Movement Disorders and Neurostimulation, Department of Neurology, Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
Department of Cognitive, Linguistic and Psychological Sciences, Carney Institute for Brain Science, Brown University, Providence, RI 02903, USA.
Brain. 2024 Nov 4;147(11):3651-3664. doi: 10.1093/brain/awae184.
Control of actions allows adaptive, goal-directed behaviour. The basal ganglia, including the subthalamic nucleus, are thought to play a central role in dynamically controlling actions through recurrent negative feedback loops with the cerebral cortex. Here, we summarize recent translational studies that used deep brain stimulation to record neural activity from and apply electrical stimulation to the subthalamic nucleus in people with Parkinson's disease. These studies have elucidated spatial, spectral and temporal features of the neural mechanisms underlying the controlled delay of actions in cortico-subthalamic networks and demonstrated their causal effects on behaviour in distinct processing windows. While these mechanisms have been conceptualized as control signals for suppressing impulsive response tendencies in conflict tasks and as decision threshold adjustments in value-based and perceptual decisions, we propose a common framework linking decision-making, cognition and movement. Within this framework, subthalamic deep brain stimulation can lead to suboptimal choices by reducing the time that patients take for deliberation before committing to an action. However, clinical studies have consistently shown that the occurrence of impulse control disorders is reduced, not increased, after subthalamic deep brain stimulation surgery. This apparent contradiction can be reconciled when recognizing the multifaceted nature of impulsivity, its underlying mechanisms and modulation by treatment. While subthalamic deep brain stimulation renders patients susceptible to making decisions without proper forethought, this can be disentangled from effects related to dopamine comprising sensitivity to benefits versus costs, reward delay aversion and learning from outcomes. Alterations in these dopamine-mediated mechanisms are thought to underlie the development of impulse control disorders and can be relatively spared with reduced dopaminergic medication after subthalamic deep brain stimulation. Together, results from studies using deep brain stimulation as an experimental tool have improved our understanding of action control in the human brain and have important implications for treatment of patients with neurological disorders.
动作控制使适应性、目标导向的行为成为可能。基底神经节，包括丘脑底核，被认为在通过与大脑皮层的递归负反馈环动态控制动作方面发挥着核心作用。在这里，我们总结了最近使用深部脑刺激来记录帕金森病患者丘脑底核神经活动并施加电刺激的转化研究。这些研究阐明了皮质-丘脑底网络中控制动作延迟的神经机制的空间、频谱和时频特征，并证明了它们在不同处理窗口中对行为的因果影响。虽然这些机制被概念化为在冲突任务中抑制冲动反应倾向的控制信号，以及在基于价值和知觉决策中调整决策阈值的信号，但我们提出了一个将决策、认知和运动联系起来的通用框架。在这个框架内，丘脑底核深部脑刺激可以通过减少患者在承诺采取行动之前进行思考的时间，导致次优选择。然而，临床研究一致表明，在进行丘脑底核深部脑刺激手术后，冲动控制障碍的发生并没有增加，而是减少了。当认识到冲动的多面性、其潜在机制以及治疗的调节作用时，就可以调和这种明显的矛盾。虽然丘脑底核深部脑刺激使患者容易在没有适当深思熟虑的情况下做出决策，但这可以与与多巴胺有关的影响区分开来，包括对收益与成本的敏感性、对奖励延迟的厌恶以及从结果中学习。据认为，这些多巴胺介导的机制的改变是冲动控制障碍发展的基础，并且在进行丘脑底核深部脑刺激后减少多巴胺能药物治疗可以相对保留这些机制。使用深部脑刺激作为实验工具的研究结果提高了我们对人类大脑动作控制的理解，并对治疗神经障碍患者具有重要意义。
