Dataset Information

Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease-A New Navigated Focal Brain Therapy.

ABSTRACT: Ultrasound-based brain stimulation techniques may become a powerful new technique to modulate the human brain in a focal and targeted manner. However, for clinical brain stimulation no certified systems exist and the current techniques have to be further developed. Here, a clinical sonication technique is introduced, based on single ultrashort ultrasound pulses (transcranial pulse stimulation, TPS) which markedly differs from existing focused ultrasound techniques. In addition, a first clinical study using ultrasound brain stimulation and first observations of long term effects are presented. Comprehensive feasibility, safety, and efficacy data are provided. They consist of simulation data, laboratory measurements with rat and human skulls and brains, in vivo modulations of somatosensory evoked potentials (SEP) in healthy subjects (sham controlled) and clinical pilot data in 35 patients with Alzheimer's disease acquired in a multicenter setting (including neuropsychological scores and functional magnetic resonance imaging (fMRI)). Preclinical results show large safety margins and dose dependent neuromodulation. Patient investigations reveal high treatment tolerability and no major side effects. Neuropsychological scores improve significantly after TPS treatment and improvement lasts up to three months and correlates with an upregulation of the memory network (fMRI data). The results encourage broad neuroscientific application and translation of the method to clinical therapy and randomized sham-controlled clinical studies.

SUBMITTER: Beisteiner R

PROVIDER: S-EPMC7001626 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease-A New Navigated Focal Brain Therapy.

Beisteiner Roland R Matt Eva E Fan Christina C Baldysiak Heike H Schönfeld Marleen M Philippi Novak Tabea T Amini Ahmad A Aslan Tuna T Reinecke Raphael R Lehrner Johann J Weber Alexandra A Reime Ulrike U Goldenstedt Cédric C Marlinghaus Ernst E Hallett Mark M Lohse-Busch Henning H

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20191223 3

Ultrasound-based brain stimulation techniques may become a powerful new technique to modulate the human brain in a focal and targeted manner. However, for clinical brain stimulation no certified systems exist and the current techniques have to be further developed. Here, a clinical sonication technique is introduced, based on single ultrashort ultrasound pulses (transcranial pulse stimulation, TPS) which markedly differs from existing focused ultrasound techniques. In addition, a first clinical ...[more]

PMID: 32042569

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Project description:BackgroundTranscranial pulse stimulation (TPS) is a novel noninvasive ultrasonic brain stimulation that can increase cortical and corticospinal excitability, induce neuroplasticity, and increase functional connectivity within the brain. Several trials have confirmed its potential in treating Alzheimer's disease (AD).ObjectiveTo investigate the effect and safety of TPS on AD.DesignA systematic review.MethodsPubMed, Embase via Ovid, Web of Science, Cochrane Library, CNKI (China National Knowledge Infrastructure), VIP (China Science and Technology Journal Database), and WanFang were searched from inception to April 1, 2023. Study selection, data extraction, and quality evaluation of the studies were conducted by two reviewers independently, with any controversy resolved by consensus. The Methodological Index for Nonrandomized Studies was used to assess the risk of bias.ResultsFive studies were included in this review, with a total of 99 patients with AD. For cognitive performance, TPS significantly improved the scores of the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) test battery, Alzheimer's Disease Assessment Scale (cognitive), Montreal Cognitive Assessment, and Mini-Mental Status Examination. For depressive symptoms, TPS significantly reduced the scores of the Alzheimer's Disease Assessment Scale (affective), Geriatric Depression Score, and Beck Depression Inventory. By functional magnetic resonance imaging, studies have shown that TPS improved cognitive performance in AD patients by increasing functional connectivity in the hippocampus, parahippocampal cortex, precuneus, and parietal cortex, and activating cortical activity in the bilateral hippocampus. TPS alleviated depressive symptoms in AD patients by decreasing functional connectivity between the ventromedial network (left frontal orbital cortex) and the salience network (right anterior insula). Adverse events in this review, including headache, worsening mood, jaw pain, nausea, and drowsiness, were reversible and lasted no longer than 1 day. No serious adverse events or complications were observed.ConclusionsTPS is promising in improving cognitive performance and reducing depressive symptoms in patients with AD. TPS may be a safe adjunct therapy in the treatment of AD. However, these findings lacked a sham control and were limited by the small sample size of the included studies. Further research may be needed to better explore the potential of TPS.Patient and public involvementPatients and the public were not involved in this study.

Project description:Purpose:An increase in resting motor threshold (RMT), prolonged cortical silent period duration (CSP), and reduced short-latency afferent inhibition (SAI), confirmed with previous transcranial magnetic stimulation (TMS), suggest decreased cortical excitability in obstructive sleep apnea syndrome (OSAS). The present study included MRI of OSAS patients for navigated TMS assessment of the RMT, as an index of the threshold for corticospinal activation at rest, and SAI as an index of cholinergic neurotransmission. We hypothesize to confirm findings on SAI and RMT with adding precision in the targeting of motor cortex in OSAS. Subjects and Methods:After acquiring head MRIs for 17 severe right-handed OSAS and 12 healthy subjects, the motor cortex was mapped with nTMS to assess the RMT and SAI, with motor evoked potentials (MEPs) recorded from the abductor-pollicis brevis (APB) muscle. The 120%RMT intensity was used for the SAI by a paired-pulse paradigm in which the electrical stimulation to the median nerve is followed by magnetic stimulation of the motor cortex at inter-stimulus intervals (ISIs) of 18-28 ms (ISIs18-28). The SAI control condition included a recording of MEPs without peripheral stimulation. Latency and amplitude of MEP at RMT at 120%RMT for eleven different at ISIs18-28 were analyzed. Results:The study showed a significantly lower percentage deviation of MEP amplitude at ISIs(18-28ms) from the control condition between OSAS and healthy subjects (U=44.0, p=0.01). The intensity of stimulation at RMT was significantly higher in OSAS subjects (U=55.0, p=0.04*). Correlation analysis showed that BMI significantly negatively correlated (?=-0.47) with MEP amplitude percentage deviation in OSAS patients. Conclusion:The nTMS study results in increased RMT, and reduced cortical afferent inhibition in OSAS patients for SAI at ISIs18-28, confirming previous findings of impaired cortical afferent inhibition in OSAS. Future nTMS studies are desirable to elucidate the role of RMT and SAI in diagnostics and treatment of OSAS, and to elucidate the usefulness of nTMS in OSAS research.

Dataset Information

Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease-A New Navigated Focal Brain Therapy.

Publications

Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease-A New Navigated Focal Brain Therapy.

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