High Connectivity Between Reduced Cortical Thickness and Disrupted White Matter Tracts in Long-Standing Type 1 Diabetes

University of Minnesota Medical School, Minneapolis, USA.
Diabetes (Impact Factor: 8.1). 10/2010; 60(1):315-9. DOI: 10.2337/db10-0598
Source: PubMed


Previous studies have observed disruptions in brain white and gray matter structure in individuals with type 1 diabetes, and these structural differences have been associated with neurocognitive testing deficiencies. This study investigated the relationship between cerebral cortical thickness reductions and white matter microstructural integrity loss in a group of patients with type 1 diabetes and in healthy control subjects using diffusion tensor imaging (DTI).
Twenty-five subjects with type 1 diabetes for at least 15 years and 25 age- and sex-matched control subjects underwent structural T1 and proton-density and DTI on a 3.0 Tesla scanner. Fractional anisotropy measurements were made on major cerebral white matter tracts, and DTI tractography was performed to identify cortical regions with high connectivity to these tracts.
Posterior white matter tracts with reduced fractional anisotropy (optic radiations, posterior corona radiata, and the splenium region of the corpus callosum) were found to have high connectivity with a number of posterior cortical regions, including the cuneus, precuneus, fusiform, and posterior parietal cortical regions. A significant reduction in cortical thickness in the diabetic group was observed in the regions with high connectivity to the optic radiations and posterior corona radiata tracts (P < 0.05).
The direct relationship between white and gray matter structural pathology has not been previously demonstrated in subjects with long-standing type 1 diabetes. The relationship between posterior white matter microstructural integrity disruption and lower cortical thickness demonstrated using a novel DTI connectivity technique suggests a common or interrelated pathophysiological mechanism in type 1 diabetes.

