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Striatal Activity is Associated with Deficits of Cognitive Control and Aberrant Salience for Patients with Schizophrenia.

ABSTRACT: A recent meta-analysis has shown that a large dopamine abnormality exists in the striatum when comparing patients with schizophrenia and controls, and this abnormality is thought to contribute to aberrant salience assignment (or a misattribution of relevance to irrelevant stimuli). This abnormality may also disrupt striatal contributions to cognitive control processing. We examined the relationship between striatal involvement in cognition and aberrant salience symptoms using a task of cognitive control that involves updating, interference control, and simple maintenance. The current study included a sample of 22 patients with schizophrenia and 20 healthy controls and used a slow event-related fMRI design. We predicted that (1) aberrant salience symptoms would be greater for patient's, (2) patients would demonstrate increased errors during interference control trials, given that patients may be inappropriately assigning salience to distracters, and (3) striatal activity during those errors would be correlated with aberrant salience symptoms. We found a trend toward a significant difference between patients and controls on aberrant salience symptoms, and a significant difference between groups on select task conditions. During interference control trials, patients were more likely to inappropriately encode distracters. For patients, both prefrontal and striatal activity was significantly greater when patients inappropriately identified the distracter as correct compared to activity during distracter rejection. During updating, patient prefrontal and striatal activity was significantly lower for incorrect than correct updating trials. Finally, as predicted, for patients the increase of activity during incorrect distracter trials was positively correlated with aberrant salience symptoms, but only for the striatal region. These relationships may have implications for treatments that improve cognitive function and reduce symptom expression.

SUBMITTER: Ceaser AE

PROVIDER: S-EPMC4738294 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Striatal Activity is Associated with Deficits of Cognitive Control and Aberrant Salience for Patients with Schizophrenia.

Ceaser Alan E AE Barch Deanna M DM

Frontiers in human neuroscience 20160203

A recent meta-analysis has shown that a large dopamine abnormality exists in the striatum when comparing patients with schizophrenia and controls, and this abnormality is thought to contribute to aberrant salience assignment (or a misattribution of relevance to irrelevant stimuli). This abnormality may also disrupt striatal contributions to cognitive control processing. We examined the relationship between striatal involvement in cognition and aberrant salience symptoms using a task of cognitive ...[more]

PMID: 26869912

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Project description:BackgroundThe 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).MethodsSZ 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.ResultsJICA 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.ConclusionsThe 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.

Project description:Importance:Efforts to remediate the multiple cognitive function impairments in schizophrenia should consider white matter as one of the underlying neural mechanisms. Objective:To determine whether altered structural brain connectivity is responsible for 2 of the core cognitive deficits in schizophrenia- reduced information processing speed and impaired working memory. Design, Setting, and Participants:This cross-sectional study design took place in outpatient clinics from August 1, 2004, to August 31, 2015. Participants included 166 patients with schizophrenia and 213 healthy control individuals. These participants were from 3 independent cohorts, each of which had its own healthy control group. No participant had current or past neurological conditions or major medical conditions. Patients were diagnosed with either schizophrenia or schizoaffective disorder as defined by the DSM-IV. Controls had no Axis I psychiatric disorder. Main Outcomes and Measures:Mediation analyses and structural equation modeling were used to analyze the associations among processing speed, working memory, and white matter microstructures. Whole-brain and regional diffusion tensor imaging fractional anisotropy were used to measure white matter microstructures. Results:Of the study participants, the 166 patients with schizophrenia had a mean (SD) age of 38.2 (13.3) years and the 213 healthy controls had a mean (SD) age of 39.2 (14.0) years. There were significantly more male patients than controls in each of the 3 cohorts (117 [70%] vs 91 [43%]), but there were no significant differences in sex composition among the 3 cohorts. Patients had significantly reduced processing speed (Cohen d?=?1.24; P?=?6.91?×?10-30) and working memory deficits (Cohen d?=?0.83; P?=?1.10?×?10-14) as well as a significant whole-brain fractional anisotropy deficit (Cohen d?=?0.63; P?=?2.20?×?10-9). In schizophrenia, working memory deficit was mostly accounted for by processing speed deficit, but this deficit remained when accounting for working memory (Cohen d?=?0.89; P?=?2.21?×?10-17). Mediation analyses showed a significant association pathway from fractional anisotropy to processing speed to working memory (P?=?5.01?×?10-7). The strength of this brain-to-cognition pathway in different white matter tracts was strongly associated with the severity of schizophrenia-associated fractional anisotropy deficits in the corresponding white matter tracts as determined by a meta-analysis (r?=?0.85-0.94; all P?<?.001). The same pattern was observed in patients and controls either jointly or independently. Conclusions and Relevance:Study findings suggest that (1) processing speed contributes to the association between white matter microstructure and working memory in schizophrenia and (2) white matter impairment in schizophrenia is regional tract-specific, particularly in tracts normally supporting processing speed performance.

Dataset Information

Striatal Activity is Associated with Deficits of Cognitive Control and Aberrant Salience for Patients with Schizophrenia.

Publications

Striatal Activity is Associated with Deficits of Cognitive Control and Aberrant Salience for Patients with Schizophrenia.

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