Stimulating at the right time to recover network states in a model of the cortico-basal ganglia-thalamic circuit.
Stimulating at the right time to recover network states in a model of the cortico-basal ganglia-thalamic circuit.
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DOI：
10.1371/journal.pcbi.1009887
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发表时间：
2022-03
影响因子：
4.3
通讯作者：
Cagnan H
中科院分区：
文献类型：
--
作者：
West TO;Magill PJ;Sharott A;Litvak V;Farmer SF;Cagnan H
神经振荡的同步被认为促进了大脑中的交流。神经退行性疾病，如帕金森病（PD）可导致运动回路的突触重组，导致神经元动力学改变和神经通讯受损。PD的治疗旨在通过多巴胺替代等药物手段或通过深部脑刺激抑制病理振荡来恢复网络功能。我们测试了脑刺激可以超越简单的“可逆损伤”效应来增强网络通信的假设。具体来说，我们研究了β带（14-30 Hz）活动的调节，这是帕金森病患者运动缺陷和潜在刺激控制信号的已知生物标志物。为了做到这一点，我们在皮质-基底神经节-丘脑（CBGT）回路中建立了一个群体活动的神经质量模型，其参数被限制为产生与实验性帕金森病相当的光谱特征。我们调节了PD中已知被破坏的两条主要通路的连通性，并构建了由此产生的自发活动的光谱和功能连通性的统计摘要。然后，这些数据被用来评估传递给运动皮层的闭环刺激和锁定到丘脑下β活动的网络范围的结果。我们的研究结果表明，β同步的空间模式依赖于STN输入的强度。精确定时刺激具有恢复网络状态的能力，刺激阶段诱导的活动具有明显的频谱和空间特性。这些结果为设计旨在恢复疾病神经通讯的下一代脑刺激器提供了理论基础。脑部疾病会影响患者的行动能力或正常思考能力，从而导致各种各样的致残症状。这些症状源于大脑网络组织的破坏，以及周围神经活动的传播时间的破坏。用药物治疗疾病可以在一定程度上恢复这些网络的组织，但很难提供具有良好空间或时间选择性的药物。脑刺激为提高治疗的空间特异性提供了一种方法，但了解如何在正确的时间刺激以达到对患者的最佳效果仍然是一个悬而未决的问题。在这项工作中，我们使用了与帕金森病有关的一个重要回路的模拟，其参数的选择反映了该疾病动物模型的记录。利用这个计算机模型，我们展示了大脑节律如何作为网络中潜在变化的标志。此外，我们模拟干预与时间精确的刺激，以显示未来的脑刺激方法如何能够恢复甚至增强神经网络退化后的疾病。
Synchronization of neural oscillations is thought to facilitate communication in the brain. Neurodegenerative pathologies such as Parkinson’s disease (PD) can result in synaptic reorganization of the motor circuit, leading to altered neuronal dynamics and impaired neural communication. Treatments for PD aim to restore network function via pharmacological means such as dopamine replacement, or by suppressing pathological oscillations with deep brain stimulation. We tested the hypothesis that brain stimulation can operate beyond a simple “reversible lesion” effect to augment network communication. Specifically, we examined the modulation of beta band (14–30 Hz) activity, a known biomarker of motor deficits and potential control signal for stimulation in Parkinson’s. To do this we setup a neural mass model of population activity within the cortico-basal ganglia-thalamic (CBGT) circuit with parameters that were constrained to yield spectral features comparable to those in experimental Parkinsonism. We modulated the connectivity of two major pathways known to be disrupted in PD and constructed statistical summaries of the spectra and functional connectivity of the resulting spontaneous activity. These were then used to assess the network-wide outcomes of closed-loop stimulation delivered to motor cortex and phase locked to subthalamic beta activity. Our results demonstrate that the spatial pattern of beta synchrony is dependent upon the strength of inputs to the STN. Precisely timed stimulation has the capacity to recover network states, with stimulation phase inducing activity with distinct spectral and spatial properties. These results provide a theoretical basis for the design of the next-generation brain stimulators that aim to restore neural communication in disease. Diseases of the brain lead to a wide range of disabling symptoms for patients, by affecting their ability to move or think properly. These symptoms arise from disruption to both the organization of networks in the brain, but also the timing of neural activity that propagates around it. Treatments for disease with drugs can restore the organization of these networks to some extent, yet it is very difficult to deliver drugs with good spatial or temporal selectivity. Brain stimulation provides one way in which to improve the spatial specificity of treatment, yet understanding how to stimulate at the right time to achieve the best outcome for patients, remains an outstanding question. In this work we use simulations of an important circuit involved in Parkinson’s disease that has parameters chosen to reflect recordings made in animal models of the disease. Using this computer model, we show how brain rhythms can act as signatures of underlying changes in networks. Further, we simulate intervention with temporally precise stimulation to show how future approaches to brain stimulation can act to restore or even augment neural networks following their degeneration in disease.
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影响因子：
16.2
作者：
Fries P
通讯作者：
Fries P
影响因子：
20.6
作者：
BOASHASH, B
通讯作者：
BOASHASH, B
影响因子：
3.4
作者：
Aparicio-Juarez, Ariadna;Duhne, Mariana;Bargas, Jose
通讯作者：
Bargas, Jose
影响因子：
5.3
作者：
Brown, P;Oliviero, A;Di Lazzaro, V
通讯作者：
Di Lazzaro, V
中脑多巴胺神经元变性后，甲状腺丘脑核核外部核核核的增殖。
DOI：
10.1523/jneurosci.5750-11.2012
发表时间：
2012-10-03
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fan KY;Baufreton J;Surmeier DJ;Chan CS;Bevan MD
通讯作者：
Bevan MD