Differential Reorganization of Episodic and Semantic Memory Systems in Epilepsy-Related Mesiotemporal Pathology

Abstract

Declarative memory encompasses episodic and semantic divisions. Episodic memory captures singular events with specific spatiotemporal relationships, while semantic memory houses context-independent knowledge. Behavioral and functional neuroimaging studies have revealed common and distinct neural substrates of both memory systems, implicating mesiotemporal lobe (MTL) regions and distributed neocortices. Here, we studied a population of patients with unilateral temporal lobe epilepsy (TLE) and variable degrees of MTL pathology as a human disease model to explore declarative memory system reorganization, and to examine neurocognitive associations. Our cohort included 20 patients with TLE as well as 60 age and sex-matched healthy controls, who underwent episodic and semantic retrieval tasks during a functional MRI session. Tasks were closely matched in terms of stimuli and trial design. Capitalizing on connectome gradient mapping techniques, we derived task-based functional topographies during episodic and semantic memory states, both in the MTL and in neocortical networks. Comparing neocortical and hippocampal functional gradients between TLE patients and healthy controls, we observed topographic reorganization during episodic but not semantic memory states, characterized by marked gradient compression in lateral temporal and midline parietal cortices in both hemispheres, cooccurring with an expansion of anterior-posterior hippocampal differentiation ipsilateral to the MTL pathology. These findings suggest that episodic processes are supported by a distributed network, implicating both hippocampus and neocortex, and such alterations can provide a compact signature of state-dependent reorganization in conditions associated with MTL damage such as TLE. Leveraging microstructural and morphological MRI proxies of MTL pathology, we furthermore observed that pathological markers selective to the hippocampus are associated with TLE-related functional reorganization. Moreover, correlation analysis and statistical mediation models revealed that these functional alterations contributed to behavioral deficits in episodic memory in patients. Altogether, our findings point to a selective mesiotemporal and neocortical functional reorganization of episodic memory systems in patients with TLE, which consistently affects behavioral memory deficits. These findings point to consistent structure-function relationships in declarative memory and reaffirm the critical role of the MTL in episodic memory systems.

Single voxel autocorrelation reflects hippocampal function in temporal lobe epilepsy

“…Recent work that examined intrinsic neural timescales in the hippocampus of patients with TLE found that when accounting for structural changes in their analyses (volume and cortical thinning) there was a reduced effect size, however patients still demonstrated reduced neural timescales compared to controls (Xie et al, 2023), suggesting that autocorrelation provides information about brain function that is distinct from brain structure. It is also possible that the impact of hippocampal structural changes due to MTS are not detectable during rest, and that the effects of structural changes become more apparent during hippocampally-dependent tasks, For example, TLE-related structural changes in the hippocampus mediated the reorganization of functional memory networks during episodic retrieval states, but not during semantic retrieval states (Cabalo et al, 2023). This suggests that the impact of hippocampal structural integrity on functional memory networks might be more robust during episodic memory tasks that recruit the hippocampus.…”

HippoMaps: Multiscale cartography of the human hippocampal formation

“…This has begun a new wave of high-sensitivity hippocampally-focused studies in topics including the mapping of histology features (J. DeKraker et al, 2020; Paquola, Benkarim, et al, 2020), blood perfusion (Haast et al ., 2023; Ngo et al ., 2023), biophysically-constrained diffusion (Karat et al ., 2023), hippocampal sclerosis (Ripart et al ., 2023), neurodevelopmental trajectories (Hanson et al ., 2023), functional connectivity (Cabalo et al ., 2023; Lariviere et al ., 2023; Xie et al ., 2023), visual receptive field mapping (Leferink et al ., 2023), and cross-species comparison (Eichert et al ., 2023). With the increasing aggregation of hippocampal features in a common reference space, it is now possible to devise repositories that allow for a broad contextualization of hippocampal findings.…”

“…Similar to neocortical surface extraction and registration procedures (Boucher et al, 2009;Dale et al, 1999;Fischl, Sereno, Tootell, et al, 1999;Kim et al, 2005;Lyttelton et al, 2007;MacDonald et al, 2000), this allows for topology-informed inter-subject registration to a standardized unfolded space (Jordan DeKraker et al, 2023). This has begun a new wave of high-sensitivity hippocampally-focused studies in topics including the mapping of histology features , blood perfusion (Haast et al, 2023;Ngo et al, 2023), biophysically-constrained diffusion (Karat et al, 2023), hippocampal sclerosis (Ripart et al, 2023), neurodevelopmental trajectories (Hanson et al, 2023), functional connectivity (Cabalo et al, 2023;Lariviere et al, 2023;Xie et al, 2023), visual receptive field mapping (Leferink et al, 2023), and crossspecies comparison (Eichert et al, 2023). With the increasing aggregation of hippocampal features in a common reference space, it is now possible to devise repositories that allow for a broad contextualization of hippocampal findings.…”