Transcranial Focused Ultrasound Modulates Visual Thalamus in a Nonhuman Primate Model
Kai Yu, Bin He
IEEE Transactions on Biomedical Engineering 2025 · 10.1109/tbme.2025.3554935
Abstract
Objective The thalamus plays a pivotal role as a neural hub, integrating and distributing visual information to cortical regions responsible for visual processing. Transcranial focused ultrasound (tFUS) has emerged as a promising non-invasive brain stimulation technology, enabling modulation of neural circuits with high spatial precision. This study investigates the tFUS neuromodulation at visual thalamus and characterizes the resultant effects on interconnected visual areas in a nonhuman primate model. Methods Experiments were conducted on a rhesus macaque trained in a visual fixation task, combining tFUS stimulation with simultaneous scalp electroencephalography (EEG) and intracranial recordings from area V4, a region closely linked to the thalamus. Ultrasound was delivered through a 128-element random array ultrasound transducer operating at 700 kHz, with the focus steered onto the pulvinar of the thalamus based on neuroanatomical atlas and individual brain model. Results EEG source imaging revealed localized tFUS-induced activities in the thalamus, midbrain, and visual cortical regions. Critically, tFUS stimulation of the pulvinar can elicit robust neural responses in V4 without visual input, manifested as significant modulations in local field potentials, elevated alpha and gamma power, corroborating the functional thalamocortical connectivity. Furthermore, the tFUS neuromodulatory effects on visually-evoked V4 activities were region-specific within the thalamus and dependent on ultrasound pulse repetition frequency. Conclusion This work provides direct electrophysiological evidence demonstrating the capability of tFUS in modulating the visual thalamus and its functional impact on interconnected cortical regions in a large mammalian model, paving the way for potential investigations for tFUS treating visual, sensory, and cognitive impairments.
Abstract via europepmc.
Exposures
Exposure 1: tFUS to frontal eye field (FEF), excitatory parameters, no concurrent visual stimulus
Target: frontal eye field — “frontal eye field (FEF)”
Device: Sonic Concepts · Sonic Concepts, Inc. · H275 (128-element random array, driven by a Verasonics Vantage 256 system) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 700 | ✓✓✓ |
| Pulse duration (ms) | 0.2 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 3,000 | ✓✓✓ |
| Duty cycle (%) | 60pulse duration × PRF gives 60% | ✓✓✓ |
| Sonication duration (s) | 0.4 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 950.9 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 6.99 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
We recorded the brain activations in response to the excitatory tFUS stimulation (PRF: 3 kHz, burst duty cycle: 60%) targeted at the FEF of the monkey brain without the concurrent presentation of visual stimuli. A butterfly plot illustrating the 12-channel scalp EEG signals averaged from 120 trials with only ultrasound stimulations (sonication duration: 400 ms), compared against 120 trials with no tFUS or visual stimulus.
Consistency checks: intensity pressure inconsistent in situ.
Exposure 2: tFUS to thalamus (pulvinar; also steered toward deep pulvinar and thalamic reticular nucleus), excitatory and inhibitory parameters, with and without concurrent visual stimulus
Target: pulvinar, reticular thalamic nucleus — “pulvinar of the thalamus (and, with axial steering, deep pulvinar / thalamic reticular nucleus, TRN)”
Device: Sonic Concepts · Sonic Concepts, Inc. · H275 (128-element random array, driven by a Verasonics Vantage 256 system) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 700 | ✓✓✓ |
| Pulse duration (ms) | 0.2 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 3,000, 40swept | ✓✓✓⚑ |
| Duty cycle (%) | 60, 8swept | ✓✓✓ |
| Sonication duration (s) | 0.4 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 950.9 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 6.99 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
The H275 transducer was driven by a Vantage 256 research ultrasound system to generate specific ultrasound pulse repetition frequency (PRF, 3 kHz or 40 Hz) and burst duty cycle (DC, 60% or 8%). Without visual stimuli, tFUS (PRF 3 kHz, DC 60%) was steered onto the pulvinar (120 of 240 randomized trials). With concurrent visual stimuli, the focus was further steered axially by +2.4 mm (deep pulvinar) or -2.4 mm (toward the thalamic reticular nucleus, TRN) and PRF was tuned to 3 kHz (excitatory) or 40 Hz (inhibitory), 120 trials per condition.
Consistency checks: intensity pressure inconsistent in situ.
Flags from extraction
exposures[0].in_situ.pressure_kpa— The 950.9 kPa / 6.99 W/cm2 value is a system characterization measured through an ex vivo monkey skull sample in a water tank (not the live subject's own skull), and is presented once in Methods as a general transducer/system output; applied to both exposures (FEF and thalamus) since the paper does not give separate per-target values.exposures[1].timing.pulse_duration_ms— Tone burst duration (0.2 ms) is stated only for the PRF 3 kHz / DC 60% configuration (Fig. 1c caption); no pulse duration is stated for the PRF 40 Hz / DC 8% configuration, so left not_reported for this exposure which uses both configurations.exposures[1].timing.pulse_repetition_frequency_hz— Pairing of PRF with duty cycle (3 kHz with 60%, 40 Hz with 8%) is inferred from the order given in Methods ('PRF, 3 kHz or 40 Hz) and burst duty cycle (DC, 60% or 8%)') and confirmed by Results text describing 'excitatory 3 kHz' and 'inhibitory 40 Hz' PRF conditions, but the DC value paired with 40 Hz is not repeated in the same sentence as the PRF value in most passages.auditory_control— A separate negative-control experiment stimulated the insular cortex (no substantial V4 connections) at increased in-situ pressure (1.14 MPa) to rule out an auditory-pathway confound; this control condition is not treated as a separate exposure per the sham/control exclusion rule.n_sessions_per_subject— Paper describes multiple experiment sets (FEF-only, thalamus-only, thalamus+visual at two steered locations) but does not state a total count of distinct sessions for this single animal.