Biology subjects

Fernandez-Real, J. M.

Publications and source records attributed to Fernandez-Real, J. M..

3 recordsLinked to original sources

bioRxiv2021

The effect of external stimulation on functional networks in the aging healthy human brain

Understanding the brain changes occurring during aging can provide new insights for developing treatments that alleviate or reverse cognitive decline. Neurostimulation techniques have emerged as potential treatments for brain disorders and to improve cognitive functions. Nevertheless, given the ethical restrictions of neurostimulation approaches, in silico perturbation protocols based on causal whole-brain models are fundamental to gaining a mechanistic understanding of brain dynamics. Furthermore, this strategy could serve as a more specific biomarker relating local activity with global brain dynamics. Here, we used a large resting-state fMRI dataset divided into middle-aged (N=310, aged < 65 years) and older adults (N=310, aged[≥] 65) to characterize brain states in each group as a probabilistic metastable substate (PMS) space, each with a probabilistic occurrence and frequency. Then, we fitted the PMS to a whole-brain model and applied in silico stimulations with different intensities in each node to force transitions from the brain states of the older group to the middle-age group. We found that the precuneus, a brain area belonging to the default mode network and the rich club, was the best stimulation target. These findings might have important implications for designing neurostimulation interventions to revert the effects of aging on whole-brain dynamics.

neuroscience↗

bioRxiv2020

Human liver microbiota modeling strategy at the early onset of fibrosis

To understand the pathophysiological impact of liver microbiota on the early stages of fibrosis we identified the corresponding microbiota sequences and overcome the impact of different group size and patient origins with adapted statistical approaches. Liver samples with low liver fibrosis scores (F0, F1, F2) were collected from Romania(n=36), Austria(n=10), Italy(n=19), and Spain(n=17). The 16SrDNA gene was sequenced. We considered the frequency, sparsity, unbalanced sample size between cohorts to identify taxonomic profiles and statistical differences. Multivariate analyses, including adapted spectral clustering with L1-penalty fair-discriminant strategies, and predicted metagenomics were used to identify that 50 % of liver taxa were Enterobacteriaceae and Pseudomonadaceae. The Caulobacteraceae, Flavobacteriaceae and Propionibacteriaceae discriminated between F0 and F1. The preQ0 biosynthesis and pathways involving glucoryranose and glycogen degradation were negatively associated with liver fibrosis F1-F2 vs F0. Altogether, our results suggest a role of bacterial translocation to the liver in the progression of fibrosis. This statistical approach can identify microbial signatures and overcome issues regarding sample size differences, the impact of environment, and sets of analyses.

pathology↗

bioRxiv2020

Whole-brain dynamics in aging: disruptions in functional connectivity and the role of the rich club

Normal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state fMRI studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent (BOLD) signals to analyze resting-state fMRI data from 620 subjects divided into two groups ( middle-age group (n=310); age range, 50-65 years vs. older group (n=310); age range, 66-91 years). Applying the Intrinsic-Ignition Framework to assess the effect of spontaneous local activation events on local-global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain.

neuroscience↗