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Transcranial Focused Ultrasound Neuromodulation of Voluntary Movement-Related Cortical Activity in Humans

Kai Yu, Chang Liu, Xiaodan Niu, Bin He

IEEE Transactions on Biomedical Engineering 2021, 68, 1923-1931 · 10.1109/tbme.2020.3030892

human healthyhealthyeeg meg

Abstract

Objective Transcranial focused ultrasound (tFUS) is an emerging non-invasive brain stimulation tool for safely and reversibly modulating brain circuits. The effectiveness of tFUS on human brain has been demonstrated, but how tFUS influences the human voluntary motor processing in the brain remains unclear. Methods We apply low-intensity tFUS to modulate the movement-related cortical potential (MRCP) originating from human subjects practicing a voluntary foot tapping task. 64-channel electroencephalograph (EEG) is recorded concurrently and further used to reconstruct the brain source activity specifically at the primary leg motor cortical area using the electrophysiological source imaging (ESI). Results The ESI illustrates the ultrasound modulated MRCP source dynamics with high spatiotemporal resolutions. The MRCP source is imaged and its source profile is further evaluated for assessing the tFUS neuromodulatory effects on the voluntary MRCP. Moreover, the effect of ultrasound pulse repetition frequency (UPRF) is further assessed in modulating the MRCP. The ESI results show that tFUS significantly increases the MRCP source profile amplitude (MSPA) comparing to a sham ultrasound condition, and further, a high UPRF enhances the MSPA more than a low UPRF does. Conclusion The present results demonstrate the neuromodulatory effects of the low-intensity tFUS on enhancing the human voluntary movement-related cortical activities evidenced through the ESI. Significance This work provides the first evidence of tFUS enhancing the human endogenous motor cortical activities through excitatory modulation.

Abstract via europepmc.

Specieshuman
Subjects15 participants
Sessions per subject2
Randomisedyes
Blindingnot reported
Sham / controlinactive transducer
Auditory controlmasking sound
Readout timingonline
Anaesthesianot applicable
Readoutseeg meg
Direction of effectexcitatorytFUS significantly increased the MRCP source profile amplitude (MSPA) relative to sham ultrasound, and a higher ultrasound pulse repetition frequency (UPRF 3000 Hz) enhanced the MSPA more than a lower UPRF (300 Hz).
Adverse eventsobservedNo adverse symptoms (headache, neck pain, dental pain, nausea, dizziness, anxiety, abnormal muscle contractions) were reported on questionnaire; however 7 of 15 subjects reported scalp tingling sensation only during the UPRF 3000 Hz session.

Exposures

Exposure 1: tFUS to primary leg motor cortex, UPRF 300 Hz and 3000 Hz

Target: primary motor cortex — “primary leg motor cortical area
Device: Blatek · Blatek Industries, Inc. · AT31529

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)0.2✓✓
Pulse repetition frequency (Hz)300, 3,000swept✓✓
Duty cycle (%)not reported
Sonication duration (s)0.5✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)809.2✓✓
Free-field Isppa (W/cm²)5.9✓✓
Free-field Ispta (W/cm²)not reported
In-situ estimatemeasurementsingle value
In-situ pressure (kPa)288.3✓✓
In-situ Isppa (W/cm²)1.17✓✓
In-situ Ispta (W/cm²)0.703✓✓
Protocol, in the paper’s words

Ultrasound was triggered by the onset of the voluntary foot-pedaling motion signal (detected by an accelerometer) and delivered as a single 500-ms sonication per trial; about 120 trials of right foot pedaling were conducted per session, with subjects initiating pedaling roughly every 3-5 seconds. Two UPRF conditions (300 Hz and 3000 Hz) plus a sham condition were tested in three sessions in random order. In the sham condition the transducer was physically detached from the scalp by 4-6 cm while still transmitting at UPRF 3000 Hz.

Consistency checks: intensity pressure inconsistent free field; intensity pressure inconsistent in situ.

Flags from extraction

  • exposures[0].timing.pulse_duration_msComputed from stated cycles-per-pulse (100) divided by fundamental frequency (0.5 MHz), a sanctioned unit conversion, not stated directly as a duration in ms.
  • exposures[0].in_situ.ispta_w_cm2Text states this ISPTA value specifically 'at UPRF=3000 Hz'; it is unclear whether the same value applies to the 300 Hz condition.
  • sham_typeSham condition kept the transducer transmitting but physically detached the acoustic aperture 4-6 cm from the scalp, rather than powering it off; classified as inactive_transducer by analogy but the exact mechanism differs from a simple power-off sham.
  • adverse_eventsPaper states 'No adverse symptoms have been reported' on questionnaire, but separately reports scalp tingling sensation in 7/15 subjects during the UPRF 3000 Hz session; coded as observed given this sensation was reported.