NeuroImage
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Clinical Trial
Measurement of OEF and absolute CMRO2: MRI-based methods using interleaved and combined hypercapnia and hyperoxia.
Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is most commonly used in a semi-quantitative manner to infer changes in brain activity. Despite the basis of the image contrast lying in the cerebral venous blood oxygenation level, quantification of absolute cerebral metabolic rate of oxygen consumption (CMRO2) has only recently been demonstrated. Here we examine two approaches to the calibration of fMRI signal to measure absolute CMRO2 using hypercapnic and hyperoxic respiratory challenges. ⋯ The combined approach to oxygen and carbon dioxide modulation, as well as taking less time to acquire data, yielded whole brain grey matter estimates of CMRO2 and OEF of 184±45 μmol/100 g/min and 0.42±0.12 respectively, along with additional estimates of the vascular parameters α=0.33±0.06, the exponent relating relative increases in CBF to CBV, and β=1.35±0.13, the exponent relating deoxyhaemoglobin concentration to the relaxation rate R2*. Maps of cerebrovascular and cerebral metabolic parameters were also calculated. We show that combined modulation of oxygen and carbon dioxide can offer an experimentally more efficient approach to estimating OEF and absolute CMRO2 along with the additional vascular parameters that form an important part of the commonly used calibrated fMRI signal model.
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Functional connectivity (FC) as measured by correlation between fMRI BOLD time courses of distinct brain regions has revealed meaningful organization of spontaneous fluctuations in the resting brain. However, an increasing amount of evidence points to non-stationarity of FC; i.e., FC dynamically changes over time reflecting additional and rich information about brain organization, but representing new challenges for analysis and interpretation. Here, we propose a data-driven approach based on principal component analysis (PCA) to reveal hidden patterns of coherent FC dynamics across multiple subjects. ⋯ We then used PCA to identify FC patterns, termed "eigenconnectivities", that reflect meaningful patterns in FC fluctuations. We then assessed the contributions of these patterns to the dynamic FC at any given time point and identified a network of connections centered on the default-mode network with altered contribution in patients. Our results complement traditional stationary analyses, and reveal novel insights into brain connectivity dynamics and their modulation in a neurodegenerative disease.
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Trial-to-trial reaction time (RT) variability is consistently higher in children and older adults than in younger adults. Converging evidence also indicates that higher RT variability is (a) associated with lower behavioral performance on complex cognitive tasks, (b) distinguishes patients with neurological deficits from healthy individuals, and also (c) predicts longitudinal cognitive decline in older adults. However, so far the processes underlying increased RT variability are poorly understood. ⋯ Importantly, this effect was strongest at high performance monitoring demands and independent of motor response execution as well as theta power. Taken together, our findings reveal that lower theta inter-trial coherence is related to greater behavioral variability within and across age groups. These results hint at the possibility that more variable MFC control may be associated with greater performance fluctuations.
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The dose-dependent effects of anesthetics on brain functional connectivity are incompletely understood. Resting-state functional magnetic resonance imaging (rsfMRI) is widely used to assess the functional connectivity in humans and animals. Propofol is an anesthetic agent with desirable characteristics for functional neuroimaging in animals but its dose-dependent effects on rsfMRI functional connectivity have not been determined. ⋯ Subcortical connectivity increased again in deep anesthesia associated with EEG burst suppression. Regional correlation analysis confirmed the breakdown of connectivity within and between specific cortical and subcortical networks with deepening propofol anesthesia. Cortical connectivity was suppressed before subcortical connectivity at a critical propofol dose associated with loss of consciousness.
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The NTRK3 gene (also known as TRKC) encodes a high affinity receptor for the neurotrophin 3'-nucleotidase (NT3), which is implicated in oligodendrocyte and myelin development. We previously found that white matter integrity in young adults is related to common variants in genes encoding neurotrophins and their receptors. This underscores the importance of neurotrophins for white matter development. ⋯ FA was optimally predicted (based on the highest false discovery rate critical p), by five SNPs (rs1017412, rs2114252, rs16941261, rs3784406, and rs7176429; overall FDR critical p=0.028). Gene effects were widespread and included the corpus callosum genu and inferior longitudinal fasciculus - regions implicated in several neuropsychiatric disorders and previously associated with other neurotrophin-related genetic variants in an overlapping sample of subjects. NTRK3 genetic variants, and neurotrophins more generally, may influence white matter integrity in brain regions implicated in neuropsychiatric disorders.