Nuffield Department of Clinical Neurosciences and Department of Experimental Psychology, Oxford University, Oxford, UK.
J Neuropsychol. 2013 Sep;7(2):255-83. doi: 10.1111/jnp.12013. Epub 2013 Apr 29.
Impulse control disorders (ICDs) and apathy are recognized as two important neuropsychiatric syndromes associated with Parkinson's disease (PD), but as yet we understand very little about the cognitive mechanisms underlying them. Here, we review emerging findings, from both human and animal studies, that suggest that impulsivity and apathy are opposite extremes of a dopamine-dependent spectrum of motivated decision making. We first argue that there is strong support for a hypodopaminergic state in PD patients with apathy, as well as for an association between dopamine therapy and development of ICDs. However, there is little evidence for a clear dose-response relationship, and great heterogeneity of findings. We argue that dopaminergic state on its own is an insufficient explanation, and suggest instead that there is now substantial evidence that both apathy and impulsivity are in fact multi-dimensional syndromes, with separate, dissociable mechanisms underlying their 'surface' manifestations. Some of these mechanisms might be dopamine-dependent. According to this view, individuals diagnosed as impulsive or apathetic may have very different mechanisms underlying their clinical states. We propose that impulsivity and apathy can arise from dissociable deficits in option generation, option selection, action initiation or inhibition and learning. Review of the behavioural and neurobiological evidence leads us to a new conceptual framework that might help understand the variety of functional deficits seen in PD.
冲动控制障碍(ICD)和淡漠是与帕金森病(PD)相关的两种重要神经精神综合征,但我们对其潜在的认知机制仍知之甚少。在这里,我们综述了来自人类和动物研究的新发现,这些发现表明,冲动和淡漠是多巴胺依赖的动机决策谱的两个极端。我们首先认为,淡漠的 PD 患者存在多巴胺能低下状态,以及多巴胺治疗与 ICD 发展之间存在关联,这一点得到了强有力的支持。然而,几乎没有证据表明存在明确的剂量反应关系,而且研究结果存在很大的异质性。我们认为,多巴胺能状态本身并不能充分解释这一现象,相反,现在有大量证据表明,淡漠和冲动都是实际上是多维综合征,其“表面”表现有独立的、可分离的机制。其中一些机制可能与多巴胺有关。根据这一观点,被诊断为冲动或淡漠的个体,其临床状态的潜在机制可能非常不同。我们提出,冲动和淡漠可能源于选项生成、选项选择、行为启动或抑制以及学习方面可分离的缺陷。对行为和神经生物学证据的回顾使我们提出了一个新的概念框架,这可能有助于理解 PD 中出现的各种功能缺陷。