Genetic and neuroanatomical support for functional brain network dynamics in epilepsy (original) (raw)
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Local structural connectivity directs seizure spread in focal epilepsy
How does the human brain's structural scaffold give rise to its intricate functional dynamics? This is a central challenge in translational neuroscience, particularly in epilepsy, a disorder that affects over 50 million people worldwide. Treatment for medication-resistant focal epilepsy is often structural - through surgery, devices or focal laser ablation - but structural targets, particularly in patients without clear lesions, are largely based on functional mapping via intracranial EEG (iEEG). Unfortunately, the relationship between structural and functional connectivity in the seizing brain is poorly understood. In this study, we quantify structure-function coupling, specifically between white matter connections and iEEG, across preictal and ictal periods in 45 seizures from 9 patients with unilateral drug-resistant focal epilepsy. We use High Angular Resolution Diffusion Imaging (HARDI) tractography to construct structural connectivity networks and correlate these networks ...
2021
Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem co-expression patterns of epilepsy risk genes. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1,328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patt...
Characterizing the role of the structural connectome in seizure dynamics
Brain, 2019
How does the human brain’s structural scaffold give rise to its intricate functional dynamics? This is a central question in translational neuroscience that is particularly relevant to epilepsy, a disorder affecting over 50 million subjects worldwide. Treatment for medication-resistant focal epilepsy is often structural—through surgery or laser ablation—but structural targets, particularly in patients without clear lesions, are largely based on functional mapping via intracranial EEG. Unfortunately, the relationship between structural and functional connectivity in the seizing brain is poorly understood. In this study, we quantify structure-function coupling, specifically between white matter connections and intracranial EEG, across pre-ictal and ictal periods in 45 seizures from nine patients with unilateral drug-resistant focal epilepsy. We use high angular resolution diffusion imaging (HARDI) tractography to construct structural connectivity networks and correlate these networks ...
Nature Communications
Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of ...
bioRxiv (Cold Spring Harbor Laboratory), 2023
Temporal lobe epilepsy (TLE) is a brain network disorder characterized by alterations at both the structural and the functional level. It remains unclear how structure and function are related and whether this has any clinical relevance. In the present work, we adopted a novel methodological approach investigating how network structural features influence the large-scale dynamics. The functional network was defined by the spatio-temporal spreading of aperiodic bursts of activations (neuronal avalanches), as observed utilizing high-density electroencephalography (hdEEG) in TLE patients. The structural network was modeled as the region-based thickness covariance. Loosely speaking, we quantified the similarity of the cortical thickness of any two brain regions, both across groups, and at the individual level, the latter utilizing a novel approach to define the personalized covariance network (pCN). In order to compare the structural and functional networks (at the nodal level), we studied the correlation between the probability that a wave of activity would propagate from a source to a target region, and the similarity of the source region thickness as compared to other target brain regions. Building on the recent evidence that large-waves of activities pathologically spread through the epileptogenic network in TLE, also during resting state, we hypothesize that the structural cortical organization might influence such altered spatio-temporal dynamics. We observed a stable cluster of structure-function correlation in the bilateral limbic areas across subjects, highlighting group specific features for left, right and bilateral TLE. The involvement of contralateral areas was observed in unilateral TLE. We showed that in temporal lobe epilepsy alterations of structural and functional networks pair in the regions where seizures propagate and are linked to disease severity. In this study we leveraged on a well-defined model of neurological disease and pushed forward personalization approaches potentially useful in clinical practice. Finally, the methods developed here could be exploited to investigate the relationship between structure-function networks at subject level in other neurological conditions.
Structural and effective connectivity in focal epilepsy
NeuroImage. Clinical, 2018
Patients with medically-refractory focal epilepsy may be candidates for neurosurgery and some may require placement of intracranial EEG electrodes to localise seizure onset. Assessing cerebral responses to single pulse electrical stimulation (SPES) may give diagnostically useful data. SPES produces cortico-cortical evoked potentials (CCEPs), which infer effective brain connectivity. Diffusion-weighted images and tractography may be used to estimate structural brain connectivity. This combination provides the opportunity to observe seizure onset and its propagation throughout the brain, spreading contiguously along the cortex explored with electrodes, or non-contiguously. We analysed CCEPs and diffusion tractography in seven focal epilepsy patients and reconstructed the effective and structural brain networks. We aimed to assess the inter-modal similarity of the networks at a large scale across the cortex, the effective and structural connectivity of the ictal-onset zone, and investi...
