Brain Stimulation最新文献_第4页

Further clarification regarding brain injury during focused ultrasound neuromodulation for substance use disorder 对聚焦超声神经调节治疗药物使用障碍期间脑损伤相关信件的回应。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2026-01-01 DOI: 10.1016/j.brs.2025.103014

Ali Rezai , Manish Ranjan, Aniruddha Bhagwat, Tasneem Arsiwala, Jeffrey Carpenter, Mark Schafer, Geoffrey Adams, Jennifer Marton, Padmashree Tirumalai, Daniel Farmer, James Mahoney, Victor Finomore

引用次数: 0

TI-Toolbox: An open-source software for temporal interference stimulation research ti -工具箱：一个用于时间干扰刺激研究的开源软件。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2026-01-01 DOI: 10.1016/j.brs.2025.103016

Ido Haber , Aksel Jackson , Axel Thielscher , Aviad Hai , Giulio Tononi

Background

Temporal interference (TI) stimulation is a novel non-invasive brain stimulation approach that promises selective targeting of deep brain structures while minimizing off-target cortical stimulation. Despite a growing interest in TI applications, there is a need for integrated computational tools that seamlessly connect neuroimaging data preprocessing through montage optimization, field simulation, and analysis within a unified framework designed for translational and clinical research.

Methods

We developed TI-Toolbox, an open-source software platform that integrates established neuroimaging tools (dcm2niix, SimNIBS, FreeSurfer) with specialized algorithms for TI research. The platform provides end-to-end workflows encompassing structural MRI preprocessing, volume conduction modeling, montage optimization, electric field simulation, and region-of-interest analysis. Both graphical user interface and command-line interface implementations ensure accessibility across user expertise levels. The platform employs containerized deployment via Docker to ensure reproducibility and cross-platform compatibility.

Results

TI-Toolbox successfully automates the complete TI research pipeline, from DICOM conversion through final field analysis. The platform demonstrates robust performance across operating systems and provides standardized workflows that enhance reproducibility. Furthermore, our case studies support the validity of our HD-EEG mapping approach for montage standardization and the need for individualized modeling for exposure assessment.

Conclusions

TI-Toolbox addresses critical infrastructure gaps in TI research by providing researchers with a unified, validated platform that reduces technical barriers and accelerates translational research in non-invasive deep brain stimulation.

背景：时间干扰（TI）刺激是一种新的非侵入性脑刺激方法，它承诺选择性靶向脑深部结构，同时最大限度地减少脱靶皮层刺激。尽管人们对TI应用越来越感兴趣，但仍需要集成的计算工具，通过蒙太奇优化、现场模拟和分析，在为转化和临床研究设计的统一框架内无缝连接神经成像数据预处理。方法：我们开发了TI- toolbox，这是一个开源软件平台，将现有的神经成像工具（dcm2niix, SimNIBS, FreeSurfer）与TI研究的专用算法集成在一起。该平台提供端到端的工作流程，包括结构MRI预处理、体积传导建模、蒙太奇优化、电场模拟和感兴趣区域分析。图形用户界面和命令行界面实现都确保了跨用户专业水平的可访问性。该平台通过Docker采用容器化部署，以确保可重复性和跨平台兼容性。结果：TI- toolbox成功实现了从DICOM转换到最终现场分析的整个TI研究流程的自动化。该平台展示了跨操作系统的强大性能，并提供了增强再现性的标准化工作流。此外，我们的案例研究支持了我们的HD-EEG映射方法在蒙太奇标准化中的有效性，以及在暴露评估中个性化建模的必要性。结论：TI- toolbox为研究人员提供了一个统一的、经过验证的平台，减少了技术障碍，加速了非侵入性深部脑刺激的转化研究，从而解决了TI研究中关键的基础设施缺口。

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引用次数: 0

Low-intensity transcranial ultrasound effects on the ventral intermediate nucleus and zona incerta in Parkinson's disease tremor 低强度经颅超声对帕金森病震颤的腹侧中间核和不规则带的影响。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2026-01-01 DOI: 10.1016/j.brs.2026.103025

Maggie Q. Vuong , Varsha Sreenivasan , Soojin Lee , Ben Quinn , Martin S. Keung , Michael Grundy , Juana Ayala Castañeda , Hongchae Baek , Martin J. McKeown

Background

Tremor in Parkinson's disease (PD) is a disabling symptom that often persists despite pharmacological treatment. High-intensity focused ultrasound (HIFU) targeting the ventral intermediate nucleus (VIM) alleviates Essential Tremor, but recent evidence suggests the zona incerta (ZI) may be a superior target for Parkinsonian tremor. This study compared the effects of transcranial ultrasound stimulation (TUS) to the VIM and ZI on postural and rest tremor, and examined related neural correlates using resting-state fMRI (rs-fMRI).

