Resolution revolution: epilepsy dynamics at the microscale

Szabó, Gergely; Schneider, Calvin J; Soltész, Iván

doi:10.1016/j.conb.2014.12.012

Cited by 7 publications

(4 citation statements)

References 48 publications

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“…Identifying properties of seizure producing networks (“ictal networks”) may enable more efficient seizure control (Baraban and Loscher, 2014; Krook-Magnuson and Soltesz, 2015). Recent advances in mapping ictal network dynamics at the microscale have unveiled unexpected complexity (Bower et al, 2012; Cymerblit-Sabba and Schiller, 2012; Feldt Muldoon et al, 2013; Keller et al, 2010; Truccolo et al, 2014; Truccolo et al, 2011), challenging the classical view of epilepsy as a condition of stereotyped ictal events (Szabo et al, 2015). In fact, the monitoring of the recruitment of neural populations to successive seizures in humans using multi-electrode arrays has led to contrasting conclusions suggesting either strict reproducibility of neuronal spiking patterns (Truccolo et al, 2011), or lack of such reproducibility close to the epileptic focus (“ictal penumbra”, or “propagation area”) (Schevon et al, 2012) or completely non-repeated recruitment patterns (Bower et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Reliable and Elastic Propagation of Cortical Seizures In Vivo

et al. 2017

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Mapping the fine-scale neural activity that underlies epilepsy is key to identify 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 two-photon calcium imaging (30-Hz) with 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 multi-layer imaging in different cortical areas we uncover reliable recruitment of local neural populations within and across cortical layers, and 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.

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Section: Introductionmentioning

confidence: 99%

Reliable and Elastic Propagation of Cortical Seizures In Vivo

et al. 2017

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“…An ongoing debate regards the dynamics of neuronal firing in the ictogenic network (Szabo et al, 2015 ). Decades of electrophysiological studies established the classical view of epileptic seizures as hypersynchronous and stereotyped events (McCormick and Contreras, 2001 ).…”

Section: Outlook: Open Questions To Design New Therapeutic Strategiesmentioning

confidence: 99%

The Enlightened Brain: Novel Imaging Methods Focus on Epileptic Networks at Multiple Scales

Rossi

Kullmann

Wykes

2018

Front. Cell. Neurosci.

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Epilepsy research is rapidly adopting novel fluorescence optical imaging methods to tackle unresolved questions on the cellular and circuit mechanisms of seizure generation and evolution. State of the art two-photon microscopy and wide-field fluorescence imaging can record the activity in epileptic networks at multiple scales, from neuronal microcircuits to brain-wide networks. These approaches exploit transgenic and viral technologies to target genetically encoded calcium and voltage sensitive indicators to subclasses of neurons, and achieve genetic specificity, spatial resolution and scalability that can complement electrophysiological recordings from awake animal models of epilepsy. Two-photon microscopy is well suited to study single neuron dynamics during interictal and ictal events, and highlight the differences between the activity of excitatory and inhibitory neuronal classes in the focus and propagation zone. In contrast, wide-field fluorescence imaging provides mesoscopic recordings from the entire cortical surface, necessary to investigate seizure propagation pathways, and how the unfolding of epileptic events depends on the topology of brain-wide functional connectivity. Answering these questions will inform pre-clinical studies attempting to suppress seizures with gene therapy, optogenetic or chemogenetic strategies. Dissecting which network nodes outside the seizure onset zone are important for seizure generation, propagation and termination can be used to optimize current and future evaluation methods to identify an optimal surgical strategy.

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“…For instance, high-resolution recordings at the meso-scale, which are currently highly tractable, offer the potential to infer neural population firing rates because it has been demonstrated that broadband local field potential power is proportional to local firing rates [33,34]. However, to validate methods that integrate between spatial scales, we need higher spatial resolution electrophysiological recordings [35,36]. Here, we briefly review the current state of the art in high-resolution electrode arrays and consider how high-resolution arrays can be useful for seizure prediction.…”

Section: High-spatial Resolution Measurementsmentioning

confidence: 99%

Seizure Prediction: Science Fiction or Soon to Become Reality?

Freestone

Karoly

Peterson

et al. 2015

Curr Neurol Neurosci Rep

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This review highlights recent developments in the field of epileptic seizure prediction. We argue that seizure prediction is possible; however, most previous attempts have used data with an insufficient amount of information to solve the problem. The review discusses four methods for gaining more information above standard clinical electrophysiological recordings. We first discuss developments in obtaining long-term data that enables better characterisation of signal features and trends. Then, we discuss the usage of electrical stimulation to probe neural circuits to obtain robust information regarding excitability. Following this, we present a review of developments in high-resolution micro-electrode technologies that enable neuroimaging across spatial scales. Finally, we present recent results from data-driven model-based analyses, which enable imaging of seizure generating mechanisms from clinical electrophysiological measurements. It is foreseeable that the field of seizure prediction will shift focus to a more probabilistic forecasting approach leading to improvements in the quality of life for the millions of people who suffer uncontrolled seizures. However, a missing piece of the puzzle is devices to acquire long-term high-quality data. When this void is filled, seizure prediction will become a reality.

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Resolution revolution: epilepsy dynamics at the microscale

Cited by 7 publications

References 48 publications

Reliable and Elastic Propagation of Cortical Seizures In Vivo

Reliable and Elastic Propagation of Cortical Seizures In Vivo

The Enlightened Brain: Novel Imaging Methods Focus on Epileptic Networks at Multiple Scales

Seizure Prediction: Science Fiction or Soon to Become Reality?

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