Brain Stimulation最新文献

英文中文

Modulating cerebrospinal fluid dynamics using pulsed photobiomodulation 利用脉冲光生物调节调节脑脊液动力学。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2025-11-26 DOI: 10.1016/j.brs.2025.102988

Ariel Motsenyat , Xiaole Z. Zhong , Hannah Van Lankveld , Joanna X. Chen , Alicia Mathew , J. Jean Chen

Introduction

The use of photobiomodulation (PBM) to enhance brain health, specifically glymphatic drainage and thus neurotoxic waste clearance, may make it a promising therapeutic tool against neurodegenerative diseases such as Alzheimer's disease.

Material and method

This study investigates whether PBM can modulate cerebrospinal fluid (CSF) flow in 45 healthy young adults. We conducted forehead transcranial PBM (tPBM) and intranasal PBM (iPBM) at the nostril, and measured CSF dynamics using blood-oxygenation level-dependent (BOLD) functional MRI (fMRI). Our data demonstrates 4 min of PBM-induced increases in CSF flow.

Conclusion and result

Our data shows that (1) even a short PBM of 4 min can induce a change in CSF dynamics, in the form of an immediate increase in intracranial CSF volume and a reduction in CSF inflow; (2) skin melanin had a significant effect on the CSF response in tPBM, with lighter skin associated with higher responses; (3) both iPBM and tPBM displayed a dose-dependent effect on CSF dynamics in terms of a wavelength-irradiance interaction; (4) intranasal PBM (iPBM) can be used to produce a significant change in CSF dynamics that is equivalent to forehead transcranial PBM (tPBM) with a small fraction of the irradiance. The most likely explanation for the observed fMRI signal changes in CSF regions of interest for both tPBM and iPBM is an increased CSF outflow pressure due to PBM-induced vasodilation that transiently increases intracranial CSF volume and reduces net CSF inflow.

Impact

This study establishes that PBM can modulate CSF flow in the healthy human brain in real time. This study also suggests that iPBM may be more efficient in CSF modulation due to the proximity to the olfactory system and the lack of melanin dependence. The influence of melanin on tPBM, the feasibility of iPBM and the dose dependence of both will require further investigation in healthy and patient populations.

利用光生物调节（PBM）来增强大脑健康，特别是淋巴引流，从而清除神经毒性废物，可能使其成为治疗神经退行性疾病如阿尔茨海默病的有前途的治疗工具。材料和方法：本研究探讨了PBM是否能调节45名健康青年的脑脊液（CSF）流动。我们在鼻孔进行了前额经颅PBM （tPBM）和鼻内PBM (iPBM)，并使用血氧水平依赖（BOLD）功能MRI （fMRI）测量了CSF动力学。我们的数据显示4分钟pbm诱导的脑脊液流量增加。结论和结果：我们的数据表明：(1)即使是4分钟的短暂脑卒中也能引起脑脊液动力学的变化，表现为颅内脑脊液容量的立即增加和脑脊液流入的减少；(2)皮肤黑色素对tPBM患者脑脊液反应有显著影响，肤色越浅反应越高；(3)在波长-辐照度相互作用方面，iPBM和tPBM对脑脊液动力学均表现出剂量依赖性；(4)鼻内PBM （iPBM）可以产生脑脊液动力学的显著变化，相当于前额经颅PBM (tPBM)，但辐照度只有一小部分。对于tPBM和iPBM在脑脊液感兴趣区域观察到的fMRI信号变化，最可能的解释是，由于pbm诱导的血管舒张，脑脊液流出压力增加，暂时性地增加了颅内脑脊液体积，减少了脑脊液净流入。影响：本研究证实PBM可以实时调节健康人大脑的脑脊液流量。该研究还表明，iPBM可能在脑脊液调节中更有效，因为它靠近嗅觉系统并且缺乏对黑色素的依赖。黑色素对tPBM的影响、iPBM的可行性以及两者的剂量依赖性需要在健康人群和患者人群中进一步研究。

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引用次数: 0

Comprehensive map of axonal pathway activation as a function of subthalamic deep brain stimulation location and parameter settings 丘脑下深部脑刺激位置和参数设置作用下轴突通路激活的综合图谱。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2025-11-21 DOI: 10.1016/j.brs.2025.102992

Anneke M. Frankemolle-Gilbert , Angela M. Noecker , Tjitske Heida , Cameron C. McIntyre

Background

Deep brain stimulation (DBS) of the subthalamic region is an established therapy for the treatment of Parkinson's disease (PD). Computational models of subthalamic DBS are commonly used in the clinical literature to estimate the brain connections activated by the stimulus. However, those analyses are typically performed with simplified DBS modeling methods. As subthalamic DBS research evolves, there is a need for more advanced modeling results.