Methods

In this within-subject, crossover study, 19 participants with PD and right-hand tremor received both left VIM- and ZI-TUS on the same day in randomized order, separated by a 4-h washout period. Tremor severity and rs-fMRI data were collected before and after each session. Normalized changes in tremor intensity, resting-state functional connectivity (Δrs-FC), and fractional amplitude of low-frequency fluctuations (ΔfALFF) within the cerebello-thalamo-cortical network were analysed.

Results

TUS effects differed by target and tremor type. VIM-TUS significantly reduced postural tremor (p < 0.001) but not rest tremor, whereas ZI-TUS improved both postural (p = 0.005) and rest (p = 0.005) tremor. Although no overall group-level rs-FC changes were observed, individual Δrs-FC of the ZI following ZI-TUS correlated with tremor improvement (postural: r = 0.762, p < 0.001; rest: r = 0.586, p = 0.008), with similar findings for ΔfALFF.

Conclusion

ZI-TUS modulates tremor more robustly than VIM-TUS, suggesting that ZI may be a promising target for treatment of Parkinsonian tremor.

背景：帕金森病（PD）的震颤是一种致残症状，尽管药物治疗仍然存在。针对腹侧中间核（VIM）的高强度聚焦超声（HIFU）可以减轻原发性震颤，但最近的证据表明，椎体带（ZI）可能是帕金森震颤的更好靶点。本研究比较了经颅超声刺激（TUS）对VIM和ZI对体位性和静息性震颤的影响，并利用静息态功能磁共振成像（rs-fMRI）检测相关的神经相关性。方法：在这项受试者内交叉研究中，19名PD和右手震颤患者在同一天随机接受左VIM-和ZI-TUS治疗，间隔4小时洗脱期。每次治疗前后收集震颤严重程度和磁共振成像数据。分析了小脑-丘脑-皮层网络中震颤强度、静息状态功能连通性（Δrs-FC）和低频波动幅度分数（ΔfALFF）的归一化变化。结果：TUS的作用因靶区和震颤类型而异。VIM-TUS可显著降低体位性震颤（p < 0.001），但对静止性震颤没有作用，而ZI-TUS可改善体位性震颤（p = 0.005）和静止性震颤（p = 0.005）。虽然没有观察到整体组水平的rs-FC变化，但ZI- tus后的个体Δrs-FC与震颤改善相关（体位：r = 0.762, p < 0.001；休息：r = 0.586, p = 0.008）， ΔfALFF也有类似的发现。结论：ZI- tus对震颤的调节作用比VIM-TUS更强，表明ZI可能是治疗帕金森震颤的一个有希望的靶点。

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引用次数: 0

Deep brain stimulation modulates ventral striatal physiology in children with severe self-injurious behaviour 脑深部刺激调节严重自伤行为儿童腹侧纹状体生理。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2026-01-01 DOI: 10.1016/j.brs.2026.103026

Karim Mithani , Sebastian C. Coleman , Sara Breitbart , Alfonso Fasano , Carolina Gorodetsky , George M. Ibrahim

引用次数: 0

Trigeminal nerve direct current stimulation modulates raphe–hippocampal network synchrony in rats 三叉神经直流电刺激调节大鼠rape -海马网络同步。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2025-12-31 DOI: 10.1016/j.brs.2025.103017

Alireza Majdi, Liyi Chen, Myles Mc Laughlin

Background

Trigeminal nerve stimulation is a promising noninvasive method to modulate subcortical circuits involved in cognition. This study investigated the influence of trigeminal nerve direct current stimulation (TN-DCS) on neuronal activity and coherence between the raphe nuclei and hippocampus.

Methods

Fourteen adult male Sprague-Dawley rats (n = 10 control; n = 4 xylocaine/agonist) were implanted with silicon probes for simultaneous recordings from the hippocampus and either the dorsal (DRN) or median raphe nucleus (MnRN). Direct currents (from ±0.25 to ±3 mA) were applied to the trigeminal nerve during 3-min sessions (1 min pre-, 1 min during, 1 min post-stimulation).