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    • "For example, Koch et al. found a significant linkage between disrupted white matter (in the superior temporal cortex) and reduced cortical thickness (in the posterior cingulate cortex, PCC) in patients with schizophrenia [24]. Franc and colleagues found that decreased FA in the optic radiations and posterior corona radiata were associated with lower average cortical thickness in individuals with type 1 diabetes using fiber tract projection analysis [25]. However, to our best knowledge, no reported study has investigated the potential linkage between disruptions in white matter and alterations in cortical thickness in patients with OCD. "
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    ABSTRACT: Disrupted white matter integrity and abnormal cortical thickness are widely reported in the pathophysiology of obsessive-compulsive disorder (OCD). However, the relationship between alterations in white matter connectivity and cortical thickness in OCD is unclear. In addition, the heritability of this relationship is poorly understood. To investigate the relationship of white matter microstructure with cortical thickness, we measure fractional anisotropy (FA) of white matter in 30 OCD patients, 19 unaffected siblings and 30 matched healthy controls. Then, we take those regions of significantly altered FA in OCD patients compared with healthy controls to perform fiber tracking. Next, we calculate the fiber quantity in the same tracts. Lastly, we compare cortical thickness in the target regions of those tracts. Patients with OCD exhibited decreased FA in cingulum, arcuate fibers near the superior parietal lobule, inferior longitudinal fasciculus near the right superior temporal gyrus and uncinate fasciculus. Siblings showed reduced FA in arcuate fibers near the superior parietal lobule and anterior limb of internal capsule. Significant reductions in both fiber quantities and cortical thickness in OCD patients and their unaffected siblings were also observed in the projected brain areas when using the arcuate fibers near the left superior parietal lobule as the starting points. Reduced FA in the left superior parietal lobule was observed not only in patients with OCD but also in their unaffected siblings. Originated from the superior parietal lobule, the number of fibers was also found to be decreased and the corresponding cortical regions were thinner relative to controls. The linkage between disrupted white matter integrity and the abnormal cortical thickness may be a vulnerability marker for OCD.
    PLoS ONE 01/2014; 9(1):e85663. DOI:10.1371/journal.pone.0085663 · 3.23 Impact Factor
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    • "These findings were associated with the neurocognitive performance and DM duration. In a more recent study, they found reduced cortical thickness in areas with high connectivity to the posterior corona radiata and optic radiation, which indicates a relation between white matter tract and cortical pathology (5). In type 2 DM patients, Hsu et al. (6) found reduced mean diffusion in a global analysis and reduced FA in frontal white matter and higher mean diffusion in the cerebellum, temporal white matter, parahippocampal gyrus, fusiform gyrus, and cuneus. "
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    ABSTRACT: OBJECTIVE In patients with long-standing diabetes mellitus (DM), there is increasing evidence for abnormal processing of gastrointestinal sensations in the central nervous system. Using magnetic resonance diffusion tensor imaging, we characterized brain microstructure in areas involved in visceral sensory processing and correlated these findings to clinical parameters.RESEARCH DESIGN AND METHODS Twenty-six patients with DM and gastrointestinal symptoms and 23 healthy control subjects were studied in a 3T scanner. The apparent diffusion coefficient (i.e., diffusivity of water) and fractional anisotropy (FA) (i.e., organization of fibers) were assessed in the "sensory matrix" (cingulate cortex, insula, prefrontal and secondary sensory cortex, amygdala, and corona radiata) and in corpus callosum.RESULTSPatients had decreased FA values compared with control subjects: 1) all areas (P = 0.025); 2) anterior (P < 0.001), mid- (P = 0.001), and posterior (P < 0.001) cingulate cortex; 3) prefrontal cortex gray matter (P < 0.001); 4) corona radiata (P < 0.001); 5) secondary sensory cortex (P = 0.008); 6) anterior white matter (P = 0.045); and anterior gray matter (P = 0.002) and posterior gray matter (P = 0.002) insula. No difference was found in corpus callosum (P > 0.05). The microstructural changes were for some areas correlated to clinical parameters such as bloating (anterior insula), mental well-being (anterior insula, prefrontal cortex, and mid-cingulated and corona radiata), autonomic function based on electrocardiographic results (posterior insula and anterior cingulate), and presence of gastroparesis (anterior insula).CONCLUSIONS The findings of this explorative study indicate that microstructural changes of brain areas involved in visceral sensory processing are associated with autonomic dysfunction and therefore may be involved in the pathogenesis of gastrointestinal symptoms in DM patients.
    Diabetes care 11/2012; 36(3). DOI:10.2337/dc12-1131 · 8.42 Impact Factor
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    • "It was shown that patients with long-standing type 1 diabetes had significantly reduced FA in the posterior corona radiata and optic radiation, which correlated with the duration of diabetes (Kodl et al., 2008). These patients also had significantly reduced cortical thickness in brain regions with high connectivity to the injured WM tracts (Franc et al., 2011). DTI assessment among individuals with type 2 diabetes demonstrated diffuse but predominantly frontal and temporal WM microstructural abnormalities (Yau et al., 2009). "
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    ABSTRACT: Diabetes mellitus affects the brain. Both type 1 and type 2 diabetic patients are associated with white matter (WM) damage observable to diffusion tensor imaging (DTI). The underlying histopathological mechanisms, however, are poorly understood. The objectives of this study are 1) to determine whether streptozotocin (STZ)-induced type 1 diabetes is associated with WM damage observable to DTI; and 2) to understand the pathophysiological aspects underlying STZ-induced brain injuries. Male Sprague-Dawley rats received a single intraperitoneal injection of STZ (62 mg/kg). DTI was used to assess brain abnormalities at 4 weeks after induction, combined with histological assessments and ultrastructural analysis. Compared to controls, the STZ-induced rats showed significantly reduced fractional anisotropy (FA) in the motor/somatosensory cortex and striatum. Histologically, the cortex and striatum of the diabetic animals are characterized by demyelination and axonal degradation. In conclusion, STZ-induced diabetes is associated with striatal/cortical injuries observable to DTI. The DTI abnormalities are likely manifestations of demyelination and axonal degradation in the affected brain regions, and can potentially be used as surrogates for evaluating diabetic brain injuries.
    Clinical neuroimaging 09/2012; 1(1):57-65. DOI:10.1016/j.nicl.2012.09.004 · 2.53 Impact Factor
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