Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression

Larivière, Sara; Royer, Jessica; Rodríguez‐Cruces, Raúl; Paquola, Casey; Caligiuri, Maria Eugenia; Gambardella, Antonio; Concha, Luis; Keller, Simon; Cendes, Fernando; Yasuda, Clarissa L.; Bonilha, Leonardo; Gleichgerrcht, Ezequiel; Focke, Niels K.; Domín, Martin; Podewills, Felix von; Langner, Soenke; Rummel, Christian; Wiest, Roland; Martin, Pascal; Kotikalapudi, Raviteja; O’Brien, Terence J.; Sinclair, Benjamin; Vivash, Lucy; Desmond, Patricia; Lui, Elaine; Vaudano, Anna Elisabetta; Meletti, Stefano; Tondelli, Manuela; Alhusaini, Saud; Doherty, Colin; Cavalleri, Gianpiero L.; Delanty, Norman; Kälviäinen, Reetta; Jackson, Graeme D.; Kowalczyk, Magdalena; Mascalchi, Mario; Semmelroch, Mira; Thomas, Rhys; Soltanian-Zadeh, Hamid; Davoodi‐Bojd, Esmaeil; Zhang, Junsong; Winston, Gavin P.; Griffin, Aoife; Singh, Aditi; Tiwari, Vijay; Kreilkamp, Barbara A.K.; Lenge, Matteo; Guerrini, Renzo; Hamandi, Khalid; Foley, Sonya; Rüber, Theodor; Weber, Bernd; Depondt, Chantal; Absil, Julie; Carr, Sarah; Abela, Eugenio; Richardson, Mark P.; Devinsky, Orrin; Severino, Mariasavina; Striano, Pasquale; Tortora, Domenico; Kaestner, Erik; Hatton, Sean N.; Vos, Sjoerd B.; Caciagli, Lorenzo; Duncan, John S.; Whelan, Christopher D.; Thompson, Paul M.; Sisodiya, Sanjay M.; Bernasconi, Andrea; Labate, Angelo; McDonald, Carrie R.; Bernasconi, Neda; Bernhardt, Boris C.

doi:10.1038/s41467-022-31730-5

Cited by 52 publications

(43 citation statements)

References 113 publications

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“…Similarly, a recent study identified associations of structural covariance network reconfigurations in TLE with disease-related transcriptomic patterns 70 . Although these results offer potential insights into the transcriptomic basis of macroscale pathophysiological processes associated with TLE, the combination of normative gene expression patterns obtained from the AHBA dataset and GWAS findings is hindered by several limitations 70 . Firstly, while AHBA offers excellent cortical coverage, data are derived from only six healthy donor brains with predominant sampling in the left hemisphere 69 .…”

Section: Discussionmentioning

confidence: 92%

“…Indeed, microstructural gradient reductions seen in temporo-limbic and higher-order association cortices co-localized with areas of elevated expression of TLE risk genes, while correlations with risk gene expression associated with other epilepsy syndromes were not significant. Similarly, a recent study identified associations of structural covariance network reconfigurations in TLE with disease-related transcriptomic patterns 70 . Although these results offer potential insights into the transcriptomic basis of macroscale pathophysiological processes associated with TLE, the combination of normative gene expression patterns obtained from the AHBA dataset and GWAS findings is hindered by several limitations 70 .…”

Section: Discussionmentioning

confidence: 92%

“…Microstructural gradient reorganization in TLE was contextualized against spatial transcriptomic signatures that are potentially relevant to epilepsy. For this purpose, we followed established procedures detailed in the ENIGMA toolbox (https://github.com/MICA-MNI/ENIGMA) 64 , which aggregates preprocessed cortical gene expression maps from the Allen Human Brain Atlas (AHBA) dataset [68][69][70] . Microarray samples were matched to parcels from the Schaefer-100 atlas 71 in each donor, and genes whose inter-donor correspondence fell below a pre-defined threshold (r<0.2) were discarded from further analysis.…”

Section: Neural Contextualization A)mentioning

confidence: 99%

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Cortical microstructural gradients capture memory network reorganization in temporal lobe epilepsy

Royer

Larivière

Rodríguez‐Cruces

et al. 2022

Preprint

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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.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 92%

Section: Neural Contextualization A)mentioning

confidence: 99%

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Cortical microstructural gradients capture memory network reorganization in temporal lobe epilepsy

