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Uncovering the underlying mechanisms and whole-brain dynamics of deep brain stimulation for Parkinson’s disease

机译:揭示帕金森氏病深层脑刺激的潜在机制和全脑动力学

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摘要

Deep brain stimulation (DBS) for Parkinson’s disease is a highly effective treatment in controlling otherwise debilitating symptoms. Yet the underlying brain mechanisms are currently not well understood. Whole-brain computational modeling was used to disclose the effects of DBS during resting-state functional Magnetic Resonance Imaging in ten patients with Parkinson’s disease. Specifically, we explored the local and global impact that DBS has in creating asynchronous, stable or critical oscillatory conditions using a supercritical bifurcation model. We found that DBS shifts global brain dynamics of patients towards a Healthy regime. This effect was more pronounced in very specific brain areas such as the thalamus, globus pallidus and orbitofrontal regions of the right hemisphere (with the left hemisphere not analyzed given artifacts arising from the electrode lead). Global aspects of integration and synchronization were also rebalanced. Empirically, we found higher communicability and coherence brain measures during DBS-ON compared to DBS-OFF. Finally, using our model as a framework, artificial in silico DBS was applied to find potential alternative target areas for stimulation and whole-brain rebalancing. These results offer important insights into the underlying large-scale effects of DBS as well as in finding novel stimulation targets, which may offer a route to more efficacious treatments.
机译:帕金森氏病的深层脑刺激(DBS)是控制其他令人衰弱的症状的高效治疗方法。然而,目前尚不清楚潜在的脑机制。使用全脑计算模型来揭示DBS在10位帕金森氏病患者静息状态下功能磁共振成像中的作用。具体来说,我们探讨了DBS在使用超临界分叉模型创建异步,稳定或临界振荡条件时所产生的局部和全局影响。我们发现,星展银行将患者的全球脑动力转向一种健康的治疗方案。在非常特定的大脑区域(如丘脑,苍白球和右半球的眶额区域)中,这种效应更为明显(鉴于电极引线产生的假象,未对左半球进行分析)。整合和同步的全球方面也得到了重新平衡。从经验上讲,我们发现与DBS-OFF相比,DBS-ON期间的交流性和连贯性大脑指标更高。最后,以我们的模型为框架,使用人工计算机模拟DBS查找潜在的替代目标区域,以进行刺激和全脑平衡。这些结果为深入了解DBS的潜在大规模效应以及寻找新的刺激靶标提供了重要的见识,这可能为实现更有效的治疗提供了途径。

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