Noninvasive, Systematic, and Sustained Modulation of Deep Brain Circuits in Awake Subjects

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 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 into deep brain targets (left/right lateral geniculate nucleus) of non-human primates while they performed a visual discrimination task. This brief stimulation induced sustained and target-specific behavioral preference that persisted up to 15 minutes following the ultrasound offset. The polarity of the behavioral and neural effects suggested that ultrasound excited the stimulated circuits. The ultrasound was delivered into the deep brain daily for a period of more than 6 months, which enabled us to evaluate the safety of longterm stimulation. There were no detrimental effects on the animals discrimination accuracy over the course of this stimulation regimen. This study demonstrates ultrasounds capacity to condition deep brain circuits in a safe and treatment-relevant manner in awake subjects, and provides a basis for effective and safe translations into humans. HighlightsO_LITranscranial ultrasound induces effective and sustained modulation of deep brain circuits. C_LIO_LIThe deep brain modulation biases choice behavior of non-human primates. C_LIO_LIThe deep brain modulation produces sustained elevation of high gamma activity. C_LIO_LIThe stimulation, applied daily for several months, is safe. C_LI