Untangling the tangled relationship between cognitive and psychological comorbidities in epilepsy: Bidirectionality and mediation

Objective Cognitive and psychological abnormalities are known to be frequently occurring complications of the epilepsies, but their patterns of co‐occurrence, directions of effect, underlying mechanism(s), and causal pathways remain uncertain. The intent of this investigation was to advance understanding of these issues in patients with temporal lobe epilepsy (TLE). Methods A total of 121 patients with TLE were administered a comprehensive neuropsychological battery, and symptoms of diverse psychological syndromes were assessed with a standardized psychological inventory. The cognitive and psychological data were reduced by factor analysis (FA) to broad‐ and narrowband indicators that were then examined by partial least squares structural equation modeling (PLS‐SEM) to inform the presence, strength, direction, and mediators of cognitive–psychological relationships. Results FA identified overarching metrics of cognition (g) and psychopathology (p) as well as their correlation and underlying factors wherein g contained three indicators (language/memory, perceptual/nonverbal reasoning, information/processing speed) and p contained two indicators (externalizing, internalizing). PLS‐SEM demonstrated direct, bidirectional associations between internalizing psychopathology and language/memory, indicating these factors express a strong interdependency. Mediation modeling showed an index of functional brain reserve served to explain this selective, shared influence, as well the relationship between the broader concepts of p and g, indicating origin in a common psychological/cognitive mechanism. Significance Neuropsychological and psychological comorbidities of TLE are represented by both broadband and narrowband indicators of clinical and theoretical relevance. These indicators exhibit multidimensionality, multimorbidity, and bidirectionality that point to a shared neurobiological core best expressed and explained by the mediating influence of brain functional reserve.