Table 3.

LIFU Trials in Psychiatric Disorders.

Author/y	Sonication target	LIFU parameters	Outcome measures	Findings	Adverse events
Ziebell et al,73 2023	Right prefrontal cortex	FF: 0.5 MHz PRF: 0.00004 MHz PW: 0.125 ms DC: 0.5% SD: 120 s ISI: N/A ISPTA: 0.199 W/cm2* ISPPA: 40 W/cm2* MI: 1.54* Total duration: 120 s Sham controlled: yes	Approach versus with drawal behavior with MFT during T-maze task VAMS	Greater approach and fewer withdrawal behaviors MFT decrease was present across all T-maze event types LIFU-induced MFT differences consistently explained greater approach and less withdrawal No significant subjective mood changes	None
Sanguinetti et al,74 2020	rIFG	Experiment 1 FF: 0.5 MHz PRF: 0.00004 MHz PW: 0.065 ms DC: 0.26% SD: 30 s ISI: N/A ISPTA: 0.130 W/cm2* ISPPA: 54 W/cm2* MI: 1.79* Total duration: 30 s Sham controlled: yes Experiment 2 FF: 0.5 MHz PRF: 0.00004 MHz PW: 0.125 ms DC: 0.50% SD: 120 s ISI: N/A ISPTA: 0.272 W/cm2* ISPPA: 54 W/cm2* MI: 1.79* Total duration: 120 s Sham controlled: no	Experiment 1 VAMS Experiment 2 FC with rsfMRI	Significant increase in mood 20 and 30 min after LIFU No significant difference in global vigor Increase in connectivity between the rIFG and rMFG Decrease in connectivity between rIFG with left prefrontal and limbic areas Regions within the DMN showed a general decrease in FC	None
Reznik et al,75 2020	Right prefrontal cortex	FF: 0.5 MHz PRF: 0.00004 MHz PW: 0.065 ms DC: 0.26% SD: 30 s ISI: N/A ISPTA: 0.071 W/cm2* ISPPA: 14 W/cm2* MI: 0.92* Total duration: 30 s Sham controlled: yes	Depressive symptoms measured with neuropsychologic battery VAMS	No change in depression severity Decrease in trait rumination No change in anxiety severity Increased happiness over the days of the study	None
Oh et al,76 2023	dlPFC	FF: 0.25 MHz PRF: 0.0005 MHz PW: 1 ms DC: 50% SD: 0.3 s ISI: 6 s ISPTA: 0.3 W/cm2 ISPPA: 0.6 W/cm2 MI: 0.27 Total duration: 20 min Sham controlled: Yes	Depressive symptoms measured with MADRS Additional neuro psychologic battery FC evaluated with rsfMRI	Significant treatment effect. Reduction of suicidal ideation and depressive symptoms. More pronounced reduction of MADRS scores More pronounced reduction of anxiety symptoms Significant network level FC changes in the right subgenual anterior cingulate cortex.	None
Mahdavi et al,77 2023		FF: 0.65 MHz PRF: 0.00001 MHz PW: 5 ms DC: 5% SD: 30 s ISI: 30 s ISPTA: 0.719.73 W/cm2* ISPPA: 14.39 W/cm2* MI: 0.75* Total duration: 10 min Sham controlled: no	Anxiety severity measured with HAM-A and BAI Participant perceived change in clinical status	60% showed a meaningful reduction (>30%) of HAM-A score at completion. 32% achieved remission of GAD symptoms according to a completion HAM-A score <14 64% reported a PGI-I score of >2, indicating significant perceived benefit	None
Peng et al,78 2024	Left NAc	FF: 0.65 MHz PRF: 0.00001 MHz PW: 5 ms DC: 5% SD: 30 s ISI: 30 s ISPTA: 0.719.73 W/cm2* ISPPA: not reported MI: not reported Total duration: 20 min Sham controlled: yes	fMRI FC Safety, tolerability, and feasibility	Inhibition in bilateral NAc Increased FC between NAc and medial PFC LIFU was safe and well tolerated	None
Mahoney et al,79 2023	Bilateral NAc	Enhanced dose FF: 0.22 MHz PRF: 0.00000033 MHz PW: 100 ms DC: 3.3% SD: 5 s ISI: 10 s ISPTA: not reported ISPPA: not reported MI: not reported Total duration: 20 min Lower dose FF: 0.22 MHz PRF: 0.00000033 MHz PW: 100 ms DC: 3.3% SD: 5 s ISI: 10 s ISPTA: not reported ISPPA: not reported MI: not reported Total duration: 20 min Sham controlled: yes	Safety, tolerability, and feasibility Cue-induced substance craving, assessed through VAS	Both LIFU doses were safe and well tolerated Brain MRIs did not indicate edema, hemorrhage, or notable changes in brain structure Attenuated craving primary substance of abuse in participants receiving enhanced dose Reductions in cue-induced craving for several substances persisted 90d after treatment.	None

BAI, Beck Anxiety Inventory; dlPFC, left dorsolateral prefrontal cortex; DMN, default mode network; FC, functional connectivity; HAM-A, Hamilton Anxiety Inventory; ISI, interstimulus interval; rMFG, right middle frontal gyrus; MADRS, Montgomery-Asberg Depression Rating Scale; PGI-I, Patient Global Impression–Improvement; rsfMRI, resting state functional magnetic resonance imaging; VAMS, Visual Analog Mood Scale; VAS, visual analog scale.

Total duration is reported in total time of LIFU intervention or the number of sonications delivered in one session.

^*Intensity reported is not the intracranial estimation. The reported values either represent the intensity measured in freeform water or are a parameter output of the LIFU system. Intracranial estimations are derived from these values.