Ultrasonic Deep Brain Neuromodulation in Acute Disorders of Consciousness: A Proof-of-Concept
Josh 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 Sciences 2022 · 10.3390/brainsci12040428
Abstract
The promotion of recovery in patients who have entered a disorder of consciousness (DOC; e.g., coma or vegetative states) following severe brain injury remains an enduring medical challenge despite an ever-growing scientific understanding of these conditions. Indeed, recent work has consistently implicated altered cortical modulation by deep brain structures (e.g., the thalamus and the basal ganglia) following brain damage in the arising of, and recovery from, DOCs. The (re)emergence of low-intensity focused ultrasound (LIFU) neuromodulation may provide a means to selectively modulate the activity of deep brain structures noninvasively for the study and treatment of DOCs. This technique is unique in its combination of relatively high spatial precision and noninvasive implementation. Given the consistent implication of the thalamus in DOCs and prior results inducing behavioral recovery through invasive thalamic stimulation, here we applied ultrasound to the central thalamus in 11 acute DOC patients, measured behavioral responsiveness before and after sonication, and applied functional MRI during sonication. With respect to behavioral responsiveness, we observed significant recovery in the week following thalamic LIFU compared with baseline. With respect to functional imaging, we found decreased BOLD signals in the frontal cortex and basal ganglia during LIFU compared with baseline. In addition, we also found a relationship between altered connectivity of the sonicated thalamus and the degree of recovery observed post-LIFU.
Abstract via europepmc.
Exposures
Exposure 1: Central thalamus LIFU, 650 kHz, 5% duty
Target: thalamus — “central thalamus”
Device: BrainSonix · Brainsonix, Santa Monica, CA, USA · single-element transducer (71.5 mm curvature) ✓
| 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 | ✓✓✓ |
Ten 30 s sonication blocks on, separated by 30 s off-periods, delivered inside the MRI; one LIFU session, or two sessions one week apart in some patients.
Flags from extraction
n_sessions_per_subject— Text says a second session was possible for 27% of the sample and elsewhere says 3 patients had 2 runs; Table 1 and the Methods say four patients had two sessions.exposures[0].in_situ.isppa_w_cm2— Intensities are stated as ISPPA.3 and ISPTA.3, derated with 0.3 dB/cm-MHz tissue absorption; the paper gives 719.73 mW/cm2 for ISPTA.3, recorded as 0.71973 W/cm2. Treated as derated values; whether skull attenuation is included is not stated.conditions— One patient had glioma/stroke etiology; the others traumatic brain injury (Table 1).exposures[0].target.terms— Target is the central thalamus, intended on the left; the beam is long (about 1.5 cm) and also reaches basal ganglia. Right thalamus was sonicated in some patients (Table 1).