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The association between cerebrovascular reactivity and resting-state fMRI functional connectivity in healthy adults: The influence of basal carbon dioxide.

ABSTRACT: Although widely used in resting-state fMRI (fMRI) functional connectivity measurement (fcMRI), the BOLD signal is only an indirect measure of neuronal activity, and is inherently modulated by both neuronal activity and vascular physiology. For instance, cerebrovascular reactivity (CVR) varies widely across individuals irrespective of neuronal function, but the implications for fcMRI are currently unknown. This knowledge gap compromises our ability to correctly interpret fcMRI measurements. In this work, we investigate the relationship between CVR and resting fcMRI measurements in healthy young adults, in both the motor and the executive-control networks. We modulate CVR within each individual by subtly increasing and decreasing resting vascular tension through baseline end-tidal CO2 (PETCO2), and measure fcMRI during these hypercapnic, hypocapnic and normocapnic states. Furthermore, we assess the association between CVR and fcMRI within and across individuals. Within individuals, resting PETCO2 is found to significantly influence both CVR and resting fcMRI values. In addition, we find resting fcMRI to be significantly and positively associated with CVR across the group in both networks. This relationship is potentially mediated by concomitant alterations in BOLD signal fluctuation amplitude. This work clearly demonstrates and quantifies a major vascular modulator of resting fcMRI, one that is also subject and regional dependent. We suggest that individualized correction for CVR effects in fcMRI measurements is essential for fcMRI studies of healthy brains, and can be even more important in studying diseased brains.

SUBMITTER: Golestani AM

PROVIDER: S-EPMC5148617 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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The association between cerebrovascular reactivity and resting-state fMRI functional connectivity in healthy adults: The influence of basal carbon dioxide.

Golestani Ali M AM Kwinta Jonathan B JB Strother Stephen C SC Khatamian Yasha B YB Chen J Jean JJ

NeuroImage 20160223

Although widely used in resting-state fMRI (fMRI) functional connectivity measurement (fcMRI), the BOLD signal is only an indirect measure of neuronal activity, and is inherently modulated by both neuronal activity and vascular physiology. For instance, cerebrovascular reactivity (CVR) varies widely across individuals irrespective of neuronal function, but the implications for fcMRI are currently unknown. This knowledge gap compromises our ability to correctly interpret fcMRI measurements. In th ...[more]

PMID: 26908321

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Project description:ObjectivesIn healthy aging, the way people cope differently with cognitive and neural decline is influenced by exposure to cognitively enriching life-experiences. Education is one of them, so that in general, the higher the education, the better the expected cognitive performance in aging. At the neural level, it is not clear yet how education can differentiate resting state functional connectivity profiles and their cognitive underpinnings. Thus, with this study, we aimed to investigate whether the variable education allowed for a finer description of age-related differences in cognition and resting state FC.MethodsWe analyzed in 197 healthy individuals (137 young adults aged 20-35 and 60 older adults aged 55-80 from the publicly available LEMON database), a pool of cognitive and neural variables, derived from magnetic resonance imaging, in relation to education. Firstly, we assessed age-related differences, by comparing young and older adults. Then, we investigated the possible role of education in outlining such differences, by splitting the group of older adults based on their education.ResultsIn terms of cognitive performance, older adults with higher education and young adults were comparable in language and executive functions. Interestingly, they had a wider vocabulary compared to young adults and older adults with lower education. Concerning functional connectivity, the results showed significant age- and education-related differences within three networks: the Visual-Medial, the Dorsal Attentional, and the Default Mode network (DMN). For the DMN, we also found a relationship with memory performance, which strengthen the evidence that this network has a specific role in linking cognitive maintenance and FC at rest in healthy aging.DiscussionOur study revealed that education contributes to differentiating cognitive and neural profiles in healthy older adults. Also, the DMN could be a key network in this context, as it may reflect some compensatory mechanisms relative to memory capacities in older adults with higher education.

Project description:The human brain at rest exhibits intrinsic dynamics transitioning among the multiple metastable states of the inter-regional functional connectivity. Accordingly, the demand for exploring the state-specific functional connectivity increases for a deeper understanding of mental diseases. Functional connectivity, however, lacks information about the directed causal influences among the brain regions, called effective connectivity. This study presents the dynamic causal modeling (DCM) framework to explore the state-dependent effective connectivity using spectral DCM for the resting-state functional MRI (rsfMRI). We established the sequence of brain states using the hidden Markov model with the multivariate autoregressive coefficients of rsfMRI, summarizing the functional connectivity. We decomposed the state-dependent effective connectivity using a parametric empirical Bayes scheme that models the effective connectivity of consecutive windows with the time course of the discrete states as regressors. We showed the plausibility of the state-dependent effective connectivity analysis in a simulation setting. To test the clinical applicability, we applied the proposed method to characterize the state- and subtype-dependent effective connectivity of the default mode network in children with combined-type attention deficit hyperactivity disorder (ADHD-C) compared with age-matched, typically developed children (TDC). All 88 children were subtyped according to the occupation times (i.e., dwell times) of the three dominant functional connectivity states, independently of clinical diagnosis. The state-dependent effective connectivity differences between ADHD-C and TDC according to the subtypes and those between the subtypes of ADHD-C were expressed mainly in self-inhibition, magnifying the importance of excitation inhibition balance in the subtyping. These findings provide a clear motivation for decomposing the state-dependent dynamic effective connectivity and state-dependent analysis of the directed coupling in exploring mental diseases.

Dataset Information

The association between cerebrovascular reactivity and resting-state fMRI functional connectivity in healthy adults: The influence of basal carbon dioxide.

Publications

The association between cerebrovascular reactivity and resting-state fMRI functional connectivity in healthy adults: The influence of basal carbon dioxide.

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