Multimodal analyses identify linked functional and white matter abnormalities within the working memory network in schizophrenia
ABSTRACT Dysconnectivity between brain regions is thought to underlie the cognitive abnormalities that characterise schizophrenia (SZ). Consistent with this notion functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) studies in SZ have reliably provided evidence of abnormalities in functional integration and in white matter connectivity. Yet little is known about how alterations at the functional level related to abnormalities in anatomical connectivity.
We obtained fMRI data during the 2-back working memory task from 25 patients with SZ and 19 healthy controls matched for age, sex and IQ. DTI data were also acquired in the same session. In addition to conventional unimodal analyses we extracted "features" [contrast maps for fMRI and fractional anisotropy (FA) for DTI] that were subjected to joint independent component analysis (JICA) in order to examine interactions between fMRI and DTI data sources.
Conventional unimodal analyses revealed both functional and structural deficits in patients with SZ. The JICA identified regions of joint, multimodal brain sources that differed in patients and controls. The fMRI source implicated regions within the anterior cingulate and ventrolateral prefrontal cortex and in the cuneus where patients showed relative hypoactivation and within the frontopolar cortex where patients showed relative hyperactivation. The DTI source localised reduced FA in patients in the splenium and posterior cingulum.
This study promotes our understanding of structure-function relationships in SZ by characterising linked functional and white matter changes that contribute to working memory dysfunction in this disorder.
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ABSTRACT: The tremendous heterogeneity in the clinical symptoms and cognitive/emotional deficits seen in patients with schizophrenia has made it challenging to determine the underlying pathogenesis of the illness. One leading hypothesis that has come to the forefront over the past several decades is that schizophrenia is caused by aberrant connectivity between brain regions. In fact, a new field of connectomics has emerged to study the effects of brain connectivity in health and illness. It is known that schizophrenia is highly heritable, although in the search for the underlying genetic factors we have only scratched the tips of the omics icebergs. One technique to help identify underlying genetic factors is the use of heritable intermediate phenotypes, or endophenotypes. Endophenotypes provide mechanisms to study the genetic underpinnings of the disorder by focusing on measureable traits that are more proximal to gene regulation and expression than are symptoms. Thus, the goal of this paper is to conduct a critical review of the evidence linking both structural and functional connectivity as an endophenotype for schizophrenia.Current topics in medicinal chemistry 01/2012; 12(21). · 3.40 Impact Factor
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ABSTRACT: Disruption within the working memory (WM) neural network is considered an integral feature of schizophrenia. The WM network, and the dorsolateral prefrontal cortex (DLPFC) in particular, undergo significant remodeling in late adolescence. Potential interactions between developmental changes in the WM network and disease-related processes for schizophrenia remain unclear. The aim of this study was to determine whether DLPFC activation and functional connectivity are impaired during WM in patients with early-onset schizophrenia (EOS; age of onset <18 years). We used functional magnetic resonance imaging and psychophysiological interaction analysis to respectively measure blood oxygenation level-dependent signal and to derive functional connectivity estimates in response to the two-back WM task from 25 youths with EOS and 20 matched healthy adolescents. Compared with healthy adolescents, patients with EOS showed reduced engagement of the DLPFC, the anterior cingulate cortex (ACC), and frontal operculum, and had reduced DLPFC connectivity within the WM network. Patients with EOS showed abnormal reduction in the coupling of the DLPFC with the ACC, the inferior parietal lobule, and the middle occipital gyrus. In contrast to healthy adolescents, patients with EOS expressed age-related decrease in the activity of the DLPFC and an increase in its connectivity with the ACC. Patients with EOS show dysfunctional engagement and reduced integration within the WM neural network. The pattern of abnormal age-related correlations in DLPFC activity and connectivity suggests that schizophrenia-related processes have an impact on brain regions that show significant late developmental changes.Journal of the American Academy of Child and Adolescent Psychiatry 09/2012; 51(9):911-20.e2. DOI:10.1016/j.jaac.2012.06.020 · 7.26 Impact Factor
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ABSTRACT: With the introduction of diffusion tensor imaging (DTI), structural differences in white matter (WM) architecture between psychiatric populations and healthy controls can be systematically observed and measured. In particular, DTI-tractography can be used to assess WM characteristics over the entire extent of WM tracts and aggregated fiber bundles. Using 64-direction DTI scanning in 27 participants with bipolar disorder (BD) and 26 age-and-gender-matched healthy control subjects, we compared relative length, density, and fractional anisotrophy (FA) of WM tracts involved in emotion regulation or theorized to be important neural components in BD neuropathology. We interactively isolated 22 known white matter tracts using region-of-interest placement (TrackVis software program) and then computed relative tract length, density, and integrity. BD subjects demonstrated significantly shorter WM tracts in the genu, body and splenium of the corpus callosum compared to healthy controls. Additionally, bipolar subjects exhibited reduced fiber density in the genu and body of the corpus callosum, and in the inferior longitudinal fasciculus bilaterally. In the left uncinate fasciculus, however, BD subjects exhibited significantly greater fiber density than healthy controls. There were no significant differences between groups in WM tract FA for those tracts that began and ended in the brain. The significance of differences in tract length and fiber density in BD is discussed.Brain Imaging and Behavior 10/2012; 7(2). DOI:10.1007/s11682-012-9202-3 · 4.60 Impact Factor