Noninvasive neuromodulation of subcortical visual pathways with transcranial focused ultrasound

PROJECT SUMMARY / ABSTRACT Human neuroscience does not currently have a noninvasive tool to focally modulate activity anywhere in the brain. This is a critical unmet need: Without a focal brain-wide neuromodulation technique, hy- potheses on neural circuit function generated from neuroimaging and behavioral studies remain corre- lational, and circuit-based treatments for central nervous system disease are limited by lack of depth and anatomical specificity. The overall objective of the current proposal is to validate the ability of transcranial ultrasound stimulation (TUS), an emerging noninvasive neuromodulation technique, to target deep areas at high focality in humans, using the visual system as an ideal test-bed. The ex- pected outcome of completing these aims is the delineation of the optimal parameters and spatial specificity of targeting that is possible with this technique. Aim 1 tests TUS parameters, efficacy and focality in the early subcortical visual system (thalamic lateral geniculate nucleus), with concurrent EEG and behavioral measures of image contrast responsiveness. Aim 2 tests TUS efficacy and focali- ty in adjacent (1-2 cm apart) visual category recognition areas in ventral temporal cortex, with EEG and behavioral measures of visual category processing. Additional innovations of this proposal are that it includes measuring and modeling how a sensory input-output function – the contrast response function – is modulated by TUS protocols, and it implements computational linking models to relate TUS-induced changes in visual pathway activity to changes in associated perceptual behavior. The significance of this work is that, if successful, it provides vision researchers with a precise brain-wide tool to causally test hypotheses of visual system function. Moreover, It will lead eventually to safer and more effective circuit-based therapeutics for CNS visual disorders including amblyopia, visual halluci- nations, dyslexia, and visual agnosias.