Transcranial Focused Ultrasound Modulates Feedforward and Feedback Cortico-Thalamo-Cortical Pathways by Selectively Activating Excitatory Neurons
Huan Gao, Sandhya Ramachandran, Kai Yu, Bin He
The Journal of Neuroscience 2025, 45, e2218242025 · 10.1523/jneurosci.2218-24.2025
Abstract
Transcranial focused ultrasound stimulation (tFUS) is a promising neuromodulation technique capable of noninvasively modulating focal neuronal activities and neural circuits in both animals and humans. The cell-type selectivity of tFUS within targeted areas such as the somatosensory cortex (S1) during sonication has been shown to be parameter related. However, it remains unclear how tFUS affects neural circuits by changing the correlation between neurons and how to optimize the tFUS parameters to modulate neural pathways. In this study, multisite intracranial recordings are used in anesthetized male rats to quantify the neuronal responses to tFUS stimulation recorded from S1 and posterior medial thalamic nucleus (POm) of cortico-thalamo-cortical (CTC) pathway. Different tFUS parameters including ranges of pulse repetition frequencies (PRFs) and duty cycles (DCs) are tested. We find that when targeting at S1, only regular-spiking units (RSUs) respond to specific tFUS parameters during sonication (DC, 6-60%; PRF, 1,500, 3,000 and 4,500 Hz), and RSUs from the POm exhibit a synchronized response. The changes of directional correlation between S1 RSUs and POm RSUs indicate the activation of feedback modulation. Delayed responses and correlation changes were further observed at ∼200 ms postsonication from the neurons in S1 and POm, indicating feedforward modulation. Our results reveal that tFUS can modulate the feedback and feedforward CTC pathways by selectively activating cortical RSUs and adjusting the tFUS parameters, particularly the PRF, to maximize cortical RSU activity could enhance the modulation of the CTC pathway.
Abstract via europepmc.
Exposures
Exposure 1: tFUS targeting S1, varying PRF and duty cycle
Target: primary somatosensory cortex — “somatosensory cortex (S1)”
Device: Sonic Concepts · Sonic Concepts · H276 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,500 | ✓✓✓ |
| Pulse duration (ms) | 0.2 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 30, 300, 1,500, 3,000, 4,500swept | ✓✓✓ |
| Duty cycle (%) | 0.6, 6, 30, 60, 90swept | ✓✓✓ |
| Sonication duration (s) | 0.067 | ✓✓✓ |
| Free-field pressure (kPa) | 1,626 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 88 | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | ⚑ |
| In-situ Ispta (W/cm²) | 0.0294 | ✓✓✓ |
Each trial used a 67 ms ultrasound duration with a 2.5 s intersonication interval (10% jitter), 500 trials per parameter, and randomized order of stimulation conditions. PRF (30-4,500 Hz) was swept at a constant 200 us pulse duration; duty cycle (0.6-90%) was separately swept at fixed 3,000 Hz and 30 Hz PRF, with pulse duration in that sweep calculated from PRF x DC rather than stated directly.
Flags from extraction
exposures[0].in_situ.isppa_w_cm2— Only the in-situ spatial-peak temporal-average intensity (Ispta, 29.42 mW/cm2) is reported for the calibrated beam-steered condition; an in-situ Isppa value is not given, so it is left not_reported.n_subjects— Group sizes are reported separately for the main CTC-pathway cohort (N=16) and a second cohort used only to test for auditory confound (N=12); the paper never states a combined total.auditory_control— The paper does not use an active auditory-masking method; instead it recorded from auditory cortex (a separate N=12 cohort) to test whether AC neurons responded to tFUS, finding low-PRF (30 Hz) tFUS produced an auditory confound while high-PRF (3,000 Hz) did not. Coded as 'other' since this is a confound analysis rather than a listed control method.randomised— 'Randomised' here refers to randomisation of the order of stimulation parameter conditions within subjects ('The order of stimulation conditions was randomized'), not random allocation to separate treatment/control groups.exposures[0].timing.pulse_duration_ms— The 200 us pulse duration is stated as constant for the PRF-effect exploration; for the separate duty-cycle exploration the paper states pulse duration was calculated from PRF x DC but does not give the resulting discrete values, so only the 200 us value is recorded.exposures[0]— A third condition -- ~170 kPa used only for target-confirmation trials before recording -- is described in Methods but is not part of the recorded 500-trial stimulation parameters, so it is not included in the pressure fields; see protocol_description.