Anterior limb of the internal capsule in schizophrenia: A diffusion tensor tractography study

Psychiatry Neuroimaging Laboratory, Department of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, 1249 Boylston Street, Boston, MA 02215, USA.
Brain Imaging and Behavior (Impact Factor: 4.6). 03/2012; 6(3):417-25. DOI: 10.1007/s11682-012-9152-9
Source: PubMed

ABSTRACT Thalamo-cortical feedback loops play a key role in the processing and coordination of processing and integration of perceptual inputs and outputs, and disruption in this connection has long been hypothesized to contribute significantly to neuropsychological disturbances in schizophrenia. To test this hypothesis, we applied diffusion tensor tractography to 18 patients suffering schizophrenia and 20 control subjects. Fractional anisotropy (FA) was evaluated in the bilateral anterior and posterior limbs of the internal capsule, and correlated with clinical and neurocognitive measures. Patients diagnosed with schizophrenia showed significantly reduced FA bilaterally in the anterior but not the posterior limb of the internal capsule, compared with healthy control subjects. Lower FA correlated with lower scores on tests of declarative episodic memory in the patient group only. These findings suggest that disruptions, bilaterally, in thalamo-cortical connections in schizophrenia may contribute to disease-related impairment in the coordination of mnemonic processes of encoding and retrieval that are vital for efficient learning of new information.

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Available from: Martha E Shenton, Dec 19, 2013
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    • "Internal capsule VBM Kubicki et al., 2005; Buchsbaum et al., 2006; Munoz Maniega et al., 2008; Skelly et al., 2008; Sussmann et al., 2009; Nakamura et al., 2012; Levitt et al., 2012 Tractography Oh et al., 2009; Rosenberger et al., 2012 TBSS Seal et al., 2008; Knochel et al., 2012 Cortico-spinal tract TBSS Knochel et al., 2012 Tractography de Weijer et al., 2011 Corona radiata VBM Cui et al., 2011 TBSS Fujino et al., 2014 Middle cerebellar peduncles VBM Okugawa et al., 2004 tracts being affected, there is more likely an array of subtly altered networks distributed throughout the brain. Nevertheless, it could also be argued that the data suggest that the connectivity of frontal regions is particularly affected. "
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    ABSTRACT: In patients with schizophrenia neuroimaging studies have revealed global differences with some brain regions showing focal abnormalities. Examining neurocircuitry, diffusion-weighted imaging studies have identified altered structural integrity of white matter in frontal and temporal brain regions and tracts such as the cingulum bundles, uncinate fasciculi, internal capsules and corpus callosum associated with the illness. Furthermore, structural co-variance analyses have revealed altered structural relationships among regional morphology in the thalamus, frontal, temporal and parietal cortices in schizophrenia patients. The distributed nature of these abnormalities in schizophrenia suggests that multiple brain circuits are impaired, a neural feature that may be better addressed with network level analyses. However, even with the advent of these newer analyses, a large amount of variability in findings remains, likely partially due to the considerable heterogeneity present in this disorder.
    Frontiers in Human Neuroscience 08/2014; 8:653. DOI:10.3389/fnhum.2014.00653 · 2.90 Impact Factor
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    • "The ALIC contains fibers connecting the thalamus to frontal lobe and corticopontine fibers (Rosenberger et al., 2012). Bilateral reductions in fractional anisotropy (FA) and increases in radial diffusivity (RD) have been reported in the ALIC of individuals with schizophrenia (Levitt et al., 2010; Rosenberger et al., 2012), and have been associated with prefrontal-based neuropsychological impairments such as episodic memory (Levitt et al., 2010). The fornix connects the hippocampus to subcortical structures, including mammillary bodies, anterior nucleus of the thalamus, nucleus accumbens, and ventral tegmental area, as well as prefrontal cortex. "
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    ABSTRACT: This study utilized diffusion tensor imaging (DTI) to analyze white matter tractography in the anterior limb of the internal capsule (ALIC), fornix, and uncinate fasciculus (UF) of individuals with 22q11.2 deletion syndrome and controls. Aberrations in these tracts have been previously associated with schizophrenia. With up to 25% of individuals with 22q11.2DS developing schizophrenia in adulthood, we hypothesized reduction in structural integrity of these tracts, including an association with prodromal symptoms of psychosis. We further predicted an association between allelic variation in a functional polymorphism of the Nogo-66 receptor gene and 22q11.2DS white matter integrity. Tractography was conducted using fiber assignment by streamline tracking algorithm in DTI Studio. Subjects were genotyped for the rs701428 SNP of the Nogo-66 receptor gene, and assessed for presence of prodromal symptoms. We found significant group differences between 22q11.2DS and controls in DTI metrics for all three tracts. DTI metrics of ALIC and UF were associated with prodromal symptoms in 22q11.2DS. Further, ALIC DTI metrics were associated with allelic variation of the rs701428 SNP of the Nogo-66 receptor gene in 22q11.2DS. Alterations in DTI metrics suggest white matter microstructural anomalies of the ALIC, fornix, and UF in 22q11.2DS. Structural differences in ALIC appear to be associated with the Nogo-66 receptor gene, which has been linked to myelin-mediated axonal growth inhibition. Moreover, the association between psychosis symptoms and ALIC and UF metrics suggests that the Nogo-66 receptor gene may represent a susceptibility gene for psychosis through its disruption of white matter microstructure and myelin-associated axonal growth.
    Schizophrenia Research 12/2013; 152(1). DOI:10.1016/j.schres.2013.11.015 · 4.43 Impact Factor
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    ABSTRACT: 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 1.5T 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.
    Schizophrenia Research 08/2012; 141(1):29-34. DOI:10.1016/j.schres.2012.06.042 · 4.43 Impact Factor
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