Ultrasound Neuromodulation With Transcranial Pulse Stimulation in Alzheimer Disease

JAMA Network Open, Год журнала: 2025, Номер 8(2), С. e2459170 - e2459170

Опубликована: Фев. 26, 2025

Importance Given the increasing prevalence of dementia and limited treatment options available, ultrasound neuromodulation could serve as a novel add-on therapy to standard treatments for Alzheimer disease (AD). As is still in its early stages, further research essential fully explore potential treating brain disorders. Objective To evaluate clinical functional imaging effects transcranial pulse stimulation (TPS) patients with AD. Design, Setting, Participants A randomized, double-blind, sham-controlled, crossover trial was conducted at Medical University Vienna between January 1, 2017, July 27, 2022. Sixty clinically diagnosed AD receiving state-of-the-art were randomly allocated sequence groups verum-sham (first cycle verum, second sham, n = 30) sham-verum (n 30). Data analysis performed from 28, 2022, September 5, 2024. Intervention Each participant received 6 verum sham TPS sessions (6000 pulses, 0.20 mJ/mm 2 , 5 Hz) frontoparietal areas. Main Outcomes Measures Neuropsychological tests, including primary outcome Consortium Establish Registry Alzheimer’s Disease (CERAD) corrected total score (CTS), baseline 1 week, month, 3 months following stimulations each cycle. Primary secondary outcomes, magnetic resonance Beck Depression Inventory-II, analyzed by intention-to-treat and, sensitivity, per protocol analysis. Results For analysis, 60 ages 51 82 years (mean [SD], 70.65 [8.16] years; 30 females; males) included. The CERAD CTS increased mean (SD) 2.22 (6.87) points condition 70.93 (14.27) 73.15 (14.90) after stimulation, while 1.00 (6.82) point vs 71.68 (13.62] 72.68 (14.48) stimulation. data × session interaction not significant ( P .68; partial η [ηp ] 0.01), but age .003; ηp 0.08, followed post hoc analyses subsamples. Although several older than 70 benefited TPS, only younger subgroup (≤70 years) showed significantly higher increases all poststimulation (condition session: .005; 0.16). At example, 3.91 (7.86)-point increase found patients, decrease 1.83 (5.80) observed sham. Memory-associated activation precuneus, visual, frontal areas, resting state connectivity upregulated dorsal attention network. In sample, reduction Inventory-II scores (verum baseline: 7.27 [5.87]; stimulation: 5.27 [5.27]; 6.70 [5.65]; 6.22 [4.40]; .008; 0.23). During both conditions, most common adverse symptom depression; no major neuropathologic change detected detailed neuroradiologic assessments. Conclusions Relevance this randomized AD, 2-week improved cognitive subgroup, ameliorated depressive symptoms, induced upregulation connectivity. These findings suggest may be safe promising treatment. Trial Registration ClinicalTrials.gov Identifier: NCT03770182

Язык: Английский

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Clinical recommendations for non-invasive ultrasound neuromodulation

Brain stimulation, Год журнала: 2024, Номер 17(4), С. 890 - 895

Опубликована: Июль 1, 2024

Non-invasive ultrasound neuromodulation has experienced exponential growth in the neuroscientific literature, recently also including clinical studies and applications. However, recommendations for secure effective application of pathological brains are currently lacking. Here, experts with expertise brain stimulation present initial relevance all techniques. The start methodological safety issues focusing on technical to avoid harm brain. This is followed by important factors concerning situations.

Язык: Английский

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Theoretical analysis of low-power deep synergistic sono-optogenetic excitation of neurons by co-expressing light-sensitive and mechano-sensitive ion-channels

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Март 6, 2025

The present challenge in neuroscience is to non-invasively exercise low-power and high-fidelity control of neurons situated deep inside the brain. Although, two-photon optogenetic excitation can activate millimeter depth with sub-cellular specificity millisecond temporal resolution, it also cause heating targeted tissue. On other hand, sonogenetics modulate cellular activity expressed mechano-sensitive proteins deeper areas brain less spatial selectivity. We a theoretical analysis synergistic sono-optogenetic method overcome these limitations by co-expressing (MscL-I92L) ion-channel light-sensitive (CoChR/ChroME2s/ChRmine) hippocampal neurons. It shown that presence low-amplitude subthreshold ultrasound pulses, threshold for neural spiking reduces drastically 73% MscL-I92L-CoChR (0.021 mW/µm2), 66% MscL-I92L-ChroME2s (0.029 64% MscL-I92L-ChRmine (0.013 mW/µm2) at 5 Hz. allows up 1.2 cm combination. useful design new experiments multimodal neuroprosthetic devices circuits.

