Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging.
Ontology highlight
ABSTRACT:
SUBMITTER: Yokoyama JS
PROVIDER: S-EPMC5382127 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Identifying genetic variation associated with brain structures in aging may elucidate new biologic mechanisms underlying resilience to cognitive decline. We investigated whether carrying one copy of the protective haplotype "KL-VS" in longevity gene KLOTHO (KL) is associated with greater gray matter volume in healthy human aging compared to carrying no copies.We performed unbiased whole-brain analysis in cognitively normal older adults from two independent cohorts to assess the relationship between KL-VS and gray matter volume using voxel-based morphometry.We found that KL-VS heterozygosity was associated with greater volume in right dorsolateral prefrontal cortex (rDLPFC). Because rDLPFC is important for executive function, we analyzed working memory and processing speed in individuals. KL-VS heterozygosity was associated with enhanced executive function. Larger rDLPFC volume correlated with better executive function across the lifespan examined. Statistical analysis suggested that volume partially mediates the effect of genotype on cognition.These results suggest that variation in KL is associated with bigger brain volume and better function.
| S-EPMC4369272 | biostudies-literature
Project description:Human beings are social animals and they vary in the degree to which they share information about themselves with others. Although brain networks involved in self-related cognition have been identified, especially via the use of resting-state experiments, the neural circuitry underlying individual differences in the sharing of self-related information is currently unknown. Therefore, we investigated the intrinsic functional organization of the brain with respect to participants' degree of self-related information sharing using resting state functional magnetic resonance imaging and self-reported social media use. We conducted seed-based correlation analyses in cortical midline regions previously shown in meta-analyses to be involved in self-referential cognition: the medial prefrontal cortex (MPFC), central precuneus (CP), and caudal anterior cingulate cortex (CACC). We examined whether and how functional connectivity between these regions and the rest of the brain was associated with participants' degree of self-related information sharing. Analyses revealed associations between the MPFC and right dorsolateral prefrontal cortex (DLPFC), as well as the CP with the right DLPFC, the left lateral orbitofrontal cortex and left anterior temporal pole. These findings extend our present knowledge of functional brain connectivity, specifically demonstrating how the brain's intrinsic functional organization relates to individual differences in the sharing of self-related information.
| S-EPMC4780087 | biostudies-other
Project description:In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that are temporally anti-correlated with a midline "DMN-like" network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans.
| S-EPMC3796325 | biostudies-literature
Project description:This observational, cross-sectional study investigates cortical signatures of developmental dyslexia, particularly from the perspective of behavioral remediation. We employed resting-state fMRI, and compared intrinsic functional connectivity (iFC) patterns of known reading regions (seeds) among three dyslexia groups characterized by (a) no remediation (current reading and spelling deficits), (b) partial remediation (only reading deficit remediated), and (c) full remediation (both reading and spelling deficits remediated), and a group of age- and IQ-matched typically developing children (TDC) (total N?=?44, age range?=?7-15 years). We observed significant group differences in iFC of two seeds located in the left posterior reading network - left intraparietal sulcus (L.IPS) and left fusiform gyrus (L.FFG). Specifically, iFC between L.IPS and left middle frontal gyrus was significantly weaker in all dyslexia groups, irrespective of remediation status/literacy competence, suggesting that persistent dysfunction in the fronto-parietal attention network characterizes dyslexia. Additionally, relative to both TDC and the no remediation group, the remediation groups exhibited stronger iFC between L.FFG and right middle occipital gyrus (R.MOG). The full remediation group also exhibited stronger negative iFC between the same L.FFG seed and right medial prefrontal cortex (R.MPFC), a core region of the default network These results suggest that behavioral remediation may be associated with compensatory changes anchored in L.FFG, which reflect atypically stronger coupling between posterior visual regions (L.FFG-R.MOG) and greater functional segregation between task-positive and task-negative regions (L.FFG-R.MPFC). These findings were bolstered by significant relationships between the strength of the identified functional connections and literacy scores. We conclude that examining iFC can reveal cortical signatures of dyslexia with particular promise for monitoring neural changes associated with behavioral remediation.