Results

Acute TN-DCS rapidly and reversibly modulated firing in the DRN, MnRN, and hippocampus in a cell–type–specific, amplitude-dependent manner. Putative non-serotonergic (p-non-SERT) raphe neurons exhibited strong increases in spike rate, whereas putative serotonergic (p-SERT) neurons did not show consistent rate changes or stimulation-induced bursts. In the hippocampus, pyramidal cells exhibited polarity-dependent, amplitude-scaled increases in spike rate, whereas interneurons displayed smaller effects that were independent of polarity. TN-DCS enhanced theta-band coupling between p-non-SERT raphe spikes and hippocampal local field potentials, increasing spike-field coherence and spike-triggered averages in both DRN and MnRN. These effects, along with spike-rate increases in MnRN and hippocampus caused by TN-DCS, were blocked or significantly reduced by local trigeminal block (xylocaine) or intra-MnRN 5-HT_1A/7 agonist (8-OH-DPAT).

Conclusions

TN-DCS dynamically modulates raphe–hippocampal firing and theta synchrony via predominantly amplitude-dependent mechanisms that require intact trigeminal input and serotonergic signaling, supporting its potential as a targeted neuromodulation approach for subcortical circuits involved in cognition and mood.

背景：三叉神经刺激是一种很有前途的无创方法来调节涉及认知的皮层下回路。本研究探讨了三叉神经直流电刺激（TN-DCS）对中缝核与海马间神经元活动和一致性的影响。方法：将14只成年雄性spraguedawley大鼠（对照组10只，木卡因/激动剂4只）植入硅探针，同时记录海马和中缝背核（DRN）或中缝中核（MnRN）的记录。直流电（±0.25至±3 mA）在3分钟的疗程中（刺激前1分钟，刺激中1分钟，刺激后1分钟）作用于三叉神经。结果：急性TN-DCS以细胞类型特异性、振幅依赖的方式快速、可逆地调节DRN、MnRN和海马的放电。假设的非血清素能（p-non-SERT）中速神经元表现出强烈的峰值速率增加，而假设的血清素能（p-SERT）神经元没有表现出一致的速率变化或刺激诱导的脉冲。在海马体中，锥体细胞表现出极性依赖的、振幅尺度的尖峰率增加，而中间神经元表现出与极性无关的较小影响。n- dcs增强了p-非sert rapt峰与海马局部场电位之间的θ -波段耦合，增加了DRN和MnRN的峰-场相干性和峰触发平均。这些作用，以及TN-DCS引起的MnRN和海马峰率增加，被局部三叉神经阻滞（xylocaine）或MnRN内5-HT1A/7激动剂（8-OH-DPAT）阻断或显著降低。结论：TN-DCS通过主要依赖于振幅的机制动态调节rape -海马放电和theta同步，这需要完整的三叉神经输入和5 -羟色胺能信号，支持其作为涉及认知和情绪的皮层下回路的靶向神经调节方法的潜力。

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引用次数: 0

Site-specific stimulation imperative: Lessons from a failed auricular-cervical transcutaneous vagus nerve stimulation comparison using closely matched parameters 部位特异性刺激势在必行：从使用紧密匹配参数的失败耳颈经皮迷走神经刺激比较的经验教训。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2025-12-31 DOI: 10.1016/j.brs.2025.103022

Xuejuan Yang , Meiling Wei , Yunyun Jiao , Xinxin Xue , Yuwei Liu , Rong Li , Xiao Zeng , Jinbo Sun , Wei Qin

Background

Transcutaneous auricular and cervical vagus nerve stimulation (taVNS/tcVNS) are promising neuromodulatory approaches. However, their site-specific effects remain poorly understood, complicating clinical protocol selection.

Objective

This study aims to directly compare taVNS and tcVNS modulation on key biomarkers, including heart-evoked potential (HEP), neuro-cardiac coupling (NCC), heart rate variability (HRV) and salivary alpha-amylase (sAA) using closely matched, taVNS-optimized parameters.

Methods

In a within-subject design, 33 healthy adults underwent taVNS, tcVNS, and sham stimulation. Electroencephalogram, electrocardiogram, and salivary samples were collected. Computational modeling was used to verify cervical vagus engagement.

Results

Modeling revealed that the applied parameters failed to activate the deep cervical vagus nerve (peak E-field: 2.07 V/m at 1.5 mA, far below the 12.3 V/m activation threshold). Consequently, the ‘‘tcVNS” condition was reassessed as non-specific cervical stimulation (nscES). A limited, post-stimulation increase in HEP amplitude was observed at the F4 electrode following taVNS. No significant Time × Condition interactions were found for NCC, HRV, or sAA. However, exploratory analyses revealed that nscES produced a robust sAA increase, highlighting the potent confound of non-specific somatic afferent activation.