Objective

The goal of this study was to create maps of DBS axonal pathway activation in the subthalamic region across a wide range of stimulation settings (i.e. polarity, pulse width, amplitude) and electrode locations.

Methods

We used an anatomically and biophysically detailed computational model of subthalamic DBS to calculate responses for 9 different axonal pathways of interest at 256 different DBS locations using ring mode, directional, and bipolar stimulation. An open access interactive software tool is provided for users to analyze the pathway activation results.

Results

Electrode location plays a major role in dictating the assortment of axonal pathways that are activated by subthalamic DBS. We implemented a pathway selectivity index to identify the electrode locations and stimulation parameter settings that theoretically bias activation toward the pallidothalamic, motor hyperdirect, or cerebellothalamic pathways, respectively. However, true selectivity is generally difficult to achieve because of pathway co-activation.

Conclusion

Evolving hypotheses suggest that activation of specific pathways may be related to the control of specific PD symptoms. This study provides detailed predictions on stimulation conditions that facilitate pathway selective DBS, as well as an interactive software tool that quantifies DBS pathway activation throughout the subthalamic region.

背景：丘脑底区深部脑刺激（DBS）是治疗帕金森病（PD）的一种既定疗法。丘脑底起搏器的计算模型在临床文献中常用来估计刺激激活的大脑连接。然而，这些分析通常是用简化的DBS建模方法进行的。随着下丘脑DBS研究的发展，需要更先进的建模结果。目的：本研究的目的是在广泛的刺激设置（即极性、脉冲宽度、振幅）和电极位置下，创建丘脑底区DBS轴突通路激活图。方法：我们使用了一个解剖和生物物理上详细的丘脑底DBS计算模型，计算了256个不同DBS位置的9个不同轴突通路在环模式、定向和双极刺激下的反应。提供了一个开放访问的交互式软件工具，供用户分析通路激活结果。结果：电极位置在决定丘脑底起搏器激活的轴突通路的分类中起主要作用。我们实施了一个通路选择性指数来确定电极的位置和刺激参数设置，理论上分别偏向于激活皮层丘脑、运动超直接通路或小脑丘脑通路。然而，由于途径共激活，真正的选择性通常难以实现。结论：不断发展的假说表明，特定通路的激活可能与特定PD症状的控制有关。该研究提供了促进DBS通路选择性的刺激条件的详细预测，以及量化整个丘脑底区DBS通路激活的交互式软件工具。

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引用次数: 0

Engineering focused ultrasound for glioblastoma 胶质母细胞瘤的工程聚焦超声。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2025-11-21 DOI: 10.1016/j.brs.2025.102986

Marcus S. Bell , Chase M. Walton , Mark J. Williams , Thomas Eckert , Joshua C. Brown , Nathan C. Rowland , Ozgur Sahin , Ben A. Strickland

Background

Focused ultrasound (FUS) is a rapidly advancing noninvasive energy delivery technology with the capacity to precisely modulate the tumor microenvironment (TME) through acoustic waves. Glioblastoma (GBM) is characterized by profound TME immune suppression and treatment resistance and has emerged as a key subject to treatment with FUS therapy.

Objective

This review examines the technical evolution of FUS and its expanded applications in GBM, including subtypes of low- and high-intensity FUS and their mechanistic contributions to therapeutic effect.

Methods

A comprehensive literature review was conducted using PubMed, Scopus, and Google Scholar to identify preclinical and clinical studies utilizing FUS in the context of GBM. Articles were included if they discussed FUS mechanisms (thermal, mechanical), bioeffects (immunomodulation, barrier permeability, cell death), or combinatory approaches (e.g., drug delivery, CAR T cells, sonodynamic therapy).

