Increased Intra-Individual Variability of Cognitive Processing in Subjects at Risk Mental State and Schizophrenia Patients

Ye Seul Shin,Ji-Won Hur,Suk Kyoon An,Min Soo Byun,Joon Hwan Jang,Wi Hoon Jung,Sung Nyun Kim,Jun Soo Kwon,Na Young Shin,Xiang Yang Zhang

doi:10.1371/journal.pone.0078354

Ye Seul Shin, Ji-Won Hur + Show 8 more

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https://doi.org/10.1371/journal.pone.0078354

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Abstract

Intra-individual variability (IIV) has received recent attention as an indicator of the stability of cognitive functioning that may outperform mean performance in reflecting putative neurobiological abnormalities. Increased IIV is regarded as a core deficit in schizophrenia patients; however, whether this deficit is present in the prodromal phase before the onset of schizophrenia has not been well established. In the present study, we investigated IIV using the stop-signal paradigm in at-risk mental state (ARMS) individuals and in schizophrenia patients. The study included 27 ARMS subjects, 37 schizophrenia patients, and 38 normal controls. The stop-signal task was administered to assess IIV and response inhibition. IIV was estimated by calculating the standard deviation across sub-blocks for the three groups. We observed increased IIV in ARMS subjects and schizophrenia patients compared with normal controls in both the “stop” and the “go” processes even though the mean response inhibition performances were not impaired in the ARMS group. Schizophrenia patients showed impaired response inhibition that was associated with the severity of negative symptoms. Our findings suggest that the analysis of IIV may identify cognitive and clinical features of ARMS that are not detectable by conventional mean performance analysis. The unstable response patterns associated with ARMS may originate from abnormal processing in neural systems caused by alterations in the integrity of functional brain networks and dopamine neuromodulation.

Highlights

The last decade has witnessed increasing interest in the prodromal states of schizophrenia and at-risk mental states (ARMS) and focused on early intervention to delay or prevent the onset of psychosis [1]
Mean performance in the stop process did not differentiate the ARMS subjects from normal controls or schizophrenia patients. These findings indicate that both ARMS subjects and schizophrenia patients exhibit less stable cognitive processing than controls during response inhibition and response execution
Two recent metaanalyses revealed small to moderate deficits across several cognitive domains in individuals at high risk for psychosis [5,40], which indicates that the neuropsychological status of high-risk individuals was intermediate between that of normal controls and schizophrenia patients [3,41]

Summary

Introduction

The last decade has witnessed increasing interest in the prodromal states of schizophrenia and at-risk mental states (ARMS) and focused on early intervention to delay or prevent the onset of psychosis [1]. IIV provides information regarding cognitive functioning that is not detectable by average measures of performance [10] and can better discriminate cognitively impaired and clinical groups from normal controls [11]. Frontal lobe circuitry is associated with IIV, which reflects a greater demand for executive control processes to maintain task performance [15,16,17,18]. Increased IIV has been reported in patients with frontal lobe dysfunctions, such as schizophrenia [16,19,20,21], ADHD [22,23], and traumatic brain injury [17]. Given that ARMS subjects show abnormal frontal lobe processing [28] and alterations in DA function [29,30], increased IIV may be present in ARMS subjects

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