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Oral Presentations Connectivity and Are Supporting the Notion of Functional Disconnec- Tion in Schizophrenia

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Oral Presentations Connectivity and Are Supporting the Notion of Functional Disconnec- Tion in Schizophrenia Schizophrenia Research 67 (2004) 3–277 www.elsevier.com/locate/schres Abstracts Oral Presentations connectivity and are supporting the notion of functional disconnec- tion in schizophrenia. Oral Presentations I References What is disconnected and where? Schlo¨sser, R., et al., 2003. Altered effective connectivity during working memory performance in schizophrenia: a study with ASSESSING THE DISCONNECTION fMRI and structural equation modeling. Neuroimage 19, SYNDROME IN SCHIZOPHRENIA: MODEL 751–763. BASED PATH ANALYSIS OF fMRI DATASETS Schlo¨sser, R., et al., in press. Altered effective connectivity in drug free schizophrenic patients. Neuroreport. R. Schlo¨sser, H. Sauer Department of Psychiatry, University of Jena A DIFFUSION TENSOR IMAGING STUDY OF SCHIZOPHRENIA presenting author contact: [email protected] Philosophenweg 3, Jena, Germany R. A. A. Kanaan1, P. K. McGuire1, G. J. Barker1, X. Chitnis1, D. K. Jones1,2, S. S. Shergill1 Background: Cognitive deficits in schizophrenia have been associated with ‘‘cognitive dysmetria’’ related to a disruption of 1 large-scale information processing networks. The present se- Institute of Psychiatry, London, UK 2NICHD, Bethesda, USA quence of fMRI studies examined the hypothesis of altered effective connectivity within a defined cortical–subcortical–cer- ebellar network subserving working memory functions. presenting author contact: [email protected] Methods: Twelve schizophrenic patients treated with either Institute of Psychiatry, Section of Neuroimaging, P067, typical or atypical antipsychotics and six drug-free schizophrenic De’Crespigny Park, London, United Kingdom patients were studied with fMRI and compared to normal controls. Tel.: +44-20-7848-0514; fax: +44-20-7848-0976. All subjects performed a 2-back working memory task. Cortical– subcortical–cerebellar effective connectivity was examined with Background: Patients with schizophrenia show subtle changes in structural equation modeling (SEM) using AMOS 4.0. pre-frontal, temporal and cerebellar volumes and evidence of Results: Drug-free patients and patients under typical antipsy- dysconnectivity in functional imaging studies. These findings may chotics demonstrated reduced interhemispheric cortico-cortical con- reflect a disruption of white matter tract connections. Previous DTI nectivity. This finding is consistent with studies indicating altered studies of white matter in schizophrenia have produced conflicting integrity of interhemispheric fiber tracts and Crow’s hypothesis of results: four have reported differences in Fractional Anisotropy schizophrenia as a ‘‘transcallosal misconnection syndrome’’. In (FA), and four have not. However, sample sizes in studies to date drug-free patients, enhanced thalamo-cortical and prefrontal intra- have been small, and the methods for processing DTI data are still hemispheric connectivity was detected. evolving. In the present study, we used a voxel-based approach Conclusion: The result could be integrated into a model of to examine the FA in frontal white matter tracts in larger deficient thalamo-cortical filter functions. The higher neuronal groups than have previously been investigated. connection strength in patients might be related to underlying cortical Methods: Thirty-three patients meeting DSM-IV criteria for inefficiency. Enhanced thalamo-cortical effective connectivity could schizophrenia, and 39 IQ- and age-matched controls, were scanned be observed in treated patients as well thereby indicating trait with an optimised, multi-direction DTI sequence, on a 1.5 T GE characteristics of this finding. The results are demonstrating the MRI scanner. After correction for eddy-current induced distortions, general feasibility to use SEM analysis for the study of effective the tensor was calculated and FA maps produced. Non-diffusion doi:10.1016/j.schres.2003.10.001 4 Abstracts weighted scans were registered to the MNI template, using FSL, space, and smoothed with a 12-mm Gaussian kernel. Group dif- giving a new template to which all scans were re-registered, and the ferences for both DTI/MTR were calculated using a General final realignment parameters then applied to the FA maps. After Linear Model. inspection for image quality and gross abnormality, group analysis Results: Lower diffusion anisotropy was observed, bilaterally, in was performed on the FA maps using XBAMM (a nonparametric the schizophrenia group compared to controls, for white matter in package), with cluster and voxel thresholds of p <0.01 and the frontal region (including the cingulate bundles), and in the left p < 0.002. posterior region (including the arcuate