New Insights into Freezing of Gait in Parkinson's Disease from Spectral Dynamic Causal Modeling

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2024-09-18 DOI:10.1002/mds.29988

Seira Taniguchi PhD, Yuta Kajiyama MD, PhD, Takanori Kochiyama PhD, Gajanan Revankar MBBS, PhD, Kotaro Ogawa MD, PhD, Emi Shirahata MD, Kana Asai MD, Chizu Saeki MD, Tatsuhiko Ozono MD, PhD, Yasuyoshi Kimura MD, PhD, Kensuke Ikenaka MD, PhD, Nicholas D'Cruz PhD, Moran Gilat PhD, Alice Nieuwboer PhD, Hideki Mochizuki MD, PhD

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Abstract

Background

Freezing of gait is one of the most disturbing motor symptoms of Parkinson's disease (PD). However, the effective connectivity between key brain hubs that are associated with the pathophysiological mechanism of freezing of gait remains elusive.

Objective

The aim of this study was to identify effective connectivity underlying freezing of gait.

Methods

This study applied spectral dynamic causal modeling (DCM) of resting-state functional magnetic resonance imaging in dedicated regions of interest determined using a data-driven approach.

Results

Abnormally increased functional connectivity between the bilateral dorsolateral prefrontal cortex (DLPFC) and the bilateral mesencephalic locomotor region (MLR) was identified in freezers compared with nonfreezers. Subsequently, spectral DCM analysis revealed that increased top-down excitatory effective connectivity from the left DLPFC to bilateral MLR and an independent self-inhibitory connectivity within the left DLPFC in freezers versus nonfreezers (>99% posterior probability) were inversely associated with the severity of freezing of gait. The lateralization of these effective connectivity patterns was not attributable to the initial dopaminergic deficit nor to structural changes in these regions.

Conclusions

We have identified novel effective connectivity and an independent self-inhibitory connectivity underlying freezing of gait. Our findings imply that modulating the effective connectivity between the left DLPFC and MLR through neurostimulation or other interventions could be a target for reducing freezing of gait in PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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通过频谱动态因果建模了解帕金森病步态冻结的新发现

背景步态冻结是帕金森病（PD）最令人不安的运动症状之一。然而，与步态冻结的病理生理机制相关的关键大脑中枢之间的有效连接性仍然难以确定。结果发现与非冻结者相比，冻结者的双侧背外侧前额叶皮层（DLPFC）和双侧间脑运动区（MLR）之间的功能连接异常增加。随后，频谱 DCM 分析表明，与非冻结者相比，冻结者从左侧 DLPFC 到双侧 MLR 的自上而下的兴奋性有效连接以及左侧 DLPFC 内部的独立自我抑制性连接（99% 后验概率）的增加与步态冻结的严重程度成反比。这些有效连通性模式的侧向性与最初的多巴胺能缺陷无关，也与这些区域的结构变化无关。我们的研究结果表明，通过神经刺激或其他干预措施调节左侧DLPFC和MLR之间的有效连接可能是减少PD步态冻结的一个目标。© 2024 The Author(s).运动障碍》由 Wiley Periodicals LLC 代表国际帕金森和运动障碍协会出版。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.