Differential reorganization of episodic and semantic memory systems in epilepsy-related mesiotemporal pathology

Donna Gift Cabalo; Jordan DeKraker; Jessica Royer; Ke Xie; Shahin Tavakol; Raúl Rodríguez-Cruces; Andrea Bernasconi; Neda Bernasconi; Alexander Weil; Raluca Pana; Birgit Frauscher; Lorenzo Caciagli; Elizabeth Jefferies; Jonathan Smallwood; Boris C. Bernhardt

doi:10.1093/brain/awae197

Differential reorganization of episodic and semantic memory systems in epilepsy-related mesiotemporal pathology

Donna Gift Cabalo^*, Jordan DeKraker, Jessica Royer, Ke Xie, Shahin Tavakol, Raúl Rodríguez-Cruces, Andrea Bernasconi, Neda Bernasconi, Alexander Weil, Raluca Pana, Birgit Frauscher, Lorenzo Caciagli, Elizabeth Jefferies, Jonathan Smallwood, Boris C. Bernhardt^*

^*Corresponding author for this work

Psychology

Research output: Contribution to journal › Article › peer-review

Abstract

Declarative memory encompasses episodic and semantic divisions. Episodic memory captures singular events with specific spatiotemporal relationships, whereas semantic memory houses context-independent knowledge. Behavioural and functional neuroimaging studies have revealed common and distinct neural substrates of both memory systems, implicating mesiotemporal lobe (MTL) regions such as the hippocampus and distributed neocortices. Here, we explored declarative memory system reorganization in patients with unilateral temporal lobe epilepsy (TLE) as a human disease model to test the impact of variable degrees of MTL pathology on memory function. Our cohort included 31 patients with TLE and 60 age- and sex-matched healthy controls, and all participants underwent episodic and semantic retrieval tasks during a multimodal MRI session. The functional MRI tasks were closely matched in terms of stimuli and trial design. Capitalizing on non-linear connectome gradient-mapping techniques, we derived task-based functional topographies during episodic and semantic memory states, in both the MTL and neocortical networks. Comparing neocortical and hippocampal functional gradients between TLE patients and healthy controls, we observed a marked topographic reorganization of both neocortical and MTL systems during episodic memory states. Neocortical alterations were characterized by reduced functional differentiation in TLE across lateral temporal and midline parietal cortices in both hemispheres. In the MTL, in contrast, patients presented with a more marked functional differentiation of posterior and anterior hippocampal segments ipsilateral to the seizure focus and pathological core, indicating perturbed intrahippocampal connectivity. Semantic memory reorganization was also found in bilateral lateral temporal and ipsilateral angular regions, whereas hippocampal functional topographies were unaffected. Furthermore, leveraging MRI proxies of MTL pathology, we observed alterations in hippocampal microstructure and morphology that were associated with TLE-related functional reorganization during episodic memory. Moreover, correlation analysis and statistical mediation models revealed that these functional alterations contributed to behavioural deficits in episodic memory, but again not in semantic memory in patients. Altogether, our findings suggest that semantic processes rely on distributed neocortical networks, whereas episodic processes are supported by a network involving both the hippocampus and the neocortex. Alterations of such networks can provide a compact signature of state-dependent reorganization in conditions associated with MTL damage, such as TLE.

Original language	English
Pages (from-to)	3918-3932
Number of pages	15
Journal	Brain
Volume	147
Issue number	11
Early online date	26 Jul 2024
DOIs	https://doi.org/10.1093/brain/awae197
Publication status	Published - 1 Nov 2024

Bibliographical note

Keywords

connectomics
declarative memory
epilepsy
gradients
mesiotemporal lobe
neuroimaging

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10.1093/brain/awae197Licence: CC BY-NC

Differential reorganization of episodic and semantic memory systems in epilepsy-related mesiotemporal pathology
© The Author(s) 2024
Final published version, 1.07 MBLicence: CC BY-NC

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Cabalo, D. G., DeKraker, J., Royer, J., Xie, K., Tavakol, S., Rodríguez-Cruces, R., Bernasconi, A., Bernasconi, N., Weil, A., Pana, R., Frauscher, B., Caciagli, L., Jefferies, E., Smallwood, J., & Bernhardt, B. C. (2024). Differential reorganization of episodic and semantic memory systems in epilepsy-related mesiotemporal pathology. Brain, 147(11), 3918-3932. https://doi.org/10.1093/brain/awae197

