A Multimodal Assessment of Neurophysiology in Focal Dystonia

局灶性肌张力障碍神经生理学的多模式评估

基本信息

项目摘要

Dystonias are a group of devastating neurological movement disorders characterized by involuntary muscle contractions that can affect any body region. There is no cure or effective treatment as the pathophysiology of the disorder remains largely unknown. In focal dystonia, symptoms are restricted to one specific body part. Dystonia affecting the hand is called focal hand dystonia (FHD), whereas when the vocal chords are affected it is termed adductor spasmodic dysphonia (AdSD). Despite different clinical manifestations (impaired voice or use of hand), both are thought to share a common underlying mechanism. But commonalities in pathophysiology of focal dystonias have not been well explored. Our central hypothesis is that focal dystonia is a brain network disorder with desynchronized connectivity (‘dysconnectivity’), or ineffective collaboration between brain areas within the network associated with the dystonic task during either resting state, active state or both. This hypothesis can be tested with functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) seeds that represent different but related parts of the voluntary motor network. Therefore, using each seed for a functional connectivity (fc) assessment elucidates more precisely the nature of the dysconnectivity. We will determine the fc during resting state (resting state fc) and active state (task fc) between the loci and through the whole brain. Aim 1 will determine the individual fc of fMRI and TMS loci for the vocalization and hand motor networks in CTL and dystonia. Sub Aim 1.1 will determine if the individual fc between fMRI and TMS loci differs between CTL and dystonia and if this difference is state dependent, meaning the fc differs between resting (resting state fc) and active (task fc); Sub Aim 1.2 will determine if the individual whole brain fc map differs between CTL and dystonia and if this difference is related to a certain loci or state; Sub Aim 1.3 will determine if fc analyzed in standard space reveal differences between CTL and dystonia and if this difference is state dependent. Aim 2 will determine the relationship between disease severity and brain behavioral findings. Relevance: The pathophysiology of focal dystonia is unknown. Recent advances in neuroimaging and brain stimulation made by this team will allow multimodal assessments of anatomical and voluntary brain networks that will provide a novel window into the pathophysiology of both FHD and AdSD individually, as well as determine unifying features in both disorders. These findings will leave us well positioned to develop common treatment strategies in all focal dystonias based upon specific physiologic underpinnings. Further, the unique nature of this focal brain-based disease also has implications for our understanding of general brain function. Understanding how brain networks interact and form faulty associations could have wide reaching implications for many other disorders.
肌张力障碍是一组破坏性的神经运动障碍,其特征是可以影响身体任何部位的不自主肌肉收缩。由于该疾病的病理生理学在很大程度上仍不清楚,因此没有治愈或有效的治疗方法。在局灶性肌张力障碍,症状仅限于一个特定的身体部位。影响手部的肌张力障碍称为局灶性手部肌张力障碍(FHD),而当声带受到影响时,则称为内收肌痉挛性发声障碍(AdSD)。尽管有不同的临床表现(声音受损或手的使用),但两者被认为具有共同的潜在机制。但是局灶性肌张力障碍的病理生理学的共同点还没有得到很好的研究。我们的中心假设是,局灶性肌张力障碍是一种大脑网络障碍,具有去神经元化的连接(“连接障碍”),或者在静息状态、活动状态或两者期间与肌张力障碍任务相关的网络内的大脑区域之间的无效协作。这一假设可以用功能性磁共振成像(fMRI)和经颅磁刺激(TMS)种子来检验,这些种子代表了自主运动网络中不同但相关的部分。因此,使用每个种子进行功能连接(fc)评估更精确地阐明了连接障碍的性质。我们将确定在静息状态(静息状态fc)和活动状态(任务fc)时各位点之间以及整个大脑的fc。目的1确定CTL和肌张力障碍患者发声和手运动网络的fMRI和TMS位点的个体fc。子目标1.1将确定fMRI和TMS位点之间的个体fc在CTL和肌张力障碍之间是否不同,以及这种差异是否是状态依赖性的,这意味着静息状态下的fc不同。子目标1.2将确定CTL和肌张力障碍之间的个体全脑fc图是否不同,以及这种差异是否与特定位点或状态有关;子目标1.3将确定在标准空间中分析的fc是否显示CTL和肌张力障碍之间的差异,以及该差异是否具有状态依赖性。目标2将确定疾病严重程度和脑行为发现之间的关系。相关性:局灶性肌张力障碍的病理生理学尚不清楚。该团队在神经成像和脑刺激方面的最新进展将允许对解剖和自愿脑网络进行多模式评估,这将为FHD和AdSD的病理生理学提供一个新的窗口,并确定这两种疾病的统一特征。这些发现将使我们能够根据特定的生理基础,在所有局灶性肌张力障碍中制定共同的治疗策略。此外,这种以脑为基础的局灶性疾病的独特性质也影响了我们对一般脑功能的理解。了解大脑网络如何相互作用并形成错误的关联可能对许多其他疾病产生广泛的影响。

