Deep cerebellar tFUS engages cortical circuits via convergent local and sensory-driven mechanisms
Anvar Sariev, Hongchae Baek, Dajung Jung, Hyungmin Kim, Alexandr Pak
2025 · 10.21203/rs.3.rs-8129088/v1
Abstract
Transcranial focused ultrasound (tFUS) enables non-invasive access to deep brain structures with high spatial precision, but its mechanisms of action remain elusive and under active investigation. The leading hypothesis posits that tFUS exerts its neuromodulatory effects through direct activation of neurons, while others attribute effects to indirect activation of auditory pathways. Here, we investigated the neuromodulatory effects of tFUS on the dentato–thalamo–cortical (DTC) pathway by targeting either the lateral cerebellar nucleus (LCN) or auditory cortex (AUD) in anesthetized rats. Electroencephalography (EEG) recordings from bilateral motor cortices and the contralateral auditory cortex revealed that tFUS reliably evoked cortical potentials, whereas sham stimulation produced no responses. Both LCN and AUD stimulation activated the auditory cortex, suggesting auditory pathway involvements. However, only LCN stimulation elicited early and significant event-related potentials and gamma-band activity in the contralateral motor cortex, consistent with DTC pathway engagement. We propose that LCN-targeted stimulation engages the DTC pathway through modulation of neuronal excitability, while concurrent auditory inputs account for global cortical activation. Proposed framework reconciles competing views of tFUS as either a direct or indirect modulator and clarifies how ultrasound can differentially influence cortical circuits depending on the stimulation target.
Abstract via europepmc.
Exposures
Exposure 1: LCN
Target: deep cerebellar nuclei — “lateral cerebellar nucleus (LCN)”
Device: Ultran · The Ultran Group · GPS350-D25_FL25 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 350 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓⚑ |
| Sonication duration (s) | 0.3 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 2.54 | ✓✓✓ |
| 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 |
50% duty cycle, 1 kHz PRF, 0.5 ms pulse duration, 300 ms pulse train duration (PTD), 3 s pulse train repetition interval (PTRI); each animal had baseline, sham, LCN and AUD sessions in randomised order.
Exposure 2: AUD
Target: primary auditory cortex — “primary auditory cortex (AUD)”
Device: Ultran · The Ultran Group · GPS350-D25_FL25 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 350 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓ |
| Sonication duration (s) | 0.3 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 2.54 | ✓✓✓ |
| 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 |
50% duty cycle, 1 kHz PRF, 0.5 ms pulse duration, 300 ms pulse train duration (PTD), 3 s pulse train repetition interval (PTRI); each animal had baseline, sham, LCN and AUD sessions in randomised order.
Flags from extraction
n_subjects— Eight rats enrolled; one animal excluded from the AUD condition, so six rats analysed for LCN/SHAM and five for AUD.n_sessions_per_subject— Four recording sessions include baseline and sham; two were active sonication sessions.exposures[0].unspecified_domain.isppa_w_cm2— Isppa 2.54 W/cm2 is given without a stated domain; the text says intensity was measured in degassed water but does not tie this value to that measurement.auditory_control— No masking or deafening; the AUD target and the uncoupled-transducer sham were used to probe auditory contribution, which the authors state cannot be quantified without cochlear blockade.exposures[0].timing.duty_cycle_pct— Quoted exposure parameters cited from ITRUSST guide ref 56 and prior stroke studies.