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title = "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, whereas semantic memory houses context-independent knowledge. Behavioural and functional neuroimaging studies have revealed common and distinct neural substrates of both memory systems, implicating mesiotemporal lobe (MTL) regions such as the hippocampus and distributed neocortices. Here, we explored declarative memory system reorganization in patients with unilateral temporal lobe epilepsy (TLE) as a human disease model to test the impact of variable degrees of MTL pathology on memory function. Our cohort included 31 patients with TLE and 60 age- and sex-matched healthy controls, and all participants underwent episodic and semantic retrieval tasks during a multimodal MRI session. The functional MRI tasks were closely matched in terms of stimuli and trial design. Capitalizing on non-linear connectome gradient-mapping techniques, we derived task-based functional topographies during episodic and semantic memory states, in both the MTL and neocortical networks. Comparing neocortical and hippocampal functional gradients between TLE patients and healthy controls, we observed a marked topographic reorganization of both neocortical and MTL systems during episodic memory states. Neocortical alterations were characterized by reduced functional differentiation in TLE across lateral temporal and midline parietal cortices in both hemispheres. In the MTL, in contrast, patients presented with a more marked functional differentiation of posterior and anterior hippocampal segments ipsilateral to the seizure focus and pathological core, indicating perturbed intrahippocampal connectivity. Semantic memory reorganization was also found in bilateral lateral temporal and ipsilateral angular regions, whereas hippocampal functional topographies were unaffected. Furthermore, leveraging MRI proxies of MTL pathology, we observed alterations in hippocampal microstructure and morphology that were associated with TLE-related functional reorganization during episodic memory. Moreover, correlation analysis and statistical mediation models revealed that these functional alterations contributed to behavioural deficits in episodic memory, but again not in semantic memory in patients. Altogether, our findings suggest that semantic processes rely on distributed neocortical networks, whereas episodic processes are supported by a network involving both the hippocampus and the neocortex. Alterations of such networks can provide a compact signature of state-dependent reorganization in conditions associated with MTL damage, such as TLE.",

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author = "Cabalo, {Donna Gift} and Jordan DeKraker and Jessica Royer and Ke Xie and Shahin Tavakol and Ra{\'u}l Rodr{\'i}guez-Cruces and Andrea Bernasconi and Neda Bernasconi and Alexander Weil and Raluca Pana and Birgit Frauscher and Lorenzo Caciagli and Elizabeth Jefferies and Jonathan Smallwood and Bernhardt, {Boris C.}",

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doi = "10.1093/brain/awae197",

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Cabalo, DG, DeKraker, J, Royer, J, Xie, K, Tavakol, S, Rodríguez-Cruces, R, Bernasconi, A, Bernasconi, N, Weil, A, Pana, R, Frauscher, B, Caciagli, L, Jefferies, E , Smallwood, J & Bernhardt, BC 2024, 'Differential reorganization of episodic and semantic memory systems in epilepsy-related mesiotemporal pathology', Brain, vol. 147, no. 11, pp. 3918-3932. https://doi.org/10.1093/brain/awae197

TY - JOUR

T1 - Differential reorganization of episodic and semantic memory systems in epilepsy-related mesiotemporal pathology

AU - Cabalo, Donna Gift

AU - DeKraker, Jordan

AU - Royer, Jessica

AU - Xie, Ke

AU - Tavakol, Shahin

AU - Rodríguez-Cruces, Raúl

AU - Bernasconi, Andrea

AU - Bernasconi, Neda

AU - Weil, Alexander

AU - Pana, Raluca

AU - Frauscher, Birgit

AU - Caciagli, Lorenzo

AU - Jefferies, Elizabeth

AU - Smallwood, Jonathan

AU - Bernhardt, Boris C.

