White matter tracts involved in subcortical unilateral spatial neglect in subacute stroke.

Background: Unilateral spatial neglect (USN) is common and associated with poor motor and cognitive outcomes as well as impaired quality of life following stroke. Traditionally, the neural substrates underlying USN have been thought to be cortical areas, such as the posterior parietal cortex. However, patients with stroke involving only subcortical structures may also present with USN. While only a few studies have reported on USN in subcortical stroke, the involvement of white matter tracts related to brain networks of visuospatial attention is one possible explanation for subcortical neglect. Therefore, this study aimed to investigate which specific white matter tracts are neural substrates for USN in patients with subcortical stroke. Methods: Twenty-two patients with subcortical stroke without cortical involvement who were admitted to the Department of Rehabilitation Medicine at Seoul National University Bundang Hospital were retrospectively enrolled. Nine subjects were subclassified into a "USN(+)" group, as they had at least two positive results on three tests (the Schenkenberg line bisection test, Albert's test, and house drawing test) and a score of 1 or higher on the Catherine Bergego scale. The remaining 13 subjects without abnormalities on those tests were subclassified into the "USN(-)" group. Stroke lesions on MRI were manually drawn using MRIcron software. Lesion overlapping and atlas-based analyses of MRI images were conducted. The correlation was analyzed between the overlapped lesion volumes with white matter tracts and the severity of USN (in the Albert test and the Catherine Bergego scale). Results: Lesions were more widespread in the USN(+) group than in the USN(-) group, although their locations in the right hemisphere were similar. The atlas-based analyses identified that the right cingulum in the cingulate cortex, the temporal projection of the superior longitudinal fasciculus, and the forceps minor significantly overlapped with the lesions in the USN(+) group than in the USN(-) group. The score of the Catherine Bergego scale correlated with the volume of the involved white matter tracts. Conclusion: In this study, white matter tracts associated with USN were identified in patients with subcortical stroke without any cortical involvement. Our study results, along with previous findings on subcortical USN, support that USN may result from damage to white matter pathways.

Decreased Cortical Thickness and Local Gyrification in Individuals with Subjective Cognitive Impairment.

OBJECTIVE: Subjective cognitive impairment (SCI) is associated with future cognitive decline. This study aimed to compare cortical thickness and local gyrification index (LGI) between individuals with SCI and normal control (NC) subjects. METHODS: Forty-seven participants (27 SCI and 20 NC) were recruited. All participants underwent brain magnetic resonance imaging scanning and were clinically assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of tests. We compared cortical thickness and LGI between the two groups and analyzed correlations between cortical thickness/LGI and scores on CERAD protocol subtests in the SCI group for region of interests with significant between-group differences. RESULTS: Cortical thickness reduction in the left entorhinal, superior temporal, insular, rostral middle frontal, precentral, superior frontal, and supramarginal regions, and right supramarginal, precentral, insular, postcentral, and posterior cingulate regions was observed in the SCI compared to the NC group. Cortical thickness in these regions correlated with scores of constructional praxis, word list memory, word list recall, constructional recall, trail making test A, and verbal fluency under the CERAD protocol. Significantly decreased gyrification was observed in the left lingual gyrus of the SCI group. In addition, gyrification of this region was positively associated with scores of constructional praxis. CONCLUSION: Our results may provide an additional reference to the notion that SCI may be associated with future cognitive impairment. This study may help clinicians to assess individuals with SCI who may progress to mild cognitive impairment and Alzheimer's dementia.

Neural substrates of subcortical aphasia in subacute stroke: Voxel-based lesion symptom mapping study.

Subcortical aphasia develops as a result of damage to subcortical brain areas without loss of cortical functions. Although earlier voxel-based lesion-symptom mapping (VLSM) studies have shown possible neural correlates for aphasia, it remains to be clarified which brain regions are associated with subcortical aphasia. The aim of this study was to investigate the neural substrates associated with subcortical aphasia in patients with stroke using VLSM and atlas-based analyses to explore the involvement of white matter tracts and subcortical structures. Fifty patients with subacute subcortical stroke without cortical involvement were retrospectively enrolled: 24 with and 26 without aphasia. We performed VLSM and atlas-based analyses of the patients' fluid-attenuated inversion recovery images and found that the left perisylvian white matter, left fronto-occipital fasciculus, uncinate fasciculus, and forceps minor were significantly more greatly affected in the aphasia than in the non-aphasia group. The left anterior thalamic radiation, cingulum (cingulate gyrus), and superior longitudinal fasciculus also showed higher involvement in this group (marginal significance). Among the subcortical regions, the left caudate and putamen were more greatly involved in the aphasia group. Our findings confirm language processing as one of the integrated sensory-motor processes that occur in the region around the left sylvian fissure. Our atlas-based analysis approach can be used to complement VLSM analyses.

Comparison of neurodegenerative types using different brain MRI analysis metrics in older adults with normal cognition, mild cognitive impairment, and Alzheimer's dementia.

