Movement Disorder and Neuromodulation Unit, Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Eur J Neurosci. 2024 Feb;59(3):457-472. doi: 10.1111/ejn.16222. Epub 2024 Jan 4.
Millions of people suffer from dopamine-related disorders spanning disturbances in movement, cognition and emotion. These changes are often attributed to changes in striatal dopamine function. Thus, understanding how dopamine signalling in the striatum and basal ganglia shapes human behaviour is fundamental to advancing the treatment of affected patients. Dopaminergic neurons innervate large-scale brain networks, and accordingly, many different roles for dopamine signals have been proposed, such as invigoration of movement and tracking of reward contingencies. The canonical circuit architecture of cortico-striatal loops sparks the question, of whether dopamine signals in the basal ganglia serve an overarching computational principle. Such a holistic understanding of dopamine functioning could provide new insights into symptom generation in psychiatry to neurology. Here, we review the perspective that dopamine could bidirectionally control neural population dynamics, increasing or decreasing their strength and likelihood to reoccur in the future, a process previously termed neural reinforcement. We outline how the basal ganglia pathways could drive strengthening and weakening of circuit dynamics and discuss the implication of this hypothesis on the understanding of motor signs of Parkinson's disease (PD), the most frequent dopaminergic disorder. We propose that loss of dopamine in PD may lead to a pathological brain state where repetition of neural activity leads to weakening and instability, possibly explanatory for the fact that movement in PD deteriorates with repetition. Finally, we speculate on how therapeutic interventions such as deep brain stimulation may be able to reinstate reinforcement signals and thereby improve treatment strategies for PD in the future.
数以百万计的人患有与多巴胺相关的疾病，这些疾病包括运动、认知和情绪方面的障碍。这些变化通常归因于纹状体多巴胺功能的改变。因此，了解纹状体和基底神经节中的多巴胺信号如何塑造人类行为，对于推进受影响患者的治疗至关重要。多巴胺能神经元支配着大规模的大脑网络，因此，已经提出了许多不同的多巴胺信号作用，例如运动的激发和奖励预测的跟踪。皮质-纹状体回路的经典电路结构引发了一个问题，即基底神经节中的多巴胺信号是否服务于一个总体的计算原理。对多巴胺功能的这种整体理解可以为精神病学和神经病学中的症状产生提供新的见解。在这里，我们回顾了多巴胺可以双向控制神经群体动力学的观点，增加或减少它们的强度和未来再次出现的可能性，这个过程以前被称为神经强化。我们概述了基底神经节通路如何驱动回路动力学的增强和减弱，并讨论了这一假设对理解帕金森病（PD）的运动症状的意义，PD 是最常见的多巴胺能障碍。我们提出，PD 中多巴胺的丧失可能导致病理性脑状态，其中神经活动的重复导致减弱和不稳定性，这可能解释了 PD 中的运动随着重复而恶化的事实。最后，我们推测，深部脑刺激等治疗干预措施如何能够恢复强化信号，并因此在未来改善 PD 的治疗策略。
