Department of Psychiatry, University of Cambridge, Cambridge, UK.
Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
Transl Psychiatry. 2018 Sep 21;8(1):196. doi: 10.1038/s41398-018-0250-3.
Abnormal salience processing has been suggested to contribute to the formation of positive psychotic symptoms in schizophrenia and related conditions. Previous research utilising reward learning or anticipation paradigms has demonstrated cortical and subcortical abnormalities in people with psychosis, specifically in the prefrontal cortex, the dopaminergic midbrain and the striatum. In these paradigms, reward prediction errors attribute motivational salience to stimuli. However, little is known about possible abnormalities across different forms of salience processing in psychosis patients, and whether any such abnormalities involve the dopaminergic midbrain. The aim of our study was, therefore, to investigate possible alterations in psychosis in neural activity in response to various forms of salience: novelty, negative emotion, targetness (task-driven salience) and rareness/deviance. We studied 14 antipsychotic naïve participants with first episode psychosis, and 37 healthy volunteers. During fMRI scanning, participants performed a visual oddball task containing these four forms of salience. Psychosis patients showed abnormally reduced signalling in the substantia nigra/ventral tegmental area (SN/VTA) for novelty, negative emotional salience and targetness; reduced striatal and occipital (lingual gyrus) signalling to novelty and negative emotional salience, reduced signalling in the amygdala, anterior cingulate cortex and parahippocamal gyrus to negative emotional salience, and reduced cerebellar signalling to novelty and negative emotional salience. Our results indicate alterations of several forms of salience processing in patients with psychosis in the midbrain SN/VTA, with additional subcortical and cortical regions also showing alterations in salience signalling, the exact pattern of alterations depending on the form of salience in question.
异常突显加工被认为有助于精神分裂症和相关疾病阳性精神病症状的形成。以前利用奖励学习或预期范式的研究表明，精神病患者存在皮质和皮质下异常，特别是在前额叶皮层、多巴胺能中脑和纹状体。在这些范式中，奖励预测误差将动机突显归因于刺激。然而，对于精神病患者不同形式的突显处理中可能存在的异常，以及任何此类异常是否涉及多巴胺能中脑，知之甚少。因此，我们的研究目的是调查精神病患者在对各种形式的突显（新奇、负性情绪、目标性（任务驱动的突显）和稀有/偏差）的神经活动中可能存在的异常。我们研究了 14 名首次发作的抗精神病药物未治疗的精神病患者和 37 名健康志愿者。在 fMRI 扫描期间，参与者执行了一个包含这四种突显形式的视觉异常任务。精神病患者在新奇、负性情绪突显和目标性方面的黑质/腹侧被盖区（SN/VTA）信号异常降低；在新奇和负性情绪突显方面的纹状体和枕叶（舌回）信号降低，在负性情绪突显方面的杏仁核、前扣带皮层和海马旁回信号降低，在新奇和负性情绪突显方面的小脑信号降低。我们的结果表明，精神病患者存在多种形式的突显处理异常，中脑 SN/VTA 存在异常，此外，还有其他皮质下和皮质区域的突显信号也存在异常，具体的异常模式取决于所研究的突显形式。
