Table 4.

LIFU Trials in Neurologic Disorders.

Author, year	Sonication target	LIFU parameters	Outcome measures	Findings	Adverse events
Jeong et al,83 2021	Right hippocampus	FF: 0.25 MHz PRF: 0.000002 MHz PW: 20 ms DC: 4% SD: 180 s ISI: N/A ISPTA: 0.02–0.12 W/cm2 ISPPA: 0.5–3 W/cm2 MI: 0.27 Total duration: 180 s Sham controlled: No	Cerebral glucose metabolism measured with F-fluoro-2-deoxyglucose positron emission tomography. BBB monitoring using MRI Neuropsychologic assessments	Significant increase in resting cerebral glucose metabolism in superior frontal gyrus. Significant increase in resting cerebral glucose metabolism in middle cingulate gyrus. Significant increase in resting cerebral glucose metabolism in fusiform gyrus. No evidence of BBB opening Mild improvement in memory, executive function, and global cognitive function.	None
Beisteiner et al,84 2020	AD population: Bilateral frontal cortex extending to Broca’s area Bilateral lateral parietal cortex extending to Wernicke’s area Precuneus cortex Healthy population: primary somatosensory	tpFUS AD population: FF: 0.000004 MHz maximum PRF: 0.000005 MHz PW: 0.003 ms DC: N/A SD: nonstandardized ISI: 0.2–0.3 s ISPTA: 0.1 W/cm2 maximum ISPPA: not reported MI: not reported Total duration: 6000 pulsed sonications Sham controlled: no Healthy population: FF: 0.000004 MHz maximum PRF: 0.000001 MHz–0.000005 MHz PW: 0.003 ms DC: N/A SD: 2.5 s, 25 s, 250 s ISI: 6.15 min ISPTA: not reported ISPPA: not reported MI: not reported Total duration: 1110 pulsed sonications Sham controlled: yes	AD population Neuropsychologic assessments fMRI Healthy population SEP at 3 different SD parameters	AD population Significant improvements in the language domains Significant improvement in memory performance Effects lasted 3 mo after treatment Enhanced activation and connectivity of the memory network Healthy population tpFUS shows dose-dependent effects predicated by total energy over time	None
Popescu et al,85 2021	AD population data obtained post hoc from Beisteiner et al84	AD population data obtained post hoc from Beisteiner et al84	Cortical thickness	Reduced cortical atrophy within the DMN Significant correlation between changes in the neuropsychologic improvement and cortical thickness increase in AD-critical brain areas Cortical thickness effects were localized to AD-relevant regions	None
Nicodemus et al,86 2019	Hippocampus Substantia nigra	Transcranial ultrasound FF: 2 MHz PRF: N/A PW: N/A DC: N/A SD: 1 h ISI: N/A ISPTA: 0.52 W/cm2 ISPPA: N/A MI: not reported Total duration: 1 h	Neuropsychologic battery	62.5% improved cognitive scores 87% stable or improved fine motor scores 87.5% had stable or improved gross motor scores	None
Monti et al,87 2016	Thalamus	FF: 0.65 MHz PRF: 0.0001 MHz PW: 0.5 ms DC: 5% SD: 30 s ISI: 30 s ISPTA: 0.72 W/cm2 ISPPA: not reported MI: not reported Total duration: 10 min	Minimally conscious state status measured with CRS-R	Patient presented a CRS-R of 13 on day of stimulation and 17 1 d after stimulation 3 d after stimulation, patient exhibited behaviors consistent with emergence from minimally conscious state 5 d after stimulation, patient attempted to walk	None
Cain et al,88 2021	Thalamus	FF: 0.65 MHz PRF: 0.0001 MHz PW: 0.5 ms DC: 5% SD: 30 s ISI: 30 s ISPTA: 0.72 W/cm2 ISSPA: 14.39 W/cm2 MI: not reported Total duration: 10 min	Minimally conscious state status measured with CRS-R	Clinically significant increases in behavioral responsiveness after exposure to each dose in 2/3 patients Novel behaviors observed before the procedure despite years after onset in 2/3 patients 1/3 patients exhibited no perceived benefit	None

BBB, blood-brain-barrier; CRS-R, Coma Recovery Scale-Revised; DMN, default mode network; ISI, interstimulus interval; tpFUS, transcranial pulse focused ultrasound.

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