Cortical microstructural gradients capture memory network reorganization in temporal lobe epilepsy

Abstract

Temporal lobe epilepsy (TLE), one of the most common pharmaco-resistant epilepsies, is associated with pathology of paralimbic brain regions, particularly in the mesiotemporal lobe. Cognitive dysfunction in TLE is frequent, and particularly affects episodic memory. Crucially, these difficulties challenge the quality of life of patients, sometimes more than seizures, underscoring the need to assess neural processes of cognitive dysfunction in TLE to improve patient management. Our work harnessed a novel conceptual and analytical approach to assess spatial gradients of microstructural differentiation between cortical areas based on high-resolution MRI analysis. Gradients track region-to-region variations in intracortical lamination and myeloarchitecture, serving as a system-level measure of structural and functional reorganization. Comparing cortex-wide microstructural gradients between 21 patients and 35 healthy controls, we observed a contracted gradient in TLE driven by reduced microstructural differentiation between paralimbic cortices and the remaining cortex with marked abnormalities in ipsilateral temporopolar and dorsolateral prefrontal regions. Findings were replicated in an independent cohort. Using an independent post mortem dataset, we observed that in vivo findings reflected topographical variations in cortical lamination patterns, confirming that TLE-related changes in the microstructural gradient reflected increased proximity of regions with more dissimilar laminar structure. Disease-related transcriptomics could furthermore show specificity of our findings to TLE over other common epilepsy syndromes. Finally, microstructural dedifferentiation was associated with cognitive network reorganization seen during an episodic memory functional MRI paradigm, and correlated with inter-individual differences in task accuracy. Collectively, our findings showing a pattern of reduced microarchitectural differentiation between paralimbic regions and the remaining cortex provide a parsimonious explanation for functional network reorganization and cognitive dysfunction characteristic of TLE.

Atypical connectome topography and signal flow in temporal lobe epilepsy

“…30 In the case of TLE, connectome gradient analyses have been applied to high-resolution quantitative T1 relaxometry data and task-based functional MRI during memory paradigms, revealing microstructural miswiring and state-specific functional reorganization. [31][32][33] Here, we expanded these findings by examining . CC-BY-NC-ND 4.0 International license made available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.…”

Pharmaco-resistant temporal lobe epilepsy gradually perturbs the cortex-wide excitation-inhibition balance

“…Previous studies have explored potential links between structural and functional alterations in TLE and impairment across various cognitive domains, including memory, language, and executive control. 14, 45, 47, 53 Reduced volumes in subregions of the prefrontal cortex, for example, have been related to poor executive functioning 91 and impaired memory. 92 Decreased activity in frontoparietal regions correlates with poorer working memory.…”

“…Emerging evidence suggests that cognitive impairment in TLE is also determined by damage to functional connectivity within the medial temporal lobe. 14, 53 To date, however, no studies have explored the extent to which E/I changes ( i.e. , the Hurst exponent) can predict cognitive impairments in TLE.…”

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

“…Previous studies have also linked network alterations in TLE patients to cognitive impairment 47,85,112,114,116 . Consistent with a recent study from our group 46 , distinct episodic task impairment was observed in TLE, while semantic task performance remained relatively intact.…”

“…Similar procedures were performed to align hippocampal gradients. Finally, we normalized neocortical and hippocampal gradient scores relative to the distribution in controls, and sorted gradients in patients relative to the hemisphere ipsilateral to the seizure focus, as in prior work 85 .…”