Search bioRxiv⌕ Search

Biology subjects

Inati, S.

Publications and source records attributed to Inati, S..

3 recordsLinked to original sources

Sex-related structural alterations across common epilepsies: a worldwide ENIGMA study

Epilepsy is characterized by widespread structural brain alterations extending beyond the epileptic zone, involving both cortical and subcortical regions. Importantly, the clinical manifestation of epilepsy, including seizure types, psychiatric comorbidities, and treatment responses, has been shown to differ between sexes. However, sex differences in structural alterations in epilepsy have been seldomly reported in neuroimaging studies, partly due to limited sample sizes and single-center designs. Here, we systematically investigated sex differences in common epilepsies and their related clinical variables using structural neuroimaging biomarkers in an international multi-center cohort of 1,253 epilepsy patients and 1,077 healthy controls. We studied cortical thickness and subcortical volume in two types of epilepsy: temporal lobe epilepsy (TLE) and genetic generalized epilepsy (GGE). Both male and female patients with TLE showed widespread cortical and subcortical thinning compared with controls. In GGE, when compared separately to controls, male patients showed only subtle structural alterations, whereas female patients exhibited more widespread structural alterations. Sex-stratified analyses revealed some variation in the extent and distribution of cortical thickness and subcortical volume alterations between male and female patients in both epilepsy cohorts. Yet, we did not find significant sex-by-diagnosis interaction effects in TLE and GGE. Similarly, no significant interaction effects were observed between sex and age of onset or disease duration in either patient group. Overall, although we observed some differences in regional cortical thickness and subcortical volume between male and female patients with epilepsy, we did not find significant sex-by-diagnosis interactions. Our findings indicate that sex differences in behavioral and clinical outcomes of epilepsy may involve biological or functional processes that require further investigation.

neuroscience↗

Source-sink connectivity: a novel resting-state EEG marker of the epileptogenic zone

Over 15 million epilepsy patients worldwide have drug-resistant epilepsy (DRE). Successful surgery is a standard of care treatment for DRE but can only be achieved through complete resection or disconnection of the epileptogenic zone (EZ), the brain region(s) where seizures originate. Surgical success rates vary between 20-80% because no clinically validated biological markers of the EZ exist. Localizing the EZ is a costly and time-consuming process beginning with non-invasive neuroimaging and often followed by days to weeks of intracranial EEG (iEEG) monitoring. Clinicians visually inspect iEEG data to identify abnormal activity (e.g., low-voltage high frequency activity) on individual channels occurring immediately before seizures or spikes that occur on interictal iEEG (i.e., between seizures). In the end, the clinical standard mainly relies on a small proportion of the iEEG data captured to assist in EZ localization (minutes of seizure data versus days of recordings), missing opportunities to leverage these largely ignored interictal data to better diagnose and treat patients. Intracranial EEG offers a unique opportunity to observe epileptic cortical network dynamics but waiting for seizures increases patient risks associated with invasive monitoring. In this study, we aim to leverage interictal iEEG data by developing a new network-based interictal iEEG marker of the EZ. We hypothesize that when a patient is not clinically seizing, it is because the EZ is inhibited by other regions. We developed an algorithm that identifies two groups of nodes from the interictal iEEG network: those that are continuously inhibiting a set of neighboring nodes ("sources") and the inhibited nodes themselves ("sinks"). Specifically, patient-specific dynamical network models (DNMs) were estimated from minutes of iEEG and their connectivity properties revealed top sources and sinks in the network, with each node being quantified by source-sink metrics (SSMs). We validated the SSMs in a retrospective analysis of 65 patients by using the SSMs of the annotated EZ to predict surgical outcomes. The SSMs predicted outcomes with an accuracy of 79% compared to an accuracy of 43% for clinicians predictions (surgical success rate of this dataset). In failed outcomes, we identified regions of the brain with high SSMs that were untreated. When compared to high frequency oscillations, the most commonly proposed interictal iEEG feature for EZ localization, SSMs outperformed in predictive power (by a factor of 1.2) suggesting SSMs may be an interictal iEEG fingerprint of the EZ.

bioengineering↗

Nodal Fragility of Intracranial EEG Networks: Towards an EEG Fingerprint for the Epileptogenic Zone

Over 15 million epilepsy patients worldwide do not respond to drugs. Successful surgical treatment requires complete removal, or disconnection of the seizure onset zone (SOZ), brain region(s) where seizures originate. Unfortunately, surgical success rates vary between 30%-70% because no clinically validated biological marker of the SOZ exists. We develop and retrospectively validate a new EEG marker - neural fragility - in a retrospective analysis of 91 patients by using neural fragility of the annotated SOZ as a metric to predict surgical outcomes. Fragility predicts 43/47 surgical failures with an overall prediction accuracy of 76%, compared to the accuracy of clinicians being 48% (successful outcomes). In failed outcomes, we identify fragile regions that were untreated. When compared to 20 EEG features proposed as SOZ markers, fragility outperformed in predictive power and interpretability suggesting neural fragility as an EEG biomarker of the SOZ.

neuroscience↗