Subthalamic deep brain stimulation (STN-DBS) for Parkinson’s disease treats motor symptoms and improves quality of life, but can be complicated by adverse neuropsychiatric side-effects, including impulsivity. Several clinically important questions remain unclear: can ‘at-risk’ patients be identified prior to DBS; do neuropsychiatric symptoms relate to the distribution of the stimulation field; and which brain networks are responsible for the evolution of these symptoms? Using a comprehensive neuropsychiatric battery and a virtual casino to assess impulsive behaviour in a naturalistic fashion, 55 patients with Parkinson’s disease (19 females, mean age 62, mean Hoehn and Yahr stage 2.6) were assessed prior to STN-DBS and 3 months postoperatively. Reward evaluation and response inhibition networks were reconstructed with probabilistic tractography using the participant-specific subthalamic volume of activated tissue as a seed. We found that greater connectivity of the stimulation site with these frontostriatal networks was related to greater postoperative impulsiveness and disinhibition as assessed by the neuropsychiatric instruments. Larger bet sizes in the virtual casino postoperatively were associated with greater connectivity of the stimulation site with right and left orbitofrontal cortex, right ventromedial prefrontal cortex and left ventral striatum. For all assessments, the baseline connectivity of reward evaluation and response inhibition networks prior to STN-DBS was not associated with postoperative impulsivity; rather, these relationships were only observed when the stimulation field was incorporated. This suggests that the site and distribution of stimulation is a more important determinant of postoperative neuropsychiatric outcomes than preoperative brain structure and that stimulation acts to mediate impulsivity through differential recruitment of frontostriatal networks. Notably, a distinction could be made amongst participants with clinically-significant, harmful changes in mood and behaviour attributable to DBS, based upon an analysis of connectivity and its relationship with gambling behaviour. Additional analyses suggested that this distinction may be mediated by the differential involvement of fibres connecting ventromedial subthalamic nucleus and orbitofrontal cortex. These findings identify a mechanistic substrate of neuropsychiatric impairment after STN-DBS and suggest that tractography could be used to predict the incidence of adverse neuropsychiatric effects. Clinically, these results highlight the importance of accurate electrode placement and careful stimulation titration in the prevention of neuropsychiatric side-effects after STN-DBS.

中文翻译：

---

丘脑深部脑刺激的结构连通性与帕金森氏病的冲动性有关。

丘脑深部脑刺激（STN-DBS）可治疗帕金森氏病，可治疗运动症状并改善生活质量，但会因不良的神经精神副作用（包括冲动）而变得复杂。几个临床上重要的问题仍不清楚：在DBS之前是否可以识别“高危”患者；神经精神症状与刺激区域的分布有关吗？哪些大脑网络负责这些症状的发展？使用综合的神经精神科药物和虚拟娱乐场以自然主义的方式评估冲动行为，在STN-DBS之前和术后3个月对55例帕金森氏病患者（19名女性，平均年龄62岁，平均Hoehn和Yahr阶段2.6）进行了评估。奖励评估和​​反应抑制网络通过概率性个体学重建，使用参与者特定的丘脑下丘脑激活的组织体积作为种子。我们发现刺激部位与这些前额窦网络的更大连通性与神经精神病学仪器评估的更大的术后冲动和抑制力有关。虚拟赌场中更大的赌注大小与术后刺激部位与左右眶额叶皮层，右腹膜前额叶皮层和左腹侧纹状体的更大连通性有关。对于所有评估，STN-DBS之前的奖励评估和​​反应抑制网络的基线连通性与术后冲动无关。而是 仅当结合了刺激场时才观察到这些关系。这表明刺激的部位和分布比术前的大脑结构更重要地决定了术后神经精神病学预后，并且刺激的作用是通过额窦网的不同募集来介导冲动。值得注意的是，根据对连接性及其与赌博行为的关系的分析，可以区分具有DBS可归因于临床意义重大，有害的情绪和行为改变的参与者。进一步的分析表明，这种区别可能是由连接腹膜下丘脑底核和眶额皮层的纤维的不同参与所介导的。这些发现确定了STN-DBS后神经精神障碍的机械机制，并提示可以使用束线照相术预测神经精神不良反应的发生率。在临床上，这些结果突出了准确放置电极和小心刺激滴定在预防STN-DBS后神经精神病副作用方面的重要性。