Deep Learning CNN and Recurrence Analysis for Alpha Gamma EEG Biomarkers in Fragile X Syndrome

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.