Brain Stimulation最新文献

英文中文

Effects of low-frequency burst stimulation of the motor thalamus on cortical neural co-firing 低频脉冲刺激丘脑运动体对皮层神经共放电的影响。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2026-01-01 DOI: 10.1016/j.brs.2025.103018

Kyungsoo Kim , Giri P. Krishnan , JaeYeon Kim , Sergio Arroyo , Maxim Bazhenov , Karunesh Ganguly

Background

Electrical stimulation targeting the motor thalamus (Mthal) represents an emerging strategy for regulating motor cortical activity patterns, however the fundamental mechanisms and optimal stimulation configurations are not well established.

Objective

To characterize how burst Mthal stimulation modulates cortical activity and to identify stimulation parameters that maximize cortical co-firing via thalamocortical rebound mechanisms.

Methods

We conducted acute electrophysiological experiments in anesthetized rats using Mthal stimulation with systematically manipulated burst stimulation parameters (i.e., number of pulses and pulse width) in the low-frequency band (1–8 Hz) modulation cycle. Cortical responses across large areas covering primary and secondary motor cortex were recorded. Additionally, intracortical recordings were performed for detailed spike activity monitoring during stimulation. Cortical activity patterns in local field potentials and spike activity were analyzed to quantify the effects of Mthal stimulation on motor cortex. Computational thalamocortical circuit models were employed to explore the mechanistic basis of frequency-selective modulation effects.

Results

Burst Mthal stimulation elicited tunable cortical excitation, with optimal modulation achieved at 3–4 Hz. This preferred frequency corresponded to the natural rebound timing of thalamocortical (TC) cells and generated maximal cortical co-firing and synchronization. Higher stimulation frequencies (e.g., 8 Hz) resulted in suppressed and diminished responses. Computational modeling further validated that the cellular mechanism of the TC cell rebound excitation leads to frequency-dependent cortical modulation.

Conclusion

Burst Mthal stimulation demonstrates frequency-selective modulation of cortical network excitability, with 3–4 Hz protocols providing optimal enhancement of synchronized activity through exploitation of thalamocortical rebound dynamics. These results establish motor thalamic stimulation as a promising and efficient methodology for precise cortical network control and offer mechanistic foundations for developing therapeutic neuromodulation interventions aimed at motor system rehabilitation.

背景：针对运动丘脑（Mthal）的电刺激是调节运动皮质活动模式的一种新兴策略，但其基本机制和最佳刺激配置尚未得到很好的确定。目的：研究脑刺激如何调节皮质活动，并通过丘脑皮质反弹机制确定刺激参数，使皮质共放电最大化。方法：采用系统控制的低频（1 ~ 8hz） Mthal刺激，对麻醉大鼠进行急性电生理实验。记录了覆盖初级和次级运动皮层的大面积皮层反应。此外，在刺激过程中进行皮层内记录以详细监测尖峰活动。分析局部场电位和峰电位的皮层活动模式，量化Mthal刺激对运动皮层的影响。利用计算丘脑皮质电路模型探讨频率选择性调制效应的机制基础。结果：突发脑脊液刺激引起可调节的皮质兴奋，在3-4 Hz达到最佳调制。这种首选频率与丘脑皮质（TC）细胞的自然反弹时间相对应，并产生最大的皮质共放电和同步。较高的刺激频率（如8赫兹）导致抑制和减弱的反应。计算模型进一步验证了TC细胞反弹兴奋的细胞机制导致频率依赖性皮质调制。结论：丘脑运动刺激显示皮层网络兴奋性的频率选择性调节，3-4 Hz方案通过利用丘脑皮质反弹动力学提供最佳的同步活动增强。这些结果确立了运动丘脑刺激作为一种有前途和有效的精确皮层网络控制方法，并为开发针对运动系统康复的治疗性神经调节干预提供了机制基础。

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引用次数: 0

Low Intensity Ultrasound-facilitated exosome delivery promotes hippocampal neurogenesis in Alzheimer's disease 低强度超声促进外泌体递送促进阿尔茨海默病海马神经发生。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2026-01-01 DOI: 10.1016/j.brs.2025.103015

Yudie Yan , Jingtong Su , Muyun Xie , Yafei Kong , Chenchao Wang , Guohao Yuan , Yi Fang , Kihwan Hwang , Chae-Yong Kim , Hong Han , Zhen Zhang

Background

Low-intensity ultrasound (LIUS) and human adipose-tissue mesenchymal stem cell–derived exosomes (hADSC-Exos) have shown neuroprotective potential, but their combined effects in Alzheimer's disease (AD) remain unclear.

