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Neuromodulatory Impact of Low-Intensity Focused Ultrasound on Early Cognitive Decline

Abdul Rehman Naeem, Mahwish Haque, Saima Kanwal Attique, Maqsooda Akram Butt, Syeda Qaima Abbas, Sameea Areeb

Link Medical Journal 2026 · 10.61919/pfm2z844

human patientotherfmribehaviour

Abstract

Background: A mild neurocognitive disorder causes problems with memory, attention and thinking skills.. There are not many good ways to treat this that do not need surgery. Objective: To see how active low-intensity focused ultrasound and fake ultrasound affect memory, attention and brain connections in people with neurocognitive disorder. Methods: This study had 76 people, aged 55 to 80. They were split into two groups. One group got ultrasound that targeted parts of the brain related to thinking and memory. The other group got a treatment. They tested the brain functions of the people before the treatment one week after and two months after. Sixty-eight people finished the study. Results: One week after the treatment people who got ultrasound had better memory than those who got the fake treatment. The difference was still there two months later. People who got ultrasound also did better on a test of attention. Their brain connections between the part of the brain and the hippocampus were stronger, than those who got the fake treatment. No serious problems happened. low-intensity focused ultrasound seems to help with memory and attention and makes brain connections stronger.. More studies are needed to be sure

Abstract via crossref.

Specieshuman
Subjects38 participants
Sessions per subject1
Randomisedyes
Blindingdouble
Sham / controlinactive transducer
Auditory controlmatched device sound
Readout timingoffline
Anaesthesianot applicable
Readoutsfmri, behaviourHopkins Verbal Learning Test-Revised delayed recall; Trail Making Test Part B completion time; resting-state fMRI seed-based fronto-hippocampal functional connectivity; visual analogue scale for post-session discomfort
Direction of effectexcitatoryActive ultrasound produced greater improvement than sham in delayed verbal recall (persisting at 2 months), faster Trail Making Test Part B completion, and increased fronto-hippocampal resting-state functional connectivity.
Adverse eventsobservedNo serious adverse events were reported; two participants in the active group withdrew due to headache and one sham participant withdrew due to procedural anxiety. Post-session discomfort (VAS) did not differ significantly between groups.

Exposures

Exposure 1: Single session of low-intensity focused ultrasound to right inferior frontal gyrus/dorsolateral prefrontal cortex

Target: inferior frontal gyrus, dorsolateral prefrontal cortex — “right inferior frontal gyrus and the adjacent dorsolateral prefrontal cortex
Device: not reported

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 3 ms (not stated by the paper)
Pulse repetition frequency (Hz)100✓✓
Duty cycle (%)30✓✓
Sonication duration (s)1,200✓✓
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)not reported
In-situ Ispta (W/cm²)not reported
Isppa, domain unspecified (W/cm²)0.8✓✓
Protocol, in the paper’s words

Participants received a single 20-minute session of low-intensity focused ultrasound aimed at the right inferior frontal gyrus and adjacent dorsolateral prefrontal cortex, with the transducer positioned using individual MRI-based neuronavigation and held in place for the whole session. The sham group underwent an identical procedure except that the transducer did not deliver any ultrasound output.

Flags from extraction

  • n_subjects76 participants were randomized (38 per arm) but only 68 completed all assessments (33 active/35 sham); enrolled count for the active-ultrasound arm (38) is reported here per the enrolled-vs-analysed rule.
  • exposures[0].unspecified_domain.isppa_w_cm2Text states only 'the intensity of the ultrasound was point eight watts per centimeter' without specifying Isppa vs Ispta or free-field vs in-situ domain, and the unit is stated incompletely (missing '-squared').
  • exposures[0].timing.sonication_duration_sThe '20-minute session' is described as the overall treatment session length; it is not explicit whether this is one continuous sonication train or contains internal breaks beyond the stated pulsing (100 Hz PRF, 30% duty cycle).
  • exposures[0].timing.pulse_duration_msNot stated directly; could be inferred from duty cycle (30%) and PRF (100 Hz) as 3 ms but per instructions this is not computed/recorded from arithmetic.
  • auditory_controlThe paper says exposure to sound and other procedural elements were standardized across groups ('what they heard') but does not describe a specific masking-sound or other defined auditory-control mechanism.
  • exposures[0].device.familyNo device manufacturer or model is given anywhere in the manuscript; limitations section explicitly states 'the ultrasound system...were not fully described.'
  • overallThis manuscript is written in unusually simplified, imprecise language throughout (e.g. 'point eight watts per centimeter') and its own discussion/limitations section states the ultrasound system, calibration, coordinates, and sham details were not fully described; numbers were extracted as stated but should be treated with caution.