Original Theoretical and Experimental Contributions to Electrophysiological Biomarker Discovery for Early Neurological Disease Detection in Nigerian Populations

Neurological diseases including epilepsy, cerebrovascular disease, and neurodegenerative conditions carry a large and growing burden in Nigeria, and the identification of electrophysiological biomarkers specific to early disease stages in Nigerian populations could enable earlier diagnosis and intervention at affordable diagnostic cost. This dissertation makes original theoretical and experimental contributions to electrophysiological biomarker discovery for early neurological disease detection in Nigerian patient populations, integrating novel signal analysis theory with a clinical electrophysiology study programme. The theoretical contribution develops a novel nonlinear dynamics-based biomarker extraction theory for electroencephalographic and event-related potential signals that explicitly accounts for the confounding effects of skull conductivity variation related to Nigerian dietary calcium deficiency on scalp-recorded signals, a source of systematic biomarker bias not addressed in existing signal analysis theory. New phase-amplitude coupling metrics adapted for non-stationary signals and validated for robustness to skull conductivity variation are derived and their statistical properties characterized theoretically. The experimental programme applies the developed theoretical biomarkers in three clinical electrophysiology studies conducted at University of Calabar Teaching Hospital, Federal Teaching Hospital Keffi, and Usmanu Danfodiyo University Teaching Hospital. The studies enrol early-stage epilepsy, silent cerebrovascular disease, and mild cognitive impairment patient groups, with age and sex-matched controls, collecting forty-channel EEG and cognitive event-related potentials during standardized protocols. Biomarker discriminant performance is characterised with discovery and replication analysis. Original biomarker contributions include a dietary calcium-corrected cortical connectivity index and a phase-amplitude coupling asymmetry index that significantly discriminates early cerebrovascular disease from controls. Keywords: electrophysiological biomarkers, neurological disease, EEG, nonlinear dynamics, Nigerian populations.