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Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : Schizophrenia Research, Volume 141, Issue 1, October 2012, Pages 29–34
Fibers connecting fronto-temporal and fronto-medial structures that pass through the anterior limb of the internal capsule (ALIC) subserve executive and psychomotor functioning. Both of these functions are adversely affected in schizophrenia, and may be abnormal at illness onset. In a study of first-episode psychosis, we used diffusion tensor imaging (DTI) and cognitive testing to examine ALIC integrity. Fourteen early psychosis patients and 29 healthy volunteers were included. Symptoms were assessed with the Positive and Negative Syndromes Scale (PANSS). All structural and diffusion scans were acquired on a GE Signa 1.5 T scanner. A T1-weighted 3D FSPGR Inversion Recovery imaging series was acquired for manual seeding in structural space. Diffusion tensor imaging (DTI) was performed, and all DTI images were co-registered to structural space. Seeds were manually drawn bilaterally on the coronal plane at a specified location. Diffusion images were post-processed for subsequent Tract-based Spatial Statistics (TBSS) analysis. First-episode psychosis patients had significantly smaller fronto-medial and fronto-temporal AIC tract volumes compared to healthy volunteers on the left and the right (p-values < 0.04). No differences in mean fractional anisotropy (FA) were seen within either left or right tracts (p-values > 0.05), nor did TBSS reveal any other differences in FA values between groups in other regions. Relationships between tract volumes and symptom severity were not observed in this study.
Recent developments in neuroimaging technology, particularly diffusion tensor imaging (DTI), allow for in vivo investigation of white matter structure and integrity. Recent imaging studies support the underlying hypothesis that white matter abnormalities in schizophrenia are central to the emergence of the core symptoms of psychosis. These symptoms include auditory and visual hallucinations, paranoid or bizarre delusions, disorganized thought and speech, and negative symptoms (APA, 1994). This wide range of symptoms is not readily localized to any single cortical or deep gray matter structure. As a result, schizophrenia is increasingly conceptualized as a disorder of connectivity, in which alterations or abnormalities of white matter pathways are part of an underlying pathophysiology of the circuits serving normal functional and cognitive processes (Andreasen et al., 1998 and Cho et al., 2008). The circuits sub-served by frontal − medial and frontal − temporal pathways are involved in executive planning, decision making, emotional attribution, memory and learning (Takahashi et al., 2007 and Wager et al., 2008). In patients with schizophrenia, abnormalities in both the volume and the structural integrity of white matter are present, particularly in frontal − temporal areas (Chan et al., 2010 and Skudlarski et al., 2010). These observations are supported by the post-mortem findings of decreased myelin-related gene expression and abnormalities of white matter cellular density and organization in the brains of schizophrenia patients (Beasley et al., 2005, Beasley et al., 2009 and Hakak et al., 2001). Negative symptoms in schizophrenia have been correlated with low fractional anisotropy (FA) in the inferior frontal white matter (Wolkin et al., 2003). Reduced white matter of the cingulum bundle and uncinate fasciculus differentially and specifically predicted deficits in executive functions and memory respectively (Nestor et al., 2008). Additionally, positive symptoms have been inversely correlated with fiber tract integrity in association tracts, such as the left superior longitudinal fasciculus (Skelly et al., 2008). The anterior limb of the internal capsule (ALIC) is of particular interest as it contains corticothalamic projections that subserve sensory processing, sensory gating and cognitive processes such as memory, attention, and psychomotor control, which are affected in schizophrenia (Mamah et al., 2010 and Rosenberger et al., 2012). Dysfunction of ALIC circuits may increase a patient's vulnerability to schizophrenia and provide a basis for the multiplicity of symptoms seen in schizophrenia (Kubicki et al., 2005). Multiple abnormalities recently demonstrated within the ALIC in patients with schizophrenia have underscored its potential role in schizophrenia. Specifically, findings of reduced ALIC volume (Lang et al., 2006) and altered fractional anisotropy (Kubicki et al., 2005 and Mitelman et al., 2007b) lend support to the potential role of fronto-medial tracts in schizophrenia. Imaging studies in the early phases of schizophrenia are of particular interest as they avoid potential confounds associated with chronic medication exposure and co-morbidities frequently seen in chronic schizophrenia. Observations of white matter changes in early and first-episode schizophrenia have been inconsistent. Absence of a single or specific cluster of white matter deficits in schizophrenia may reflect methodological issues (scanning protocols, segmentation techniques) or population sampling differences (Peters et al., 2008). Data pertaining to the anterior limb of the internal capsule in drug naïve first episode schizophrenia remains sparse and further data are required to assess its role in the pathophysiology of schizophrenia. In this study, the volume and integrity of the ALIC in drug naïve first episode psychosis patients were investigated with DTI using both region of interest (ROI) tractography and Tract-Based Spatial Statistics (TBSS). TBSS has been proposed as a more robust method of analysis, overcoming alignment and smoothing issues (Smith et al., 2006). In this study, results from ROI tractography were confirmed with TBSS analysis.