Micrurus limbatus

Number of Pages: 3Integrative BiologyGeological Science

Multimodal Imaging Evidence for Axonal and Myelin Deterioration in Amnestic Mild Cognitive Impairment

White matter (WM) microstructural declines have been demonstrated in Alzheimer\u27s disease and amnestic mild cognitive impairment (aMCI). However, the pattern of WM microstructural changes in aMCI after controlling for WM atrophy is unknown. Here, we address this issue through joint consideration of aMCI alterations in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, as well as macrostructural volume in WM and gray matter compartments. Participants were 18 individuals with aMCI and 24 healthy seniors. Voxelwise analyses of diffusion tensor imaging data was carried out using tract-based spatial statistics (TBSS) and voxelwise analyses of high-resolution structural data was conducted using voxel based morphometry. After controlling for WM atrophy, the main pattern of TBSS findings indicated reduced fractional anisotropy with only small alterations in mean diffusivity/radial diffusivity/axial diffusivity. These WM microstructural declines bordered and/or were connected to gray matter structures showing volumetric declines. However, none of the potential relationships between WM integrity and volume in connected gray matter structures was significant, and adding fractional anisotropy information improved the classificatory accuracy of aMCI compared to the use of hippocampal atrophy alone. These results suggest that WM microstructural declines provide unique information not captured by atrophy measures that may aid the magnetic resonance imaging contribution to aMCI detection

Alterations in Multiple Measures of White Matter Integrity in Normal Women at High Risk for Alzheimer\u27s Disease

There is evidence that disruption of white matter (WM) microstructure is an early event in the course of Alzheimer\u27s disease (AD). However, the neurobiological bases of WM microstructural declines in presymptomatic AD are unknown. In the present study we address this issue using a multimodal imaging approach to the study of presymptomatic AD. Participants were 37 high-risk (both family history of dementia and one or more APOE4 alleles) women and 20 low-risk (neither family history nor APOE4) women. Groups were matched for age, education, neuropsychological performance, and vascular factors that could affect white matter. Whole-brain analyses of diffusion tensor imaging data [including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA) and radial diffusivity (DR)] and volumetric comparisons of medial temporal lobe (MTL) structures were conducted. Results indicated equivalent entorhinal cortex and hippocampal volumes between risk groups. Nevertheless, the high risk group showed decreased microstructural integrity in WM tracts with direct and secondary connections to the MTL. The predominant alteration in WM integrity in the high AD-risk group was decreased FA not solely driven by either DA or DR changes alone in regions where no MD changes were observed. A second pattern observed in a smaller number of regions involved decreased FA and increased DR. These results suggest that disconnection of MTL-neocortical fiber pathways represents a very early event in the course of AD and suggest that demyelination may represent one contributing mechanism

White matter integrity and vulnerability to Alzheimer's disease: Preliminary findings and future directions

AbstractNeuroimaging biomarkers that precede cognitive decline have the potential to aid early diagnosis of Alzheimer's disease (AD). A body of diffusion tensor imaging (DTI) work has demonstrated declines in white matter (WM) microstructure in AD and its typical prodromal state, amnestic mild cognitive impairment. The present review summarizes recent evidence suggesting that WM integrity declines are present in individuals at high AD-risk, prior to cognitive decline. The available data suggest that AD-risk is associated with WM integrity declines in a subset of tracts showing decline in symptomatic AD. Specifically, AD-risk has been associated with WM integrity declines in tracts that connect gray matter structures associated with memory function. These tracts include parahippocampal WM, the cingulum, the inferior fronto-occipital fasciculus, and the splenium of the corpus callosum. Preliminary evidence suggests that some AD-risk declines are characterized by increases of radial diffusivity, raising the possibility that a myelin-related pathology may contribute to AD onset. These findings justify future research aimed at a more complete understanding of the neurobiological bases of DTI-based declines in AD. With continued refinement of imaging methods, DTI holds promise as a method to aid identification of presymptomatic AD. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease

Cortical Iron Disrupts Functional Connectivity Networks Supporting Working Memory Performance in Older Adults

Excessive brain iron negatively affects working memory and related processes but the impact of cortical iron on task-relevant, cortical brain networks is unknown. We hypothesized that high cortical iron concentration may disrupt functional circuitry within cortical networks supporting working memory performance. Fifty-five healthy older adults completed an N-Back working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Participants also underwent quantitative susceptibility mapping (QSM) imaging for assessment of non-heme brain iron concentration. Additionally, pseudo continuous arterial spin labeling scans were obtained to control for potential contributions of cerebral blood volume and structural brain images were used to control for contributions of brain volume. Task performance was positively correlated with strength of task-based functional connectivity (tFC) between brain regions of the frontoparietal working memory network. However, higher cortical iron concentration was associated with lower tFC within this frontoparietal network and with poorer working memory performance after controlling for both cerebral blood flow and brain volume. Our results suggest that high cortical iron concentration disrupts communication within frontoparietal networks supporting working memory and is associated with reduced working memory performance in older adults