Objective

To evaluate the safety and efficacy of intranasal hADSC-Exos alone or combined with LIUS in APP/PS1 mice, and explore underlying molecular mechanisms.

Methods

Female APP/PS1 mice (30 weeks) were randomized into five groups (n = 6). Treatments included intranasal hADSC-Exos, LIUS, or both for 2 months. Behavioral tests, histology, and hippocampal RNA-seq were performed.

Results

LIUS enhanced Exo uptake in HT22 cells by ∼8 % without toxicity. Combined treatment improved learning and memory (escape latency ↓45 s→20 s; P < 0.01), increased neurogenesis markers (GFAP/SOX2, DCX, Ki67), and reduced amyloid and microglial activation. RNA-seq identified 93 specific DEGs in the combination group, with enrichment in synaptic and mitochondrial pathways. Fos and Kcnj13 were top DEGs and both downregulated after therapy (P < 0.05).

Conclusions

Intranasal hADSC-Exos combined with LIUS is safe, enhances brain delivery, and synergistically improves cognition and neurogenesis in AD mice. The Fos–Kcnj13 axis may mediate these effects, suggesting a promising noninvasive therapeutic strategy.

背景：低强度超声（LIUS）和人脂肪组织间充质干细胞来源的外显体（hADSC-Exos）已显示出神经保护潜力，但它们在阿尔茨海默病（AD）中的联合作用尚不清楚。目的：评价hADSC-Exos单用或联用LIUS治疗APP/PS1小鼠的安全性和有效性，并探讨其分子机制。方法：30周龄的APP/PS1雌性小鼠随机分为5组（n=6）。治疗包括经鼻hADSC-Exos、LIUS或两者同时治疗2个月。进行行为测试、组织学检查和海马rna测序。结果：LIUS使HT22细胞的Exo摄取增加了约8%而没有毒性。结论：经鼻hADSC-Exos联合LIUS是安全的，可增强脑传递，并协同改善AD小鼠的认知和神经发生。Fos-Kcnj13轴可能介导这些作用，提示一种有前途的无创治疗策略。

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引用次数: 0

Reducing scalp pain for pTES of motor cortex using background hums 背景嗡嗡声减轻运动皮层pTES的头皮疼痛。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2026-01-01 DOI: 10.1016/j.brs.2026.103024

Mats Forssell , Rabira Tusi , Jeehyun Kim , Maxwell D. Murphy , Jonathan A. Shulgach , Prakarsh Yadav , Alonso Buitano Tang , Maya Maurer , Vishal Jain , Douglas J. Weber , Benedict J. Alter , Pulkit Grover

引用次数: 0

Subthreshold electric fields bidirectionally modulate neurotransmitter release through axon polarization 阈下电场通过轴突极化双向调节神经递质释放。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2026-01-01 DOI: 10.1016/j.brs.2025.103006

Aman S. Aberra, Madelyn W. Miles, Michael B. Hoppa

Background

Subthreshold electric fields modulate brain activity and show promise in several therapeutic applications. Although therapeutic electric fields are often uniform at the cellular level, they generate non-uniform membrane polarization within neurons due to their complex morphologies. Despite extensive modeling of neuronal membrane polarization by electric fields, subthreshold axonal polarization has not been measured and the resulting effects on neurotransmitter release are unknown.

Objective

To investigate the mechanisms by which subthreshold electric fields alter synaptic function using next-generation optogenetic indicators.

Methods

We combined noninvasive optogenetic indicators of voltage, glutamate, and calcium release to study the subcellular response to subthreshold electric fields in single neurons at high spatiotemporal resolution.

