Neuromodulation Using Transcranial Focused Ultrasound on the Bilateral Medial Prefrontal Cortex
Young Goo Kim, Song E. Kim, Jihye Lee, Sungeun Hwang, Seung-Schik Yoo, Hyang Woon Lee
Journal of Clinical Medicine 2022, 11, 3809 · 10.3390/jcm11133809
Abstract
Transcranial focused ultrasound (tFUS) is a promising technique of non-invasive brain stimulation for modulating neuronal activity with high spatial specificity. The medial prefrontal cortex (mPFC) has been proposed as a potential target for neuromodulation to prove emotional and sleep qualities. We aim to set up an appropriate clinical protocol for investigating the effects of tFUS stimulation of the bilateral mPFC for modulating the function of the brain-wide network using different sonication parameters. Seven participants received 20 min of 250 kHz tFUS to the bilateral mPFC with excitatory (70% duty cycle with sonication interval at 5 s) or suppressive (5% duty cycle with no interval) sonication protocols, which were compared to a sham condition. By placing the cigar-shaped sonication focus on the falx between both mPFCs, it was possible to simultaneously stimulate the bilateral mPFCs. Brain activity was analyzed using continuous electroencephalographic (EEG) recording during, before, and after tFUS. We investigated whether tFUS stimulation under the different conditions could lead to distinctive changes in brain activity in local brain regions where tFUS was directly delivered, and also in adjacent or remote brain areas that were not directly stimulated. This kind of study setting suggests that dynamic changes in brain cortical responses can occur within short periods of time, and that the distribution of these responses may differ depending on local brain states and functional brain architecture at the time of tFUS administration, or perhaps, at least temporarily, beyond the stimulation time. If so, tFUS could be useful for temporarily modifying regional brain activity, modulating functional connectivity, or reorganizing brain functions associated with various neuropsychiatric diseases, such as insomnia and depression.
Abstract via europepmc.
Exposures
Exposure 1: Bilateral mPFC tFUS with excitatory (70% duty cycle) or suppressive (5% duty cycle) parameters
Target: ventromedial prefrontal cortex — “bilateral medial prefrontal cortex (mPFC), targeted via the anterior falx between both mPFCs”
Device: Neurosona · Neurosona Co., Ltd. · NS-US100 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | not reported | ⚑ |
| Duty cycle (%) | 70, 5swept | ✓✓✓ |
| Sonication duration (s) | 0.3 | ✓✓✓ |
| Free-field pressure (kPa) | 300 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | ⚑ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingmean or range across subjects | |
| In-situ pressure (kPa) | 150, 180swept | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Isppa, domain unspecified (W/cm²) | 3 | ✓✓✓ |
Sonication parameters: 20 min treatment duration of 250 kHz tFUS to bilateral mPFC; excitatory protocol used 70% duty cycle with a 5 s sonication interval, suppressive protocol used 5% duty cycle with no interval; tone-burst duration 0.5 ms and sonication duration 300 ms in both. Participants underwent screening/baseline, a single tFUS session (randomly assigned to excitatory, suppressive, or sham), and a follow-up visit for safety assessment. EEG was recorded 10 min before, continuously during the 20 min stimulation, and 10 min after, with additional follow-up EEG at 1 week.
Flags from extraction
sham_type— Paper states only that 'Sham stimulus was set in the tFUS system' without describing the mechanism (e.g. powered off, blocked, aimed away); coded as other.auditory_control— No active auditory-masking method was used; the paper only asked subjects post-hoc whether they heard sounds from the transducer (none did). Coded as other since this is a subjective check, not a listed masking/deafening method.exposures[0].free_field.isppa_w_cm2— Paper states 'acoustic intensity at a focus (AIF) of 3 W/cm2' without specifying whether this is Isppa or Ispta; recorded as Isppa by convention.exposures[0].in_situ.pressure_kpa— The two in-situ values (0.18 MPa, 0.36 MI at 40% attenuation; 0.15 MPa, 0.30 MI at 50% attenuation) are two assumed-attenuation scenarios rather than a measured range across subjects; recorded as a range with reported_as='mean_or_range_across_subjects' as the closest available category.exposures[0].timing.pulse_repetition_frequency_hz— Not stated numerically anywhere in the text or Figure 2 table.n_sessions_per_subject— Participants visited the lab on three occasions (screening/baseline, sonication, follow-up), but tFUS was delivered only during the single second visit; recorded as 1 session involving sonication.