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Behavioral effects of targeting the central thalamus and pulvinar with transcranial ultrasound stimulation in healthy volunteers

Amber R. Hopkins, Joshua A. Cain, Elizabeth A. White, Stephanie M. Abakians, Martin M. Monti

2025 · 10.1101/2025.02.27.640692

human healthyhealthybehaviour

Abstract

We present the first causal evidence in the healthy human brain linking the central thalamus to vigilance and the pulvinar to visuospatial attention using low-intensity transcranial focused ultrasound stimulation (tFUS). In a within-subjects, counterbalanced design, 27 healthy volunteers completed the Psychomotor Vigilance Task (PVT), a vigilance task, and the Egly-Driver Task (EDT), which assesses visuospatial attention, before and after central thalamus, pulvinar, and sham sonication with tFUS. Central thalamic sonication significantly impaired performance on both tasks in a manner consistent with decreases in arousal. Targeting the pulvinar with tFUS resulted in more subtle changes in visuospatial attention. Participants were less reactive to visual stimuli presented in the visual field contralateral to the affected pulvinar. These results demonstrate that tFUS can elicit measurable behavioral changes in healthy volunteers and underscores its potential as a high-resolution tool for non-invasive brain mapping, capable of differentiating functional contributions of thalamic regions only millimeters apart.

Abstract via europepmc.

Specieshuman
Subjects27 participants
Sessions per subject3
Randomisednot reported
Blindingsingle
Sham / controlinactive transducer
Auditory controldeafened subjects
Readout timingoffline
Anaesthesianot applicable
Readoutsbehaviour — Psychomotor Vigilance Task; Egly-Driver Task
Direction of effectinhibitoryCentral thalamic sonication slowed responses and increased lapses on the PVT and reduced target detection on the EDT, consistent with reduced arousal; pulvinar sonication produced more subtle contralateral visuospatial attention deficits.
Adverse eventsnot reportedThe paper states the intensities comply with FDA diagnostic ultrasound guidelines and have no known adverse thermal bioeffects; no adverse event reporting is given.

Exposures

Exposure 1: Central thalamus (left)

Target: thalamus — “central thalamus”
Device: BrainSonix · Brainsonix Corp. · BXPulsar 1002 drive system with fixed-focal-length single-element spherical transducer (80 mm focal length, 61 mm aperture) ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)650✓✓✓
Pulse duration (ms)0.5✓✓✓
Pulse repetition frequency (Hz)100✓✓✓⚑
Duty cycle (%)5pulse duration × PRF gives 5%✓✓✓
Sonication duration (s)30✓✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)14.4✓✓✓
In-situ Ispta (W/cm²)0.72✓✓✓
Protocol, in the paper’s words

Ultrasound was delivered in an on/off block design including 10 blocks with 30 seconds of sonication and 30 seconds of rest (30 s pulse train duration; 0.5 ms pulse duration, 100 Hz PRF, 5% duty cycle). Tasks (PVT and EDT) were run before and after sonication in each session; sessions at least 24 hours apart.

Exposure 2: Pulvinar (left)

Target: pulvinar — “pulvinar”
Device: BrainSonix · Brainsonix Corp. · BXPulsar 1002 drive system with fixed-focal-length single-element spherical transducer (80 mm focal length, 61 mm aperture) ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)650✓✓✓
Pulse duration (ms)0.5✓✓✓
Pulse repetition frequency (Hz)100✓✓✓
Duty cycle (%)5pulse duration × PRF gives 5%✓✓✓
Sonication duration (s)30✓✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)14.4✓✓✓
In-situ Ispta (W/cm²)0.72✓✓✓
Protocol, in the paper’s words

Ultrasound was delivered in an on/off block design including 10 blocks with 30 seconds of sonication and 30 seconds of rest (30 s pulse train duration; 0.5 ms pulse duration, 100 Hz PRF, 5% duty cycle). Tasks (PVT and EDT) were run before and after sonication in each session; sessions at least 24 hours apart.

Flags from extraction

  • exposures[0].timing.pulse_repetition_frequency_hz — Methods text gives a 60 s pulse repetition interval while the Figure 1 legend gives a 10 ms PRI (100 Hz PRF); recorded the stated 100 Hz PRF and 5% duty cycle.
  • exposures[0].unspecified_domain.isppa_w_cm2 — Intensities are labelled Ispta.3 / Isppa.3 (derated notation) but the paper does not say whether they are free-field or in situ; placed in unspecified_domain. Given as upper bounds (<=720 mW/cm2, <=14.40 W/cm2). Methods write '<' and the legend writes '<='.
  • exposures[1].unspecified_domain.isppa_w_cm2 — Same intensity statement applies to both targets; domain not stated.
  • exposures[0].target.terms — Central thalamus 'includes the intralaminar thalamic nuclei and adjacent areas'; mapped to generic thalamus.
  • direction_of_effect — Behavioural impairment after central thalamic sonication; authors suggest this is consistent with suppression but no neural readout was recorded.
  • blinding — Only participants stated to be blinded; experimenter blinding not stated.