Large scale brain networks in epilepsy
2008
Two studies of brain networks, performed on interictal intracranial EEGs recorded during the presurgical evaluation of patients with epilepsy, are presented in this report. In the first we examine pairwise relationships between pre-defined brain regions in 12 patients, 6 with medial temporal onset of seizures and 6 with frontal and parietal onset of seizures. We demonstrate that differences, in pairwise relationships between brain regions, allow a distinction of these two groups of patients. In the second study we evaluate short, mid, and long-distance brain connectivity as a function of distance to the seizure onset area in another 2 patients. We demonstrate that the measures of brain connectivity distinguish between brain areas which are close to and far from the seizure onset area. The results of the two studies may help both define large scale brain networks involved in the generation of seizures, and localize the area of seizure onset.
PLOS Computational Biology, 2015
Drug-resistant epilepsy is traditionally characterized by pathologic cortical tissue comprised of seizure-initiating 'foci'. These 'foci' are thought to be embedded within an epileptic network whose functional architecture dynamically reorganizes during seizures through synchronous and asynchronous neurophysiologic processes. Critical to understanding these dynamics is identifying the synchronous connections that link foci to surrounding tissue and investigating how these connections facilitate seizure generation and termination. We use intracranial recordings from neocortical epilepsy patients undergoing pre-surgical evaluation to analyze functional connectivity before and during seizures. We develop and apply a novel technique to track network reconfiguration in time and to parse these reconfiguration dynamics into distinct seizure states, each characterized by unique patterns of network connections that differ in their strength and topography. Our approach suggests that seizures are generated when the synchronous relationships that isolate seizure 'foci' from the surrounding epileptic network are broken down. As seizures progress, foci reappear as isolated subnetworks, marking a shift in network state that may aid seizure termination. Collectively, our observations have important theoretical implications for understanding the spatial involvement of distributed cortical structures in the dynamics of seizure generation, propagation and termination, and have practical significance in determining which circuits to modulate with implantable devices. epileptic networks | seizure focus | network state | synchrony | graph theory | community detection | dynamic network neuroscience Abbreviations: ECoG, electrocorticography Significance Statement. Localization-related epilepsy affects ≈80% of epilepsy patients and is often resistant to medication. The challenge for treating patients is mapping dynamic connectivity between cortical structures in the epileptic network during seizures. While it is well known that whole-brain functional architecture reconfigures during tasks, we hypothesize that epileptic networks reconfigure at the meso-scale leading to seizure initiation, propagation, and termination. We develop new methods to track dynamic network reconfiguration amongst connections of different strength as seizures evolve. Our results indicate that seizure onset is primarily driven by the breakdown of strong connections that re-surge in an isolated focal sub-network as seizures transition to termination. These findings have practical implications for targeting specific connections with implantable, therapeutic devices to control seizures. Footline Author PNAS Issue Date Volume Issue Number 7 arXiv:1407.5105v1 [q-bio.NC]
Quantitative Multimodal Mapping Of Seizure Networks In Drug-Resistant Epilepsy
2018
Over 15 million people worldwide suffer from localization-related drug-resistant epilepsy. These patients are candidates for targeted surgical therapies such as surgical resection, laser thermal ablation, and neurostimulation. While seizure localization is needed prior to surgical intervention, this process is challenging, invasive, and often inconclusive. In this work, I aim to exploit the power of multimodal highresolution imaging and intracranial electroencephalography (iEEG) data to map seizure networks in drugresistant epilepsy patients, with a focus on minimizing invasiveness. Given compelling evidence that epilepsy is a disease of distorted brain networks as opposed to well-defined focal lesions, I employ a graph-theoretical approach to map structural and functional brain networks and identify putative targets for removal. The first section focuses on mesial temporal lobe epilepsy (TLE), the most common type of localization-related epilepsy. Using high-resolution structural a...