Thalamic sonication in chronic disorders of consciousness: a mechanistic single-arm clinical trial
Martin M. Monti, Amber R. Hopkins, Norman M. Spivak, Joshua A. Cain, Jeannette Gumarang, David Patterson, Emily R. Rosario, Caroline Schnakers
2026 · 10.64898/2026.05.26.26354167
Abstract
Background Thalamic low-intensity transcranial focused ultrasound (tFUS) has shown promise for increasing behavioral responsiveness in disorders of consciousness (DOC), but no study has examined whether it can causally modulate the well-validated behavioral, electrophysiological, and metabolic biomarkers of DOC impairment. Methods Sixteen adult patients (44% Female; Age, M=37.81, SD=15.97) with a chronic DOC (Time Since Injury, M=3.39, SD=1.94 years) secondary to severe brain injury (TBI 44%, non-TBI 56%) underwent a 10-day inpatient, longitudinal, single-arm, open-label protocol. tFUS was delivered in a single session targeting the left central thalamus. Well-known behavioral (CRS-R), electrophysiological (EEG δ/β ratio), metabolic (18F-FDG PET), and polysomnographic outcomes were assessed at baseline and after sonication. Results The maximum CRS-R total score increased significantly following tFUS compared to baseline (M=13.27 vs. M=10.33; t(14)=7.407, p Conclusion Thalamic tFUS can causally modulate well-validated behavioral, electrophysiological, and metabolic biomarkers of DOC. The convergent inhibitory signature across these measures suggests a thalamocortical reset mechanism, complementing existing excitatory neuromodulation approaches and providing the mechanistic foundation for a large, randomized sham-controlled trial.
Abstract via europepmc.
Exposures
Exposure 1: Left central thalamus tFUS
Target: thalamus — “left central thalamus”
Device: BrainSonix · BrainSonix Corp · BX Pulsar 1002 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | 30 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 0.72 | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | 14.4 | ✓✓✓⚑ |
Sonication was administered in 20 blocks of 30 s, with 30 s rest intervals in between, for a total of 10 minutes of (non-continuous) cumulative sonication, at a PRF of 100 Hz and a pulse width of 0.5 ms. Single session; transducers with 55 mm or 65 mm focal depth chosen per patient.
Flags from extraction
exposures[0].in_situ.ispta_w_cm2— Derated ISPTA (14.4 W/cm2) is larger than derated ISPPA (0.72 W/cm2), which is impossible for a 5% duty cycle; the two values look swapped. Recorded as written.exposures[0].in_situ.isppa_w_cm2— See ISPTA flag: values appear swapped in the source. The text says 'derated' without giving the method or skull model.n_subjects— 16 enrolled; one withdrawn before tFUS and one after, so 15 or 14 sonicated and analysed counts vary by outcome (N=11 to 15). Enrolled count given.n_sessions_per_subject— Single sonication session within a 10-day inpatient protocol.exposures[0].timing.sonication_duration_s— 30 s is the length of each sonication block; 20 blocks with 30 s rest, 10 min cumulative sonication.exposures[0].device.family— Transducers of two focal depths (55 and 65 mm) were used depending on anatomy; frequency stated as 650 kHz.