Dataset Information

The dynamics of functional connectivity in neocortical focal epilepsy.

ABSTRACT: Focal epilepsy is characterised by paroxysmal events, reflecting changes in underlying local brain networks. To capture brain network activity at the maximal temporal resolution of the acquired functional magnetic resonance imaging (fMRI) data, we have previously developed a novel analysis framework called Dynamic Regional Phase Synchrony (DRePS). DRePS measures instantaneous mean phase coherence within neighbourhoods of brain voxels. We use it here to examine how the dynamics of the functional connections of regional brain networks are altered in neocortical focal epilepsy. Using task-free fMRI data from 21 subjects with focal epilepsy and 21 healthy controls, we calculated the power spectral density of DRePS, which is a measure of signal variability in local connectivity estimates. Whole-brain averaged power spectral density of DRePS, or signal variability of local connectivity, was significantly higher in epilepsy subjects compared to healthy controls. Maximal increase in DRePS spectral power was seen in bilateral inferior frontal cortices, ipsilateral mid-cingulate gyrus, superior temporal gyrus, caudate head, and contralateral cerebellum. Our results provide further evidence of common brain abnormalities across people with focal epilepsy. We postulate that dynamic changes in specific cortical brain areas may help maintain brain function in the presence of pathological epileptiform network activity in neocortical focal epilepsy.

SUBMITTER: Pedersen M

PROVIDER: S-EPMC5429237 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The dynamics of functional connectivity in neocortical focal epilepsy.

Pedersen Mangor M Omidvarnia Amir A Curwood Evan K EK Walz Jennifer M JM Rayner Genevieve G Jackson Graeme D GD

NeuroImage. Clinical 20170411

Focal epilepsy is characterised by paroxysmal events, reflecting changes in underlying local brain networks. To capture brain network activity at the maximal temporal resolution of the acquired functional magnetic resonance imaging (fMRI) data, we have previously developed a novel analysis framework called Dynamic Regional Phase Synchrony (DRePS). DRePS measures instantaneous mean phase coherence within neighbourhoods of brain voxels. We use it here to examine how the dynamics of the functional ...[more]

PMID: 28529877

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Project description:Objective: Whilst stimulation of the anterior nucleus of the thalamus has shown efficacy for reducing seizure frequency in adults, alterations in thalamic connectivity have not been explored in children. We tested the hypotheses that (a) the anterior thalamus has increased functional connectivity in children with focal epilepsy, and (b) this alteration in the connectome is a persistent effect of the disease rather than due to transient epileptiform activity. Methods: Data from 35 children (7-18 years) with focal, drug-resistant epilepsy and 20 healthy children (7-17 years) were analyzed. All subjects underwent functional magnetic resonance imaging (fMRI) whilst resting and were simultaneously monitored with scalp electroencephalography (EEG). The fMRI timeseries were extracted for each Automated Anatomical Labeling brain region and thalamic subregion. Graph theory metrics [degree (DC) and eigenvector (EC) centrality] were used to summarize the connectivity profile of the ipsilateral thalamus, and its thalamic parcellations. The effect of interictal epileptiform discharges (IEDs) captured on EEG was used to determine their effect on DC and EC. Results: DC was significantly higher in the anterior nucleus (p = 0.04) of the thalamus ipsilateral to the epileptogenic zone in children with epilepsy compared to controls. On exploratory analyses, we similarly found a higher DC in the lateral dorsal nucleus (p = 0.02), but not any other thalamic subregion. No differences in EC measures were found between patients and controls. We did not find any significant difference in DC or EC in any thalamic subregion when comparing the results of children with epilepsy before, and after the removal of the effects of IEDs. Conclusions: Our data suggest that the anterior and lateral dorsal nuclei of the thalamus are more highly functionally connected in children with poorly controlled focal epilepsy. We did not detect a convincing change in thalamic connectivity caused by transient epileptiform activity, suggesting that it represents a persistent alteration to network dynamics.

Project description:Some of the most clinically consequential aspects of focal epilepsy, e.g. loss of consciousness, arise from the generalization or propagation of seizures through local and large-scale neocortical networks. Yet, the dynamics of such neocortical propagation remain poorly understood. Here, we studied the microdynamics of focal seizure propagation in neocortical patches (4×4 mm) recorded via high-density microelectrode arrays (MEAs) implanted in people with pharmacologically resistant epilepsy. Our main findings are threefold: (1) a newly developed stage segmentation method, applied to local field potentials (LFPs) and multiunit activity (MUA), revealed a succession of discrete seizure stages, each lasting several seconds. These different stages showed characteristic evolutions in overall activity and spatial patterns, which were relatively consistent across seizures within each of the 5 patients studied. Interestingly, segmented seizure stages based on LFPs or MUA showed a dissociation of their spatiotemporal dynamics, likely reflecting different contributions of non-local synaptic inputs and local network activity. (2) As previously reported, some of the seizures showed a peak in MUA that happened several seconds after local seizure onset and slowly propagated across the MEA. However, other seizures had a more complex structure characterized by, for example, several MUA peaks, more consistent with the succession of discrete stages than the slow propagation of a simple wavefront of increased MUA. In both cases, nevertheless, seizures characterized by spike-wave discharges (SWDs, ~2-3 Hz) eventually evolved into patterns of phase-locked MUA and LFPs. (3) Individual SWDs or gamma oscillation cycles (25-60 Hz), characteristic of two different types of recorded seizures, tended to propagate with varying degrees of directionality, directions of propagation and speeds, depending on the identified seizure stage. However, no clear relationship was observed between the MUA peak onset time (in seizures where such peak onset occurred) and changes in MUA or LFP propagation patterns. Overall, our findings indicate that the recruitment of neocortical territories into ictal activity undergoes complex spatiotemporal dynamics evolving in slow discrete states, which are consistent across seizures within each patient. Furthermore, ictal states at finer spatiotemporal scales (individual SWDs or gamma oscillations) are organized by slower time scale network dynamics evolving through these discrete stages.

Dataset Information

The dynamics of functional connectivity in neocortical focal epilepsy.

Publications

The dynamics of functional connectivity in neocortical focal epilepsy.

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