Abstract:Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by reduced expression of fragile X mental retardation protein (FMRP), leading to disrupted synaptic plasticity, cortical hyperexcitability, and impaired network synchronization. Electroencephalography (EEG) provides a noninvasive window into these mechanisms and consistently reveals abnormalities in alpha (8 to 12 Hz) and gamma (30 to 100 Hz) oscillations that relate to inhibitory control, sensory processing, and cognition. This paper proposes a multi representation deep learning framework for automated characterization of FXS EEG phenotypes by integrating convolutional neural networks (CNNs), long short-term memory (LSTM) networks, and recurrence plot (RP) analysis. Band limited EEG signals are decomposed into alpha and gamma components and transformed into complementary representations, including temporal feature sequences, time frequency maps, and RP images encoding the nonlinear recurrence structure. CNN modules learn discriminative spatial-spectral and dynamical textures from image based representations, while LSTM modules model temporal modulation of oscillatory activity; a hybrid CNN LSTM architecture jointly captures spatial, temporal, and nonlinear dependencies. Subject-independent evaluation demonstrates that the hybrid model outperforms single modality baselines, with gamma features providing strong discriminative power and alpha gamma integration yielding the best overall performance. These findings support deep learning with nonlinear representations as a scalable approach for EEG biomarker development in FXS, with potential utility for diagnosis, stratification, and treatment monitoring in translational settings.
Abstract:Clinical biomarker workflows in translational research settings often rely on spreadsheet-driven tracking, manual quality control (QC) reconciliation, and loosely integrated systems, resulting in limited state visibility, delayed reporting, and increased operational risk. These challenges are particularly pronounced in multi-day assays such as Luminex-based quantification of Fragile X Messenger Ribonucleoprotein (FMRP), where HIPAA-compliant data governance, deterministic workflow progression, and coordinated communication across laboratory and clinical teams are required. This paper presents FMRP-LEAN, a HIPAA-compliant, AI-augmented Laboratory Information Management System (LIMS) architecture that formalizes biospecimen lifecycle management through a finite-state workflow model with explicit transition guards and dwell-time observability. The system integrates a self-hosted Supabase/PostgreSQL stack deployed within hospital-controlled infrastructure, hybrid edge-internal isolation with encrypted tunneling and loopback-only services, and bi-directional REDCap synchronization. A unified MRN-UUIDv7 identifier framework with QR-based tracking ensures traceable clinical-research linkage under PHI residency constraints. FMRP-LEAN incorporates automated statistical QC pre-screening and a governance-constrained AI operations module that operates exclusively on aggregate projections, with deterministic fallback guarantees. Deployment demonstrates improved workflow observability, reduced QC latency, and enhanced cross-role transparency between laboratory technicians, research coordinators, and patient-facing teams. The architecture provides a reproducible model for secure, state-explicit, and AI-augmented clinical research workflows in regulated healthcare environments.
Abstract:The electroencephalogram (EEG) is a valuable and widely applied tool for investigating brain disorders and behavioral changes. It offers a minimally restrictive and non-invasive method. However, challenges in using EEG for cognitive development studies include temporal resolution, signal source localization, and EEG artifacts. Careful consideration of these factors is essential for informed application of EEG technology. Independent component analysis (ICA) effectively isolates source generator processes from signals recorded by multiple, adjacent EEG scalp electrodes. Although ICA decomposition requires manual inspection, selection, and interpretation of independent components (ICs), this process is time consuming and demands expertise. Automated IC classification can achieve sufficient accuracy, expediting large scale EEG research and enabling near real time applications in conjunction with brain activity rejection tasks, which are crucial for medical specialists. This study introduces an automated computer vision based ICA rejection labeling tool compatible with widely used software interfaces like ICLabel and EEGLab. By automating the manual task, the proposed system reduces processing time by 7200 fold and achieves an accuracy of 89.45%.
Abstract:Neurodevelopmental disorders such as Fragile X Syndrome (FXS) and Autism Spectrum Disorder (ASD) are characterized by disrupted cortical oscillatory activity, particularly in the alpha and gamma frequency bands. These abnormalities are linked to deficits in attention, sensory processing, and cognitive function. In this work, we present an adaptive machine learning-based brain-computer interface (BCI) system designed to modulate neural oscillations through frequency-specific auditory stimulation to enhance cognitive readiness in individuals with FXS. EEG data were recorded from 38 participants using a 128-channel system under a stimulation paradigm consisting of a 30-second baseline (no stimulus) followed by 60-second auditory entrainment episodes at 7Hz, 9Hz, 11Hz, and 13Hz. A comprehensive analysis of power spectral features (Alpha, Gamma, Delta, Theta, Beta) and cross-frequency coupling metrics (Alpha-Gamma, Alpha-Beta, etc.) was conducted. The results identified Peak Alpha Power, Peak Gamma Power, and Alpha Power per second per channel as the most discriminative biomarkers. The 13Hz stimulation condition consistently elicited a significant increase in Alpha activity and suppression of Gamma activity, aligning with our optimization objective. A supervised machine learning framework was developed to predict EEG responses and dynamically adjust stimulation parameters, enabling real-time, subject-specific adaptation. This work establishes a novel EEG-driven optimization framework for cognitive neuromodulation, providing a foundational model for next-generation AI-integrated BCI systems aimed at personalized neurorehabilitation in FXS and related disorders.