Results

A literature search yielded 312 studies; 95 met inclusion criteria (67 preclinical, 14 clinical trials, 14 reviews) with defined FUS parameters and biological endpoints. FUS enables spatiotemporal control of thermal and mechanical effects in GBM. Modulation of duty cycle, acoustic pressure, and exposure time allows FUS to operate across therapeutic regimes. Preclinical data support using FUS for targeted drug delivery, immune cell repolarization, and synergistic effects with immunotherapies. Clinical trials demonstrate the safety and feasibility of several FUS platforms.

Conclusions

FUS offers a tunable multimodal platform with the potential to overcome core resistance mechanisms in GBM. Recurrent glioblastoma could be effectively treated by integrating FUS as an adjunct therapy alongside emerging immunotherapies and targeted drug delivery systems.

背景：聚焦超声（FUS）是一种快速发展的无创能量传递技术，具有通过声波精确调节肿瘤微环境（TME）的能力。胶质母细胞瘤（GBM）具有严重的TME免疫抑制和治疗耐药的特点，已成为FUS治疗的关键主题。目的：本文综述了FUS技术的发展及其在GBM中的广泛应用，包括低强度和高强度FUS亚型及其对治疗效果的机制贡献。方法：通过PubMed、Scopus和谷歌Scholar进行全面的文献综述，以确定在GBM背景下使用FUS的临床前和临床研究。讨论FUS机制（热、机械）、生物效应（免疫调节、屏障渗透性、细胞死亡）或组合方法（如药物传递、CAR - T细胞、声动力治疗）的文章均被纳入。结果：文献检索获得312项研究；95项符合纳入标准（67项临床前试验，14项临床试验，14项综述），明确了FUS参数和生物学终点。FUS使热和机械效应在GBM中的时空控制成为可能。占空比、声压和暴露时间的调制允许FUS在各种治疗方案中工作。临床前数据支持使用FUS进行靶向药物递送、免疫细胞复极化以及与免疫疗法的协同作用。临床试验证明了几种FUS平台的安全性和可行性。结论：FUS提供了一个可调节的多模式平台，具有克服GBM核心耐药机制的潜力。复发性胶质母细胞瘤可以通过将FUS作为一种辅助疗法与新兴的免疫疗法和靶向药物传递系统相结合来有效治疗。

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引用次数: 0

Theta-burst intermittent deep brain stimulation (iDBS) in childhood-onset genetic dystonia 脑波爆发间歇性深部脑刺激（iDBS）治疗儿童期遗传性肌张力障碍。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2025-11-20 DOI: 10.1016/j.brs.2025.102993

Eleonora Minacapilli , Vincenzo Levi , Antonio Spagarino , Federica Zibordi , Federica Rachele Danti , Giovanna Zorzi , Federica Graziola

引用次数: 0

Depression relief from cranial nerve stimulation tracked with decreased prefrontal alpha power and connectivity similar to prefrontal stimulation: an exploratory analysis 一项探索性分析：颅神经刺激对抑郁的缓解与前额叶α能量和连接的降低相似。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2025-11-19 DOI: 10.1016/j.brs.2025.102991

Justin Riddle , Eric Tirrell , Lauren Hindley , Andrew F. Leuchter , Flavio Frohlich , Linda L. Carpenter

引用次数: 0

Inter-pulse interval and motor evoked potential variability: Bridging insights from healthy adults to post-stroke TMS protocols 脉间间隔和运动诱发电位变异性：从健康成人到脑卒中后颅磁刺激方案的桥梁见解。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2025-11-15 DOI: 10.1016/j.brs.2025.102987

Ergi Spiro , Lei Zhu , Ziping Huang , Salman Ikramuddin , Angel V. Peterchev , Charalambos C. Charalambous , Wuwei Feng

引用次数: 0

DLPFC TMS suppresses high-frequency neural activity in the human sgACC DLPFC TMS抑制人类sgACC的高频神经活动。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2025-11-14 DOI: 10.1016/j.brs.2025.11.012

Ethan A. Solomon , Umair Hassan , Nicholas T. Trapp , Aaron D. Boes , Corey J. Keller

