Karlsgodt KH, Glahn DC, van Erp TG, Therman S, Huttunen M, Manninen M et al. The relationship between performance and fMRI signal during working memory in patients with schizophrenia, unaffected co-twins, and control subjects. Schizophr Res 89: 191-197

Department of Psychiatry, University of Helsinki, Helsinki, Uusimaa, Finland
Schizophrenia Research (Impact Factor: 3.92). 02/2007; 89(1-3):191-7. DOI: 10.1016/j.schres.2006.08.016
Source: PubMed


While behavioral research shows working memory impairments in schizophrenics and their relatives, functional neuroimaging studies of patients and healthy controls show conflicting findings of hypo- and hyperactivation, possibly indicating different relationships between physiological activity and performance. In a between-subjects regression analysis of fMRI activation and performance, low performance was associated with relatively lower activation in patients than controls, while higher performance was associated with higher activation in patients than controls in DLPFC and parietal cortex, but not occipital cortex, with unaffected twins of schizophrenics being intermediate between the groups. Accordingly, this supports the idea that both hyper and hypoactivation may be possible along a continuum of behavioral performance in a way consistent with a neural inefficiency model. Further, this study offers preliminary evidence that the relationship between behavior and physiology in schizophrenia may be heritable.


Available from: Mark S Cohen
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    • "Neuroimaging studies have identified brain regions and networks involved in cognitive processing (Alnaes et al., 2015; Cabeza and Nyberg, 2000; Cole et al., 2014), and both hypo-and hyperactivation (Brandt et al., 2014; Glahn et al., 2005; Kraguljac et al., 2013; Ragland et al., 2007), as well as brain network dysconnectivity (Brandt et al., 2015; Fornito et al., 2012b; Kaufmann et al., 2015; Pettersson-Yeo et al., 2011) have been reported in SZ. In particular, fMRI studies have demonstrated abnormal neuronal recruitment during working memory processing (Anticevic et al., 2013; Callicott et al., 2003; Glahn et al., 2005; Henseler et al., 2009; Karlsgodt et al., 2007; Kim et al., 2010; Potkin et al., 2009; Schneider et al., 2007; Thormodsen et al., 2011) reflecting dysfunction of a fronto-parietal network including the lateral prefrontal cortex and posterior parietal cortex, as well as anterior cingulate and other regions related to execution of challenging cognitive tasks (Owen et al., 2005). This network shows increased activation during cognitive processing and is thought to reflect focus on task-relevant information, like updating information in working memory. "
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    ABSTRACT: Schizophrenia (SZ) is a psychotic disorder with significant cognitive dysfunction. Abnormal brain activation during cognitive processing has been reported, both in task-positive and task-negative networks. Further, structural cortical and subcortical brain abnormalities have been documented, but little is known about how task-related brain activation is associated with brain anatomy in SZ compared to healthy controls (HC). Utilizing linked independent component analysis (LICA), a data-driven multimodal analysis approach, we investigated structure–function associations in a large sample of SZ (n = 96) and HC (n = 142). We tested for associations between task-positive (fronto-parietal) and task-negative (default-mode) brain networks derived from fMRI activation during an n-back working memory task, and brain structural measures of surface area, cortical thickness, and gray matter volume, and to what extent these associations differed in SZ compared to HC. A significant association (p b .05, corrected for multiple comparisons) was found between a component reflecting the task-positive fronto-parietal network and another component reflecting cortical thickness in fronto-temporal brain regions in SZ, indicating increased activation with increased thickness. Other structure–function associations across, between and within groups were generally moderate and significant at a nominal p-level only, with more numerous and stronger associations in SZ compared to HC. These results indicate a complex pattern of moderate associations between brain activation during cognitive processing and brain morphometry, and extend previous findings of fronto-temporal brain abnormalities in SZ by suggesting a coupling between cortical thickness of these brain regions and working memory-related brain activation.