项目成果

期刊论文数量(0)
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Teresa Jacobson Kimberley其他文献

A validated E-field based approach for equalizing stimulator output between different TMS coils
一种基于经验证的电场方法,用于均衡不同经颅磁刺激线圈之间的刺激器输出。
  • DOI:
    10.1016/j.brs.2024.12.826
  • 发表时间:
    2025-01-01
  • 期刊:
  • 影响因子:
    8.400
  • 作者:
    Evgenii Kim;Mohammad Daneshzand;Keren Zhu;Sergey Makarov;Teresa Jacobson Kimberley;Dylan Edwards;Netri Pajankar;Tommi Raij;Aapo Nummenmaa
  • 通讯作者:
    Aapo Nummenmaa
Effect of head positioning on TMS intensity: E-field modeling with BEM-FMM and modeling validation
  • DOI:
    10.1016/j.brs.2023.01.071
  • 发表时间:
    2023-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Yuchao Wang;William A. Wartman;Alton Miles;Isha Vora;Baothy Huynh;Sergey N. Makaroff;Teresa Jacobson Kimberley
  • 通讯作者:
    Teresa Jacobson Kimberley

Teresa Jacobson Kimberley的其他文献

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{{ truncateString('Teresa Jacobson Kimberley', 18)}}的其他基金

The effects of neural modulation on phonatory function in laryngeal dystonia
神经调节对喉肌张力障碍发声功能的影响
  • 批准号:
    10578816
  • 财政年份:
    2021
  • 资助金额:
    $ 24.64万
  • 项目类别:
DYT1 Genotype- and Phenotype-Specific Brain Circuits in Dystonia
肌张力障碍中 DYT1 基因型和表型特异性脑回路
  • 批准号:
    10303426
  • 财政年份:
    2021
  • 资助金额:
    $ 24.64万
  • 项目类别:
The effects of neural modulation on phonatory function in laryngeal dystonia
神经调节对喉肌张力障碍发声功能的影响
  • 批准号:
    10347323
  • 财政年份:
    2021
  • 资助金额:
    $ 24.64万
  • 项目类别:
A Multimodal Assessment of Neurophysiology in Focal Dystonia
局灶性肌张力障碍神经生理学的多模式评估
  • 批准号:
    9239016
  • 财政年份:
    2017
  • 资助金额:
    $ 24.64万
  • 项目类别:
Pathophysiology of Spasmodic Dysphonia: a TMS study
痉挛性发声障碍的病理生理学:一项 TMS 研究
  • 批准号:
    8443814
  • 财政年份:
    2012
  • 资助金额:
    $ 24.64万
  • 项目类别:
Pathophysiology of Spasmodic Dysphonia: a TMS study
痉挛性发声障碍的病理生理学:一项 TMS 研究
  • 批准号:
    8281729
  • 财政年份:
    2012
  • 资助金额:
    $ 24.64万
  • 项目类别:
INTEGRATION OF NEUROIMAGING AND BIOMECHANICS OF LOW BACK PAIN
腰痛的神经影像学和生物力学的整合
  • 批准号:
    8362836
  • 财政年份:
    2011
  • 资助金额:
    $ 24.64万
  • 项目类别:
INTEGRATION OF NEUROIMAGING AND BIOMECHANICS OF LOW BACK PAIN
腰痛的神经影像学和生物力学的整合
  • 批准号:
    8170441
  • 财政年份:
    2010
  • 资助金额:
    $ 24.64万
  • 项目类别:
EFFECT OF AEROBIC EXERCISE ON BRAIN ACTIVITY FOLLOWING TRAUMATIC BRAIN INJURY
有氧运动对脑外伤后大脑活动的影响
  • 批准号:
    7954954
  • 财政年份:
    2009
  • 资助金额:
    $ 24.64万
  • 项目类别:
INTEGRATION OF NEUROIMAGING AND BIOMECHANICS OF LOW BACK PAIN
腰痛的神经影像学和生物力学的整合
  • 批准号:
    7954975
  • 财政年份:
    2009
  • 资助金额:
    $ 24.64万
  • 项目类别:

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