The efficacy of low-intensity transcranial ultrasound stimulation on negative symptoms in schizophrenia: A double-blind, randomized sham-controlled study

Zhaolin Zhai, Liyuan Ren, Zhenhua Song, Qiong Xiang, Kaiming Zhuo, Suzhen Zhang, Xuan Li, Yi Zhang, Xiong Jiao, Shanbao Tong, Junfeng Sun, Dengtang Liu

Brain Stimulation 2023, 16, 790-792 · 10.1016/j.brs.2023.04.021

human patientschizophreniaclinical scalebehaviouremg mep

Specieshuman

Subjects13 participants

Sessions per subject15

Randomisedyes

Blindingdouble

Sham / controlinactive transducer

Auditory controlnot reported

Readout timingoffline

Anaesthesianot applicable

Readoutsclinical scale, behaviour, emg mep — Scale for the Assessment of Negative Symptoms (SANS); Positive and Negative Syndrome Scale (PANSS); Chinese Brief Cognitive Test (C-BCT: TMT-A, Symbol Coding, CPT, Digital Span); single-pulse TMS-elicited MEP of ipsilateral M1

Direction of effectexcitatoryThe excitatory rTUS protocol to left DLPFC significantly decreased SANS and PANSS scores (negative symptom improvement), enhanced CPT cognitive performance, and increased ipsilateral M1 MEP amplitude (LTP-like plasticity) lasting up to 15 min post-stimulation.

Adverse eventsobservedOnly 2 of 13 active-group patients reported difficulty falling asleep, resolved within 7 days; 3 sham-group patients reported dizziness throughout the intervention; no serious adverse events (SAEs) were reported.

Exposures

Exposure 1: Excitatory rTUS to left DLPFC

Target: dorsolateral prefrontal cortex — “left DLPFC”
Device: Olympus / Panametrics · Olympus NDT · V391-SU ✓

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	500	✓✓✓
Pulse duration (ms)	not reported	⚑
Pulse repetition frequency (Hz)	not reported
Duty cycle (%)	not reported
Sonication duration (s)	not reported

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 estimate	not 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

rTUS delivered via an immersion-type focused ultrasound transducer (focal length 3.8 cm, 500 kHz), driven by a custom-made TUS system, using pulsed ultrasound waves per the authors' previously published excitatory protocol for healthy humans; delivered on workdays for three consecutive weeks (15 sessions total) to the left DLPFC; ultrasound intensity was well below FDA guidelines. Numeric pulse parameters are shown only in a figure schematic (Fig. 1A), not stated in the text.

Flags from extraction

n_subjects — Recorded as the 13 patients who received active rTUS ('exposed to ultrasound'); the other 13 patients received sham stimulation with the TUS system's power shut off, so no pulses were delivered to them.
exposures[0].timing.pulse_duration_ms — Pulse timing parameters (T1-T4, PRF, duty cycle) are shown only in a figure schematic (Fig. 1A), not stated in the main text.
exposures[0].free_field.pressure_kpa — No numeric pressure or intensity value is given in the text; only a statement that intensity is 'well below FDA guidelines.'