| S-EPMC3569450 | biostudies-literature
Project description:Although previous studies have emphasized the vulnerability of the default mode network (DMN) in Alzheimer's disease (AD), little is known about the involvement of other functional networks and their relationship to clinical phenotype. To test whether clinicoanatomic heterogeneity in AD is driven by the involvement of specific networks, network connectivity was assessed in healthy subjects by seeding regions commonly and specifically atrophied in three clinical AD variants: early-onset AD (age at onset, <65 y; memory and executive deficits), logopenic variant primary progressive aphasia (language deficits), and posterior cortical atrophy (visuospatial deficits). Four-millimeter seed regions of interest were used to obtain intrinsic connectivity maps in 131 healthy controls (age, 65.5 ± 3.5 y). Atrophy patterns in independent cohorts of AD variant patients and their correspondence to connectivity networks in controls were also assessed. The connectivity maps of commonly atrophied regions of interest support posterior DMN and precuneus network involvement across AD variants, whereas seeding regions specifically atrophied in each AD variant revealed distinct, syndrome-specific connectivity patterns. Goodness-of-fit analysis of each connectivity map with network templates showed the highest correspondence between the early-onset AD seed connectivity map and anterior salience and right executive-control networks, the logopenic aphasia seed connectivity map and the language network, and the posterior cortical atrophy seed connectivity map and the higher visual network. Connectivity maps derived from controls matched regions commonly and specifically atrophied in the patients. Our findings indicate that the posterior DMN and precuneus network are commonly affected in AD variants, whereas syndrome-specific neurodegenerative patterns are driven by the involvement of specific networks outside the DMN.
| S-EPMC3710820 | biostudies-other
Project description:Intrinsic functional connectivity magnetic resonance imaging (iFCMRI) provides an encouraging approach for mapping large-scale intrinsic connectivity networks (ICNs) in the "resting" brain. Structural connections as measured by diffusion tensor imaging (DTI) are a major constraint on the identified ICNs. This study aimed at the combined investigation of ten well-defined ICNs in healthy elderly subjects at single subject level as well as at the group level, together with the underlying structural connectivity. IFCMRI and DTI data were acquired in twelve subjects (68 ± 7 years) at a 3T scanner and were studied using the tensor imaging and fiber tracking software package. The seed-based iFCMRI analysis approach was comprehensively performed with DTI analysis, following standardized procedures including an 8-step processing of iFCMRI data. Our findings demonstrated robust ICNs at the single subject level and conclusive brain maps at the group level in the healthy elderly sample, supported by the complementary fiber tractography. The findings demonstrated here provide a methodological framework for future comparisons of pathological (e.g., neurodegenerative) conditions with healthy controls on the basis of multiparametric functional connectivity mapping.
| S-EPMC4058120 | biostudies-literature
Project description:Cortical single neuron activity and local field potential patterns change at different depths of general anesthesia. Here, we investigate the associated network level changes of functional connectivity. We recorded ongoing electrocorticographic (ECoG) activity from temporo-parieto-occipital cortex of 6 ferrets at various levels of isoflurane/nitrous oxide anesthesia and determined functional connectivity by computing amplitude envelope correlations. Through hierarchical clustering, we derived typical connectivity patterns corresponding to light, intermediate and deep anesthesia. Generally, amplitude correlation strength increased strongly with depth of anesthesia across all cortical areas and frequency bands. This was accompanied, at the deepest level, by the emergence of burst-suppression activity in the ECoG signal and a change of the spectrum of the amplitude envelope. Normalization of functional connectivity to the distribution of correlation coefficients showed that the topographical patterns remained similar across depths of anesthesia, reflecting the functional association of the underlying cortical areas. Thus, while strength and temporal properties of amplitude co-modulation vary depending on the activity of local neural circuits, their network-level interaction pattern is presumably most strongly determined by the underlying structural connectivity.
| S-EPMC6041950 | biostudies-literature
Project description:BackgroundPosterior cortical atrophy (PCA) is a clinical variant of Alzheimer's disease (AD) that presents with progressive visuospatial symptoms. While amnestic AD is characterized by disrupted default mode network (DMN) connectivity with corresponding increases in salience network (SN) connectivity, a visuospatial network appears to be disrupted early in PCA. Based on PCA patients' clinical features, we hypothesized that, in addition to early decreased integrity within the visuospatial network, patients with PCA would show increases in SN connectivity despite relative preservation of DMN. As the lateral pulvinar nucleus of the thalamus has direct anatomical connections with striate and extrastriate cortex and DMN, and the medial pulvinar is anatomically interconnected with SN, we further hypothesized that lateral and medial pulvinar nuclei might be implicated in intrinsic connectivity changes in PCA.Methods26 patients with PCA and 64 matched controls were recruited through UCSF Memory and Aging Center research programs. Each completed a standardized neuropsychological battery, structural MRI, and task-free fMRI. Seed-based functional correlations were used to probe networks of interest, including those seeded by the medial and lateral pulvinar thalamic nuclei, across the whole brain, and functional data analyses were adjusted for brain atrophy.ResultsPatients with PCA showed disproportionate deficits in the visuospatial domain; they also showed preserved social sensitivity and endorsed more depressive symptoms than HCs. PCA patients had significant parietooccipital atrophy accompanied by widespread connectivity decreases within the visuospatial network, enhanced connectivity between some structures in SN, and enhanced connectivity between key nodes of the DMN compared to controls. Increased SN connectivity correlated with a measure of social sensitivity, and increased DMN connectivity correlated with short-term memory performance. Medial pulvinar connectivity increases in PCA were topographically similar to SN (anterior insula) connectivity increases, while lateral pulvinar connectivity increases were similar to DMN (posterior cingulate) connectivity increases.ConclusionsPCA is characterized by preserved to heightened connectivity in the SN and DMN despite decreased visuospatial network connectivity. The spatial similarity of medial and lateral pulvinar connectivity changes to those seen in the SN and DMN suggests a role for the pulvinar in intrinsic connectivity network changes in PCA.
