Sustained Modulation of Deep Brain Circuits with Focused Ultrasonic Waves

Abstract

Transcranial focused ultrasound has the potential to noninvasively and systematically modulate deep brain circuits and impart sustained, neuroplastic effects in awake subjects. The intersection of these key properties is critical for effective treatments of brain disorders, yet remains to be shown. Harnessing the full potential of transcranial ultrasound, we delivered 30-second stimuli to deep brain targets (left/right lateral geniculate nucleus) in non-human primates while they performed a visual discrimination task. This brief sonication induced a sustained bias in choice behavior that persisted up to 15 minutes following the ultrasound offset. This behavioral effect was accompanied by an increase in gamma activity with dynamics that matched the effects on behavior. Moreover, the ultrasound was delivered into the targets daily for a period of more than 6 months. There were no detrimental effects on the animals’ discrimination accuracy over the course of this stimulation regimen, even though the stimuli exceeded the FDA 510(k) Track 3 intensity values. This study highlights ultrasound’s capacity to modify deep brain activity in a safe and therapeutically relevant way in awake subjects, thus bringing the approach closer to therapeutic options for patients suffering from treatment-resistant disease.