Controlled noninvasive modulation of deep brain regions in humans

Transcranial focused ultrasound provides noninvasive and reversible approaches for precise and personalized manipulations of brain circuits, with the potential to transform our understanding of brain function and treatments of brain dysfunction. However, effective applications in humans have been limited by the human head, which attenuates and distorts ultrasound severely and unpredictably. This has led to uncertain ultrasound intensities delivered into the brain. Here, we address this lingering barrier using a direct measurement approach that can be repeatedly applied to the human brain. The approach uses an ultrasonic scan of the head to measure and compensate for the attenuation of the ultrasound by all obstacles within the ultrasound path. No other imaging modality is required and the method is parameter-free and personalized to each subject. The approach accurately restores operators’ intended intensities inside ex-vivo human skulls. Moreover, the approach is critical for effective modulation of deep brain regions in humans. When applied, the approach modulates fMRI Blood Oxygen Level Dependent (BOLD) activity in disease-relevant deep brain regions. This tool unlocks the potential of emerging approaches based on low-intensity ultrasound for controlled manipulations of neural circuits in humans.