Institution: Stanford University School of Medicine
Talk Title: Noninvasive neuromodulation of human visual thalamus with transcranial ultrasound stimulation
Abstract: Clinical neuroscience has led to a revolution in our understanding of how different neural circuits contribute to phenotypes of neuropsychiatric conditions. Unfortunately, the tools to modulate these circuits in the human brain and thereby ameliorate symptoms are limited by poor focality and depth penetration. Transcranial ultrasound stimulation (TUS) is an emerging tool to achieve noninvasive focal brain-wide neuromodulation with high focality (<1cm) and the ability to achieve high intensities in-depth. This technology is at an early stage of development, and many key optimizations are needed to accelerate clinical trials in psychiatry. One key need is to better understand how different sonication parameters relate to neuromodulatory effects. Key parameters include the pulse repetition frequency (PRF), intensity, and duty cycle (DC). Importantly, by varying these parameters it may be possible to have either predominantly suppressive/inhibitory effects or facilitatory/excitatory effects on neural activity and synaptic strength. Previous work by our group and others in large animal models (e.g. Fry et al Science 1958, Mohammadjavadi, Ash et al., Scientific Reports 2022) have demonstrated a suppression of EEG visual-evoked potentials (VEPs) when TUS is targeted to the visual thalamus (lateral geniculate nucleus). We are therefore adapting this paradigm into human, as an efficient testbed to evaluate TUS effects. We implemented steady-state visual evoked potential (ssVEP) measures of contrast-response (Ash, Norcia Psychophysiology 2023) and contrast increment detection psychophysics as robust neural and behavioral readouts of subcortical visual pathway function. We developed a robust neuroimaging and simulation pipeline to target LGN, and we are using a neuronavigated depth-steerable 4-element TUS transducer. Our preliminary data suggests that VEPs can be reversibly suppressed with TUS to the human LGN. We are parametrically varying PRF, intensity, and DC to determine which parameters lead to the most robust suppressive and/or facilitatory effects. This work provides the foundation for a dissection of the roles of subcortical and deep cortical nuclei in cognition, emotion, and sensory processing in health and disease.