Share
About event
A Multi-Scale Dissection of Transcranial Ultrasound Neuromodulation
Transcranial Ultrasound Stimulation (TUS) can noninvasively manipulate neuronal activity with millimeter precision, offering immense potential for studying brain function and treating neurological disorders. Yet how ultrasound engages neural circuits – from individual cells to distributed networks – remains poorly understood, limiting our ability to optimize TUS for clinical use. In this talk, I will present two complementary studies that investigate TUS’ effects on neural function at different scales. I will first focus on the mesoscopic scale, outlining recent work developing holographic transcranial ultrasound to simultaneously target multiple cortical regions.
Using widefield calcium imaging, we demonstrated that multi-focal holographic stimulation produces supra-linear summation of neural responses, revealing that TUS efficacy can be dramatically enhanced by engaging distributed circuits cooperatively. I will then zoom in on the cellular scale, presenting our efforts to develop a coaxial focused ultrasound and two-photon (2P) imaging platform to characterize TUS effects on cortical microcircuits in awake mice with single-cell resolution and genetic cell-type specificity. We found that TUS evokes highly focal responses with distinct dose-response profiles across excitatory and inhibitory neurons, all of which unify under a scaling law based on time-average acoustic intensity. A physiologically realistic circuit model revealed that these responses arise from cell-type-specific intrinsic responses modulated by local network interactions, producing two distinct circuit regimes at low versus high acoustic doses. Beyond physiological effects, we discovered that TUS directly alters the 2P fluorescence signal within the acoustic focus, enabling real-time confirmation of in situ acoustic targeting and dose.
Together, these studies establish a multi-scale framework for understanding ultrasonic neuromodulation. I will conclude by discussing how this framework opens three research directions: leveraging circuit models to optimize TUS protocols that predictably steer brain circuits toward net excitation or inhibition; understanding how acute circuit responses shape longer-term offline effects; and translating these insights to disease models such as epilepsy, where cell-type-informed stimulation could enhance therapeutic outcomes.
