# Cortico-hippocampal networks underpin verbal memory encoding in temporal lobe epilepsy

## TL;DR

This study identifies brain regions linked to verbal memory in epilepsy patients, showing how damage to specific areas affects memory performance.

## Contribution

The study reveals a cortico-hippocampal network critical for verbal memory in temporal lobe epilepsy patients.

## Key findings

- Smaller grey matter volumes in prefrontal, temporal, and cingulate cortices correlate with worse verbal learning.
- Reduced volumes in left dentate gyrus, CA4, and CA3 hippocampal subfields are associated with impaired verbal memory.
- Findings were consistent across the entire cohort and in a subgroup of hippocampal sclerosis patients.

## Abstract

Knowledge of the structural underpinnings of human verbal memory is scarce. Understanding the human verbal memory network at a finer anatomical scale will have important clinical implications for the management of patients with verbal memory impairment. In this cross-sectional study, we aimed to assess the contributions of cerebral cortex and hippocampal subfields to verbal memory encoding in temporal lobe epilepsy. We included consecutive patients (n = 84) with radiologically and pathologically defined hippocampal sclerosis (HS) (44 left-sided) and unilateral temporal lobe epilepsy, and healthy volunteers (n = 43) who were comparable regarding age and sex. The morphometric and volumetric measures of cerebral cortex and hippocampal subfields were extracted from high-resolution MRI scans. People included in this study underwent standardized neuropsychological evaluation, including measures of verbal memory assessed through the Adult Memory and Information Processing Battery. Verbal memory performances were Z-scores corrected by using means and standard deviations published for sample standardization. Associations between verbal learning Z-scores and the grey matter volume of the cerebral cortex and hippocampal subfields were investigated. Reduction of grey matter volumes in the left and right medial and dorsolateral prefrontal cortex (Pcorr < 0.0001), superior and middle temporal gyri (Pcorr < 0.0001), anterior and posterior cingulate cortex (Pcorr < 0.0001) and of the left ventrolateral prefrontal cortex (Pcorr < 0.0001) and parietal–temporal–occipital junction (Pcorr < 0.0001) were associated with worse verbal learning. These findings were consistent across both the entire cohort and in a subgroup analysis focused exclusively on HS patients. Within hippocampi, smaller volumes of the left dentate gyrus (P = 0.003), cornu ammonis 4 (P = 0.005) and cornu ammonis 3 (P = 0.03) were associated with worse verbal learning Z-scores. This study demonstrates that verbal learning in patients with temporal lobe epilepsy is strongly related to the volume of distinct regions of the prefrontal, temporal and cingulate cortices and left dentate gyrus, cornu ammonis 4 and cornu ammonis 3 hippocampal subfields. It provides the basis to suggest a corticohippocampal network for verbal learning in these patients, improving our understanding of human verbal memory. These biomarkers may inform attractive targets for forthcoming modulating therapies. Future work may also analyse the impact of sparing part of the left dentate gyrus, cornu ammonis 4 and cornu ammonis 3 as a protective measure against verbal memory impairment after surgery for temporal lobe epilepsy.

In this cross-sectional study of 84 hippocampal sclerosis patients and 43 healthy controls, Fiore et al. linked verbal learning variability to cortical and hippocampal morphometry. Smaller volumes in prefrontal, temporal, cingulate cortices and left dentate gyrus, CA4 and CA3 were associated with poorer verbal learning in temporal lobe epilepsy.

Graphical Abstract