Transcranial focused ultrasound modulates spiking, LFP, and BOLD activity in the primate thalamus
Ning Zheng, Pai-Feng Yang, M. Anthony Phipps, Jiro Kusunose, Arabinda Mishra, Jixin Xia, William Rodriguez, Allen T. Newton, Benoit M. Dawant, John C. Gore, Charles F. Caskey, Li Min Chen
Nature Communications 2026, 17 · 10.1038/s41467-026-75826-8
Abstract
Transcranial-focused ultrasound (FUS) is a non-invasive neuromodulation technique capable of targeting deep brain regions with high precision. However, its mechanisms of action - particularly how it modulates neuronal activity and relates to fMRI BOLD signals - remain poorly understood. Using the macaque monkey thalamus and insular cortex as a model system, we show that low-intensity FUS evokes localized BOLD increases and preferentially modulates low-frequency (Delta, Theta, and Alpha) local field potentials and single-unit spiking in the ventroposterior lateral (VPL) nucleus, as well as through remote stimulation of the insular cortex. Compared with vibrotactile stimulation, FUS-evoked responses exhibit slower peak latencies. Importantly, we observe strong spatial correspondence between ultrasound-induced changes in spiking, LFP activity, and BOLD signals. These findings define the temporal and spatial characteristics of FUS neuromodulation and demonstrate the feasibility of precise, non-invasive targeting of deep brain circuits, supporting its translational potential for neuroscience and therapeutic applications.
Abstract via europepmc.
Exposures
Exposure 1: FUS to thalamic VPL nucleus
Target: ventral posterolateral nucleus — “ventroposterior lateral (VPL) thalamic nucleus, hand representation”
Device: IGT / Imasonic · Imasonic ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓ |
| Sonication duration (s) | 0.5 | ✓✓✓ |
| Free-field pressure (kPa) | 2,690, 3,720swept | ✓✓✓⚑ |
|---|---|---|
| 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) | 550, 700, 1,450swept | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
650 kHz pulse trains (500 ms train duration, PRF 1 kHz, 0.5 ms pulses, 50% duty cycle, 50 microsecond ramp up/down) were used for both fMRI and electrophysiology experiments targeting the VPL. For fMRI, trains were repeated at 0.5 Hz for a 16-s stimulation block (8 trains/block) followed by a minimum 30-s rest, targeting an in vivo pressure of 550 kPa (assuming 39% transmission through the skull). For electrophysiology, single 500-ms trains were delivered with a 5-s inter-stimulation interval (20-50 trials/run) at higher targeted in vivo pressures (0.70-1.45 MPa across the two subjects) than the fMRI protocol, to obtain robust electrophysiological signals while limiting thermal risk.
Exposure 2: Remote FUS to posterior insular cortex
Target: posterior insula — “posterior insular cortex”
Device: IGT / Imasonic · Imasonic ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓ |
| Sonication duration (s) | 0.5 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | 550, 1,000swept | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Same 650 kHz pulse parameters as the VPL target (500 ms train, PRF 1 kHz, 0.5 ms pulses, 50% duty cycle) were used to remotely stimulate the posterior insular cortex while recording LFP and spiking in the thalamic VPL; only 3 locations and 4 runs of insula stimulation were performed (versus 35 locations/41 runs for VPL). The fMRI protocol's common 550 kPa in-vivo target also applied to insula stimulation; a representative electrophysiology insula-stimulation run targeted 1.00 MPa in vivo.
Flags from extraction
n_subjects— Paper states 'Four monkeys participated in fMRI experiments, and two macaque monkeys (two female Macaca fascicularis and two male Macaca mulatta) participated in electrophysiology studies' - 'two macaque monkeys' is inconsistent with the four sex/species identifiers listed immediately after; unclear whether the electrophysiology animals overlap with the four fMRI animals or add to the total. n_subjects here uses the explicit 'Four monkeys underwent five MRI and FUS stimulation sessions' statement.exposures[0].in_situ.pressure_kpa— List combines the fMRI-protocol target pressure (550 kPa, single stated value, method: assumed 39% transmission) with the electrophysiology-protocol targeted range across two subjects (0.70-1.45 MPa); these were two distinct experimental sessions/modalities at the same target and frequency.exposures[0].free_field.pressure_kpa— 2.69 MPa (subject 1) is the free-field pressure used specifically for a thermal-safety verification run at the highest transmit power tested; a second free-field pressure (3.72 MPa, subject 2, two runs) was also tested but is not included in this single value.exposures[1].in_situ.pressure_kpa— 550 kPa is the common fMRI-protocol target pressure (also used for VPL); 1.00 MPa is the value reported specifically for an electrophysiology insula-stimulation run (Figure 6 legend).