ABSTRACTObjectiveLow-Intensity Focused Ultrasound Pulsations (LIFUP) is a promising new potential neuromodulation tool. However, the safety of LIFUP neuromodulation has not yet been adequately assessed. Patients with refractory temporal lobe epilepsy electing to undergo an anterior temporal lobe resection present a unique opportunity to evaluate the safety and efficacy of LIFUP neuromodulation. Because the brain tissue in these patients will be removed, histological changes in tissue after LIFUP can be examined. Evidence of effective neuromodulation was assessed using functional MRI and EEG, while further potential safety concerns were assessed using neuropsychological testing.MethodsEEG, functional MRI, and neuropsychology were assessed in six patients before and after focused ultrasound sonication of the temporal lobe at intensities up to 5760 mW/cm2. Using the BrainSonix Pulsar 1002, LIFUP was delivered under MR guidance, using the Siemens Magnetom 3T Prisma scanner. Neuropsychological changes were assessed using various batteries. EEG was recorded using the Electrical Geodesics EGI 256 channel system. Histological changes were assessed using hematoxylin and eosin staining, among others.ResultsLIFUP was not able to modulate the BOLD signal on fMRI in a reliable and consistent manner. The EEG data that was available did not demonstrate a change in activity after LIFUP in all but one subject. Likewise, the neuropsychology testing did not show any statistically significant changes in any test, except for a slight decrease in performance on the one test after LIFUP. Lastly, the histology did not reveal any detectable damage to the tissue, except for one subject for whom the histology findings were inconclusive.SignificanceThe safety in the histology was the primary endpoint, and as such, longer exposure at the highest intensity levels will be administered moving forward.Key PointsLIFUP is a novel brain stimulation technique with not yet fully established safety guidelines.LIFUP was administered to patients electing to undergo resective brain surgery.LIFUP does not appear to cause damage to tissue.Longer exposure times are needed to further show safety at these intensity levels.