Sonication of the anterior thalamus with MRI-Guided transcranial focused ultrasound (tFUS) alters pain thresholds in healthy adults: A double-blind, sham-controlled study
Bashar W. Badran, Kevin A. Caulfield, Sasha Stomberg-Firestein, Philipp M. Summers, Logan T. Dowdle, Matt Savoca, Xingbao Li, Christopher W. Austelle, E. Baron Short, Jeffrey J. Borckardt, Norman Spivak, Alexander Bystritsky, Mark S. George
Brain Stimulation 2020, 13, 1805-1812 · 10.1016/j.brs.2020.10.007
Abstract
Background Transcranial focused ultrasound (tFUS) is a noninvasive brain stimulation method that may modulate deep brain structures. This study investigates whether sonication of the right anterior thalamus would modulate thermal pain thresholds in healthy individuals. Methods We enrolled 19 healthy individuals in this three-visit, double-blind, sham-controlled, crossover trial. Participants first underwent a structural MRI scan used solely for tFUS targeting. They then attended two identical experimental tFUS visits (counterbalanced by condition) at least one week apart. Within the MRI scanner, participants received two, 10-min sessions of either active or sham tFUS spread 10 min apart targeting the right anterior thalamus [fundamental frequency: 650 kHz, Pulse repetition frequency: 10 Hz, Pulse Width: 5 ms, Duty Cycle: 5%, Sonication Duration: 30s, Inter-Sonication Interval: 30 s, Number of Sonications: 10, ISPTA. 0 995 mW/cm2, ISPTA. 3 719 mW/cm2, Peak rarefactional pressure 0.72 MPa]. The primary outcome measure was quantitative sensory thresholding (QST), measuring sensory, pain, and tolerance thresholds to a thermal stimulus applied to the left forearm before and after right anterior thalamic tFUS. Results The right anterior thalamus was accurately sonicated in 17 of the 19 subjects. Thermal pain sensitivity was significantly attenuated after active tFUS. The pre-post x active-sham interaction was significant (F(1,245.95) = 4.03, p = .046). This interaction indicates that in the sham stimulation condition, thermal pain thresholds decreased 1.08 °C (SE = 0.28) pre-post session, but only decreased .51 °C (SE = 0.30) pre-post session in the active stimulation group. Conclusions Two 10-min sessions of anterior thalamic tFUS induces antinociceptive effects in healthy individuals. Future studies should optimize the parameter space, dose and duration of this effect which may lead to multi-session tFUS interventions for pain disorders.
Abstract via europepmc.
Exposures
Exposure 1: Active tFUS to right anterior thalamus
Target: anterior thalamic nucleus — “right anterior thalamus”
Device: BrainSonix · BrainSonix Corp., Sherman Oaks, CA, USA · BXPulsar 1002 tFUS System ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| 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) | 0.995 | ✓✓✓⚑ |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | 0.719 | ✓✓✓ |
| Pressure, domain unspecified (kPa) | 720 | ✓✓✓ |
Fundamental frequency 650 kHz, PRF 10 Hz, pulse width 5 ms, duty cycle 5%, sonication duration 30 s, inter-sonication interval 30 s, 10 sonications per session (conventional 30s ON/30s OFF block design), two 10-min tFUS sessions spread 10 min apart per visit.
Flags from extraction
exposures[0].free_field.ispta_w_cm2— Text lists 'ISPTA. 995 mW/cm2, ISPTA. 719 mW/cm2' with garbled subscripts; interpreted as free-field ISPTA=995 mW/cm2 and FDA-derated ISPTA.3=719 mW/cm2 based on the following sentence explaining the derating approach. Please verify against original PDF formatting.exposures[0].free_field.pressure_kpa— Domain (free-field vs in-situ) of the stated 'Peak rarefactional pressure 0.72 MPa' is not explicitly labelled; assigned to free_field per the rule to default there when domain is unclear.n_sessions_per_subject— Interpreted as 2 (one active tFUS visit, one sham tFUS visit); each visit itself comprised two 10-min sonication sessions.
Notes: Sham condition: tFUS device turned off (transducer coupled identically but not activated). Two, 10-min sonication sessions occurred within each of the two experimental visits (one active, one sham).