| S-EPMC6411779 | biostudies-literature
Project description:ObjectiveGrowing evidence has implicated dysfunction of the thalamus and its projection cortical targets in depression. However, the anatomical specificity of thalamo-cortical connectivity in major depressive disorder (MDD) remains unknown due to the regional heterogeneity of the thalamus and limited methods to examine this.MethodsResting-state fMRI was collected on 70 MDD patients and 70 healthy controls. The thalamus was parcellated based on connectivity with six predefined cortical regions of interest (ROIs). The segmented thalamic nuclei were used as seeds to map connectivity with the rest of the whole brain. The cortical-to-thalamus connectivity values and thalamus-based connectivity maps were compared between groups.ResultsThe cortical ROIs demonstrated correlations with spatially distinct zones within the thalamus. We found a trend toward reduced parietal ROI-to-thalamus connectivity in MDD. Importantly, MDD patients demonstrated reduced connectivity between prefrontal and parietal thalamus ROIs and bilateral middle frontal gyrus (MFG) and the right posterior default mode network (DMN) and between the prefrontal and motor thalamus ROIs and lateral temporal regions. Conversely, increased connectivity emerged between the motor thalamus ROI and right MFG and right medial frontal gyrus/anterior cingulate; between motor/somatosensory thalamus ROIs and right posterior DMN; between prefrontal/somatosensory thalamus ROIs and cerebellum; and between the parietal thalamus ROI and left insula.ConclusionsThis study is the first to examine the anatomical specificity of thalamo-cortical connectivity disturbances in MDD. Subjects with MDD demonstrated altered thalamo-cortical connectivity characterized by a complex pattern of region-dependent hypo- or hyperconnectivity. We therefore speculate that selectively modulating the connectivity of thalamo-cortical circuitry may be a potential novel therapeutic mechanism for MDD.
| S-EPMC6490069 | biostudies-literature
Project description:Aging is associated with a high prevalence of hypertension due to elevated susceptibility of BP to dietary salt, but its mechanism is unknown. Serum levels of Klotho, an anti-aging factor, decline with age. We found that high salt (HS) increased BP in aged mice and young heterozygous Klotho-knockout mice and was associated with increased vascular expression of Wnt5a and p-MYPT1, which indicate RhoA activity. Not only the Wnt inhibitor LGK974 and the Wnt5a antagonist Box5 but Klotho supplementation inhibits HS-induced BP elevation, similarly to the Rho kinase inhibitor fasudil, associated with reduced p-MYPT1 expression in both groups of mice. In cultured vascular smooth muscle cells, Wnt5a and angiotensin II (Ang II) increased p-MYPT1 expression but knockdown of Wnt5a with siRNA abolished Ang II-induced upregulation of p-MYPT1, indicating that Wnt5a is indispensable for Ang II-induced Rho/ROCK activation. Notably, Klotho inhibited Wnt5a- and Ang II-induced upregulation of p-MYPT1. Consistently, Klotho supplementation ameliorated HS-induced augmentation of reduced renal blood flow (RBF) response to intra-arterial infusion of Ang II and the thromboxane A2 analog U46619, which activated RhoA in both groups of mice and were associated with the inhibition of BP elevation, suggesting that abnormal response of RBF to Ang II contributes to HS-induced BP elevation. Thus, Klotho deficiency underlies aging-associated salt-sensitive hypertension through vascular non-canonical Wnt5a/RhoA activation.
| S-EPMC7410076 | biostudies-literature