Transcranial ultrasound neuromodulation for epilepsy: A pilot safety trial

Ellen J. Bubrick, Nathan J. McDannold, Janet Orozco, Timothy Y. Mariano, Laura Rigolo, Alexandra J. Golby, Yanmei Tie, P. Jason White

Brain Stimulation 2024, 17, 7-9 · 10.1016/j.brs.2023.11.013

human patientepilepsyfmriclinical scale

Specieshuman

Subjects6 participants

Sessions per subject6

Randomisednot reported

Blindingnot reported

Sham / controlnone

Auditory controlnot reported

Readout timingboth

Anaesthesianot applicable

Readoutsfmri, clinical scale — Seizure frequency diary; mood and memory evaluations (self-report depression inventory, CERAD neuropsychological battery); resting-state fMRI independent component analysis (default mode network).

Direction of effectinhibitoryAll six subjects experienced seizure reduction (average ~50%) post-treatment, five with significant reductions; two of three subjects with rs-fMRI data showed improved default mode network organization 1 month post-treatment, correlating with greater seizure improvement.

Adverse eventsnone observedThere were no adverse events, and no side effects reported during or after treatment. The first subject had one of her typical seizures during the first treatment session (association with TUS unclear); her duty cycle was subsequently lowered from 50% to 18.3% for the remainder of her treatments and for all subsequent subjects.

Exposures

Exposure 1: hippocampal TUS across 4 sequential targets per session

Target: hippocampus — “anterior hippocampus”
Device: custom-built

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	548	✓✓✓
Pulse duration (ms)	not reported	⚑
Pulse repetition frequency (Hz)	500	✓✓✓
Duty cycle (%)	18.3, 50swept	✓✓✓
Sonication duration (s)	140	✓✓✓

Pressure and intensity, by domain
Free-field pressure (kPa)	140, 420swept	✓✓✓
Free-field Isppa (W/cm²)	not reported
Free-field Ispta (W/cm²)	0.5, 1.1swept	✓✓✓⚑
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

Four targets (4mm apart) in the anterior hippocampus were landmarked for sequential sonication beginning anteriorly and moving posteriorly; for each target, 140-s sonications were performed over 6 sessions (2 per week for 3 weeks). Duty cycle was varied by changing the number of wavelengths per burst: Subject 1 used 50% in session 1, then 18.3% thereafter; Subjects 2-6 used 18.3% throughout. The paper separately states 'the burst repetition period remained 2 ms (f=500 Hz) and the pulse repetition period remained 7 s (f=0.14 Hz)', i.e. a nested burst structure within the 140-s sonication; it is unclear from the text which of these two periods (2 ms or 7 s) corresponds to the 'BRP = 7 s' cited alongside PRF=500 Hz in the main parameter summary, so pulse_duration_ms (derivable only via duty_cycle/PRF arithmetic) is left not_reported.

Flags from extraction

exposures[0].timing.pulse_duration_ms — Paper gives duty cycle (18.3-50%) and PRF (500 Hz) plus two differently-named periods ('burst repetition period' = 2 ms and 'pulse repetition period' = 7 s); the burst rule would require dividing duty cycle by PRF to get pulse duration, which is arithmetic not explicitly stated in the text, so left not_reported.
exposures[0].free_field.ispta_w_cm2 — Per-subject/session ISPTA values reported later in the text range from 0.18 to 1.1 W/cm2 (e.g. Subject 1 session 2 used 0.18 W/cm2), which falls outside the main summary range of 0.50-1.1 W/cm2 quoted here; flagging the inconsistency between the summary statement and per-session detail.
n_subjects — All 6 enrolled subjects received active TUS (single-arm safety trial, no sham comparator).