A Functional Magnetic Resonance Imaging Study of Working Memory Abnormalities in Schizophrenia

Olin Neuropsychiatry Research Center, The Institute of Living at Hartford Hospital, Hartford, CT, USA.
Biological Psychiatry (Impact Factor: 10.25). 08/2006; 60(1):11-21. DOI: 10.1016/j.biopsych.2005.11.012
Source: PubMed

ABSTRACT Previous neuroimaging studies of working memory (WM) in schizophrenia, typically focusing on dorsolateral prefrontal cortex, yield conflicting results, possibly because of varied choice of tasks and analysis techniques. We examined neural function changes at several WM loads to derive a more complete picture of WM dysfunction in schizophrenia.
We used a version of the Sternberg Item Recognition Paradigm to test WM function at five distinct loads. Eighteen schizophrenia patients and 18 matched healthy controls were scanned with functional magnetic resonance imaging at 3 Tesla.
Patterns of both overactivation and underactivation in patients were observed depending on WM load. Patients' activation was generally less responsive to load changes than control subjects', and different patterns of between-group differences were observed for memory encoding and retrieval. In the specific case of successful retrieval, patients recruited additional neural circuits unused by control subjects. Behavioral effects were generally consistent with these imaging results.
Differential findings of overactivation and underactivation may be attributable to patients' decreased ability to focus and allocate neural resources at task-appropriate levels. Additionally, differences between encoding and retrieval suggest that WM dysfunction may be manifested differently during the distinct phases of encoding, maintenance, and retrieval.

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Available from: Daniel H Mathalon, Sep 01, 2015
    • "However, unlike Lee et al. (2014), we observed hypoactivity in that region. Given that prefrontal activity shows load-dependent pattern (i.e., overactive in low loads and underactive in high loads) (Johnson et al., 2006), the difference between the study of Lee et al. and our own study may be related to the higher social task load in the present study. SD has been proposed to mediate the relationship of urbanicity and schizophrenia (Selten et al., 2013). "
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    ABSTRACT: The social defeat (SD) hypothesis of schizophrenia posits that repeated experiences of SD may lead to sensitization of the mesolimbic dopaminergic system and to precipitation of psychosis. Based on previous definitions adapted to a human experimental paradigm, we prepared a computer simulation of SD to mimic this subjective experience. We measured prefrontal cortex (PFC) activity in subjects with schizophrenia and healthy controls during exposure to a single SD experience with functional near infrared spectroscopy. PFC activity declined in both groups. Compared with the control condition, SD exposure was associated with a broader decline in left ventromedial, right medial and right lateral PFC activity in healthy controls (n=25), and a sharper decline in right ventrolateral PFC activity in subjects with schizophrenia (n=25). The activity in the right ventrolateral PFC, was significantly lower in patients compared with controls. This may be due to a deficiency in emotion regulation or self-control, or it may be related to impaired empathy in schizophrenia. Different patterns of brain activity during the SD experience in subjects with schizophrenia versus healthy controls may provide indirect evidence regarding the SD hypothesis of schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    07/2015; DOI:10.1016/j.pscychresns.2015.07.017
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    • "When presented with a shorter stimulus, the stimuli's entrance into working memory may be less complete [8]. Currently, tests for working memory include the n-back task [9] which is a continuous performance task commonly used to measure a part of working memory [10], the Sternberg Item Recognition Paradigm [11] [12], the Visual Patterns Test Neural Plasticity [13], the Spatial Working Memory task (SPWM) [14], and others [15] [16] [17] [18]. Existing tests for attention include the Continuous Performance Test (CPT) [19] [20] and the Sustained Attention Test [21]. "
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    ABSTRACT: People with neuropsychiatric disorders such as schizophrenia often display deficits in spatial working memory and attention. Evaluating working memory and attention in schizophrenia patients is usually based on traditional tasks and the interviewer's judgment. We developed a simple Spatial Working Memory and Attention Test on Paired Symbols (SWAPS). It takes only several minutes to complete, comprising 101 trials for each subject. In this study, we tested 72 schizophrenia patients and 188 healthy volunteers in China. In a healthy control group with ages ranging from 12 to 60, the efficiency score (accuracy divided by reaction time) reached a peak in the 20-27 age range and then declined with increasing age. Importantly, schizophrenia patients failed to display this developmental trend in the same age range and adults had significant deficits compared to the control group. Our data suggests that this simple Spatial Working Memory and Attention Test on Paired Symbols can be a useful tool for studies of spatial working memory and attention in neuropsychiatric disorders.
    Neural Plasticity 11/2013; 2013:130642. DOI:10.1155/2013/130642 · 3.60 Impact Factor
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    • "However, as WM load demands reach and exceed capacity limitations, DLPFC signals begin to drop, presumably due to information load exceeding available computational resources (Braver et al., 1997; Goldman-Rakic et al., 2000). In line with this hypothesis, recent evidence suggests that patients with schizophrenia may exhibit a shifted inverted-U function, such that capacity limitations are reached faster (i.e., with lower WM load levels), which may result in overor under-recruitment when compared to healthy controls, depending on the level of WM load at which the groups are compared (Johnson et al., 2006). For instance, the hypothesis states that at low difficulty levels patients may find performance more effortful and may have to recruit more prefrontal computational resources to accomplish the task. "
    Cognitive impairment in schizophrenia: characteristics, assessment, and treatment, 01/2013: chapter 12: pages 486-580; Cambridge University Press.
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