引用次数: 0

Effectiveness of transcranial magnetic stimulation for posttraumatic stress disorder: A multisite, propensity-matched cohort study of treatment parameters 经颅磁刺激治疗创伤后应激障碍的有效性：一项多地点、倾向匹配的治疗参数队列研究。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2025-11-13 DOI: 10.1016/j.brs.2025.11.007

Yosef A. Berlow , Samantha L. Cilli , F. Andrew Kozel , Amin Zandvakili , Noelle Marcotullio , Camila Cosmo , Miriam A. Goldberg , Bo Dehm Wicklund , Michelle R. Madore , Noah S. Philip

Background

Transcranial magnetic stimulation (TMS) is increasingly used off-label for posttraumatic stress disorder (PTSD), often applying protocols developed for depression. While prior studies suggest high-frequency TMS can improve PTSD symptoms, few have been adequately powered to compare protocols. We examined whether three common TMS protocols yield equivalent outcomes for PTSD in a large, multisite cohort of veterans.

Methods

Clinical outcomes were analyzed from 756 veterans with comorbid PTSD and depression treated with antidepressant TMS across multiple VA sites. Protocols included left prefrontal 10 Hz TMS (n = 526), left prefrontal intermittent theta burst TMS (iTBS; n = 71), and deep TMS (dTMS; n = 61). PTSD symptoms were measured with the PTSD symptom checklist for DSM-5 (PCL-5). Primary outcomes included PTSD response (>10-point reduction) and remission (PCL-5 <33). Propensity score matching adjusted for baseline differences. Equivalence was set at 10 % for categorical outcomes and Cohen's d = 0.25 for continuous outcomes. Depression outcomes were also analyzed.

Results

All three TMS protocols produced substantial PTSD symptom reductions (18–22 points). PTSD response rates were 63 % (10 Hz), 65 % (iTBS), and 78 % (dTMS); remission rates were 47 %, 48 %, and 49 %, respectively. Both iTBS and dTMS were noninferior to 10 Hz (all ps < 0.05). Depression outcomes demonstrated similar patterns.

Discussion

In this large multisite cohort study of veterans with PTSD and depression, 10 Hz, iTBS, and dTMS protocols demonstrated comparable clinical effectiveness. Limitations are those inherent to cohort studies of veterans. These findings support the effectiveness of TMS for PTSD, and protocol selection based on patient-specific or logistical considerations rather than efficacy differences.

背景：经颅磁刺激（TMS）越来越多地被用于治疗创伤后应激障碍（PTSD），通常用于治疗抑郁症。虽然先前的研究表明高频经颅磁刺激可以改善创伤后应激障碍症状，但很少有足够的动力来比较方案。我们研究了三种常见的经颅磁刺激方案是否在一个大型、多地点的退伍军人队列中产生相同的PTSD结果。方法：对756例合并创伤后应激障碍和抑郁症的退伍军人在多个退伍军人事务部接受抗抑郁TMS治疗的临床结果进行分析。方案包括左侧前额叶10hz经颅磁刺激（n=526）、左侧前额叶间歇性θ波爆发经颅磁刺激（iTBS, n=71）和深部经颅磁刺激（dTMS, n=61）。用DSM-5 (PCL-5) PTSD症状检查表测量PTSD症状。主要结局包括PTSD反应（>减轻10分）和缓解（PCL-5）。结果：三种TMS方案均显著减轻PTSD症状（18-22分）。PTSD反应率分别为63% （10 Hz）、65% （iTBS）和78% (dTMS)；缓解率分别为47%、48%和49%。讨论：在这项针对PTSD和抑郁症退伍军人的大型多地点队列研究中，10hz、iTBS和dTMS方案显示出相当的临床效果。局限性在于退伍军人队列研究固有的局限性。这些发现支持经颅磁刺激治疗创伤后应激障碍的有效性，以及基于患者特异性或后勤考虑的方案选择，而不是疗效差异。

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引用次数: 0

Mark Hallett (1943–2025): A pioneer in brain stimulation 马克·哈雷特（1943-2025）：脑刺激的先驱。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2025-11-12 DOI: 10.1016/j.brs.2025.11.009