Conclusion

The inability to activate the cervical vagus nullifies direct comparison, illustrates a critical methodological consideration for cross-site comparisons: anatomical depth necessitates site-specific stimulation protocols. We therefore propose that future cross-site tVNS comparisons adopt a “verify-first” framework, where target engagement is validated (e.g., via modeling or neuroimaging) prior to physiological comparison. The pronounced sAA response to cervical stimulation, which we demonstrate can be elicited independently of vagal engagement, questions the specificity of sAA as a vagus biomarker and underscores the necessity of rigorous active controls to isolate vagus-specific effects.

背景：经皮耳颈迷走神经刺激（taVNS/tcVNS）是一种很有前途的神经调节方法。然而，它们的部位特异性作用仍然知之甚少，使临床方案的选择复杂化。目的：本研究旨在直接比较taVNS和tcVNS对关键生物标志物的调节，包括心脏诱发电位（HEP）、神经-心脏偶联（NCC）、心率变异性（HRV）和唾液α -淀淀酶（sAA），使用密切匹配的taVNS优化参数。方法：在受试者内设计中，33名健康成人接受taVNS、tcVNS和假刺激。采集脑电图、心电图、唾液样本。计算模型用于验证颈椎迷走神经接合。结果：建模结果显示，应用的参数未能激活颈深迷走神经（1.5mA时峰值电场为2.07 V/m，远低于12.3 V/m的激活阈值）。因此，“tcVNS”情况被重新评估为非特异性宫颈刺激（nscES）。在taVNS后F4电极观察到HEP振幅有限的刺激后增加。未发现NCC、HRV或sAA有显著的时间×条件相互作用。然而，探索性分析显示，nscES产生了强劲的sAA增加，突出了非特异性体细胞传入激活的强大混淆。结论：不能激活颈迷走神经使直接比较无效，说明了跨部位比较的关键方法学考虑：解剖深度需要特定部位的刺激方案。因此，我们建议未来的跨站点tVNS比较采用“验证优先”的框架，即在生理比较之前验证目标接触（例如，通过建模或神经成像）。我们证明了sAA对宫颈刺激的明显反应可以独立于迷走神经参与引起，这质疑了sAA作为迷走神经生物标志物的特异性，并强调了严格主动控制以分离迷走神经特异性效应的必要性。

{"title":"Site-specific stimulation imperative: Lessons from a failed auricular-cervical transcutaneous vagus nerve stimulation comparison using closely matched parameters","authors":"Xuejuan Yang , Meiling Wei , Yunyun Jiao , Xinxin Xue , Yuwei Liu , Rong Li , Xiao Zeng , Jinbo Sun , Wei Qin","doi":"10.1016/j.brs.2025.103022","DOIUrl":"10.1016/j.brs.2025.103022","url":null,"abstract":"<div><h3>Background</h3><div>Transcutaneous auricular and cervical vagus nerve stimulation (taVNS/tcVNS) are promising neuromodulatory approaches. However, their site-specific effects remain poorly understood, complicating clinical protocol selection.</div></div><div><h3>Objective</h3><div>This study aims to directly compare taVNS and tcVNS modulation on key biomarkers, including heart-evoked potential (HEP), neuro-cardiac coupling (NCC), heart rate variability (HRV) and salivary alpha-amylase (sAA) using closely matched, taVNS-optimized parameters.</div></div><div><h3>Methods</h3><div>In a within-subject design, 33 healthy adults underwent taVNS, tcVNS, and sham stimulation. Electroencephalogram, electrocardiogram, and salivary samples were collected. Computational modeling was used to verify cervical vagus engagement.</div></div><div><h3>Results</h3><div>Modeling revealed that the applied parameters failed to activate the deep cervical vagus nerve (peak E-field: 2.07 V/m at 1.5 mA, far below the 12.3 V/m activation threshold). Consequently, the ‘‘tcVNS” condition was reassessed as non-specific cervical stimulation (nscES). A limited, post-stimulation increase in HEP amplitude was observed at the F4 electrode following taVNS. No significant Time × Condition interactions were found for NCC, HRV, or sAA. However, exploratory analyses revealed that nscES produced a robust sAA increase, highlighting the potent confound of non-specific somatic afferent activation.</div></div><div><h3>Conclusion</h3><div>The inability to activate the cervical vagus nullifies direct comparison, illustrates a critical methodological consideration for cross-site comparisons: anatomical depth necessitates site-specific stimulation protocols. We therefore propose that future cross-site tVNS comparisons adopt a “verify-first” framework, where target engagement is validated (e.g., via modeling or neuroimaging) prior to physiological comparison. The pronounced sAA response to cervical stimulation, which we demonstrate can be elicited independently of vagal engagement, questions the specificity of sAA as a vagus biomarker and underscores the necessity of rigorous active controls to isolate vagus-specific effects.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"19 2","pages":"Article 103022"},"PeriodicalIF":8.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sleep-aware adaptive deep brain stimulation to mitigate insomnia in OCD 睡眠意识适应性深部脑刺激减轻强迫症患者失眠

