Focused ultrasound to bilateral thalamic nuclei significantly improves human cognitive attention in a frequency- and intensity-dependent manner
Kevin A. Caulfield, Christopher T. Sege, Jacob Weaver, Keith R. Murphy, Tony Passaro, Kristy Meads, Ehsan Dadgar-Kiani, Michael U. Antonucci, Cameron Good, Lisa M. McTeague
Brain Stimulation 2026, 19, 103171 · 10.1016/j.brs.2026.103171
Abstract
Background The centromedian nucleus of the thalamus (CMT) is a core arousal center with potential for enhancing attention and alertness. While emergent low intensity focused ultrasound (LIFU) can reach this area, the stimulation paradigms which may enhance function in humans remain unknown. Methods In a within-subject, double-blind, sham-controlled paradigm, we administered bilateral stimulation of the CMT in N = 16 healthy adult participants using a novel wearable focused ultrasound neuromodulation device and 3 distinct pulse frequencies (1Hz, 5Hz, and 25Hz) and a diffuse unfocused sham stimulation (4 LIFU sessions per person; 64 total sessions). We tested neuroradiological MRI scan reads for safety, and single session effects of LIFU on alertness using a visual Oddball task and recorded electroencephalography (EEG) during the task. Results We found that a brief period of 50 s 25Hz LIFU stimulation (20% duty cycle) significantly enhanced reaction time in comparison to sham on a directed attention Oddball task for at least 40 min post-stimulation (linear mixed effects model; post-hoc p Conclusions Collectively, these findings demonstrate that targeted LIFU stimulation of the CMT can safely enhance attention and alertness in healthy individuals with carefully designed parameters.
Abstract via europepmc.
Exposures
Exposure 1: LIFU to bilateral centromedian nucleus of the thalamus (1/5/25 Hz PRF)
Target: centromedian nucleus — “bilateral Centromedian Nucleus of the Thalamus (CMT)”
Device: Attune · Attune Neurosciences, Inc. · ATTN201 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓⚑ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | 1, 5, 25swept | ✓✓✓ |
| Duty cycle (%) | 20 | ✓✓✓ |
| Sonication duration (s) | 50 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 4.38 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
In Visits 2-5, ... 50 s of active 1Hz, active 5Hz, active 25Hz, or sham stimulation was delivered in each session. Sham stimulation was delivered via unfocused diffuse ultrasonic beams at the same scalp-level intensity but without focusing stimulation to the bilateral CMT. For each condition, stimulation was delivered at a 500Hz fundamental frequency, 20% duty cycle, and 60 V/pulse at the scalp level.
Flags from extraction
exposures[0].fundamental_frequency_khz— Paper states '500Hz fundamental frequency', which is unusually low for an ultrasound carrier frequency (typical LIFU devices use hundreds of kHz to a few MHz); recorded as stated (0.5 kHz) rather than assuming a typo of 500 kHz.randomised— Paper describes the 4 stimulation conditions as 'fully counterbalanced' but never uses the word 'randomised/randomized' for condition order; not assumed.sham_type— Unfocused diffuse ultrasound sham (elements fired in a deprogrammed sequence, same scalp intensity) does not match a listed sham_type category; coded as other.auditory_control— Paper does not discuss auditory/masking confounds explicitly; sham matched scalp-level sensation but no auditory-control method is named.