Ulf Ziemann (Prof), John C. Rothwell (Prof)

引用次数: 0

Theta-paced stimulation of the thalamic nucleus reuniens entrains mPFC-HPC oscillations and facilitates the acquisition of extinction memories 以theta为节奏的丘脑核刺激可抑制mPFC-HPC振荡，促进消失记忆的获得。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2025-11-12 DOI: 10.1016/j.brs.2025.11.011

Tuğçe Tuna , Flávio Afonso Gonçalves Mourão , Stephen Maren

Background

The nucleus reuniens (RE) is a midline thalamic nucleus interconnecting the medial prefrontal cortex (mPFC) and the hippocampus (HPC), structures known to be involved in aversive memory processes. Recent work indicates that the RE plays a critical role in the acquisition and retrieval of fear extinction memories. Functional inactivation of the RE impairs both mPFC-HPC coherence and extinction memory. Here we examine whether imposing theta activity on the RE entrains oscillations in the mPFC and HPC and facilitates extinction learning.

Methods

To deliver theta-paced (8 Hz) optogenetic stimulation, we expressed an excitatory opsin, (channelrhodopsin; AAV9-CaMKIIa-hChR2(H134R)-mCherry) or control virus (AAV9-CaMKIIa-mCherry) in the RE in male and female rats. A single optic fiber targeting the RE was implanted during the same surgery. After recovery, animals underwent auditory fear conditioning, extinction training, and an extinction retrieval test, each separated by 24-h. During extinction training, conditioned stimuli (CS) presentations were paired with 8-Hz sinusoidal optostimulation (450 nM, 10 mW) of the RE. In another experiment, we recorded local field potentials (LFPs) from the mPFC and dorsal HPC (dHPC) during RE optostimulation.

Results

Theta-paced stimulation of the RE during extinction training significantly decreased freezing behavior compared to the control group. Notably, the reduction in conditioned behavior was evident during the subsequent stimulation-free retrieval test. This reveals that RE stimulation during extinction not only suppresses conditioned fear responses acutely, but also facilitates the acquisition of long-term extinction memories. Theta-paced RE stimulation markedly enhanced both neural activity and entrained theta oscillations in the mPFC and dHPC.

Conclusion

This work suggests that the RE oscillatory activity is critical for the acquisition of extinction memories through the modulation of hippocampal-prefrontal network dynamics. In the future, RE theta-paced stimulation can be an important therapeutic tool by strengthening extinction memories.

背景：团聚核（RE）是连接内侧前额叶皮层（mPFC）和海马体（HPC）的丘脑中线核，已知参与厌恶记忆过程的结构。最近的研究表明，可记忆性在恐惧消退记忆的获取和恢复中起着至关重要的作用。RE的功能失活损害了mPFC-HPC的相干性和消光记忆。在这里，我们研究了施加θ活动在RE上是否会抑制mPFC和HPC的振荡，并促进消退学习。方法：在雄性和雌性大鼠视网膜中表达一种兴奋性视蛋白（通道视紫红质；AAV9-CaMKIIa-hChR2(H134R)-mCherry）或对照病毒（AAV9-CaMKIIa-mCherry），以传递θ -节奏（8 Hz）光遗传刺激。在同一次手术中，植入了一根针对RE的单一光纤。恢复后，动物进行听觉恐惧条件反射、消失训练和消失恢复测试，每隔24小时进行一次。在消退训练中，条件刺激（CS）的呈现与8 hz的正弦光刺激（473 nM, 10 mW）配对。在另一项实验中，我们在使用这些行为过程中记录了来自mPFC和背侧HPC的局部场电位（LFPs）。结果：与对照组相比，在消退训练期间，θ节奏刺激可显著降低小鼠的冻结行为。值得注意的是，在随后的无刺激检索测试中，条件行为的减少是明显的。这表明，在消退过程中刺激可再生神经系统不仅能显著抑制条件性恐惧反应，还能促进长期消退记忆的获得。以θ节律刺激可显著增强mPFC和dHPC的神经活动和携带θ振荡。结论：海马-前额叶网络的动态调节对消退记忆的获取起着至关重要的作用。在未来，以θ为节奏的刺激可以成为加强消失记忆的重要治疗工具。

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