Ryan Ash¹, Martin Scott¹, Patricia Limon¹, Morteza Mohammadjavadi¹, Kim Butts Pauly¹, Anthony Norcia¹; ¹Stanford University

Clinical neuroscience has led to a revolution in our understanding of how different neural circuits contribute to sensory processing, cognition, emotion, and behavior. Unfortunately, the tools to causally investigate these circuits in the human brain 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 optimizations are needed. One need is to better understand how different sonication parameters relate to neuromodulatory effects. Key parameters include pulse repetition frequency (PRF), intensity, and duty cycle (DC). Importantly, by varying these parameters it may be possible to have either suppressive/inhibitory effects or facilitatory/excitatory effects on neural activity and synaptic strength. We developed a paradigm to target TUS to the human lateral geniculate nucleus (LGN) as an efficient testbed to evaluate TUS effects. We implemented steady-state visual evoked potential (ssVEP) measures of contrast-response and contrast increment detection psychophysics as neural and behavioral readouts of subcortical visual pathway function. We developed a neuroimaging and simulation pipeline to target LGN, and we are using a neuronavigated depth-steerable 4-element TUS transducer. Our preliminary data suggests that 5 Hz TUS to left LGN reversibly suppresses VEP responses specifically to stimuli in the contralateral hemifield (P=0.001, n=8 participants), while 500 Hz TUS shows a trend toward enhanced responses to contralateral stimuli (P=0.1). We are now measuring the effect of TUS across the full range of visual contrasts. This work provides the foundation for a dissection of the roles of subcortical and deep cortical nuclei in contrast normalization, attention, object recognition, and other visual functions.

Acknowledgements: National Eye Institute