Verbal Paired Associates Learning Lateralizes Left Hippocampal Sclerosis in Temporal Lobe Epilepsy

Objective: Left hippocampal sclerosis (HS) is associated with verbal-specific memory impairment. This association is well established for word list learning tasks, and there is some evidence that this may also be relevant to verbal paired associates learning (PAL), though the evidence is limited. We aimed to evaluate the utility of verbal PAL as a marker for left HS, compare this with word list learning, and derive cutoff scores to facilitate clinical application.

Methods: Retrospective analysis of Rey Auditory Verbal Learning Test (RAVLT) and PAL scores obtained from 116 surgically naïve temporal lobe epilepsy patients with HS (14 bilateral, 57 left, 45 right; range of N across test indices: 77-110).

Results: Relative to right HS, left HS and bilateral HS were associated with poorer performance on PAL Hard Pairs (p < 0.001) and all RAVLT indices (p < 0.001), with performance comparable in left HS and bilateral HS (p > 0.05). PAL Hard Pairs and all RAVLT indices displayed acceptable discriminatory ability (AUC > 0.70) in classifying left-sided HS (unilateral left or bilateral HS), with RAVLT delayed recall the strongest predictor (AUC = 0.87; PAL Hard Pairs Learning and Delay = 0.80 and 0.83, respectively). Optimal cutoff scores for left-sided HS classification were generated.

Significance: Although the RAVLT delayed recall was the strongest predictor of left-sided HS, PAL Hard Pairs also demonstrated excellent discriminatory capacity, offering an additional cognitive marker of left hippocampal integrity to complement word list learning in clinical assessments.

Plain Language Statement: The results of the study show that the ability to learn unrelated pairs of words (e.g., "silver"-"run") is compromised in the setting of epilepsy with left-sided hippocampal sclerosis (HS), be it unilateral left HS or bilateral HS. The ability of unrelated word pair learning to discriminate left vs. right HS was comparable to word list learning, a task with demonstrated sensitivity to left HS. Our results suggest that the ability to learn unrelated pairs of words provides another useful marker of left-sided hippocampal compromise in epilepsy. We provide cutoff scores to facilitate clinical interpretation.