San Francisco VA Medical Center, 4150 Clement St, San Francisco, CA 94110, United States; University of California, Department of Psychiatry, 401 Parnassus Avenue, San Francisco, CA 94143, United States.
San Francisco VA Medical Center, 4150 Clement St, San Francisco, CA 94110, United States.
Neuroimage Clin. 2019;24:101960. doi: 10.1016/j.nicl.2019.101960. Epub 2019 Jul 23.
The N400 event-related potential (ERP) is triggered by meaningful stimuli that are incongruous, or unmatched, with their semantic context. Functional magnetic resonance imaging (fMRI) studies have identified brain regions activated by semantic incongruity, but their precise links to the N400 ERP are unclear. In schizophrenia (SZ), N400 amplitude reduction is thought to reflect overly broad associations in semantic networks, but the abnormalities in brain networks underlying deficient N400 remain unknown. We utilized joint independent component analysis (JICA) to link temporal patterns in ERPs to neuroanatomical patterns from fMRI and investigate relationships between N400 amplitude and neuroanatomical activation in SZ patients and healthy controls (HC).
SZ patients (n = 24) and HC participants (n = 25) performed a picture-word matching task, in which words were either matched (APPLE→apple) by preceding pictures, or were unmatched by semantically related (in-category; IC, APPLE→lemon) or unrelated (out of category; OC, APPLE→cow) pictures, in separate ERP and fMRI sessions. A JICA "data fusion" analysis was conducted to identify the fMRI brain regions specifically associated with the ERP N400 component. SZ and HC loading weights were compared and correlations with clinical symptoms were assessed.
JICA identified an ERP-fMRI "fused" component that captured the N400, with loading weights that were reduced in SZ. The JICA map for the IC condition showed peaks of activation in the cingulate, precuneus, bilateral temporal poles and cerebellum, whereas the JICA map from the OC condition was linked primarily to visual cortical activation and the left temporal pole. Among SZ patients, fMRI activity from the IC condition was inversely correlated with unusual thought content.
The neural networks associated with the N400 ERP response to semantic violations depends on conceptual relatedness. These findings are consistent with a distributed network underlying neural responses to semantic incongruity including unimodal visual areas as well as integrative, transmodal areas. Unusual thoughts in SZ may reflect impaired processing in transmodal hub regions such as the precuneus, leading to overly broad semantic associations.
N400 事件相关电位（ERP）是由与语义上下文不一致或不匹配的有意义刺激触发的。功能磁共振成像（fMRI）研究已经确定了由语义不一致引起的大脑区域的激活，但它们与 N400 ERP 的精确联系尚不清楚。在精神分裂症（SZ）中，N400 幅度的减少被认为反映了语义网络中过于广泛的联想，但导致 N400 缺陷的大脑网络异常仍然未知。我们利用联合独立成分分析（JICA）将 ERP 中的时间模式与 fMRI 中的神经解剖模式联系起来，并研究 N400 幅度与 SZ 患者和健康对照（HC）的神经解剖激活之间的关系。
SZ 患者（n=24）和 HC 参与者（n=25）进行了图片-单词匹配任务，其中单词要么与前面的图片匹配（APPLE→apple），要么与语义相关（类别内；IC，APPLE→lemon）或不相关（类别外；OC，APPLE→cow）的图片不匹配，分别在 ERP 和 fMRI 会议中进行。进行了 JICA“数据融合”分析，以确定与 ERP N400 成分特别相关的 fMRI 大脑区域。比较了 SZ 和 HC 的加载权重，并评估了与临床症状的相关性。
JICA 确定了一个 ERP-fMRI“融合”成分，该成分捕获了 N400，其加载权重在 SZ 中降低。IC 条件的 JICA 图谱显示出扣带回、楔前叶、双侧颞极和小脑的激活峰值，而 OC 条件的 JICA 图谱主要与视觉皮质激活和左侧颞极有关。在 SZ 患者中，IC 条件的 fMRI 活性与异常思维内容呈负相关。
与语义违反的 N400 ERP 反应相关的神经网络取决于概念上的相关性。这些发现与语义不一致的神经反应的分布式网络一致，包括单模态视觉区域以及整合的、跨模态区域。SZ 中的异常思维可能反映了跨模态枢纽区域（如楔前叶）处理能力受损，导致语义联想过于广泛。
