Ultrasonic thalamic stimulation in chronic disorders of consciousness
Joshua A. Cain, Norman M. Spivak, John P. Coetzee, Julia S. Crone, Micah A. Johnson, Evan S. Lutkenhoff, Courtney Real, Manuel Buitrago-Blanco, Paul M. Vespa, Caroline Schnakers, Martin M. Monti
Brain Stimulation 2021 · 10.1016/j.brs.2021.01.008
human patientdisorders of consciousnessclinical scaleautonomic physiology
Specieshuman
Subjects3 participants
Sessions per subject2
Randomisednot reported
Blindingnone
Sham / controlnone
Auditory controlnot reported
Readout timingoffline
Anaesthesianot applicable
Readoutsclinical scale, autonomic physiology — JFK Coma Recovery Scale-Revised (CRS-R), including CRS-R index; vital signs (blood pressure, heart rate, blood oxygen) for safety monitoring
Direction of effectmixed or unclearTwo of three chronic disorders-of-consciousness patients showed clinically significant increases in behavioural responsiveness (including, in one patient, transient emergence from MCS) following thalamic LIFU sessions; the third patient showed no benefit from either exposure.
Adverse eventsnone observedThe intervention was reported as well tolerated and safe: no alteration in vital parameters (blood pressure, heart rate, blood oxygen), no evidence of structural damage, and no other adverse event were noted.
Exposures
Exposure 1: Thalamic LIFU in chronic disorders of consciousness patients
Target: thalamus — “left central thalamus”
Device: BrainSonix · Brainsonix ✓
| 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) | 14.39 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.72 | ✓✓✓ |
Protocol, in the paper’s words
Patients underwent two MR-guided thalamic LIFU sessions one week apart. In each session, sonication was delivered inside the MRI scanner for ten 30-s blocks, separated by 30 s off periods. The transducer focus (55 mm from its surface) was positioned over the left central thalamus using MR guidance.
Flags from extraction
exposures[0].in_situ.method— The paper labels the intensities 'ISPPA.3'/'ISPTA.3' where the figure legend explains '0.3 denotes deration (attenuation) due to absorption by tissue at 0.3 dB/cm-MHz', implying a derating method, but the main text itself does not state the method in the quoted sentence, so in_situ.method is left not_reported and captured only via the figure legend context.blinding— The paper explicitly states assessments were unblinded with respect to the LIFU procedure (e.g. due to visible indicators such as hair removal).