Garofalo Sara, Justicia Azucena, Arrondo Gonzalo, Ermakova Anna O, Ramachandra Pranathi, Tudor-Sfetea Carina, Robbins Trevor W, Barker Roger A, Fletcher Paul C, Murray Graham K
Department of Psychiatry, University of Cambridge, Cambridge, UK.
Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
Front Neurol. 2017 Apr 24;8:156. doi: 10.3389/fneur.2017.00156. eCollection 2017.
Psychotic symptoms frequently occur in Parkinson's disease (PD), but their pathophysiology is poorly understood. According to the National Institute of Health RDoc programme, the pathophysiological basis of neuropsychiatric symptoms may be better understood in terms of dysfunction of underlying domains of neurocognition in a trans-diagnostic fashion. Abnormal cortico-striatal reward processing has been proposed as a key domain contributing to the pathogenesis of psychotic symptoms in schizophrenia. This theory has received empirical support in the study of schizophrenia spectrum disorders and preclinical models of psychosis, but has not been tested in the psychosis associated with PD. We, therefore, investigated brain responses associated with reward expectation and prediction error signaling during reinforcement learning in PD-associated psychosis. An instrumental learning task with monetary gains and losses was conducted during an fMRI study in PD patients with ( = 12), or without ( = 17), a history of psychotic symptoms, along with a sample of healthy controls ( = 24). We conducted region of interest analyses in the ventral striatum (VS), ventromedial prefrontal and posterior cingulate cortices, and whole-brain analyses. There was reduced activation in PD patients with a history of psychosis, compared to those without, in the posterior cingulate cortex and the VS during reward anticipation ( < 0.05 small volume corrected). The results suggest that cortical and striatal abnormalities in reward processing, a putative pathophysiological mechanism of psychosis in schizophrenia, may also contribute to the pathogenesis of psychotic symptoms in PD. The finding of posterior cingulate dysfunction is in keeping with prior results highlighting cortical dysfunction in the pathogenesis of PD psychosis.
帕金森病(PD)中经常出现精神病性症状,但其病理生理学仍知之甚少。根据美国国立卫生研究院的RDoc计划,神经精神症状的病理生理基础可能通过跨诊断方式从神经认知的潜在领域功能障碍方面得到更好的理解。异常的皮质-纹状体奖赏处理已被提出是导致精神分裂症精神病性症状发病机制的一个关键领域。该理论在精神分裂症谱系障碍研究和精神病临床前模型中得到了实证支持,但尚未在与PD相关的精神病中得到验证。因此,我们研究了与PD相关精神病强化学习过程中奖赏期望和预测误差信号相关的脑反应。在一项功能磁共振成像(fMRI)研究中,对有(n = 12)或无(n = 17)精神病性症状病史的PD患者以及健康对照样本(n = 24)进行了一项涉及金钱得失的工具性学习任务。我们在腹侧纹状体(VS)、腹内侧前额叶和后扣带回皮质进行了感兴趣区域分析,并进行了全脑分析。与无精神病性症状病史的PD患者相比,有精神病性症状病史的PD患者在奖赏预期期间后扣带回皮质和VS的激活减少(p < 0.05,小体积校正)。结果表明,奖赏处理中的皮质和纹状体异常,这是精神分裂症中精神病的一种假定病理生理机制,也可能导致PD中精神病性症状的发病机制。后扣带回功能障碍的发现与先前强调PD精神病发病机制中皮质功能障碍的结果一致。