AUTHOR=Citarella Jae , Siekierski Peyton , Ethridge Lauren , Westerkamp Grace , Liu Yanchen , Blank Elizabeth , Voorhees Lynxie , Batterink Laura , Jones Stephanie R. , Smith Elizabeth , Reisinger Debra L. , Nelson Meredith , Binder Devin K. , Razak Khaleel A. , Miyakoshi Makoto , Wu Steve , Gilbert Donald , Horn Paul S. , De Stefano Lisa A. , Erickson Craig A. , Pedapati Ernest V. 

TITLE=FX ENTRAIN: scientific context, study design, and biomarker driven brain-computer interfaces in neurodevelopmental conditions

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 19 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1618804

DOI=10.3389/fnins.2025.1618804

ISSN=1662-453X

ABSTRACT=Fragile X Syndrome (FXS), caused by the loss of function of the Fmr1 gene, is characterized by varying degrees of intellectual disability, autistic features, and sensory hypersensitivity. Despite phenotypic rescue in animal deletion models, clinical trials in humans have been unsuccessful, likely due to the heterogeneous nature of FXS. To uncover the basis of individual- and subgroup-level variation driving treatment failures, we propose to test and modulate thalamocortical drive as a novel “bottom-up” neural probe to understand the mechanics of FXS-relevant circuits. Our study employs trial-level EEG analyses (neurodynamics) to detect fine-grained differences in brain activity using sensory and statistical learning paradigms in children with FXS, autism spectrum disorder (ASD), and typically developing controls. Parallel analysis in the FXS knockout mouse model will clarify its relevance to human FXS subgroups. In a randomized crossover study, we will evaluate the efficacy of closed-loop auditory entrainment, indexed on individual neurodynamic measures, aiming to normalize neural responses and enhance statistical learning performance. We anticipate this approach will yield opportunities to identify more effective early interventions that alter the trajectory of intellectual development in FXS.