Alterations in brain connectivity underlying beta oscillations in Parkinsonism.
Alterations in brain connectivity underlying beta oscillations in Parkinsonism.
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帕金森氏症中β振荡的大脑连通性改变。
DOI：
10.1371/journal.pcbi.1002124
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发表时间：
2011-08
影响因子：
4.3
通讯作者：
Brown P
中科院分区：
文献类型：
--
作者：
Moran RJ;Mallet N;Litvak V;Dolan RJ;Magill PJ;Friston KJ;Brown P
帕金森病（PD）的多巴胺耗竭严重破坏了皮质-基底节-丘脑皮质回路，导致病理性放大的β振荡。在几个回路节点中发现的异常节律与运动障碍相关，但其神经基础仍不清楚。在这里，我们使用动态因果模型（DCM）和6-羟基多巴胺损伤的大鼠模型的PD检查这些频谱异常的有效连接。我们从额叶皮层、纹状体、苍白球外核（GPe）和丘脑底核（STN）同时进行的局部场电位记录中获得了β振荡（10-35 Hz）的自谱和交叉谱测量，并使用这些数据优化神经生物学上合理的模型。慢性多巴胺耗竭重组了皮质-基底神经节-丘脑皮质回路，从皮质到丘脑的有效连接增加，从丘脑到GPe的连接减少。此外，帕金森电路的贡献分析区分致病和代偿过程，并揭示了如何有效的连接沿着间接途径获得了战略重要性，巩固β振荡。在PD中过度β同步的建模中，这些发现提供了一个新的视角，即基底神经节-丘脑皮层回路的连接性改变如何反映发病机制和补偿之间的平衡，并预测了克服功能失调振荡的潜在新治疗靶点。帕金森病是一种与年龄相关的进行性神经退行性疾病，严重干扰运动。帕金森病的主要病理是一组神经元的退化，这些神经元含有一种称为多巴胺的化学物质。帕金森症的治疗包括旨在取代多巴胺的药物干预，以及最近旨在通过电刺激大脑运动回路恢复运动的植入设备。了解多巴胺耗尽后出现的电特性可能会揭示开发这些技术的新途径。通过将一种新的基于模型的方法与帕金森病动物模型的多位点电生理记录相结合，我们为帕金森病患者大脑中异常电活动及其生理基础之间的联系提供了经验证据。我们已经检查了大脑运动回路的沿着连接，发现了一个特定神经通路的区域间连接异常，这是一个严重依赖多巴胺的通路。该方案作出了强有力的和可检验的预测神经通路显着改变的病理状态，因此代表经验动机的治疗目标。
Cortico-basal ganglia-thalamocortical circuits are severely disrupted by the dopamine depletion of Parkinson's disease (PD), leading to pathologically exaggerated beta oscillations. Abnormal rhythms, found in several circuit nodes are correlated with movement impairments but their neural basis remains unclear. Here, we used dynamic causal modelling (DCM) and the 6-hydroxydopamine-lesioned rat model of PD to examine the effective connectivity underlying these spectral abnormalities. We acquired auto-spectral and cross-spectral measures of beta oscillations (10–35 Hz) from local field potential recordings made simultaneously in the frontal cortex, striatum, external globus pallidus (GPe) and subthalamic nucleus (STN), and used these data to optimise neurobiologically plausible models. Chronic dopamine depletion reorganised the cortico-basal ganglia-thalamocortical circuit, with increased effective connectivity in the pathway from cortex to STN and decreased connectivity from STN to GPe. Moreover, a contribution analysis of the Parkinsonian circuit distinguished between pathogenic and compensatory processes and revealed how effective connectivity along the indirect pathway acquired a strategic importance that underpins beta oscillations. In modelling excessive beta synchrony in PD, these findings provide a novel perspective on how altered connectivity in basal ganglia-thalamocortical circuits reflects a balance between pathogenesis and compensation, and predicts potential new therapeutic targets to overcome dysfunctional oscillations. Parkinson's disease is a progressive age-related neurodegenerative disorder that severely disrupts movement. The major pathology in Parkinson's disease is the degeneration of a group of neurons that contain a chemical known as dopamine. Treatment of Parkinsonism includes pharmacological interventions that aim to replace dopamine and more recently, implanted devices that aim to restore movement through electrical stimulation of the brain's movement circuits. Understanding the electrical properties that emerge as a result of depleted dopamine may reveal new avenues for developing these technologies. By combining a novel model-based approach with multi-site electrophysiological recordings from an animal model of Parkinson's disease we provide empirical evidence for a link between abnormal electrical activity in the Parkinsonian brain and its physiological basis. We have examined the connections along the brain's motor circuits, and found an abnormality in inter-area connections in a particular neural pathway, a pathway critically dependent on dopamine. The scheme makes strong and testable predictions about which neural pathways are significantly altered in the pathological state and so represent empirically motivated therapeutic targets.
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影响因子：
5.3
作者：
Holgado, Alejo J. Nevado;Terry, John R.;Bogacz, Rafal
通讯作者：
Bogacz, Rafal
影响因子：
2.7
作者：
BRILLING.DR
通讯作者：
BRILLING.DR
DOI：
10.1098/rstb.2005.1634
发表时间：
2005-05-29
影响因子：
6.3
作者：
Beckmann, CF;DeLuca, M;Smith, SM
通讯作者：
Smith, SM
影响因子：
2.5
作者：
AERTSEN, AMHJ;GERSTEIN, GL;PALM, G
通讯作者：
PALM, G
影响因子：
5.7
作者：
Friston, Karl J.;Mattout, Jeremie;Penny, Will
通讯作者：
Penny, Will