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2025-12-17 DOI: 10.1016/j.brs.2025.103009

Noah Guillermo , Leela Mohan , Audrey Kist , Kelly Kadlec , Emma Anderson , Sneha Ray , Joline M. Fan , Philip A. Starr , A Moses Lee

引用次数: 0

Transcranial temporal interference stimulation of the globus pallidus internus ameliorates gait variability in early- to mid-stage Parkinson's disease: A pilot study 经颅颞干扰刺激内苍白球改善早期至中期帕金森病的步态变异性：一项初步研究

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2025-12-17 DOI: 10.1016/j.brs.2025.103007

Tingting Li , Chenhao Yang , Yongxin Xu , Yichao Du , Xiaonan Shen , Junhong Zhou , Yu Liu

引用次数: 0

Increasing the quantity of electrical stimulation pulses reduces cortical response inhibition 增加电刺激脉冲的数量可以减少皮质反应抑制。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2025-12-13 DOI: 10.1016/j.brs.2025.103003

Sabrina J. Meikle , Maureen A. Hagan , Nicholas S.C. Price , Yan T. Wong

Background

Neural prostheses can potentially restore sensory experiences by electrically stimulating the brain, with effectiveness determined by the stimulation parameters. Understanding the effects of individual stimulation parameters is therefore critical for optimizing stimulation outcomes. The number of stimulation pulses delivered in a train (pulse quantity) is a parameter that has been difficult to analyze, as each pulse generates artifacts that can obscure the measurement of neural signals. However, pulse trains are known to more reliably evoke perceptual responses than single-pulse stimulation, implying that increased pulse quantity modulates post-stimulation activity for perceptual consistency.

Objective

We investigated how pulse quantity and current amplitude interact to shape neural responses, as both stimulation parameters affect total charge delivered but often produce different perceptual outcomes.

Methods

We implanted a 64-channel electrode array into the primary visual cortex (V1) of anesthetized marmosets and monitored neural responses evoked by 300 Hz trains of 1–5 biphasic electrical stimulation pulses. In each trial, all pulses delivered the same current (2–10 μA). Trials with increasing pulses were stitched together to recover the responses obscured by artifacts.

Results

We found that current amplitude determined the intensity and duration of the early excitatory response to stimulation, while increasing pulse quantity reduced the amplitude and duration of post-stimulation inhibition.

Conclusions

Decreasing post-stimulation inhibition with increasing pulse quantity may explain why pulse trains more reliably generate perceptual responses. Considering current amplitude and pulse quantity influence different components of the post-stimulation response, developing customized stimulation paradigms may be crucial for optimization of neural prostheses.

背景：神经假体可以通过电刺激大脑来恢复感官体验，其有效性取决于刺激参数。因此，理清单个增产参数的影响对于优化增产效果至关重要。在一个序列中传递的刺激脉冲的数量（脉冲量）是一个难以分析的参数，因为每个脉冲产生的伪影可能会模糊神经信号的测量。然而，已知脉冲序列比单脉冲刺激更可靠地唤起知觉反应，这意味着增加脉冲量可以调节刺激后的知觉一致性活动。目的：我们研究了脉冲量和电流振幅如何相互作用以形成神经反应，因为这两个参数都会影响总电荷传递，但通常会产生不同的感知结果。方法：在麻醉的狨猴初级视觉皮层（V1）内植入64通道电极阵列，监测1 ~ 5次300 Hz双相电刺激脉冲引起的神经反应。在每次试验中，所有脉冲输出相同的电流（2-10 μA）。将脉冲增加的试验拼接在一起，以恢复被伪影掩盖的响应。结果：我们发现电流振幅决定了刺激早期兴奋反应的强度和持续时间，而增加脉冲量会降低刺激后抑制的幅度和持续时间。结论：随着脉冲量的增加，刺激后抑制的减少可能解释了为什么脉冲序列更可靠地产生知觉反应。考虑到电流振幅和脉冲量对刺激后反应的不同组成部分的影响，开发定制的刺激范式可能是优化神经假体的关键。