Several metrics of analysis of magnetic resonance imaging (MRI) have been used to assess Alzheimer's disease (AD)-related neurodegeneration. We compared four structural brain MRI analysis metrics, cortical thickness, volume, surface area, and local gyrification index (LGI), in different stages of AD-related cognitive decline. Participants with normal cognition, mild cognitive impairment, and AD were included (34 participants per group). All undertook the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of neuropsychological tests and brain MRI scanning. We analyzed associations between morphometric measures and CERAD total/ Mini Mental State Examination (MMSE) scores for the regions of interest (ROIs), identifying three types of curves: U-shaped, inverted U-shaped, and linear. Cortical thickness and volume analyses showed linear types in most of the significant ROIs. Significant ROIs for the cortical thickness analysis were located in the temporal and limbic lobes, whereas those for volume and surface area were distributed over more diffuse areas of the brain. LGI analysis showed few significant ROIs. CERAD total scores were more sensitive to early changes of cortical structures than MMSE scores. Cortical thickness analysis may be preferable in assessing brain structural MRI changes during AD-related cognitive decline, whereas LGI analysis may have limited capability to reflect the cognitive decrease. Our findings may provide a reference for future studies and help to establish optimal analytical approaches to brain structural MRI in neurodegenerative diseases.

Diffusion tensor imaging reveals abnormal brain networks in elderly subjects with subjective cognitive deficits.

PURPOSE: Some elders with subjective cognitive deficits (SCD) develop prodromal phase of dementia over time; however, little is known about how they differ from those with normal cognition (NC). Thus, we aim to distinguish the differences in the brain network of elders with SCD and NC. METHODS: Multiple diffusion-weighted images (DWI) and T1-weighted images were obtained from 18 subjects with NC and 26 subjects with SCD. Using network-based statistics (NBS) analysis, we extracted abnormal brain subnetworks and localized abnormal brain connectivity. We also ran correlation analysis to compare the affected regions and the results of the neurocognitive assessments. RESULTS: Altered subnetworks were found in the superior parietal gyrus, angular gyrus, precuneus, posterior cingulum, putamen, precentral gyrus, postcentral gyrus, and paracentral lobule. They were also associated with scores on the word list recall, word list recognition, and Boston naming test. CONCLUSIONS: Elders with SCD had distinctive brain network alterations when compared with those of elders with NC. The results are also in line with the previously identified characteristics of mild cognitive impairment (MCI) and of Alzheimer's disease (AD) in a milder form. We speculate that it may be possible to predict AD progression early in the SCD stage using NBS analysis.

Effects of Omega-3-Rich Harp Seal Oil on the Production of Pro-Inflammatory Cytokines in Mouse Peritoneal Macrophages.

Omega-3, a polyunsaturated fatty acid, is an essential fatty acid necessary for human health, and it protects against cardiovascular disease, inflammation, autoimmune diseases, and cancer. In the present study, we investigated the effects of omega-3-rich harp seal oil (HSO) on the production of nitric oxide (NO) and cytokines, such as tumor necrosis factor (TNF)-α, interleukin-(IL)-1ß, IL-6, and IL-12/IL-23 (p40) in peritoneal macrophages of mice. The culture supernatants of murine macrophages exposed to lipopolysaccharide (LPS), HSO, or HSO+LPS were harvested to assay IL-1ß, TNF-α, IL-6, and IL-12/IL-23 (p40) cytokines and NO. TNF-α, IL-1 ß, and IL-12/IL-23 (p40) levels, except IL-6, were lower in the culture supernatants of mouse peritoneal macrophages exposed to LPS plus HSO than those of the groups exposed to LPS alone. These observations demonstrate that omega-3-rich harp seal oil downregulates the production of the pro-inflammatory cytokines such as IL-1ß, TNF-α, and IL-12/IL-23 (p40). These results suggest that HSO could be potentially used as a preventive agent or as an adjunct in anti-inflammatory therapy, if more research results were accumulated.

Effects of ß-lapachone on the production of Th1 and Th2 cytokines in C57BL/6 mice.

In this study, we investigated the effects of ß-lapachone (ß-lap) on the production of cytokines in C57BL/6 mice. The culture supernatants of splenocytes exposed to ß-lap plus lipopolysaccharide or concanavalin A (Con A) were harvested to determine Th1 (tumor necrosis factor-α, interferon-γ, interleukin [IL]-1ß, IL-2, IL-17A, and IL-12) and Th2 (IL-4, IL-5, IL-6, and IL-10) cytokines. IL-2, a Th1 cytokine, was expressed at higher levels in splenocytes treated with ß-lap and with lipopolysaccharide plus ß-lap. Expression of Th2 cytokines, including IL-4, IL-5, IL-6, and IL-10, was lower in the culture supernatants of mouse splenocytes exposed to Con A plus ß-lap than in supernatants from cells that were exposed to Con A alone. These findings demonstrate that ß-lap downregulates the immediate hypersensitivity reaction induced by Con A. Therefore, Th2 responses involve the downregulation of IL-4, IL-5, IL-6, and IL-10, preventing the occurrence of allergies and various manifestations of allergic inflammation. These results suggest that ß-lap may have potential preventive or adjunct anti-inflammatory therapy applications because of its function in modulating the production of cytokines. However, further in vivo investigations of this process are necessary to elucidate the mechanisms involved.