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Effects of transcranial focused ultrasound on human primary motor cortex using 7T fMRI: a pilot study

Leo Ai, Priya Bansal, Jerel K. Mueller, Wynn Legon

BMC Neuroscience 2018, 19 · 10.1186/s12868-018-0456-6

human healthyhealthyfmri

Abstract

Background Transcranial focused ultrasound (tFUS) is a new non-invasive neuromodulation technique that uses mechanical energy to modulate neuronal excitability with high spatial precision. tFUS has been shown to be capable of modulating EEG brain activity in humans that is spatially restricted, and here, we use 7T MRI to extend these findings. We test the effect of tFUS on 7T BOLD fMRI signals from individual finger representations in the human primary motor cortex (M1) and connected cortical motor regions. Participants (N = 5) performed a cued finger tapping task in a 7T MRI scanner with their thumb, index, and middle fingers to produce a BOLD signal for individual M1 finger representations during either tFUS or sham neuromodulation to the thumb representation. Results Results demonstrated a statistically significant increase in activation volume of the M1 thumb representation for the tFUS condition as compared to sham. No differences in percent BOLD changes were found. This effect was spatially confined as the index and middle finger M1 finger representations did not show similar significant changes in either percent change or activation volume. No effects were seen during tFUS to M1 in the supplementary motor area or the dorsal premotor cortex. Conclusions Single element tFUS can be paired with high field MRI that does not induce significant artifact. tFUS increases activation volumes of the targeted finger representation that is spatially restricted within M1 but does not extend to functionally connected motor regions. Trial registration ClinicalTrials.gov NCT03634631 08/14/18.

Abstract via europepmc.

Specieshuman
Subjects5 participants
Sessions per subject1
Randomisednot reported
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingonline
Anaesthesianot applicable
Readoutsfmri7T BOLD fMRI activation volume and percent signal change in M1 finger representations (thumb, index, middle), supplementary motor area (SMA) and dorsal premotor cortex (PMd) during a cued finger-tapping task
Direction of effectmixed or uncleartFUS to the M1 thumb representation increased BOLD activation volume (703+/-334 mm3 vs 375+/-167 mm3 for sham, p=0.039) without changing percent BOLD signal change; the effect was spatially confined to the thumb representation, with no significant change in adjacent index/middle finger representations or in downstream SMA/PMd. The authors could not determine whether the volume increase reflects excitation or increased activity of inhibitory interneuron populations.
Adverse eventsnot reported

Exposures

Exposure 1: tFUS to M1 thumb representation

Target: primary motor cortex — “M1 thumb representation (hand knob), targeted via fMRI-localised finger representation
Device: custom-built

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)0.36✓✓
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)36pulse duration × PRF gives 36%✓✓
Sonication duration (s)0.5✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)16.95✓✓
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Each tFUS stimulation delivered 180 cycles per pulse at 500 kHz (0.36 ms pulse duration) at a pulse repetition frequency of 1 kHz for 500 pulses, giving a 500 ms stimulus duration; this waveform was delivered every two TRs (2.75 s) for a total of 54 stimulations per scan, interleaved with a cued finger-tapping task.

Flags from extraction

  • exposures[0].timing.pulse_duration_msPulse duration is derived from the stated 180 cycles per pulse and 500 kHz driving frequency (180/500000 s = 0.36 ms) via the cycles-per-pulse/frequency conversion the schema explicitly permits, and matches the '36% duty cycle' separately stated in the Discussion (0.36 ms / 1 ms period).
  • exposures[0].deviceTransducer is described only as 'custom made' with no manufacturer name; classified as custom_or_research.
  • exposures[0].in_situThe paper qualitatively states that skull attenuates free-field pressure by a factor of 6-7 (based on prior modelling) but does not report a specific derated in-situ intensity or pressure value for this cohort.
  • randomisedThe order of tFUS and sham conditions was counterbalanced across participants, which is a systematic (non-random) design; the paper does not use the word randomised, so this field is recorded as not_reported rather than inferred as true or false.