← Explore

Transcranial ultrasound stimulation to human middle temporal complex improves visual motion detection and modulates electrophysiological responses

Christopher R. Butler, Edward Rhodes, Joseph Blackmore, Xinghao Cheng, Robert L. Peach, Michele Veldsman, Fintan Sheerin, Robin O. Cleveland

Brain Stimulation 2022, 15, 1236-1245 · 10.1016/j.brs.2022.08.022

human healthyhealthybehavioureeg meg

Abstract

Background Transcranial ultrasound stimulation (TUS) holds promise as a novel technology for non-invasive neuromodulation, with greater spatial precision than other available methods and the ability to target deep brain structures. However, its safety and efficacy for behavioural and electrophysiological modulation remains controversial and it is not yet clear whether it can be used to manipulate the neural mechanisms supporting higher cognitive function in humans. Moreover, concerns have been raised about a potential TUS-induced auditory confound. Objectives We aimed to investigate whether TUS can be used to modulate higher-order visual function in humans in an anatomically-specific way whilst controlling for auditory confounds. Methods We used participant-specific skull maps, functional localisation of brain targets, acoustic modelling and neuronavigation to guide TUS delivery to human visual motion processing cortex (hMT+) whilst participants performed a visual motion detection task. We compared the effects of hMT+ stimulation with sham and control site stimulation and examined EEG data for modulation of task-specific event-related potentials. An auditory mask was applied which prevented participants from distinguishing between stimulation and sham trials. Results Compared with sham and control site stimulation, TUS to hMT+ improved accuracy and reduced response times of visual motion detection. TUS also led to modulation of the task-specific event-related EEG potential. The amplitude of this modulation correlated with the performance benefit induced by TUS. No pathological changes were observed comparing structural MRI obtained before and after stimulation. Conclusions The results demonstrate for the first time the precision, efficacy and safety of TUS for stimulation of higher-order cortex and cognitive function in humans whilst controlling for auditory confounds.

Abstract via europepmc.

Specieshuman
Subjects16 participants
Sessions per subject2
Randomisedyes
Blindingsingle
Sham / controlinactive transducer, active control site
Auditory controlmasking sound
Readout timingonline
Anaesthesianot applicable
Readoutsbehaviour, eeg megvisual motion coherence detection task (accuracy, reaction time); event-related potentials (ERP)
Direction of effectexcitatoryTUS to hMT+ improved motion-detection accuracy and reduced response time on correct trials compared with sham and control-site (FFA) stimulation, and modulated (increased) the amplitude of a motion-specific ERP component.
Adverse eventsnone observedNo side effects of stimulation were reported by any participant. Examination of T1-weighted, T2-weighted and susceptibility weighted imaging (SWI) MRI scans by an experienced Consultant Neuroradiologist (FS) revealed no difference in pre- and post-stimulation images for any of the 13 scanned participants.

Exposures

Exposure 1: TUS to human middle temporal complex (hMT+)

Target: extrastriate visual cortex — “human middle temporal complex (hMT+, also known as V5)
Device: Sonic Concepts · Sonic Concepts Inc · H-107

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)0.5✓✓
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)50pulse duration × PRF gives 50%✓✓
Sonication duration (s)0.3✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatesimulationmean or range across subjects
In-situ pressure (kPa)440✓✓
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

A stimulation trial comprised a 300 ms burst applied at a 1 kHz pulse repetition frequency (PRF) and a 50% burst duty cycle (BDC). The main experiment was divided into three runs each of 90 trials and was run twice, once with TUS targeted at hMT+ and once at the control site (FFA), the order counterbalanced across participants; a maximum of 250 ultrasound stimulation bursts per brain site was imposed as a safety limit.

Flags from extraction

  • exposures[0].free_field.pressure_kpaThe ~3.5 MPa value is the transducer's calibrated maximum free-field output capability at 100V, not necessarily the pressure delivered during the experiment (amplifier voltages used in the study were up to 60V).
  • blindingPaper does not use the word 'blind' explicitly; coded as single-blind based on the described auditory-masking design, which the stimulation-detection task confirmed prevented participants from distinguishing stimulation from sham trials.
  • sham_typeDesign includes both a genuine inactive/no-output sham (sham trials, no TUS delivered) and an active control site (FFA received real TUS), so both sham_type categories are recorded; per the exposures rule, the FFA control-site stimulation is not given its own exposure entry.