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引用次数: 0

Trigeminal nerve stimulation modulates dopaminergic circuits and neuroinflammation to alleviate depression 三叉神经刺激调节多巴胺能回路和神经炎症以减轻抑郁。

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation

Pub Date : 2025-12-12 DOI: 10.1016/j.brs.2025.103005

Qian Yang , Lifang Huo , Qian Zhang , Haiyun Ma , Lijiaqi Liu , Shengnuo Fan , Shaoling Wu , Congping Shang , Chao Ma

Background

Trigeminal nerve stimulation (TNS) is a promising noninvasive neuromodulation therapy for depression; however, its mechanisms remain unclear.

Objective

This study investigated antidepressant-like effects of TNS and its underlying mechanisms in post-traumatic brain injury depression (PTD).

Methods

The antidepressant efficacy of TNS was evaluated in multiple depression models using standardized behavioral assays. Peripheral mechanisms were probed by chemogenetic activation or inhibition of trigeminal ganglion (TG) neuronal subpopulations in Cre-line mice. Centrally, pathway-selective chemogenetic manipulations tested the role of the paraventricular nucleus–ventral tegmental area–nucleus accumbens (PVN-VTA-NAc) circuit, coupled with in vivo (GPCR)-activation-based dopamine (GRAB-DA) fluorescence monitoring to quantify dopamine dynamics. Receptor-specific contributions were assessed using shRNA knockdown of D1/D2 or D3 receptors (D1/D2 or D3) in the NAc. Cerebrospinal fluid (CSF) cytokine profiling was used to evaluate inflammatory modulation. Primary endpoints were analyzed after the 10-day TNS treatment and following a 10-day post-stimulation period.

Results

TNS alleviated depressive-like behaviors across models. TG TRPV1⁺ neurons are both necessary and sufficient for efficacy. Chemogenetic modulation of the PVN-VTA-NAc pathway reproduced or abolished TNS effects, while GRAB-DA recordings confirmed increased dopamine release during stimulation. In the NAc, D1/D2 knockdown impaired effects of treatment, whereas D3 knockdown eliminated persistence after stimulation. TNS reduced CSF cytokines in controls and D1/D2 knockdown mice, but not in D3 knockdown mice, indicating that early D3-dependent anti-inflammatory effects sustain long-term benefits.

Conclusions

TNS alleviates depressive-like behaviors through TG TRPV1⁺ neurons and PVN-VTA-NAc circuit activation, with D1/D2 receptors mediating acute effects and D3 receptors maintaining lasting anti-inflammatory benefits.

背景：三叉神经刺激（TNS）是治疗抑郁症的一种很有前途的无创神经调节疗法；然而，其机制尚不清楚。目的：探讨TNS对创伤后脑损伤抑郁症（PTD）的类抗抑郁作用及其机制。方法：采用标准化行为分析方法，在多种抑郁模型中评价TNS的抗抑郁效果。通过化学发生激活或抑制creline小鼠三叉神经节（TG）神经元亚群来探索外周机制。中心，途径选择性化学发生操作测试了室旁核-腹侧被盖区-伏隔核（PVN-VTA-NAc）回路的作用，结合体内（GPCR）激活的多巴胺（grabda）荧光监测来量化多巴胺动力学。通过shRNA敲低NAc中D1/D2或D3受体（D1/D2或D3）来评估受体特异性贡献。脑脊液（CSF）细胞因子谱分析用于评估炎症调节。主要终点在TNS治疗10天后和刺激后10天进行分析。结果：TNS减轻了各模型的抑郁样行为。TG TRPV1+神经元对疗效既是必要的又是充分的。PVN-VTA-NAc通路的化学发生调节再现或消除了TNS效应，而graba - da记录证实刺激期间多巴胺释放增加。在NAc中，D1/D2敲低损害了治疗效果，而D3敲低则消除了刺激后的持久性。TNS在对照组和D1/D2敲低小鼠中降低脑脊液细胞因子，但在D3敲低小鼠中没有，表明早期D3依赖性抗炎作用维持长期益处。结论：TNS通过激活TG TRPV1+神经元和PVN-VTA-NAc回路来缓解抑郁样行为，其中D1/D2受体介导急性作用，D3受体维持持久的抗炎作用。

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引用次数: 0