Young Jared W, Bismark Andrew W, Sun Yinming, Zhang Wendy, McIlwain Meghan, Grootendorst Ibrahim, Light Gregory A
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Research Service, VA San Diego Healthcare System, San Diego, CA, USA.
Neuropsychopharmacology. 2017 May;42(6):1338-1348. doi: 10.1038/npp.2016.268. Epub 2016 Dec 5.
Attentional dysfunction in schizophrenia (SZ) contributes to the functional deficits ubiquitous to the disorder. Identifying the neural substrates of translational measures of attentional dysfunction would prove invaluable for developing therapeutics. Attentional performance is typically assessed via continuous performance tasks (CPTs), though many place additional cognitive demands with little cross-species test-relevance. Herein, event-related potentials (ERPs) were used to investigate the neurophysiological correlates of attention and response inhibition of SZ and healthy participants, whereas they performed the cross-species-translated five-choice CPT (5C-CPT). Chronically ill, medicated SZ patients and matched controls (n=25 SZ and 26 controls) were tested in the 5C-CPT, in conjunction with ERP and source localization assessments. The ERPs generated in response to correctly identified target and non-target trials revealed three peaks for analysis, corresponding to sensory registration (P), response selection (N), and response action (P). Behavioral responses revealed that SZ patients exhibited impaired attention driven by impaired and slower target detection, and poorer cognitive control. ERPs revealed decreased N amplitudes reflecting poorer response selection for both target and non-target trials, plus reduced non-target Ps in SZ patients, the latter accounting for 37% of variance in negative symptoms. Source analyses revealed that the brain regions of significant differences localized to the left dorsolateral prefrontal cortex during response selection and the posterior cingulate cortex for cognitive processes. SZ patients exhibited impaired attention and cognitive control, characterized by less robust frontal and parietal ERP distributions across the response selection and cognitive response time windows, providing neurophysiological characterization of attentional dysfunction in SZ using the reverse-translated 5C-CPT.
精神分裂症（SZ）中的注意力功能障碍导致了该疾病普遍存在的功能缺陷。确定注意力功能障碍转化指标的神经基础对于开发治疗方法将具有极高的价值。注意力表现通常通过连续性能任务（CPT）进行评估，不过许多此类任务还会带来额外的认知需求，且与跨物种测试的相关性很小。在此，事件相关电位（ERP）被用于研究SZ患者和健康参与者在注意力和反应抑制方面的神经生理相关性，他们执行的是跨物种翻译的五选CPT（5C-CPT）。对慢性病态、正在服药的SZ患者和匹配的对照组（25名SZ患者和26名对照组）进行了5C-CPT测试，并结合ERP和源定位评估。对正确识别的目标和非目标试验产生的ERP显示出三个用于分析的峰值，分别对应感觉登记（P）、反应选择（N）和反应动作（P）。行为反应表明，SZ患者由于目标检测受损和速度减慢以及认知控制较差而表现出注意力受损。ERP显示N波幅降低，反映出目标和非目标试验的反应选择都较差，此外SZ患者的非目标P波也降低，后者占阴性症状方差的37%。源分析表明，在反应选择过程中，显著差异的脑区定位于左侧背外侧前额叶皮层，而认知过程的显著差异脑区定位于后扣带回皮层。SZ患者表现出注意力和认知控制受损，其特征是在反应选择和认知反应时间窗口内，额叶和顶叶ERP分布不那么明显，这为使用反向翻译的5C-CPT对SZ患者的注意力功能障碍提供了神经生理学特征描述。
