Impaired Behavioral Pattern Separation in Refractory Temporal Lobe Epilepsy and Mild Cognitive Impairment

Abstract

Objective: Episodic memory impairment and hippocampal pathology are hallmark features of both temporal lobe epilepsy (TLE) and amnestic mild cognitive impairment (aMCI). Pattern separation (PS), which enables the distinction between similar but unique experiences, is thought to contribute to successful encoding and retrieval of episodic memories. Impaired PS has been proposed as a potential mechanism underling episodic memory impairment in aMCI, but this association is less established in TLE. In this study, we examined behavioral PS in patients with TLE and explored whether profiles of performance in TLE are similar to aMCI.

Method: Patients with TLE, aMCI, and age-matched, healthy controls (HCs) completed a modified recognition task that relies on PS for the discrimination of highly similar lure items, the Mnemonic Similarity Task (MST). Group differences were evaluated and relationships between clinical characteristics, California Verbal Learning Test-Second Edition scores, and MST performance were tested in the TLE group.

Results: Patients with TLE and aMCI demonstrated poorer PS performance relative to the HCs, but performance did not differ between the two patient groups. Neither the side of seizure focus nor having hippocampal sclerosis affected performance in TLE. However, TLE patients with clinically defined memory impairment showed the poorest performance.

Conclusion: Memory performance on a task that relies on PS was disrupted to a similar extent in TLE and aMCI. The MST could provide a clinically useful tool for measuring hippocampus-dependent memory impairments in TLE and other neurological disorders associated with hippocampal damage.

Keywords: Aging; Cognition; Episodic memory; Hippocampus; Memory impairment; Seizure disorder.

Figure 1.

The Mnemonic Similarity Task (A) The two phases of the MST showing examples of stimuli presented during the incidental encoding and subsequent “old”/”similar”/”new” recognition memory task. Colored boxes illustrate the three conditions, but were not shown during task administration. (B) Examples of images for each of the lure bins, ranging from most similar (lure bin 1) to least similar (lure bin 5). The figure was borrowed with the permission of the journal/authors and was previously published in Stark et al., 2019.

Figure 2.

Memory Metrics of the Mnemonic Similarity Task. A) Lure discrimination index (LDI) for the TLE, aMCI, Young-HC, and Older-HC groups. B) Recognition memory discriminability scores for the four groups. The LDI responses are correct responses (“Similar” responses to lure items) minus incorrect responses (“Similar” responses to foil items). The recognition discriminability responses are hits (“Old” responses to target items) minus false alarms (“Old” responses to foils). TLE = temporal lobe epilepsy, young-HC = younger age-matched healthy controls, aMCI = amnestic mild cognitive impairment, older-HC = older age-matched healthy controls. Error bars indicate SEM. * group difference, p < 0.05, ** group difference, p < 0.01.

Figure 3.

Behavioral Pattern Separation by Level of Similarity. A) Performance of TLE group and the young-HC and B) Performance of aMCI group and the older-HC as a function of the similarity between the target and the lure. Probability of correctly identifying foil items as “New” (i.e., avoiding the propensity to mistake them as old or previously seen) is shown. Of particular interest is performance with lure items, for which similarity with their corresponding targets is systematically varied in the MST as a way to differentially tax PS ability. Accordingly, performances shown here are binned by level of lure similarity, with items from lure bin 1 being the most difficult to distinguish and items from lure bin 5 being the least difficult. C) Mean Z-scores depict the patient-versus-control differences shown in panels A (TLE) and B (aMCI). Individual patient performance was standardized according to the mean of the corresponding age-matched HC group, and these standardized (Z) scores are then averaged for each patient group. Abbreviations are as in Figure 2.

Figure 4.

Temporal Lobe Epilepsy Performance on the MST and Clinical Measures. The dashed line represents the average performance from the age-matched healthy control group (young-HC) on each metric. A) Individuals with and without hippocampal sclerosis (HS+ and HS−), respectively. B) Individuals with left, right, or bilateral seizure onset. C) Individuals with or without impairment on CVLT-II long delay free recall, relative to age-adjusted norms. Impaired performance reflects a standard score 1.5 standard deviations or more below the age-based mean. Box plots show the minimum, first quartile, median, third quartile, and the maximum response values; outliers appear as black dots.