Background: Epilepsy is a common neurological disorder, which is attributed to uncontrollable abnormal hyper-excitability of neurons. We investigated the feasibility of using low-intensity, pulsed radiation of focused ultrasound (FUS) to non-invasively suppress epileptic activity in an animal model (rat), which was induced by the intraperitonial injection of pentylenetetrazol (PTZ).Results: After the onset of induced seizures, FUS was transcranially administered to the brain twice for three minutes each while undergoing electroencephalographic (EEG) monitoring. An air-backed, spherical segment ultrasound transducer (diameter: 6 cm; radius-of-curvature: 7 cm) operating at a fundamental frequency of 690 KHz was used to deliver a train of 0.5 msec-long pulses of sonication at a repetitive rate of 100 Hz to the thalamic areas of the brain. The acoustic intensity (130 mW/cm²) used in the experiment was sufficiently within the range of safety guidelines for the clinical ultrasound imaging. The occurrence of epileptic EEG bursts from epilepsy-induced rats significantly decreased after sonication when it was compared to the pre-sonication epileptic state. The PTZ-induced control group that did not receive any sonication showed a sustained number of epileptic EEG signal bursts. The animals that underwent sonication also showed less severe epileptic behavior, as assessed by the Racine score. Histological analysis confirmed that the sonication did not cause any damage to the brain tissue.Conclusions: These results revealed that low-intensity, pulsed FUS sonication suppressed the number of epileptic signal bursts using acute epilepsy model in animal. Due to its non-invasiveness and spatial selectivity, FUS may offer new perspectives for a possible non-invasive treatment of epilepsy.

Transcranial focused ultrasound (FUS) is gaining momentum as a novel non-invasive brain stimulation method, with promising potential for superior spatial resolution and depth penetration compared to transcranial magnetic stimulation or transcranial direct current stimulation. We examined the presence of tactile sensations elicited by FUS stimulation of two separate brain regions in humans—the primary (SI) and secondary (SII) somatosensory areas of the hand, as guided by individual-specific functional magnetic resonance imaging data. Under image-guidance, acoustic stimulations were delivered to the SI and SII areas either separately or simultaneously. The SII areas were divided into sub-regions that are activated by four types of external tactile sensations to the palmar side of the right hand—vibrotactile, pressure, warmth, and coolness. Across the stimulation conditions (SI only, SII only, SI and SII simultaneously), participants reported various types of tactile sensations that arose from the hand contralateral to the stimulation, such as the palm/back of the hand or as single/neighboring fingers. The type of tactile sensations did not match the sensations that are associated with specific sub-regions in the SII. The neuro-stimulatory effects of FUS were transient and reversible, and the procedure did not cause any adverse changes or discomforts in the subject’s mental/physical status. The use of multiple FUS transducers allowed for simultaneous stimulation of the SI/SII in the same hemisphere and elicited various tactile sensations in the absence of any external sensory stimuli. Stimulation of the SII area alone could also induce perception of tactile sensations. The ability to stimulate multiple brain areas in a spatially restricted fashion can be used to study causal relationships between regional brain activities and their cognitive/behavioral outcomes.

Purpose: Increasing attention has been paid to low-intensity transcranial focused ultrasound (tFUS) for its potential therapeutic effects in Alzheimer's disease (AD). While preclinical studies have shown promising therapeutic effects of low-intensity tFUS in AD models, its efficacy and safety remain unclear in humans. In this pilot study, we investigated the effects of low-intensity tFUS on blood-brain barrier opening, the regional cerebral metabolic rate of glucose (rCMRglu), and cognition in patients with AD.Methods: After receiving institutional review board approval, four patients with AD received tFUS to the hippocampus immediately after an intravenous injection of a microbubble ultrasound contrast agent. Sonication was delivered at low-intensity, at a pressure level below the threshold for blood-brain barrier opening. Patients underwent brain magnetic resonance imaging, 18F-fluoro-2-deoxyglucose positron emission tomography, and neuropsychological assessments before and after the tFUS procedure. A whole-brain voxel-wise paired t test was conducted to compare rCMRglu before and after tFUS.Results: The sonication, as anticipated, did not show evidence of active blood-brain barrier opening on T1 dynamic contrast-enhanced magnetic resonance imaging. rCMRglu in the superior frontal gyrus (P<0.001), middle cingulate gyrus (P<0.001), and fusiform gyrus increased after tFUS (P=0.001). Patients demonstrated mild improvement in measures of memory, executive, and global cognitive function following tFUS. No adverse events were reported.Conclusion: These results suggest that hippocampal sonication with low-intensity tFUS may have beneficial effects on cerebral glucose metabolism and cognitive function in patients with AD. Further larger studies are needed to confirm the therapeutic efficacy of tFUS in AD.

Background: Mild cognitive impairment (MCI) is a syndrome that disrupts an individual’s cognitive function but preserves activities of daily living. MCI is thought to be a prodromal stage of dementia, which disrupts patients’ daily lives and causes severe cognitive dysfunction. Although extensive clinical trials have attempted to slow or stop the MCI to dementia conversion, the results have been largely unsuccessful. The purpose of this study was to determine whether noninvasive electrical stimulation of MCI changes glucose metabolism. Methods: Sixteen MCI patients participated in this study. We used transcranial direct current stimulation (tDCS) (2 mA/day, three times per week for 3 weeks) and assessed positron emission tomography (18 F-FDG) before and after 3 weeks of stimulation. Results: We showed that regular and relatively long-term use of tDCS significantly increased regional cerebral metabolism in MCI patients. Furthermore, subjective memory satisfaction and improvement of the memory strategies of participants were observed only in the real tDCS group after 3 weeks of stimulation. Conclusion: Our findings suggest that neurophysiological intervention of MCI could improve glucose metabolism and transient memory function in MCI patients.

Preclinical studies have suggested that low-intensity transcranial focused ultrasound (tFUS) may have therapeutic potential for Alzheimer’s disease (AD) by opening the blood–brain barrier (BBB), reducing amyloid pathology, and improving cognition. This study investigated the effects of tFUS on BBB opening, regional cerebral metabolic rate of glucose (rCMRglu), and cognitive function in AD patients. Eight patients with AD received image-guided tFUS to the right hippocampus immediately after intravenous injection of microbubble ultrasound contrast agents. Patients completed magnetic resonance imaging (MRI), ¹⁸F-fluoro-2-deoxyglucose positron emission tomography (PET), and cognitive assessments before and after the sonication. No evidence of transient BBB opening was found on T1 dynamic contrast-enhanced MRI. However, immediate recall (p = 0.03) and recognition memory (p = 0.02) were significantly improved on the verbal learning test. PET image analysis demonstrated increased rCMRglu in the right hippocampus (p = 0.001). In addition, increases of hippocampal rCMRglu were correlated with improvement in recognition memory (Spearman’s ρ = 0.77, p = 0.02). No adverse event was observed. Our results suggest that tFUS to the hippocampus of AD patients may improve rCMRglu of the target area and memory in the short term, even without BBB opening. Further larger sham-controlled trials with loger follow-up are warranted to evaluate the efficacy and safety of tFUS in patients with AD.