The motor movements and pupillary dilation observed in this study demonstrate the capability of FUS to modulate cortical and subcortical brain structures without inducing any damage. The variety of responses observed here demonstrates the capability of FUS to perform functional brain mapping.

Brain diseases including neurological disorders and tumors remain under treated due to the challenge to access the brain, and blood-brain barrier (BBB) restricting drug delivery which, also profoundly limits the development of pharmacological treatment. Focused ultrasound (FUS) with microbubbles is the sole method to open the BBB noninvasively, locally, and transiently and facilitate drug delivery, while translation to the clinic is challenging due to long procedure, targeting limitations, or invasiveness of current systems. In order to provide rapid, flexible yet precise applications, we have designed a noninvasive FUS and monitoring system with the protocol tested in monkeys (from in silico preplanning and simulation, real-time targeting and acoustic mapping, to post-treatment assessment). With a short procedure (30 min) similar to current clinical imaging duration or radiation therapy, the achieved targeting (both cerebral cortex and subcortical structures) and monitoring accuracy was close to the predicted 2-mm lower limit. This system would enable rapid clinical transcranial FUS applications outside of the MRI system without a stereotactic frame, thereby benefiting patients especially in the elderly population.

Objective. Focused ultrasound (FUS) has recently been demonstrated capable of exciting motor neuronal activity. However, comprehensive understanding of elucidated excitatory and inhibitory effects is required to better assess FUS-mediated modulation. In this study, we demonstrate that image-guided FUS can selectively modulate motor neuron activity in the mouse sciatic nerve in vivo and attribute motor responses to thermal effects. Approach. FUS was applied on the sciatic nerve of anesthetized mice in vivo through the intact skin and muscle using ultrasound imaging for targeting. Both excitatory and inhibitory effects were recorded using electromyography (EMG) along with muscle response of the hind limb. The effects of FUS modulation versus heating by invasive alternative heating source (AHS) on electrically evoked EMG responses in the sciatic nerve in vivo were also investigated. The safety and reversibility of the technique were validated using histology and EMG recovery. Main results. The FUS was capable of eliciting motor neuronal activity comparable to electrical stimulation ES, and facilitating motor neuronal response on electrically evoked potentials with temperature elevation up to 11.5 °C  ±  0.3 °C (PRF  ⩽  40 Hz). On the other hand, FUS-induced temperature elevations above 15.1 °C  ±  1.6 °C (PRF  ⩾  100 Hz) resulted in the suppression of electrically-evoked motor neuronal activity along with a decrease in EMG latency and area under the curve (AUC), which was validated against the invasive AHS with temperature elevation of 18.1 °C  ±  8.5 °C. Histological findings along with EMG responses after FUS modulation demonstrated a reversible or irreversible modulation. Significance. The findings reported herein indicate that image-guided FUS (PRF  ⩽  100 Hz) induces safe and controllable modulation of involuntarily evoked motor neuron activity in vivo.

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Purpose of review The past decade has seen rapid growth in the application of focused ultrasound (FUS) as a tool for basic neuroscience research and potential treatment of brain disorders. Here, we review recent developments in our understanding of how FUS can alter brain activity, perception and behavior when applied to the central nervous system, either alone or in combination with circulating agents. Recent findings Focused ultrasound in the central nervous system can directly excite or inhibit neuronal activity, as well as affect perception and behavior. Combining FUS with intravenous microbubbles to open the blood-brain barrier also affects neural activity and behavior, and the effects may be more sustained than FUS alone. Opening the BBB also allows delivery of drugs that do not cross the intact BBB including viral vectors for gene delivery. Summary While further research is needed to elucidate the biophysical mechanisms, focused ultrasound, alone or in combination with other factors, is rapidly maturing as an effective technology for altering brain activity. Future challenges include refining control over targeting specificity, the volume of affected tissue, cell-type specificity (excitatory or inhibitory), and the duration of neural and behavioral effects.