Tensors, non-Gaussianities, and the future of potential reconstruction

We present projections for reconstruction of the inflationary potential expected from ESA's upcoming Planck Surveyor CMB mission. We focus on the effects that tensor perturbations and the presence of non-Gaussianities have on reconstruction efforts in the context of non-canonical inflation models. We consider potential constraints for different combinations of detection/null-detection of tensors and non-Gaussianities. We perform Markov Chain Monte Carlo and flow analyses on a simulated Planck-precision data set to obtain constraints. We find that a failure to detect non-Gaussianities precludes a successful inversion of the primordial power spectrum, greatly affecting uncertainties, even in the presence of a tensor detection. In the absence of a tensor detection, while unable to determine the energy scale of inflation, an observable level of non-Gaussianities provides correlations between the errors of the potential parameters, suggesting that constraints might be improved for suitable combinations of parameters. Constraints are optimized for a positive detection of both tensors and non-Gaussianities.Comment: 12 pages, 5 figures, LaTeX; V2: version submitted to JCA

Dissociation of Automatic and Strategic Lexical-semantics: Functional Magnetic Resonance Imaging Evidence for Differing Roles of Multiple Frontotemporal Regions

Behavioral research has demonstrated three major components of the lexical-semantic processing system: automatic activation of semantic representations, strategic retrieval of semantic representations, and inhibition of competitors. However, these component processes are inherently conflated in explicit lexical-semantic decision tasks typically used in functional magnetic resonance imaging (fMRI) research. Here, we combine the logic of behavioral priming studies and the neurophysiological phenomenon of fMRI priming to dissociate the neural bases of automatic and strategic lexical-semantic processes across a series of three studies. A single lexical decision task was used in all studies, with stimulus onset asynchrony or linguistic relationship between prime and target being manipulated. Study 1 demonstrated automatic semantic priming in the left mid-fusiform gyrus (mid-FFG) and strategic semantic priming in five regions: left middle temporal gyrus (MTG), bilateral anterior cingulate, anterior left inferior prefrontal cortex (aLIPC), and posterior LIPC (pLIPC). These priming effects were explored in more detail in two subsequent studies. Study 2 replicated the automatic priming effect in mid-FFG and demonstrated that automatic priming in this region is preferential for the semantic domain. Study 3 demonstrated a neural dissociation in regions contributing to the strategic semantic priming effect. Strategic semantic facilitation was observed in the aLIPC and MTG, whereas strategic semantic inhibition was observed in the pLIPC and anterior cingulate. These studies provide reproducible evidence for a neural dissociation between three well established components of the lexical-semantic processing system

White Matter Diffusion Alterations in Normal Women at Risk of Alzheimer\u27s Disease

Increased white matter mean diffusivity and decreased fractional anisotropy (FA) has been observed in subjects diagnosed with mild cognitive impairment (MCI) and Alzheimer\u27s disease (AD). We sought to determine whether similar alterations of white matter occur in normal individuals at risk of AD. Diffusion tensor images were acquired in 42 cognitively normal right-handed women with both a family history of dementia and at least one apolipoprotein E4 allele. These were compared with images from 23 normal women without either AD risk factor. Group analyses were performed using tract-based spatial statistics. Reduced FA was observed in the fronto-occipital and inferior temporal fasciculi (particularly posteriorly), the splenium of the corpus callosum, subcallosal white matter and the cingulum bundle. These findings demonstrate that specific white matter pathways are altered in normal women at increased risk of AD years before the expected onset of cognitive symptoms

Expression of chemokine receptors CXCR1 and CXCR2 during cardiopulmonary bypass

AbstractObjective: This study investigated the effects of cardiopulmonary bypass on neutrophil expression of chemokine receptors, CXCR1 and CXCR2, and the β2 integrin CD11b. Methods: Ten patients undergoing coronary artery grafting with cardiopulmonary bypass were studied. Blood samples were collected preoperatively, before bypass, at termination of bypass, and 12 to 18 hours postoperatively. In vitro studies were performed on control subjects to determine changes in the surface expression of CXCR1, CXCR2, and CD11b on stimulation with interleukin 8. Receptor expression was measured by flow cytometry. Plasma levels of interleukin 8 from the patients were determined by enzyme-linked immunoassay. Results: After bypass, CXCR2 expression fell by 66% (P <.0001) and remained low postoperatively (P <.0001). CXCR1 expression persisted at preoperative levels. CD11b expression increased significantly after bypass (P <.0001), returning to prebypass levels postoperatively. In vitro studies showed a dose-related fall of both CXCR1 (P <.0001) and CXCR2 expression (P <.0001) and a significant rise in CD11b expression (P <.0001). Plasma interleukin 8 increased significantly after bypass (P <.0001), remaining elevated 12 to 18 hours postoperatively (P =.02). Correlations between interleukin 8 levels and CXCR2 expression (P <.0001) and CD11b expression (P <.03) were demonstrated. Conclusions: CXCR2 expression is significantly down-regulated after bypass; in contrast, CXCR1 expression remains unchanged. In addition, whereas interleukin 8 is an important determinant of both CXCR1 and CXCR2 expression in vitro, it only correlates with CXCR2 and CD11b expression in vivo. This has implications in the search for antagonists against CXC chemokines and their receptor