Uncinate Fasciculus Findings in Schizophrenia: A Magnetic Resonance Diffusion Tensor Imaging Study

Department of Psychiatry, Harvard Medical School and VA Boston Healthcare System-Brockton Division, MA 02301, USA.
American Journal of Psychiatry (Impact Factor: 12.3). 06/2002; 159(5):813-20. DOI: 10.1176/appi.ajp.159.5.813
Source: PubMed


Disruptions in connectivity between the frontal and temporal lobes may explain some of the symptoms observed in schizophrenia. Conventional magnetic resonance imaging (MRI) studies, however, have not shown compelling evidence for white matter abnormalities, because white matter fiber tracts cannot be visualized by conventional MRI. Diffusion tensor imaging is a relatively new technique that can detect subtle white matter abnormalities in vivo by assessing the degree to which directionally organized fibers have lost their normal integrity. The first three diffusion tensor imaging studies in schizophrenia showed lower anisotropic diffusion, relative to comparison subjects, in whole-brain white matter, prefrontal and temporal white matter, and the corpus callosum, respectively. Here the authors focus on fiber tracts forming temporal-frontal connections.
Anisotropic diffusion was assessed in the uncinate fasciculus, the most prominent white matter tract connecting temporal and frontal brain regions, in 15 patients with chronic schizophrenia and 18 normal comparison subjects. A 1.5-T GE Echospeed system was used to acquire 4-mm-thick coronal line-scan diffusion tensor images. Maps of the fractional anisotropy were generated to quantify the water diffusion within the uncinate fasciculus.
Findings revealed a group-by-side interaction for fractional anisotropy and for uncinate fasciculus area, derived from automatic segmentation. The patients with schizophrenia showed a lack of normal left-greater-than-right asymmetry seen in the comparison subjects.
These findings demonstrate the importance of investigating white matter tracts in vivo in schizophrenia and support the hypothesis of a disruption in the normal pattern of connectivity between temporal and frontal brain regions in schizophrenia.

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    • "The current finding is in line with previous reports of frontotemporal and insular gray matter reductions in SZ (Glahn et al., 2008; Nesvag et al., 2008; Rimol et al., 2010; Schultz et al., 2012b; Shepherd et al., 2012), which may reflect alterations at the neuronal and synaptic level, with consequences for cognitive networks and processing. Evidence from DTI studies suggests disruptions of fronto-temporal white matter bundles in SZ, including the uncinate fasciculus (Kubicki et al., 2002; Samartzis et al., 2014). Similarly, functional imaging studies have reported connectivity alterations between frontal and temporal Fig. 2. The task-positive fronto-parietal network (FPN) and fronto-temporal thickness (FTT) components showing a significant association in schizophrenia, from (A) the main analysis using matched smoothness across modalities, and (B) the additional analysis using less smoothing of COPE and GMV maps (3 b z b 10). "
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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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    • "Diffusion-Tensor Imaging (DTI) Acquisition Diffusion-weighted images were acquired on a 1.5 Tesla GE scanner with a quadrature head coil. A line scan diffusion imaging protocol (LSDI) was employed (Kubicki et al., 2002), with the following parameters: 6 orthogonal gradient directions with high diffusion weighting (b = 1000 s/mm 2 ), 2 images with low diffusion weighting (b = 5 s/mm 2 ), FOV = 220 × 165 mm, matrix = 128 × 128 mm, in-plane resolution = 1.7 × 1.7 mm, slice thickness = 4 mm, interslice distance = 1 mm, echo time = 64 ms, effective repetition time = 2592 ms, NEX = 1, receiver bandwidth = 4 kHz, 31–35 coronal slices to provide full brain coverage, and acquisition time = approximately 30 min. Diffusion-Tensor Images (DTIs) were constructed from the diffusion-weighted images using a least-squares estimation method. "
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    ABSTRACT: Background: Delusions of control are among the most distinctive and characteristic symptoms of schizophrenia. Several theories have been proposed that implicate aberrant communication between spatially disparate brain regions in the etiology of this symptom. Given that white matter fasciculi represent the anatomical infrastructure for long-distance communication in the brain, the present study investigated whether delusions of control were associated with structural abnormalities in four major white matter fasciculi. Methods: Ten schizophrenia patients with current delusions of control, 13 patients with no clinical history of delusions of control, and 12 healthy controls underwent a Diffusion-Tensor Imaging (DTI) scan. Deterministic tractography was used to extract the corpus callosum, superior longitudinal fasciculus, arcuate fasciculus, and cingulum bundle. The structural integrity of these four fasciculi was quantified with fractional anisotropy (FA) and compared between groups. Results: The patients with delusions of control exhibited significantly lower FA in all four fasciculi, relative to the healthy controls. Furthermore, the patients with delusions of control also exhibited significantly lower FA in the cingulum bundle relative to patients without a history of this symptom, and this difference remained significant when controlling for between-group differences in global SAPS score and medication dosage. Conclusions: The results suggest that structural damage to the cingulum bundle may be involved in the etiology of delusions of control, possibly because of its role in connecting the action initiation areas of the premotor cortex with the cingulate gyrus.
    Schizophrenia Research 10/2014; 161(1). DOI:10.1016/j.schres.2014.08.033 · 3.92 Impact Factor
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    • "In that context, WM asymmetries have been observed, mainly focusing on the arcuate fasciculus because of its relationship to hemispheric specialization of language [e.g., Buchel et al., 2004; Catani et al., 2007; Nucifora et al., 2005; Rodrigo et al., 2007; Takao et al., 2011; Thiebaut de Schotten et al., 2011; Vernooij et al., 2007]. Other DTI studies have explored fractional anisotropy asymmetry in the cingulum [e.g., Gong et al., 2005; Kubicki et al., 2003; Takao et al., 2011], corticospinal tract [e.g., Park et al., 2004; Westerhausen et al., 2007], and uncinate fasciculus [Kubicki et al., 2002]. Our understanding of structural asymmetries is still largely limited to the level of individual structures. "
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    ABSTRACT: The study on structural brain asymmetries in healthy individuals plays an important role in our understanding of the factors that modulate cognitive specialization in the brain. Here, we used fiber tractography to reconstruct the left and right hemispheric networks of a large cohort of 346 healthy participants (20–86 years) and performed a graph theoretical analysis to investigate this brain laterality from a network perspective. Findings revealed that the left hemisphere is significantly more “efficient” than the right hemisphere, whereas the right hemisphere showed higher values of “betweenness centrality” and “small-worldness.” In particular, left-hemispheric networks displayed increased nodal efficiency in brain regions related to language and motor actions, whereas the right hemisphere showed an increase in nodal efficiency in brain regions involved in memory and visuospatial attention. In addition, we found that hemispheric networks decrease in efficiency with age. Finally, we observed significant gender differences in measures of global connectivity. By analyzing the structural hemispheric brain networks, we have provided new insights into understanding the neuroanatomical basis of lateralized brain functions. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 09/2014; 35(9). DOI:10.1002/hbm.22524 · 5.97 Impact Factor
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