directly contributes to episodic memory processes in the human brain.