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At least 37 records · Page 2Linked to original sources

Mapping functionally related regions of brain with functional connectivity MR imaging.

BACKGROUND AND PURPOSE: In subjects who are performing no prescribed cognitive task, functional connectivity mapped with MR imaging (fcMRI) shows regions with synchronous fluctuations of cerebral blood flow. When specific tasks are performed, functional MR imaging (fMRI) can map locations in which regional cerebral blood flow increases synchronously with the performance of the task. We tested the hypothesis that fcMRI maps, based on the synchrony of low-frequency blood flow fluctuations, identify brain regions that show activation on fMRI maps of sensorimotor, visual, language, and auditory tasks. METHODS: In four volunteers, task-activation fMRI and functional connectivity (resting-state) fcMRI data were acquired. A small region of interest (in an area that showed maximal task activation) was chosen, and the correlation coefficient of the corresponding resting-state signal with the signal of all other voxels in the resting data set was calculated. The correlation coefficient was decomposed into frequency components and its distribution determined for each fcMRI map. The fcMRI maps were compared with the fMRI maps. RESULTS: For each task, fcMRI maps based on one to four seed voxel(s) produced clusters of voxels in regions of eloquent cortex. For each fMRI map a closely corresponding fcMRI map was obtained. The frequencies that predominated in the cross-correlation coefficients for the functionally related regions were below 0.1 Hz. CONCLUSION: Functionally related brain regions can be identified by means of their synchronous slow fluctuations in signal intensity. Such blood flow synchrony can be detected in sensorimotor areas, expressive and receptive language regions, and the visual cortex by fcMRI. Regions identified by the slow synchronous fluctuations are similar to those activated by motor, language, or visual tasks.

Adult↗

Functional connectivity networks are disrupted in left temporal lobe epilepsy.

OBJECTIVE: Functional connectivity maps the distributed network of brain regions fluctuating synchronously during a continuous brain state. This study sought to investigate whether patients with left temporal lobe epilepsy (TLE) differ from controls in their resting-state functional connectivity between typical language regions. METHODS: We studied 17 patients with left TLE, together with eight healthy controls, using seeded functional connectivity. Seed regions were defined using the regions of maximal activation and deactivation during a language functional magnetic resonance imaging (fMRI) task in a separate cohort of 30 controls. RESULTS: Language fMRI produced the expected activation pattern, which was not different between patients and controls. However, functional connectivity between language areas during rest was markedly different; whereas controls showed connectivity between each of the seed areas and the majority of the language areas, patients showed connectivity only with a few areas, particularly the seed area itself. This difference was significant in the direct comparison of patients and control connectivity maps. INTERPRETATION: We suggest that this reduced connectivity in left temporal lobe epilepsy may reflect a disturbance of the language network during resting state in patients and may be related to subtle language difficulties in this patient population.

Adult↗

Combined functional MRI and tractography to demonstrate the connectivity of the human primary motor cortex in vivo.

In this study, we combined advanced MR techniques to explore primary motor cortex (M1) connectivity in the human brain. We matched functional and anatomical information using motor functional MRI (fMRI) and white matter tractography inferred from diffusion tensor imaging (DTI). We performed coregistered DTI and motor task fMRI in 8 right-handed healthy subjects and in 1 right-handed patient presenting with a left precentral tumour. We used the fast-marching tractography (FMT) algorithm to define 3D connectivity maps within the whole brain, from seed points selected in the white matter adjacent to the location of the maximum of fMRI activation. Connectivity maps were then anatomically normalised and analysed using statistical parametric mapping software (SPM99) allowing group comparisons (left versus right hemisphere in control subjects and patient versus control subjects). The results demonstrated, in all control subjects, strong connections from M1 to the pyramidal tracts, premotor areas, parietal cortices, thalamus, and cerebellum. M1 connectivity was asymmetric, being more extensive in the dominant hemisphere. The patient had differences in M1 connectivity from the control group. Thus, fMRI-correlated DTI-FMT is a promising tool to study the structural basis of functional networks in the human brain in vivo.

Adult↗

Functional connectivity changes with concentration of sevoflurane anesthesia.

Low-frequency oscillations (<0.08 Hz) have been detected in functional magnetic resonance imaging studies, and appear to be synchronized between functionally related areas. The effect of anesthetic agents on cortical activity is not completely characterized. This study assessed the effect of anesthesia on the temporal relations in activity in the motor cortices. Resting-state magnetic resonance data were acquired on six volunteers under different anesthetic states (using 0.0%, 2.0% and 1.0% stable end-tidal sevoflurane). Across all volunteers, the number of significant voxels (p<2.5 x 10) in the functional connectivity maps was reduced by 78% for light anesthesia and by 98% for deep anesthesia, compared with the awake state. Additionally, significant correlations in the connectivity maps were bilateral in the awake state but unilateral in the light anesthesia state.

Adult↗

Left atrial fibrillation with regular right atrial activation and a single left-to-right electrical interatrial connection: multisite mapping of dissimilar atrial rhythms.

