Special Collection: Transcranial Ultrasound Neuromodulation
Activation of Piezo1 but Not NaV1.2 Channels by Ultrasound at 43 MHzUltrasound (US) can modulate the electrical activity of the excitable tissues, but the mechanisms underlying this effect are not understood at the molecular level or in terms of the physical modality through which US exerts its effects. Here, we report an experimental system that allows for stable patch-clamp recording in the presence of US at 43 MHz, a frequency known to stimulate neural activity. We describe the effects of US on two ion channels proposed to be involved in the response of excitable cells to US: the mechanosensitive Piezo1 channel and the voltage-gated sodium channel NaV1.2.
Comparison of Electrical and Ultrasound Neurostimulation in Rat Motor CortexUltrasound (US) is known to non-invasively stimulate and modulate brain function; however, the mechanism of action is poorly understood. This study tested US stimulation of rat motor cortex (100 W/cm2, 200 kHz) in combination with epidural cortical stimulation. US directly evoked hindlimb movement. This response occurred even with short US bursts (3 ms) and had short latency (10 ms) and long refractory (3 s) periods. Unexpectedly, the epidural cortical stimulation hindlimb response was not altered during the 3-s refractory period of the US hindlimb response.
Frequency Dependence of Ultrasound Neurostimulation in the Mouse BrainUltrasound neuromodulation holds promise as a non-invasive technique for neuromodulation of the central nervous system. However, much remains to be determined about how the technique can be transformed into a useful technology, including the effect of ultrasound frequency. Previous studies have demonstrated neuromodulation in vivo using frequencies <1 MHz, with a trend toward improved efficacy with lower frequency. However, using higher frequencies could offer improved ultrasound spatial resolution.
Image-Guided Focused Ultrasound-Mediated Regional Brain Stimulation in SheepNon-invasive brain stimulation using focused ultrasound has largely been carried out in small animals. In the present study, we applied stimulatory focused ultrasound transcranially to the primary sensorimotor (SM1) and visual (V1) brain areas in sheep (Dorset, all female, n = 8), under the guidance of magnetic resonance imaging, and examined the electrophysiologic responses. By use of a 250-kHz focused ultrasound transducer, the area was sonicated in pulsed mode (tone-burst duration of 1 ms, duty cycle of 50%) for 300 ms.
Effective Parameters for Ultrasound-Induced In Vivo NeurostimulationUltrasound-induced neurostimulation has recently gained increasing attention, but little is known about the mechanisms by which it affects neural activity or about the range of acoustic parameters and stimulation protocols that elicit responses. We have established conditions for transcranial stimulation of the nervous system in vivo, using the mouse somatomotor response. We report that (1) continuous-wave stimuli are as effective as or more effective than pulsed stimuli in eliciting responses, and responses are elicited with stimulus onset rather than stimulus offset; (2) stimulation success increases as a function of both acoustic intensity and acoustic duration; (3) interactions of intensity and duration suggest that successful stimulation results from the integration of stimulus amplitude over a time interval of 50 to 150 ms; and (4) the motor response elicited appears to be an all-or-nothing phenomenon, meaning stronger stimulus intensities and durations increase the probability of a motor response without affecting the duration or strength of the response.
Noninvasive Transcranial Stimulation of Rat Abducens Nerve by Focused UltrasoundNonpharmacologic and nonsurgical transcranial modulation of the nerve function may provide new opportunities in evaluation and treatment of cranial nerve diseases. This study investigates the possibility of using low-intensity transcranial focused ultrasound (FUS) to selectively stimulate the rat abducens nerve located above the base of the skull. FUS (frequencies of 350 kHz and 650 kHz) operating in a pulsed mode was applied to the abducens nerve of Sprague-Dawley rats under stereotactic guidance.
Focused Ultrasound Modifications of Neural Circuit Activity in a Mammalian BrainThe application of focused, pulsed ultrasound was studied as a method of modifying the activity of a local neural circuit of the mammalian brain. An in vitro hippocampal preparation was used to facilitate delivery, dosimetry and assessment of mechanisms of ultrasound effects. Extracellular evoked potentials were recorded from cell and dendritic layers of the rat hippocampal dentate gyrus. Focused pulses of ultrasound with center frequency of 500 kHz and repetition rate of 200 kHz were studied and found both to enhance and to depress electrically evoked field potentials.