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Neuroimage Clin. 2019 Jul 23;24:101960. doi: 10.1016/j.nicl.2019.101960. [Epub ahead of print]

Aberrant activity in conceptual networks underlies N400 deficits and unusual thoughts in schizophrenia.

Author information

1
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. Electronic address: Michael.Jacob@ucsf.edu.
2
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. Electronic address: Judith.Ford@ucsf.edu.
3
San Francisco VA Medical Center, 4150 Clement St, San Francisco, CA 94110, United States. Electronic address: Brian.Roach@ncire.org.
4
The Mind Research Network, 1101 Yale Blvd. NE, Albuquerque, NM 87106, United States; The University of New Mexico, 1 University of New Mexico, Albuquerque, NM 87108, United States. Electronic address: vcalhoun@mrn.org.
5
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. Electronic address: Daniel.Mathalon@ucsf.edu.

Abstract

BACKGROUND:

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).

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Joint-ICA; N400; Schizophrenia; Semantic priming; fMRI

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