fasciculus, internal capsules Results: Preliminary analysis found the schizophrenic subjects and corpus callosum). MTR maps showed lower myelin density in to have decreased FA in the areas of the left uncinate, right superior the internal capsules and in frontal regions, but not in the corpus longitudinal fasciculus and bilateral corpus callosum. callosum or in arcuate fasciculus. Conclusion: Schizophrenia is associated with changes in white Conclusion: Findings demonstrate that some of the diffu- matter pathways connecting frontal, temporal and posterior cortical sion changes in schizophrenia may be attributed to myelin areas. alterations. This disruption may be secondary to neuronal disorganization. WHITE MATTER INTEGRITY IN SCHIZOPHRENIA—DTI AND MTR A DTI STUDY OF THE CORPUS CALLOSUM IN VOXEL-WISE ANALYSIS FIRST-EPISODE SCHIZOPHRENIA M. Kubicki1,2, H. -J. Park1, C. -F. Westin2, R. Mulkern2, G. Price, M. Cercignani, M. A. Ron M. Frumin1, E. Connor1, F. A. Jolesz2, 1 1 R. W. McCarley , M. E. Shenton Neuropsychiatry, Institute of Neurology, London, United Kingdom 1 Clinical Neuroscience Division, Laboratory of Neuroscience, presenting author contact: [email protected] Boston VA Healthcare System-Brockton Division, 6th Floor Queen Square House, London, United Kingdom Department of Psychiatry, Harvard Medical School, Brockton, MA Tel.: +44-207-837-3611. 2Surgical Planning Laboratory, MRI Division, Department of Radiology, Brigham and Women’s Hospital, Background/objective: The corpus callosum (CC) is the largest Harvard Medical School, Boston, MA white matter tract in the brain. Diffusion Tensor Imaging (DTI) enables examination of cellular cytoarchitecture in vivo. A previ- presenting author contact: [email protected] ous study in our group, using region of interest (ROI) methodol- Department of Psychiatry-116A, VA Boston Health Care System- ogy with DTI, has shown evidence of neuropathological changes Brockton Division, Harvard Medical School, 940 Belmont Street, in the CC, in patients with chronic schizophrenia. Other studies Brockton, MA, United States have also shown evidence of change in the CC. However, little is Tel.: +1-508-583-4500x1371; fax: +1-508-580-0059. known about the biological correlates and functional significance of these findings, or if these changes are the result of illness Background/objective: Diffusion Tensor Imaging (DTI) is a chronicity. The aim of this study was to examine the CC for technique that is sensitive to the water movement in the brain neuropathological changes, with DTI, in patients with first-episode and may help to characterize white matter abnormalities in schizophrenia (FE-SCZ)—removing the confounder of illness schizophrenia. To date, diffusion studies in schizophrenia show chronicity. lower anisotropic diffusion within white matter, likely due to Methods: DTI was performed in 20 FE-SCZ (mean age = 25 loss of coherence of white matter fiber tracts. Candidate pro- years) and 29 healthy controls (mean age = 28 years). Mean diffu- cesses involve changes in the number and/or density of inter- sivity and fractional anisotropy were used to measure fibre organi- connecting fiber tracts as well as changes in myelination. The sation and directionality. The same ROI (splenium and genu of the aim of this study is to compare white matter findings using two CC) matching our previous study of patients with chronic schizo- imaging techniques, DTI and magnetization transfer imaging phrenia were chosen. (MTR), the latter a saturation technique sensitive to myelin Results: No significant differences were seen in both the alterations. splenium and genu when the FE-SCZ and control groups Methods: Ten right-handed chronic male schizophrenia were compared. Age also had no effect in predicting DTI patients and 10 male controls were scanned using Line-Scan- changes. Diffusion-Imaging and T1-weighted techniques with/without sat- Conclusion: The absence of DTI changes in the splenium and uration pulse (MTR). Four-millimeter-thick coronal images were genu of the CC in FE-SCZ patients contrasts with changes found acquired for DTI/MTR on a 1.5-T GE Echo-speed-system and previously using DTI in chronic patients. A possible conclusion is analyzed using SPM99 software. Both DTI relative anisotropy that focal disruptions, as measured by DTI in these regions, are not and MTR maps of the white matter were normalized to the MNI present at an early stage of the illness. Abstracts 5 CONFIRMATION OF SEVERE LOSS OF presenting author contact: [email protected] SUBICULAR DENDRITIC SPINES Leipziger Strasse 44, Magdeburg, Germany Tel.: +49-391-6715029; fax: +49-391-6715223. IN SCHIZOPHRENIA 1,2,3 1,2 1,2 2 Background: A broad spectrum of schizophrenic symptoms may G. Rosoklija , B. Mancevski , R. Berman , S. Rauski , T. Serafimova3, A. Duma3, N. Davceva3, Z. Jakovski3, by explained by disturbed mechanisms of neuronal inhibition.
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