We report two patients who had isolated atrial fibrillation in the left atrium and regular activation of the entire right atrium. Mapping of the arrhythmia was performed using a 64-electrode basket catheter that was inserted intravenously and deployed in the right and left atria. Both patients manifested a single, stable interatrial electrical connection conducting in a left-to-right direction, consistent with Bachmann's bundle location. The right and left sides of the interatrial septum were activated discordantly, each reflecting activation characteristics of the respective atria. A filtering effect at the level of interatrial septum was demonstrated by calculating the fibrillation intervals on both sides of the operative interatrial connection. It was concluded that differences in activation of the left and right surfaces of the interatrial septum and preferential use and the filtering effect of the interatrial connections play a significant role in explaining the differences in activation patterns of the left and right atria in patients with atrial fibrillation.

Atrial Fibrillation↗

Web GIS in practice IV: publishing your health maps and connecting to remote WMS sources using the Open Source UMN MapServer and DM Solutions MapLab.

Open Source Web GIS software systems have reached a stage of maturity, sophistication, robustness and stability, and usability and user friendliness rivalling that of commercial, proprietary GIS and Web GIS server products. The Open Source Web GIS community is also actively embracing OGC (Open Geospatial Consortium) standards, including WMS (Web Map Service). WMS enables the creation of Web maps that have layers coming from multiple different remote servers/sources. In this article we present one easy to implement Web GIS server solution that is based on the Open Source University of Minnesota (UMN) MapServer. By following the accompanying step-by-step tutorial instructions, interested readers running mainstream Microsoft(R) Windows machines and with no prior technical experience in Web GIS or Internet map servers will be able to publish their own health maps on the Web and add to those maps additional layers retrieved from remote WMS servers. The 'digital Asia' and 2004 Indian Ocean tsunami experiences in using free Open Source Web GIS software are also briefly described.

Geographic Information Systems↗

Cell signaling: from beginning to end.

The Connections Maps database and the graphical Web interface at Science's STKE for accessing the data represent an emerging Web-based tool through which researchers in cell signaling can share their knowledge with the scientific community. This tool provides a mechanism by which researchers, students, and clinicians can transform information about interactions between biomolecules into knowledge about a cellular process. In 2005, new Pathways were added to the Connections Maps database and several of the existing Pathways were updated.

Cooperative Behavior↗

Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging.

Evidence concerning anatomical connectivities in the human brain is sparse and based largely on limited post-mortem observations. Diffusion tensor imaging has previously been used to define large white-matter tracts in the living human brain, but this technique has had limited success in tracing pathways into gray matter. Here we identified specific connections between human thalamus and cortex using a novel probabilistic tractography algorithm with diffusion imaging data. Classification of thalamic gray matter based on cortical connectivity patterns revealed distinct subregions whose locations correspond to nuclei described previously in histological studies. The connections that we found between thalamus and cortex were similar to those reported for non-human primates and were reproducible between individuals. Our results provide the first quantitative demonstration of reliable inference of anatomical connectivity between human gray matter structures using diffusion data and the first connectivity-based segmentation of gray matter.

Adult↗

Functional connectivity of dissociative responses in posttraumatic stress disorder: a functional magnetic resonance imaging investigation.

BACKGROUND: The purpose of this study was to assess interregional brain activity covariations during traumatic script-driven imagery in subjects with posttraumatic stress disorder (PTSD). METHODS: Functional magnetic resonance imaging and functional connectivity analyses were used to assess interregional brain activity covariations during script-driven imagery in PTSD subjects with a dissociative response, PTSD subjects with a flashback response, and healthy control subjects. RESULTS: Significant between-group differences in functional connectivity were found. Comparing dissociated PTSD patients and control subjects' connectivity maps in the left ventrolateral thalamus (VLT) [-14, -16, 4] revealed that control subjects had higher covariations between activations in VLT and in the left superior frontal gyrus (Brodmann's area [BA] 10), right parahippocampal gyrus (BA 30), and right superior occipital gyrus (BA 19, 39), whereas greater covariation with VLT in dissociated PTSD subjects occurred in the right insula (BA 13, 34), left parietal lobe (BA 7), right middle frontal gyrus (BA 8), superior temporal gyrus (BA 38, 34), and right cuneus (BA 19). Comparing dissociated PTSD and flashback PTSD connectivity maps in the right cingulate gyrus [3, 16, 30] revealed that dissociated PTSD subjects had higher covariations between activations in this region and the left inferior frontal gyrus (BA 47). CONCLUSIONS: Greater activation of neural networks involved in representing bodily states was seen in dissociated PTSD subjects than in non-PTSD control subjects. These findings might illuminate the mechanisms underlying distorted body perceptions often observed clinically during dissociative episodes.

Accidents, Traffic↗

Integrative Transcriptomic and Proteomic Profiling Identifies S100P as a Potential Functional Biomarker for Sessile Serrated Lesions.

