Paper List
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Simulation and inference methods for non-Markovian stochastic biochemical reaction networks
This paper addresses the computational bottleneck of simulating and performing Bayesian inference for non-Markovian biochemical systems with history-d...
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Translating Measures onto Mechanisms: The Cognitive Relevance of Higher-Order Information
This review addresses the core challenge of translating abstract higher-order information theory metrics (e.g., synergy, redundancy) into defensible, ...
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Emergent Bayesian Behaviour and Optimal Cue Combination in LLMs
This paper addresses the critical gap in understanding whether LLMs spontaneously develop human-like Bayesian strategies for processing uncertain info...
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Vessel Network Topology in Molecular Communication: Insights from Experiments and Theory
This work addresses the critical lack of experimentally validated channel models for molecular communication within complex vessel networks, which is ...
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Modulation of DNA rheology by a transcription factor that forms aging microgels
This work addresses the fundamental question of how the transcription factor NANOG, essential for embryonic stem cell pluripotency, physically regulat...
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Imperfect molecular detection renormalizes apparent kinetic rates in stochastic gene regulatory networks
This paper addresses the core challenge of distinguishing genuine stochastic dynamics of gene regulatory networks from artifacts introduced by imperfe...
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Approximate Bayesian Inference on Mechanisms of Network Growth and Evolution
This paper addresses the core challenge of inferring the relative contributions of multiple, simultaneous generative mechanisms in network formation w...
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An AI Implementation Science Study to Improve Trustworthy Data in a Large Healthcare System
This paper addresses the critical gap between theoretical AI research and real-world clinical implementation by providing a practical framework for as...
Personalized optimization of pediatric HD-tDCS for dose consistency and target engagement
Southern University of Science and Technology | Brown University | University of Illinois Urbana-Champaign | University of Warwick | Carle Foundation Hospital
The 30-Second View
IN SHORT: This paper addresses the critical limitation of one-size-fits-all HD-tDCS protocols in pediatric populations by developing a personalized optimization framework that accounts for developmental anatomical variability and tissue conductivity uncertainty.
Innovation (TL;DR)
- Methodology First dual-objective optimization framework for pediatric HD-tDCS that generates personalized Pareto fronts balancing target intensity and focality, enabling systematic trade-off analysis.
- Methodology Introduction of two clinically actionable strategies: dose-consistency (enforcing fixed target intensity across individuals) and target-engagement (maximizing intensity under safety limits), both robust to conductivity variations.
- Biology First systematic quantification of depth-dependent tissue conductivity sensitivity: superficial targets dominated by scalp/bone conductivities (R² up to 0.85), while deep targets shaped by gray/white matter conductivities.
Key conclusions
- Conventional montages show significant age-dependent reductions in target intensity (p<0.05, FDR-corrected) and systematic sex differences mediated by scalp volume (mediation effect p<0.05).
- Optimized solutions Pareto-dominate conventional approaches, achieving 15-25% higher focality at matched intensity and 20-30% higher intensity at matched focality (Mann-Whitney U, p<0.001).
- Both optimization strategies remain robust under large conductivity variations (1,800 optimizations across 600 perturbed models), with sparse electrode configurations (<0.1 mA threshold) preserving performance (n.s., Mann-Whitney U).
Abstract: High-definition transcranial direct current stimulation (HD-tDCS) dosing in children remains largely empirical, relying on one-size-fits-all protocols despite rapid developmental changes in head anatomy and tissue properties that strongly modulate how transcranial currents reach the developing brain. Using 70 pediatric head models (ages 6–17) and commonly used cortical targets (primary motor cortex and left dorsolateral prefrontal cortex), our forward simulations find that standard montages produce marked age-dependent reductions in target electric-field intensity and systematic sex differences linked to tissue-volume covariation, underscoring the profound limitations of conventional uniform montages. To overcome these limitations, we introduce a developmentally informed, dual-objective optimization framework designed to generate personalized Pareto fronts summarizing the trade-off between electric-field intensity and focality. These subject-specific fronts reveal systematic performance improvements over conventional montages, yielding both higher focality at matched target intensity and higher intensity at matched focality. From these optimized solutions, we derive two clinically practical dosing prescriptions: a dose-consistency strategy that, for the first time, explicitly enforces fixed target intensity across individuals to implicitly mitigate demographic effects, and a target-engagement strategy that maximizes target intensity under safety limits. Both strategies remain robust to large conductivity variations, and we further show that dense HD-tDCS solutions admit sparse equivalents without performance loss under the target-engagement strategy. Across 1,800 optimizations in 600 conductivity-perturbed head models, we also find that tissue conductivity sensitivity is depth-dependent, with Pareto-front distributions for superficial cortical targets most influenced by gray matter, scalp, and bone conductivities, and those for a deep target predominantly shaped by gray and white matter conductivities. Together, these results establish a principled framework for pediatric HD-tDCS planning that explicitly accounts for developmental anatomy and physiological uncertainty, enabling reliable and individualized neuromodulation dosing in vulnerable pediatric populations.