Transcranial focused ultrasound neuromodulation of the human primary motor cortex

Wynn Legon, Priya Bansal, Roman Tyshynsky, Leo Ai, Jerel K Mueller, Wynn Legon, Priya Bansal, Roman Tyshynsky, Leo Ai, Jerel K Mueller

Abstract

Transcranial focused ultrasound is an emerging form of non-invasive neuromodulation that uses acoustic energy to affect neuronal excitability. The effect of ultrasound on human motor cortical excitability and behavior is currently unknown. We apply ultrasound to the primary motor cortex in humans using a novel simultaneous transcranial ultrasound and magnetic stimulation paradigm that allows for concurrent and concentric ultrasound stimulation with transcranial magnetic stimulation (TMS). This allows for non-invasive inspection of the effect of ultrasound on motor neuronal excitability using the motor evoked potential (MEP). We test the effect of ultrasound on single pulse MEP recruitment curves and paired pulse protocols including short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). In addition, we test the effect of ultrasound to motor cortex on a stimulus response reaction time task. Results show ultrasound inhibits the amplitude of single-pulse MEPs and attenuates intracortical facilitation but does not affect intracortical inhibition. Ultrasound also reduces reaction time on a simple stimulus response task. This is the first report of the effect of ultrasound on human motor cortical excitability and motor behavior and confirms previous results in the somatosensory cortex that ultrasound results in effective neuronal inhibition that confers a performance advantage.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Transcranial ultrasound and magnetic stimulation. (A) Photograph of the Ultrasound/TMS device showing the TMS coil (beige), ultrasound transducer (white) and the holder (purple). Tracking bulbs are also visible and used to guide Ultrasound/TMS to a specific brain target using stereotaxic neuronavigation. (B) Ultrasound pulsing strategy. PRF = pulse repetition frequency; Af = acoustic frequency. (C) Pseudo-color and line free water plots of ultrasound pressure field. Scales are normalized to maximum pressure. Black arrow indicates direction of sonication.
Figure 2
Figure 2
Interaction of ultrasound and TMS. (A) Ultrasound field as measured in free water. Grey line represents on time of ultrasound. (Middle) Artifact from single 100% TMS stimulator output pulse. Black line depicts length of pulse artifact. (Bottom) Both ultrasound and TMS are delivered at the same time to determine impact of TMS on the sound field pressure. No effect of the TMS pulse was found on the sound field. The US transducer does not impact the amplitude of the TMS pulse. msec = milliseconds; MPa = megapascals. (B) Average magnetic vector potential (A) relative to maximum (Amax) as measured from the plane of the face of the TMS coil without the ultrasound transducer (TMS) and with the ultrasound transducer affixed to the TMS coil (TMS + US). There was no difference in the average magnetic vector potential with the addition of the ultrasound transducer. The central line is the median, the edges of the box represent the 25% and 75% percentiles and the whiskers extend to the most extreme data points.
Figure 3
Figure 3
Modelled Ultrasound/TMS field and ultrasound field in the brain. (A) Modelled induced electric field in the human brain from the TMS coil without the ultrasound transducer (left) and with the ultrasound transducer (right). (B) Acoustic model of the ultrasound waveform positioned over primary motor cortex. CS = central sulcus. Note: Middle figure is transverse section taken through the plane (white dashed line) in the left coronal figure. kPa = kilopascals.
Figure 4
Figure 4
Ultrasound effects on single pulse TMS recruitment curves. (A) Group average (N = 12) raw data ± SEM recruitment curves for Ultrasound/TMS (grey) and sham (black) neuromodulation. *Represents p < 0.05 from post hoc testing. (B) Main effect of Ultrasound/TMS versus Sham neuromodulation collapsed across stimulator intensities 75–100%. *Represents p = 0.0126.
Figure 5
Figure 5
Ultrasound effects on paired-pulse TMS. (A) Raw group average (N = 10) paired pulse average motor evoked potential (MEP) amplitude ± SEM for inter-stimulus intervals (ISI) 1–15 milliseconds. Transcranial ultrasonic and magnetic stimulation (Ultrasound/TMS) (grey) and sham (black) neuromodulation. Amplitudes are presented relative to a single pulse baseline (horizontal dashed line). *Represents p < 0.05. (B) Averaged normalized MEP amplitude ± SEM collapsed across grouped ISIs known to reflect short intracortical inhibition (SICI) and intracortical facilitation (ICF). *Represents p < 0.05.
Figure 6
Figure 6
Effect of ultrasound on motor behavior. (A) Group average (N = 28) reaction time ± SEM in milliseconds (msec) to a stimulus response task. Active sham represents ultrasound delivered to the vertex. M1 sham represents transducer over primary motor cortex (M1) but no ultrasound. M1 tFUS is transcranial focused ultrasound to primary motor cortex. *Denotes p < 0.05. (B) Data from catch trials during the reaction time task. Data is represented as percent correct ± SEM.

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