---
title: "Histological morphometry linked to MRI cortical thinning in temporal lobe epilepsy"
id: "biorxiv-1-histological-morphometric-correlates-of-mri-defined-cortical-thinning-in"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-1-histological-morphometric-correlates-of-mri-defined-cortical-thinning-in"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.22.761130v1?rss=1"
published_at: "2026-10-25T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Histological morphometry linked to MRI cortical thinning in temporal lobe epilepsy
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-1-histological-morphometric-correlates-of-mri-defined-cortical-thinning-in
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.22.761130v1?rss=1)
- **Published At:** 2026-10-25T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The team analyzed resected **middle temporal gyrus** tissue from 117 surgical TLE cases to relate histology to preoperative **MRI-defined cortical thinning** quantified with CAT12. - Cases included 74 with **hippocampal sclerosis** (HS), 12 with temporal lobe sclerosis (TLS/FCD IIIa), and remaining cases without HS; tissue was NeuN-immunolabelled for neuronal morphometry. - Automated image analysis measured neuronal density, cell-size distributions, neuronal spatial organization, relative cortical layer thickness, and sulcal–gyral cytoarchitectural variation. - MRI cortical thinning did not correspond to diffuse neuronal loss; investigators reported increased neuronal packing density and altered cell-size spatial distributions in superficial and deep layers associated with thinning. - Layer-specific laminar thinning on histology was limited, observed only in layer VI of right TLE with HS; TLS cases lacked MRI thinning yet showed altered neuronal composition beyond superficial cortex. - MRI thinning associated with attenuation of normal sulcal/gyral cytoarchitectural gradients, indicating disrupted cortical architectural variation rather than wide-area atrophy. - Right-versus-left lateralised clinical–pathological correlations appeared, including age of onset differences, suggesting hemisphere-specific mechanisms for cortical thinning. - Authors conclude cortical thinning likely reflects altered neuropil volume (myelin, dendritic remodeling) and network-related changes that could be dynamic and potentially reversible; they did not report certain imaging threshold details or longitudinal progression metrics in the preprint. - The study challenges the assumption that MRI thinning equals progressive neuronal degeneration and raises specific histological questions that remain unanswered in the source text.
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Joanna Bartkiewicz 1 UCL; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Joanna%2BBartkiewicz%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Bartkiewicz%20J&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJoanna%2BBartkiewicz%2B) * [ORCID record for Joanna Bartkiewicz](http://orcid.org/0000-0002-5020-6109 "Open in new tab") Fenglai Xiao 1 UCL; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Fenglai%2BXiao%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Xiao%20F&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AFenglai%2BXiao%2B) Yau Mun Lim 1 UCL; 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These findings are frequently interpreted as evidence of cumulative neurodegeneration. However, the histopathological substrates underlying MRI-confirmed cortical thinning in epilepsy remain poorly defined. In particular, it is unknown whether cortical thinning reflects irreversible neuronal loss or potentially reversible epilepsy-related network alterations in cortical microstructure. We analysed the resected middle temporal gyrus from 117 individuals undergoing surgery for temporal lobe epilepsy, including cases with (n= 74) or without hippocampal sclerosis (HS) and 12 cases with additional temporal lobe sclerosis (TLS, or Focal Cortical Dysplasia IIIa), defined by a distinct pattern of cytoarchitectural reorganisation and gliosis involving superficial layers. All cases were stratified by the presence or absence of pre-operative MRI-defined cortical thinning of the middle temporal gyrus, quantified using CAT12 relative to healthy controls. On NeuN-immuno-labelled sections using automated image analysis we assessed neuronal spatial distributions relative to their size and packing density; relative cortical layer thickness and sulcal-gyral cytoarchitectural variation were also quantified. MRI-defined cortical thinning was not associated with diffuse neuronal loss. Instead, thinning correlated with increased neuronal density and altered cell-size spatial organisation in superficial and deep layers, particularly in right temporal lobe epilepsy cases with HS. There was limited evidence of layer-specific laminar thinning, being confined to layer VI in the right TLE/HS group only. Of note, TLS cases did not show either cortical thinning on MRI or laminar thinning on histology compared to cases without TLS but altered neuronal densities and composition that was not confined to the superficial cortex. MRI cortical thinning was also characterised by attenuation of normal sulcal/gyral cytoarchitectural variations suggesting disruption of cortical architectural gradients. In contrast, cases with HS but without MRI cortical thinning demonstrated loss of the expected inter-hemispheric cytoarchitectural asymmetry, indicating a distinct pathological process dissociated from thinning. Clinical-pathological correlations were lateralised, including age of onset, further supporting distinct mechanisms contributing to MRI cortical thinning between left and right TLE. These findings challenge the prevailing assumption that MRI-defined cortical thinning in epilepsy reflects progressive neuronal degeneration. Rather than laminar neuronal loss and atrophy, thinning was associated with altered neuronal packing and cell-size distributions between layers. This points towards altered neuropil volumes, including myelin content and dendritic remodelling, in turn suggesting potentially reversible dynamic seizure- or network-related processes. ### Competing Interest Statement The authors have declared no competing interest. ## Funder Information Declared Wellcome Trust, 221 934/Z/20/Z Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY-NC 4.0 International license](http://creativecommons.org/licenses/by-nc/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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