Язык: Английский

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Electrical brain networks before and after transcranial pulsed shockwave stimulation in Alzheimer’s patients

GeroScience, Год журнала: 2024, Номер unknown

Опубликована: Авг. 27, 2024

Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder that dramatically affects cognitive abilities and represents the most common cause of dementia. Currently, pharmacological interventions represent main treatment to deal with symptoms AD; however, alternative approaches are readily sought. Transcranial pulse stimulation (TPS) an emerging non-invasive neuromodulation technique uses short, repetitive shockwaves potential provide wide range vascular, metabolic, neurotrophic changes has recently been shown improve in AD. This exploratory study aims gain insight into neurophysiological effect one session TPS AD as reflected electroencephalographic measures, e.g., spectral power, coherence, Tsallis entropy (TE), cross-frequency coupling (cfc). We document power (frontal occipital), coherence (frontal, occipital temporal), TE (temporal frontal) well cfc (parietal-frontal, parietal-temporal, frontal–temporal). Our results emphasize role measures prospective markers for TPS.

Язык: Английский

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A retrospective analysis of ultrasound neuromodulation therapy using transcranial pulse stimulation in 58 dementia patients

Psychological Medicine, Год журнала: 2025, Номер 55

Опубликована: Янв. 1, 2025

Abstract Background Novel ultrasound neuromodulation techniques allow therapeutic brain stimulation with unmet precision and non-invasive targeting of deep areas. Transcranial pulse (TPS), a multifrequency sonication technique, is approved for the clinical treatment Alzheimer’s disease (AD). Here, we present largest real-world retrospective analysis therapy in dementia (AD, vascular, mixed) mild cognitive impairment (MCI). Methods The consecutive sample involved 58 patients already receiving state-of-the-art an open-label, uncontrolled, study. TPS typically comprises 10 sessions (range 8–12) individualized MRI-based target areas defined according to pathology individual pathophysiology. We compared CERAD-Plus neuropsychological test battery results before after treatment, CERAD Corrected Total Score ( CTS) as primary outcome. Furthermore, analyzed side effects reported by during period. Results (CTS) significantly improved p = .017, d .32) (Baseline: M 56.56, SD 18.56; Post-treatment: 58.65, 19.44). group top-responders (top quartile) even 9.8 points. Fewer than one-third all any sensation treatment. Fatigue transient headaches were most common, no severe adverse events. Conclusions findings implicate novel safe add-on or MCI potential further improve current results. Despite benefits, randomized, sham-controlled, longitudinal trials are needed differentiate verum placebo.

Язык: Английский

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Transcranial Focused Ultrasound Neuromodulation in Psychiatry: Main Characteristics, Current Evidence, and Future Directions

Brain Sciences, Год журнала: 2024, Номер 14(11), С. 1095 - 1095

Опубликована: Окт. 30, 2024

Non-invasive brain stimulation (NIBS) techniques are designed to precisely and selectively target specific regions, thus enabling focused modulation of neural activity. Among NIBS technologies, low-intensity transcranial ultrasound (tFUS) has emerged as a promising new modality. The application tFUS can safely non-invasively stimulate deep structures with millimetric precision, offering distinct advantages in terms accessibility non-cortical regions over other methods. However, date, several aspects still need be characterized; furthermore, there only handful studies that have utilized psychiatric populations. This narrative review provides an up-to-date overview key this technique, including the main components system, neuronavigational tools used simulations optimize parameters delivery tFUS, experimental protocols employed evaluate efficacy disorders. findings from populations presented discussed, future directions highlighted.

Язык: Английский

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Ultrasound neuromodulation – How deep can we stimulate?

Brain stimulation, Год журнала: 2024, Номер 18(1), С. 15 - 18

Опубликована: Дек. 12, 2024

Язык: Английский

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