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    • "Due to the well-replicated deficits in working memory functioning in schizophrenia, this aspect of cognitive dysfunction has attracted particular attention. In contrast to matched healthy controls, schizophrenia patients were shown to recruit more neural resources in prefrontal and parietal brain regions (hyperactivity) at low levels of task difficulty but decreased neural activity (hypoactivity) when task difficulty increases (i.e. they seem to disengage from the task; Callicott et al., 2003; Karlsgodt et al., 2007; Manoach et al., 1999; Potkin et al., 2009). This pattern (which is based on an inverted U-shape like relationship between BOLD response and task difficulty that is shifted in schizophrenia compared to healthy controls) has been termed " neural inefficiency " (Manoach et al., 1999). "
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    ABSTRACT: Stable neuropsychological deficits may provide a reliable basis for identifying etiological subtypes of schizophrenia. The aim of this study was to identify clusters of individuals with schizophrenia based on dimensions of neuropsychological performance, and to characterize their neural correlates. We acquired neuropsychological data as well as structural and functional magnetic resonance imaging from 129 patients with schizophrenia and 165 healthy controls. We derived eight cognitive dimensions and subsequently applied a cluster analysis to identify possible schizophrenia subtypes. Analyses suggested the following four cognitive clusters of schizophrenia: (1) Diminished Verbal Fluency, (2) Diminished Verbal Memory and Poor Motor Control, (3) Diminished Face Memory and Slowed Processing, and (4) Diminished Intellectual Function. The clusters were characterized by a specific pattern of structural brain changes in areas such as Wernicke's area, lingual gyrus and occipital face area, and hippocampus as well as differences in working memory-elicited neural activity in several fronto-parietal brain regions. Separable measures of cognitive function appear to provide a method for deriving cognitive subtypes meaningfully related to brain structure and function. Because the present study identified brain-based neural correlates of the cognitive clusters, the proposed groups of individuals with schizophrenia have some external validity. Copyright © 2015. Published by Elsevier Ireland Ltd.
    08/2015; 234(1). DOI:10.1016/j.pscychresns.2015.08.008
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    • "Unaffected siblings have genetic backgrounds and early-life environments that are similar to those of patients and are subject to a nearly ninefold greater risk of developing schizophrenia [Sadock and Sadock, 2007]. Although unaffected siblings of patients do not develop schizophrenia , they share 50% of their genes with the patients [Brunelin , et al., 2008] and may have similar but less severe impairments [Karlsgodt, et al., 2007]. Consequently, the estimated values of trait markers in unaffected siblings should be similar to those of patients and intermediate between those of controls and patients [Knochel, et al., 2012; Oertel, et al., 2010]. "
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    ABSTRACT: Trait markers of schizophrenia aid the dissection of the heterogeneous phenotypes into distinct subtypes and facilitate the genetic underpinning of the disease. The microstructural integrity of the white matter tracts could serve as a trait marker of schizophrenia, and tractography-based analysis (TBA) is the current method of choice. Manual tractography is time-consuming and limits the analysis to preselected fiber tracts. Here, we sought to identify a trait marker of schizophrenia from among 74 fiber tracts across the whole brain using a novel automatic TBA method. Thirty-one patients with schizophrenia, 31 unaffected siblings and 31 healthy controls were recruited to undergo diffusion spectrum magnetic resonance imaging at 3T. Generalized fractional anisotropy (GFA), an index reflecting tract integrity, was computed for each tract and compared among the three groups. Ten tracts were found to exhibit significant differences between the groups with a linear, stepwise order from controls to siblings to patients; they included the right arcuate fasciculus, bilateral fornices, bilateral auditory tracts, left optic radiation, the genu of the corpus callosum, and the corpus callosum to the bilateral dorsolateral prefrontal cortices, bilateral temporal poles, and bilateral hippocampi. Posthoc between-group analyses revealed that the GFA of the right arcuate fasciculus was significantly decreased in both the patients and unaffected siblings compared to the controls. Furthermore, the GFA of the right arcuate fasciculus exhibited a trend toward positive symptom scores. In conclusion, the right arcuate fasciculus may be a candidate trait marker and deserves further study to verify any genetic association. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 11/2014; 36(3). DOI:10.1002/hbm.22686 · 5.97 Impact Factor
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