Royer

Larivière

Rodríguez‐Cruces

et al. 2022

Preprint

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“…Seizures can be caused by even the tiniest muscle twitches or cognitive impairments, as well as by powerful spasms that linger for a long period [ 79 , 92 ]. Seizures might happen less frequently fewer than one per year or more frequently more than one per day [ 96 , 99 , 101 , 102 , 103 ].…”

Section: Common Brain Diseasesmentioning

confidence: 99%

Emerging Materials, Wearables, and Diagnostic Advancements in Therapeutic Treatment of Brain Diseases

et al. 2022

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Among the most critical health issues, brain illnesses, such as neurodegenerative conditions and tumors, lower quality of life and have a significant economic impact. Implantable technology and nano-drug carriers have enormous promise for cerebral brain activity sensing and regulated therapeutic application in the treatment and detection of brain illnesses. Flexible materials are chosen for implantable devices because they help reduce biomechanical mismatch between the implanted device and brain tissue. Additionally, implanted biodegradable devices might lessen any autoimmune negative effects. The onerous subsequent operation for removing the implanted device is further lessened with biodegradability. This review expands on current developments in diagnostic technologies such as magnetic resonance imaging, computed tomography, mass spectroscopy, infrared spectroscopy, angiography, and electroencephalogram while providing an overview of prevalent brain diseases. As far as we are aware, there hasn’t been a single review article that addresses all the prevalent brain illnesses. The reviewer also looks into the prospects for the future and offers suggestions for the direction of future developments in the treatment of brain diseases.

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“…Network approaches -based on the mapping of inter-regional connectivity or covarianceshowed that focal epilepsy indeed affects the whole-brain and that focal structural and functional changes within the EZ appear to act more as a set of nodes in a larger network of affected regions 6,7 . For example, changes in cortical morphometry and connectivity have been consistently observed across the cortical mantle [8][9][10][11][12] . Direct longitudinal relaxation time (T 1 ) mapping showed a prolongation of T 1 relaxation times in temporopolar, orbitofrontal and para-hippocampal regions indicating alterations at the microstructural level as well 13 .…”

Section: Introductionmentioning

confidence: 99%

Multi-scale structural alterations of the thalamus and basal ganglia in focal epilepsy as demonstrated by 7T MRI

Haast

Testud

Scholly

et al. 2022

Preprint

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Focal epilepsy is characterized by repeated spontaneous seizures that originate from one or multiple epileptogenic zones (EZ). These epileptic activities rapidly propagate to other regions in the brain following a hierarchical organization defined by a decrease in epileptogenicity and the anatomical specificity of subnetworks, also known as EZ networks (EZN). More recently, analysis of intracerebral recordings showed that subcortical structures, and in particular the thalamus, play an important role in facilitating and/or propagating epileptic activity. This supports previously reported structural alterations of these structures. Nonetheless, between-patient differences in EZN (e.g., temporal vs. non-temporal lobe epilepsy) as well as other clinical features (e.g., number of EZs) might impact the magnitude and spatial distribution of subcortical structural changes. Here we used 7 Tesla MRI T1data to provide a comprehensive description of subcortical morphological (volume, tissue deformation, and shape) and longitudinal relaxation (T1) changes in focal epilepsy patients to evaluate the impact of the EZN and patient-specific clinical features. Our results revealed widespread morphometric alterations as well as reduction in T1, with volume acting as the dominant discriminator between patients and controls, while thalamic T1measures looked promising to further differentiate patients based on EZN. In particular, the observed differences in T1changes between thalamic nuclei indicated differential involvement of thalamic nuclei based on EZN. Finally, the number of EZs was found to best explain the observed variability between patients. To conclude, this work revealed multi-scale subcortical alterations in focal epilepsy as well their dependence on several clinical characteristics. Our results provide a basis for further, in-depth investigations using (quantitative) MRI and SEEG data and warrant further personalization of intervention strategies, such as deep brain stimulation, for treating focal epilepsy patients.

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Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression

Cited by 52 publications

References 113 publications

Cortical microstructural gradients capture memory network reorganization in temporal lobe epilepsy

Cortical microstructural gradients capture memory network reorganization in temporal lobe epilepsy

Emerging Materials, Wearables, and Diagnostic Advancements in Therapeutic Treatment of Brain Diseases

Multi-scale structural alterations of the thalamus and basal ganglia in focal epilepsy as demonstrated by 7T MRI

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