Neuronal basis of impaired motivation and inhibition of actions in patients with Parkinson's disease and behavioural addictions

病态赌博和性欲亢奋越来越被认为是非物质(行为)成瘾。对于物质相关成瘾的发展，有一个有影响的神经生物学模型，该模型假设多巴胺能奖赏信号的异常增加导致了用于食欲动机/显著归因和抑制反应控制的神经系统功能障碍。目前还不清楚，这种模式是否也适用于行为成瘾的发展。行为成瘾的发展相对较快是一种频繁的(约.帕金森病(PD)患者多巴胺能治疗的不良反应占14%。建议的研究方案的目的是确定与帕金森病患者病理性赌博或性欲亢进相关的功能障碍的神经网络。我们将检验两个假设。根据第一种假设，在有药物诱导的行为成瘾(如性欲亢进)的帕金森病患者中，多巴胺激动剂导致自下而上的食欲动机系统过度活跃，以及自上而下的抑制控制系统活动不足。在功能磁共振实验中，将研究多巴胺激动剂在抑制性启动(例如传染性皮肤病的图像)或中性启动(例如健康皮肤的图像)之后因成瘾相关刺激(例如性内容的图像)而对大脑激活的影响。假设在有药物诱导的行为成瘾的帕金森病患者中，多巴胺激动剂增加了由于成瘾相关刺激而引起的奖赏系统的激活，同时还降低了对刺激相关的奖赏系统激活的抑制启动效应。行为成瘾的行为疗法有时是基于积极强化对成瘾行为的省略。然而，很可能是多巴胺激动剂阻断了导致行为适应这一重要因素的神经生物学机制。这是将被检验的第二个假设。在健康的个体中，当预期某个行为的疏忽会得到奖励时，奖励系统的活动会短暂减少。如果多巴胺激动剂抵消这种短暂的奖赏系统失活，它将通过功能磁共振进行实验测试。拟议的研究结果可能会通过靶向调节已识别的功能失调的网络来推动治疗或二级预防行为成瘾的创新策略。

Pathological gambling and hypersexuality are increasingly recognized as non-substance (behavioural) addictions. For the development of substance related addictions, there is an influential neurobiological model which postulates that abnormally increased dopaminergic reward signalling drives dysfunction of neuronal systems for appetitive motivation / salience attribution and inhibitory response control. It is unclear, whether this model may also apply to the development of behavioural addictions. Relatively rapid development of behavioural addictions is a frequent (approx. 14%) adverse effect of dopaminergic therapy in patients with Parkinson’s disease (PD). The aim of the proposed research scheme is to identify dysfunctional neuronal networks, which are associated with the development of pathological gambling or hypersexuality in PD patients. Two hypotheses will be tested. According to the first hypothesis, in PD patients with medication-induced behavioural addictions (e.g. hypersexuality), dopamine agonists lead to a hyperactive bottom-up system of appetitive motivation along with a hypoactivity of top-down systems of inhibitory control. In an fMRI experiment, the effect of dopamine agonists on brain activation due to addiction-related stimuli (e.g. images of sexual content) following an inhibitory priming (e.g. images of contagious skin diseases) or neutral priming (e.g. images of healthy skin) will be investigated. It is hypothesized, that in PD patients with medication-induced behavioural addictions, dopamine agonists are increasing activation of the reward system due to addiction-related stimuli, while additionally decreasing the inhibitory priming effect on stimulus-related activation of the reward system. Behavioural therapy of behavioural addictions is sometimes based on positive reinforcement of the omission of addictive behaviour. However, it may well be that dopamine agonists block the very neurobiological mechanism that is responsible for this important factor of behavioural adaptation. This is the second hypothesis that will be tested. In healthy individuals, activity of the reward system briefly decreases when it is anticipated that the omission of an action is rewarded. It will be experimentally tested with fMRI, if dopamine agonists counteract this brief deactivation of the reward system.Results of the proposed studies could drive innovative strategies in therapy or secondary prevention of behavioural addictions by targeting modulation of identified dysfunctional networks.