Dataset Information

Reliable and Elastic Propagation of Cortical Seizures In Vivo.

ABSTRACT: Mapping the fine-scale neural activity that underlies epilepsy is key to identifying potential control targets of this frequently intractable disease. Yet, the detailed in vivo dynamics of seizure progression in cortical microcircuits remain poorly understood. We combine fast (30-Hz) two-photon calcium imaging with local field potential (LFP) recordings to map, cell by cell, the spread of locally induced (4-AP or picrotoxin) seizures in anesthetized and awake mice. Using single-layer and microprism-assisted multilayer imaging in different cortical areas, we uncover reliable recruitment of local neural populations within and across cortical layers, and we find layer-specific temporal delays, suggesting an initial supra-granular invasion followed by deep-layer recruitment during lateral seizure spread. Intriguingly, despite consistent progression pathways, successive seizures show pronounced temporal variability that critically depends on GABAergic inhibition. We propose an epilepsy circuit model resembling an elastic meshwork, wherein ictal progression faithfully follows preexistent pathways but varies flexibly in time, depending on the local inhibitory restraint.

SUBMITTER: Wenzel M

PROVIDER: S-EPMC5551439 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Reliable and Elastic Propagation of Cortical Seizures In Vivo.

Wenzel Michael M Hamm Jordan P JP Peterka Darcy S DS Yuste Rafael R

Cell reports 20170601 13

Mapping the fine-scale neural activity that underlies epilepsy is key to identifying potential control targets of this frequently intractable disease. Yet, the detailed in vivo dynamics of seizure progression in cortical microcircuits remain poorly understood. We combine fast (30-Hz) two-photon calcium imaging with local field potential (LFP) recordings to map, cell by cell, the spread of locally induced (4-AP or picrotoxin) seizures in anesthetized and awake mice. Using single-layer and micropr ...[more]

PMID: 28658617

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Project description:ObjectivePatients with generalized epilepsy exhibit different epileptiform events including asymptomatic interictal spikes (IS), absence seizures with spike-wave discharges (SWDs), and myoclonic seizures (MS). Our objective was to determine the spatiotemporal patterns of cortical activation in SWDs, IS, and MS in the Gabra1+/A322D juvenile myoclonic epilepsy mouse.MethodsWe fabricated affordable, flexible high-density electroencephalography (HdEEG) arrays and recorded spontaneous SWD, IS, and MS with video/HdEEG. We determined differences among the events in amplitude spectral density (ASD) in the δ/θ/α/β/γ frequency bands at baseline (3.5-4.0 seconds before the first spike time, t0 ) and the prespike period (0.1-0.5 seconds before t0 ), and we elucidated the spatiotemporal activation during the t0 spike.ResultsAll three events had an increase in ASD between baseline and prespike in at least one frequency band. During prespike, MS had the largest δ-band ASD, but SWD had the greatest α/β/γ band ASD. For all three events, the ASD was largest in the anterior regions. The t0 spike voltage was also greatest in the anterior regions for all three events and IS and MS had larger voltages than SWD. From 7.5 to 17.5 msec after t0 , MS had greater voltage than IS and SWD, and maximal voltage was in the posterior parietal region.SignificanceChanges in spectral density from baseline to prespike indicate that none of these generalized events are instantaneous or entirely unpredictable. Prominent engagement of anterior cortical regions during prespike and at t0 suggest that common anterior neural circuits participate in each event. Differences in prespike ASD signify that although the events may engage similar brain regions, they may arise from distinct proictal states with different neuronal activity or connectivity. Prolonged activation of the posterior parietal area in MS suggests that posterior circuits contribute to the myoclonic jerk. Together, these findings identify brain regions and processes that could be specifically targeted for further recording and modulation.

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

Reliable and Elastic Propagation of Cortical Seizures In Vivo.

Publications

Reliable and Elastic Propagation of Cortical Seizures In Vivo.

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