Results

We first captured the spatiotemporal profile of membrane polarization produced by uniform electric fields within individual neurons. Clinically relevant electric field intensities produced small polarizations of presynaptic boutons (<5 mV), yet caused rapid and powerful modulation of neurotransmitter release. We determined that subthreshold electric fields drive these effects by shifting resting calcium levels and altering the number of synaptic vesicles participating in neurotransmission.

Conclusions

Using subcellular optical measurements, we directly resolved the effects of electric fields on axonal and synaptic function, overcoming fundamental limitations of classical electrophysiology. Our results provide key insights into the cellular mechanisms of subthreshold electric field stimulation paradigms and may inform the design of neuromodulation therapies.

背景：阈下电场调节大脑活动，并在几种治疗应用中显示出前景。虽然治疗电场在细胞水平上通常是均匀的，但由于其复杂的形态，它们在神经元内产生不均匀的膜极化。尽管通过电场对神经元膜极化进行了广泛的建模，但阈下轴突极化尚未被测量，因此对神经递质释放的影响尚不清楚。目的：利用新一代光遗传学指标探讨阈下电场改变突触功能的机制。方法：结合电压、谷氨酸和钙释放等无创光遗传学指标，在高时空分辨率下研究单个神经元对阈下电场的亚细胞反应。结果：我们首次捕获了单个神经元内均匀电场产生的膜极化的时空分布。结论：利用亚细胞光学测量，我们直接解决了电场对轴突和突触功能的影响，克服了经典电生理学的基本局限性。我们的研究结果为阈下电场刺激范式的细胞机制提供了关键的见解，并可能为神经调节疗法的设计提供信息。

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引用次数: 0

A wireless, 60-channel, AI-enabled neurostimulation platform 无线60通道人工智能神经刺激平台。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2026-01-01 DOI: 10.1016/j.brs.2025.103013

Daniel S. Rizzuto , Haydn G. Herrema , Zhe Hu , Daniil Utin , Joshua Kahn , Chris Ho , Andrew B. Smiles , Robert E. Gross , Bradley C. Lega , Sandhitsu R. Das , Michael J. Kahana

Objective:

Closed-loop neuromodulatory therapies require devices that can decode ongoing brain states and deliver multi-site stimulation.

Methods:

We describe the Smart Neurostimulation System (SNS), a cranially mounted implant with 60 configurable recording/stimulation channels, inductive power, and onboard spectral-feature classification. In three freely-moving sheep, we streamed local-field potentials and conducted two parameter-sweep experiments.

Results:

Cross-validated movement classifiers achieved an average AUC exceeding 0.95. Increasing stimulation amplitude and frequency produced post-stimulation elevations in

α

-band (8–12 Hz) and

γ

-band (78–82 Hz) power at most target locations.

Conclusion:

The SNS unifies high-density sensing, real-time brain state decoding, and programmable closed-loop stimulation in a single device, demonstrating behavioral-state prediction and parameter-dependent neuromodulation in vivo.

Significance:

These findings establish a preclinical foundation for biomarker-guided stimulation targeting distributed cortical networks underlying memory and cognition.

目的：闭环神经调节疗法需要能够解码正在进行的大脑状态并提供多位点刺激的设备。方法：我们描述了智能神经刺激系统（SNS），这是一种颅骨植入物，具有60个可配置的记录/刺激通道，感应功率和机载光谱特征分类。在三只自由运动的羊身上，我们进行了场电位流和两次参数扫描实验。结果：交叉验证的运动分类器的平均AUC超过0.95。随着刺激幅度和频率的增加，大部分靶区α波段（8 ~ 12 Hz）和γ波段（78 ~ 82 Hz）功率均有所升高。结论：SNS将高密度传感、实时脑状态解码和可编程闭环刺激统一在一个设备中，在体内表现出行为状态预测和参数依赖的神经调节。意义：这些发现为生物标志物引导的刺激为记忆和认知的分布式皮质网络奠定了临床前基础。

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引用次数: 0

Deep brain stimulation-responsive subthalamo-cortical coupling in obsessive-compulsive disorder 强迫症的深部脑刺激反应性丘脑下皮层耦合。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2026-01-01 DOI: 10.1016/j.brs.2025.103008

Lucie Winkler , Lucy M. Werner , Markus Butz , Christian J. Hartmann , Alfons Schnitzler , Jan Hirschmann

