A region-specific brain dysfunction underlies cognitive impairment in long COVID brain fog
arXiv (Cornell University) 2025 · 10.48550/arxiv.2511.14188
human patientotherfmribehaviourclinical scale
Specieshuman
Subjects20 participants
Sessions per subject1
Randomisedyes
Blindingnot reported
Sham / controlsound only
Auditory controlsound only sham
Readout timingoffline
Anaesthesianot applicable
Readoutsfmri, behaviour, clinical scale — Continuous random dot motion (cRDM) task false-alarm and correct-response rates; brain-fog severity rating scale; resting-state fMRI seed-based functional connectivity from the right inferior insula
Direction of effectexcitatoryExcitatory theta-burst TUS targeting the right inferior insula increased insula-seeded resting-state functional connectivity and significantly reduced the false-alarm rate on the cRDM perceptual task relative to sham (mean change -47.4% vs -23.7%), without a significant immediate change in self-reported brain fog severity.
Adverse eventsnot reportedAcoustic simulations confirmed exposure remained within safety guidelines and thermal simulations verified the maximum target temperature increase did not exceed 2 C; mechanical index was maintained at 0.693 +/- 0.045.
Exposures
Exposure 1: Theta-burst TUS of right inferior insula
Target: insular cortex — “right inferior insula (inferior circular sulcus, Destrieux atlas)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · H-104MR_4AA-4CH transducer with NeuroFUS TPO-203 ✓
| Waveform | theta burst | |
|---|---|---|
| Fundamental frequency (kHz) | not reported | ⚑ |
| Pulse duration (ms) | 20 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 5 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 80 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 33.8 | ✓✓✓ |
| 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) | 7.37 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
Protocol, in the paper’s words
Theta-burst TUS consisted of 20 ms pulses within a 200 ms pulse-repetition interval (5 Hz PRF, 10% duty cycle), for a total of 400 cycles (80 s), delivered once to the right inferior insula under MRI/Brainsight neuronavigation guidance. The sham group underwent an identical procedure with no ultrasound output but matched auditory/procedural cues (transducer operational sound via bone-conduction headphones plus a pre-recorded TPO sound).
Flags from extraction
exposures[0].fundamental_frequency_khz— Transducer model (H-104MR_4AA-4CH, Sonic Concepts) is stated but the operating fundamental frequency is never given in the text.n_subjects— n_subjects reflects only the 20 participants who received real ultrasound (TUS group); the sham group (n=20) received no ultrasound output.