BACKGROUND: Sessile serrated lesions (SSLs) account for 15% of colorectal cancers (CRCs) but detection remains difficult due to flat morphology, mucinous features, and subtle histology. AIMS: This study aimed to identify novel and functionally relevant biomarkers of SSLs using transcriptomic screening and multi-omics validation. METHODS: Paired SSL and normal mucosa specimens (n&#x2009;=&#x2009;6) underwent RNA sequencing. Differentially expressed genes (DEGs) were filtered for membrane or secretory proteins and validated across TCGA and adenoma transcriptomes. Functional significance was assessed using CRISPR dependency profiling, proteotranscriptomic concordance, pharmacogenomic sensitivity, and connectivity map analysis. RESULTS: We identified 216 upregulated genes in SSLs, including 68 encoding secretory/membrane proteins that better discriminated SSLs from controls and were enriched for adhesion and neuronal signaling while suppressing TNF&#x3b1;-NF&#x3ba;B inflammatory pathways. Cross-cohort comparison revealed five overlapping candidates between SSLs and TCGA CMS1 tumors. Among them, S100P emerged as the primary biomarker candidate, showing consistent upregulation in SSLs and CMS1 tumors while remaining low in normal mucosa and conventional adenomas. TFF1 also showed RNA-level upregulation but appeared more context-dependent. S100P demonstrated strong RNA-protein concordance in CRC cell-line profiling, supporting its detectability as a biomarker candidate. Pharmacogenomic profiling of LS411N cells revealed marked sensitivity to SN-38 and fluoropyrimidines, consistent with serrated CRC vulnerabilities. Connectivity map analysis identified perturbations, including MAPK1 and histone acetyltransferase suppression, that may reverse parts of the SSL transcriptional program. CONCLUSION: These findings prioritize S100P as a promising biomarker candidate for SSLs that warrants further validation in larger cohorts and clinically applicable platforms.

Humans↗

Mapping disulfide connectivity using backbone ester hydrolysis.

The site-specific incorporation of alpha-hydroxy acids into proteins using nonsense suppression can provide a powerful probe of protein structure and function. The resulting backbone ester may be selectively hydrolyzed in the presence of the peptide backbone, providing an "orthogonal" chemistry that can be useful both as an analytical tool and as a structural probe. Here we describe in detail a substantial substituent effect on this hydrolysis reaction. Consistent with mechanistic expectations, the steric bulk of the amino acid immediately N-terminal of the hydroxy acid has a large effect on the hydrolysis rate. On the basis of these results, we also describe a simple protocol for identifying disulfide loops in soluble and membrane proteins, exemplified by the alpha subunit of the muscle nicotinic acetylcholine receptor (nAChR). If a backbone ester is incorporated outside a disulfide loop, hydrolysis alone gives two fragments, but if the ester is incorporated within a disulfide loop, both hydrolysis and reduction are required for cleavage. This test could be useful in characterizing the disulfide topology of complex, membrane proteins.

Amino Acid Substitution↗

Ephrin-A5 modulates the topographic mapping and connectivity of commissural axons in murine hippocampus.

Entorhinal and commissural/associational projections show a non-overlapping distribution in the hippocampus proper and the dentate gyrus. The expression of Ephrins and their Eph receptors in the developing hippocampus indicates that this family of axonal guidance molecules may modulate the formation of these connections. Here we focused on the role of the ephrin-A5 ligand in the development of the main hippocampal afferents. In situ hybridization showed that ephrin-A5 mRNA was detected mainly in the principal cells of the hippocampus proper and in the dentate gyrus throughout postnatal development. Immunocytochemical analyses revealed prominent expression of the EphA3 receptor, a putative receptor for ephrin-A5, in the main cells and the neuropil of the developing hippocampus. Tracing experiments in ephrin-A5(-/-) mice showed that commissural projections were transiently altered in the hippocampus proper at P5, but they were mistargeted throughout the postnatal development in the dentate gyrus. Immunocytochemistry with anti-calbindin antibodies revealed that the dentate mossy fiber projection was not altered in ephrin-A5(-/-) mice. Electron microscopy studies showed alterations in the density of synapses and spines in commissural/associational layers, but not in entorhinal layers, and in the mossy fibers in these animals. Taken together, these findings indicate that ephrin-A5 signaling is involved in the formation and maturation of synapses in the hippocampus.

Animals↗

High resolution 3D exchange NMR spectroscopy and the mapping of connectivities between half-integer quadrupolar nuclei.

A novel approach to the determination of structure and potential dynamics in the solid-state NMR spectroscopy of half-integer quadrupolar nuclei is proposed and demonstrated. The new experiment combines into a single three-dimensional sequence, 2D multiple-quantum magic-angle-spinning NMR and 2D exchange NMR protocols. The result separates for each inequivalent chemical site its spin-diffusion powder line shape to proximate homonuclei. A peculiar feature of the experiment is the asymmetry it displays in the individual 2D powder patterns, resulting from its encoding of isotropic shifts before the mixing period. The resulting spectra facilitate the interpretation of the structural and dynamic features for the individual sites; experimental applications of this new method to relative geometry determinations in 23Na-23Na spin pairs are presented, and the quantitative evaluation of the resulting data is briefly discussed.

Journal Article↗