Initiation and inhibition are executive functions whose disruption in Parkinson's disease impacts substantially on everyday activities. Management of Parkinson's disease with subthalamic deep brain stimulation (DBS) modifies initiation and inhibition, with prior work suggesting that these effects may be mediated via the connectivity of the subthalamic nucleus (STN) with the frontal cortex. Here, we employed high-resolution structural neuroimaging to investigate the variability in initiation, inhibition and strategy use in a cohort of twenty-five (ten females, mean age 62.5, mean Hoehn and Yahr stage 2.5) participants undertaking subthalamic DBS for Parkinson's disease. Neuropsychological assessment of initiation and inhibition was performed preoperatively and at six months postoperatively. We first reconstructed the preoperative connectivity of the STN with a frontal network of anterior and superior medial cortical regions. We then modelled the postoperative site of subthalamic stimulation and reconstructed the connectivity of the stimulation field within this same network. We found that, at both pre- and postoperative intervals, inter-individual variability in inhibition and initiation were strongly associated with structural network connectivity. Measures of subcortical atrophy and local stimulation effects did not play a significant role. Preoperatively, we replicated prior work, including a role for the right inferior frontal gyrus in inhibition and strategy use, as well as the left inferior frontal gyrus in tasks requiring selection under conditions of maintained inhibition. Postoperatively, greater connectivity of the stimulation field with right anterior cortical regions was associated with greater rule violations and suppression errors, supporting prior work implicating right-hemispheric STN stimulation in disinhibition. Our findings suggest that, in Parkinson's disease, connectivity of the frontal cortex with the STN is an important mediator of individual variability in initiation and inhibition,. Personalised information on brain network architecture could guide individualised brain circuit manipulation to minimise neuropsychological disruption after STN-DBS.

中文翻译：

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下丘脑深部脑刺激识别支持帕金森病启动、抑制和策略使用的额叶网络

启动和抑制是执行功能，它们在帕金森氏病中的破坏对日常活动产生重大影响。用丘脑底深部脑刺激 (DBS) 治疗帕金森病可改变启动和抑制，先前的工作表明这些影响可能是通过丘脑底核 (STN) 与额叶皮层的连接来介导的。在这里，我们采用高分辨率结构神经影像学研究了 25 名（10 名女性，平均年龄 62.5 岁，平均 Hoehn 和 Yahr 2.5 级）参与者进行丘脑下 DBS 治疗帕金森病的队列中启动、抑制和策略使用的变异性。开始和抑制的神经心理学评估在术前和术后六个月进行。我们首先用前内侧和上内侧皮质区域的额叶网络重建了 STN 的术前连接。然后，我们对丘脑底刺激的术后部位进行建模，并在同一网络内重建刺激场的连通性。我们发现，在术前和术后的时间间隔内，抑制和启动的个体间差异与结构网络连接密切相关。皮质下萎缩和局部刺激效应的测量没有发挥重要作用。术前，我们复制了先前的工作，包括右侧额下回在抑制和策略使用中的作用，以及左侧额下回在维持抑制条件下需要选择的任务中的作用。术后，刺激场与右前皮层区域的更大连通性与更大的规则违规和抑制错误相关，支持先前的工作暗示右半球 STN 刺激解除抑制。我们的研究结果表明，在帕金森病中，额叶皮层与 STN 的连接是启动和抑制个体差异的重要介质。脑网络结构的个性化信息可以指导个性化的脑回路操作，以最大限度地减少 STN-DBS 后的神经心理破坏。额叶皮层与 STN 的连接是引发和抑制个体差异的重要介质。脑网络结构的个性化信息可以指导个性化的脑回路操作，以最大限度地减少 STN-DBS 后的神经心理破坏。额叶皮层与 STN 的连接是引发和抑制个体差异的重要介质。脑网络结构的个性化信息可以指导个性化的脑回路操作，以最大限度地减少 STN-DBS 后的神经心理破坏。