Estimation of the spatial profile of neuromodulation and the temporal latency in motor responses induced by focused ultrasound brain stimulation
Hyungmin Kim, Stephanie D. Lee, Alan Chiu, Seung-Schik Yoo, Shinsuk Park
NeuroReport 2014, 25, 475-479 · 10.1097/wnr.0000000000000118
Abstract
This study investigates the spatial profile and the temporal latency of the brain stimulation induced by the transcranial application of pulsed focused ultrasound (FUS). The site of neuromodulation was detected using 2-deoxy-2-[¹⁸F]fluoro-D-glucose PET immediately after FUS sonication on the unilateral thalamic area of Sprague-Dawley rats. The latency of the stimulation was estimated by measuring the time taken from the onset of the stimulation of the appropriate brain motor area to the corresponding tail motor response. The brain area showing elevated glucose uptake from the PET image was much smaller (56±10% in diameter, 24±6% in length) than the size of the acoustic focus, which is conventionally defined by the full-width at half-maximum of the acoustic intensity field. The spatial dimension of the FUS-mediated neuromodulatory area was more localized, approximated to be full-width at 90%-maximum of the acoustic intensity field. In addition, the time delay of motor responses elicited by the FUS sonication was 171±63 (SD) ms from the onset of sonication. When compared with latencies of other nonultrasonic neurostimulation techniques, the longer time delay associated with FUS-mediated motor responses is suggestive of the nonelectrical modes of neuromodulation, making it a distinctive brain stimulation method.
Abstract via europepmc.
Exposures
Exposure 1: Unilateral thalamus, 350 kHz, fixed pulsed parameters (PET/metabolic mapping experiment)
Target: thalamus — “unilateral thalamic area”
Device: custom-built
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 350 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 50% | ⚑ |
| Sonication duration (s) | 0.3 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| 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 | |
| Ispta, domain unspecified (W/cm²) | 3 | ✓✓✓⚑ |
Sonication began immediately after 18F-FDG injection and continued for 40 min, using repeated 300 ms trains (0.5 ms TBD, 1 kHz PRF) with 2 s inter-stimulus intervals; the sonicated hemisphere (left/right) was randomised and balanced across animals. PET scanning for glucose-uptake mapping was performed immediately after sonication ended.
Exposure 2: Tail motor cortex, 350 kHz, pulsed parameter sweep (tone-burst duration x duty cycle), motor-response-latency experiment
Target: primary motor cortex — “specific brain area for tail movement (2 mm posterior to the Bregma along the midline)”
Device: custom-built
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 350 | ✓✓✓ |
| Pulse duration (ms) | 0.25, 0.5, 1, 2, 3, 5swept | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓⚑ |
| Duty cycle (%) | 30, 50, 70swept | ✓✓✓ |
| Sonication duration (s) | 0.3 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| 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 | |
| Ispta, domain unspecified (W/cm²) | 4.5, 3.5swept | ✓?⚑ |
The same fixed parameters as the PET experiment (0.5 ms TBD, 1 kHz PRF, 300 ms SD) were first used briefly at a higher intensity (4.5 W/cm2 Ispta) to localise a responsive area; the acoustic intensity was then reduced to the minimum needed to elicit tail movement (3.5+-1.5 W/cm2 Ispta) while systematically varying tone-burst duration (0.25-5 ms) across three duty-cycle groups (30/50/70%, separate animals per group); the parameter set for each session was randomised and balanced across animals, and response latency was averaged over up to six sonication events per condition.
Flags from extraction
n_subjects— Paper reports two separate cohorts: n=7 for the PET experiment ('Male Sprague-Dawley rats (n = 7, 279+-15 g) were anesthetized with isoflurane...') and n=17 for the motor-delay experiment (quoted); no combined total is given, so both group sizes are listed. Only the n=17 sentence is quoted above due to the single-quote-per-field format; the n=7 value is quoted verbatim in the paper's PET-experiment methods paragraph.exposures[0].unspecified_domain.ispta_w_cm2— Domain (free-field vs in-situ/derated) of the reported acoustic intensity is not stated in this paper; placed in unspecified_domain.exposures[1].unspecified_domain.ispta_w_cm2— Value 4.5 W/cm2 Ispta was a brief initial calibration intensity and 3.5+-1.5 W/cm2 Ispta the subsequently used minimum threshold for the TBD/DC sweep; domain not stated so placed in unspecified_domain.exposures[0].timing.duty_cycle_pct— Duty cycle is defined elsewhere in the paper as the product of TBD and PRF, which would make it computable (0.5 ms x 1 kHz = 50%) for this exposure, but no explicit duty-cycle percentage is stated for the PET experiment's parameters, so it is left not_reported per the no-arithmetic rule.exposures[1].timing.pulse_repetition_frequency_hz— PRF is stated only for the initial brief calibration condition (1 kHz), not for the actual tone-burst-duration/duty-cycle sweep used to measure response latency (Table 1), so it is left not_reported for the sweep.