Increased Excitability Induced in the Primary Motor Cortex by Transcranial Ultrasound Stimulation

Abstract

Background: Transcranial Ultrasound Stimulation (tUS) is an emerging technique that uses ultrasonic waves to noninvasively modulate brain activity. As with other forms of non-invasive brain stimulation (NIBS), tUS may be useful for altering cortical excitability and neuroplasticity for a variety of research and clinical applications. The effects of tUS on cortical excitability are still unclear, and further complications arise from the wide parameter space offered by various types of devices, transducer arrangements, and stimulation protocols. Diagnostic ultrasound imaging devices are safe, commonly available systems that may be useful for tUS. However, the feasibility of modifying brain activity with diagnostic tUS is currently unknown.Objective: We aimed to examine the effects of a commercial diagnostic tUS device using an imaging protocol on cortical excitability. We hypothesized that imaging tUS applied to motor cortex could induce changes in cortical excitability as measured using a transcranial magnetic stimulation (TMS) motor evoked potential (MEP) paradigm.Methods: Forty-three subjects were assigned to receive either verum (n = 21) or sham (n = 22) diagnostic tUS in a single-blind design. Baseline motor cortex excitability was measured using MEPs elicited by TMS. Diagnostic tUS was subsequently administered to the same cortical area for 2 min, immediately followed by repeated post-stimulation MEPs recorded up to 16 min post-stimulation.Results: Verum tUS increased excitability in the motor cortex (from baseline) by 33.7% immediately following tUS (p = 0.009), and 32.4% (p = 0.047) 6 min later, with excitability no longer significantly different from baseline by 11 min post-stimulation. By contrast, subjects receiving sham tUS showed no significant changes in MEP amplitude.Conclusion: These findings demonstrate that tUS delivered via a commercially available diagnostic imaging ultrasound system transiently increases excitability in the motor cortex as measured by MEPs. Diagnostic tUS devices are currently used for internal imaging in many health care settings, and the present results suggest that these same devices may also offer a promising tool for noninvasively modulating activity in the central nervous system. Further studies exploring the use of diagnostic imaging devices for neuromodulation are warranted.

Repeated Application of Transcranial Diagnostic Ultrasound Towards the Visual Cortex Induced Illusory Visual Percepts in Healthy Participants

“…Yoo et al (2011a) noticed altered visually evoked potentials for up to 35 min after nDU exposure of the somatosensory areas of anesthetized rats. The increased receptivity found by Gibson et al (2018) discussed above lasted at least 6 min (but less than 11 min) after cessation of ultrasound exposure. Dallapiazza et al (2018) reported decreased somatosensory evoked potentials for up to 10 min after targeting the thalamus of anesthetized pigs with nDU, which was the full extent of their measurement time.…”

“…We hypothesize that participants have a natural tendency to spontaneously produce percepts during our experiment, perhaps as an effect of top-down attentional drives from higher-level cortical areas (Gilbert and Li, 2013;Zhang et al, 2014), and that DU increased the excitability of lower-level visual cortices, thus enhancing the effect. Gibson et al (2018) employed DU to achieve similar results by applying DU directly towards the human motor cortex: they found DU significantly increased cortical excitability inducible by subsequent TMS application to the same area. Our observations are also consistent with the discussion offered by Folloni et al (2019) who used nDU to stimulate deep structures in the primate brain and observed changes downstream from their stimulation point.…”

“…Subsequent studies have substantially increased upwards the frequency range of ultrasound that can modulate brain function (Bobola et al, 2018). Gibson et al (2018) used a DU transducer with a frequency range of 1-5 MHz and a central frequency of 2.32 MHz. In the present study, the transducer had a range of 6-13 MHz, and setting the device to penetration mode pushed this close to 6 MHz.…”

“…In one study, researchers applied DU through the temporal window towards the amygdala, thereby producing improved self-reported mood in patients with chronic pain (Hameroff et al, 2013). Another study (Gibson et al, 2018) applied DU directly over the motor cortex of healthy participants, observing an increased likelihood that subsequent application of transcranial magnetic stimulation (TMS) to the same motor cortex would generate motor evoked potentials.…”

“…Motivated by observations of alterations of brain function discernible by the participants themselves (Hameroff et al, 2013;Legon et al, 2014;Mueller et al, 2014;Lee et al, 2015Lee et al, , 2016aLosey et al, 2016;Gibson et al, 2018), including by DU, we sought as our primary goal to determine if DU could alter the visual perception of a target (that is, their ''percept'') when applied at the anatomical location where TMS could induce phosphenes. As a secondary goal, we sought to determine if the hypothesized effects on the visual cortex arose due to the short-term or long-term effects of ultrasound exposure.…”