引用次数: 0

Chronometric interleaved TMS-fMRI shows state-dependent network effects underlying speech production 时序交织TMS-fMRI显示语音产生背后的状态依赖网络效应。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2026-01-01 DOI: 10.1016/j.brs.2025.103010

Maria Vasileiadi , Anna-Lisa Schuler , Michael Woletz , Verena Witz , Sarah Grosshagauer , John Coetzee , Martin Tik

Introduction

Speech production engages a distributed network of cortical regions, but the causal dynamics within this system remain incompletely understood. Transcranial magnetic stimulation (TMS) offers a unique opportunity to modulate brain activity and assess functional contributions to behavior. However, the temporal specificity of these effects and how stimulation timing during speech impacts behavior and neural activity remains unclear.

Materials and methods

We developed a novel chronometric interleaved TMS-fMRI paradigm to deliver TMS during an overt object naming task while simultaneously recording whole-brain BOLD responses. Stimulation was applied to the left superior temporal gyrus (STG) at two task-relevant stages: during early conceptual processing and during subsequent linguistic processing. Task-related BOLD activation patterns were analyzed across conditions.

Results

TMS delivered during linguistic processing consistently induced speech arrest outside of the scanner environment and was associated with increased activation in key language areas, including the inferior frontal gyrus (IFG) and STG. In contrast, stimulation during early conceptual processing had minimal effects on neural activation. These findings suggest that stimulation-induced disruption of speech is mediated by task-state-dependent overactivation rather than suppression.

Conclusion

Our results challenge the classic “virtual lesion” view of TMS by demonstrating that stimulation can amplify neural activity in a state-dependent manner. This work establishes a novel methodological framework for temporally precise causal mapping of speech networks and emphasizes the critical role of cognitive state in shaping brain responses to stimulation.

语音产生涉及到皮质区域的分布式网络，但该系统内的因果动力学仍然不完全清楚。经颅磁刺激（TMS）提供了一个独特的机会来调节大脑活动和评估功能对行为的贡献。然而，这些效应的时间特异性以及说话时的刺激时间如何影响行为和神经活动仍不清楚。材料和方法：我们开发了一种新的时序交错TMS- fmri范式，在公开对象命名任务期间提供TMS，同时记录全脑BOLD反应。在两个与任务相关的阶段，即早期概念处理阶段和随后的语言处理阶段，对左颞上回（STG）施加刺激。在不同条件下分析与任务相关的BOLD激活模式。结果：在语言处理过程中，经颅磁刺激在扫描环境之外持续诱导语言停止，并与包括额下回（IFG）和STG在内的关键语言区域的激活增加有关。相比之下，在早期概念处理过程中，刺激对神经激活的影响很小。这些发现表明，刺激诱导的言语中断是由任务状态依赖的过度激活介导的，而不是抑制。结论：我们的研究结果挑战了经典的经颅磁刺激“虚拟损伤”观点，证明刺激可以以状态依赖的方式放大神经活动。这项工作为语音网络的时间精确因果映射建立了一个新的方法框架，并强调了认知状态在塑造大脑对刺激的反应中的关键作用。

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引用次数: 0

Investigating the attentional state dependency of interhemispheric interactions - a TMS-EEG study 研究大脑半球间相互作用的注意状态依赖性——一项颅磁-脑电图研究。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2026-01-01 DOI: 10.1016/j.brs.2025.103011

Arianna Brancaccio , Cora M. Lanza , Selene Schintu

引用次数: 0

Objective DBS program selection using smartphone-based kinematics 目的基于智能手机运动学的DBS程序选择。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2026-01-01 DOI: 10.1016/j.brs.2026.103029

Florian Lange , Philipp Köberle , Gamze Adaçay , Diego L. Guarin , Jens Volkmann , Robert Peach , Martin M. Reich

引用次数: 0

Timing the dialogue: What the 100-ms hippocampo-cortical lag tells us about memory-informed neuromodulation 对话的时间：100毫秒海马体-皮层滞后告诉我们关于记忆信息的神经调节。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2026-01-01 DOI: 10.1016/j.brs.2025.103001

Wei Wu , Ning Li , Huiyong Zhang

引用次数: 0

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