PY - 2024/11/1

Y1 - 2024/11/1

N2 - Declarative memory encompasses episodic and semantic divisions. Episodic memory captures singular events with specific spatiotemporal relationships, whereas semantic memory houses context-independent knowledge. Behavioural and functional neuroimaging studies have revealed common and distinct neural substrates of both memory systems, implicating mesiotemporal lobe (MTL) regions such as the hippocampus and distributed neocortices. Here, we explored declarative memory system reorganization in patients with unilateral temporal lobe epilepsy (TLE) as a human disease model to test the impact of variable degrees of MTL pathology on memory function. Our cohort included 31 patients with TLE and 60 age- and sex-matched healthy controls, and all participants underwent episodic and semantic retrieval tasks during a multimodal MRI session. The functional MRI tasks were closely matched in terms of stimuli and trial design. Capitalizing on non-linear connectome gradient-mapping techniques, we derived task-based functional topographies during episodic and semantic memory states, in both the MTL and neocortical networks. Comparing neocortical and hippocampal functional gradients between TLE patients and healthy controls, we observed a marked topographic reorganization of both neocortical and MTL systems during episodic memory states. Neocortical alterations were characterized by reduced functional differentiation in TLE across lateral temporal and midline parietal cortices in both hemispheres. In the MTL, in contrast, patients presented with a more marked functional differentiation of posterior and anterior hippocampal segments ipsilateral to the seizure focus and pathological core, indicating perturbed intrahippocampal connectivity. Semantic memory reorganization was also found in bilateral lateral temporal and ipsilateral angular regions, whereas hippocampal functional topographies were unaffected. Furthermore, leveraging MRI proxies of MTL pathology, we observed alterations in hippocampal microstructure and morphology that were associated with TLE-related functional reorganization during episodic memory. Moreover, correlation analysis and statistical mediation models revealed that these functional alterations contributed to behavioural deficits in episodic memory, but again not in semantic memory in patients. Altogether, our findings suggest that semantic processes rely on distributed neocortical networks, whereas episodic processes are supported by a network involving both the hippocampus and the neocortex. Alterations of such networks can provide a compact signature of state-dependent reorganization in conditions associated with MTL damage, such as TLE.

AB - Declarative memory encompasses episodic and semantic divisions. Episodic memory captures singular events with specific spatiotemporal relationships, whereas semantic memory houses context-independent knowledge. Behavioural and functional neuroimaging studies have revealed common and distinct neural substrates of both memory systems, implicating mesiotemporal lobe (MTL) regions such as the hippocampus and distributed neocortices. Here, we explored declarative memory system reorganization in patients with unilateral temporal lobe epilepsy (TLE) as a human disease model to test the impact of variable degrees of MTL pathology on memory function. Our cohort included 31 patients with TLE and 60 age- and sex-matched healthy controls, and all participants underwent episodic and semantic retrieval tasks during a multimodal MRI session. The functional MRI tasks were closely matched in terms of stimuli and trial design. Capitalizing on non-linear connectome gradient-mapping techniques, we derived task-based functional topographies during episodic and semantic memory states, in both the MTL and neocortical networks. Comparing neocortical and hippocampal functional gradients between TLE patients and healthy controls, we observed a marked topographic reorganization of both neocortical and MTL systems during episodic memory states. Neocortical alterations were characterized by reduced functional differentiation in TLE across lateral temporal and midline parietal cortices in both hemispheres. In the MTL, in contrast, patients presented with a more marked functional differentiation of posterior and anterior hippocampal segments ipsilateral to the seizure focus and pathological core, indicating perturbed intrahippocampal connectivity. Semantic memory reorganization was also found in bilateral lateral temporal and ipsilateral angular regions, whereas hippocampal functional topographies were unaffected. Furthermore, leveraging MRI proxies of MTL pathology, we observed alterations in hippocampal microstructure and morphology that were associated with TLE-related functional reorganization during episodic memory. Moreover, correlation analysis and statistical mediation models revealed that these functional alterations contributed to behavioural deficits in episodic memory, but again not in semantic memory in patients. Altogether, our findings suggest that semantic processes rely on distributed neocortical networks, whereas episodic processes are supported by a network involving both the hippocampus and the neocortex. Alterations of such networks can provide a compact signature of state-dependent reorganization in conditions associated with MTL damage, such as TLE.

KW - connectomics

KW - declarative memory

KW - epilepsy

KW - gradients

KW - mesiotemporal lobe

KW - neuroimaging

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U2 - 10.1093/brain/awae197

DO - 10.1093/brain/awae197

M3 - Article

C2 - 39054915

AN - SCOPUS:85208478081

SN - 0006-8950

VL - 147

SP - 3918

EP - 3932

JO - Brain

JF - Brain

IS - 11

ER -

Differential reorganization of episodic and semantic memory systems in epilepsy-related mesiotemporal pathology

Abstract

Bibliographical note

Keywords

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