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Arias, I.

Publications and source records attributed to Arias, I..

2 recordsLinked to original sources
bioRxiv2026

PRIME: A Neurophysiology-Informed Bayesian Optimization Framework for Adaptive TMS Motor Hotspot Mapping, Algorithm Design and Monte Carlo Evaluation

BackgroundAccurate primary motor cortex (M1) hotspot identification is a prerequisite for reliable transcranial magnetic stimulation (TMS) protocols, yet conventional grid search is stimulation-intensive and operator-dependent. Existing Bayesian optimization (BO) implementations, including BOOST and 3D-BOOST, do not model within-session neurophysiological variability. MethodsWe present PROBE (Probabilistic Response-guided Optimization for Brain Exploration), a closed-loop BO framework for three-parameter TMS hotspot mapping over coil position (X, Y) and orientation ({theta}), with five innovations targeting cortical excitability drift, amplitude-dependent noise, transient artifacts, sub-threshold MEP integration (10 {micro}V floor), and cross-subject Gaussian process (GP) prior warm-starting. These were evaluated alone and in combination with amplitude-weighted center-of-gravity (CoG) convergence and estimation across 18 configurations in a Monte Carlo simulation (30 subjects, 3 repetitions each). ResultsAlgorithm configuration significantly affected all outcomes (Friedman tests, all p < 0.001, Kendalls W = 0.50-0.65). MultiFid_CoG_10uV achieved the lowest median XY error (1.14 [0.62-2.12] mm; 50.9 {+/-} 6.2 stimuli; 96.7% convergence), a 68.2% error reduction and 41.5% stimulus reduction relative to grid Search (3.58 [2.66-5.12] mm; 87 stimuli). CoG estimation significantly reduced XY error relative to peak-response selection in 10 of 11 non-CoG configurations (largest gain: MultiFid, 58.7%; adjusted p < 0.001). ConclusionsNeurophysiology-informed BO improved simulated performance under the specified model, extending the 3-DOF approach of Grano et al. (2025) with explicit noise modeling and CoG-based convergence. MultiFid_CoG_10uV and DeltaBO_CoG are selected as candidates for prospective validation in a prospective triple-blind human study.

neuroscience↗
bioRxiv2025

Bile acids target an exposed cavity in the glucocorticoid receptor modulating receptor self-assembly, chromatin binding and transcriptional activity

The glucocorticoid receptor (GR) is an essential transcription factor that controls metabolism and homeostasis. Glucocorticoids (GCs) activate the GR upon occupying the internal ligand-binding pocket (LBP) of its ligand-binding domain (GR-LBD), which has been the focus of most previous structure-function studies. Synthetic GCs such as dexamethasone are widely used to treat inflammatory diseases, but their chronic use results in major side effects, whose molecular underpinnings remain unresolved. Here we present a thorough analysis of the topography of GR-LBD and its ability to bind small-molecule compounds, especially cholesterol derivatives. We show that one important class of steroids, bile acids, bind to previously unidentified and highly conserved, surface-exposed cavities on GR-LBD. We show that bile acids affect GR turnover and self-assembly in living cells, modulating receptor transcriptional activity. These findings reveal a previously unrecognized mechanism of GR regulation, with implications for the design of GCs with novel mechanisms of action. TeaserBile acids modulate the activity of the glucocorticoid receptor upon binding to an exposed allosteric pocket thereby influencing transcriptional regulation and receptor self-assembly in living cells.

molecular biology↗