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August 2010 - present
August 2010 - present
October 2008 - October 2019
Publications
Publications (129)
Echo State Networks (ESN) are reservoir networks that satisfy well-established criteria for stability when constructed as feedforward networks. Recent evidence suggests that stability criteria are altered in the presence of reservoir substructures, such as clusters. Understanding how the reservoir architecture affects stability is thus important fo...
Electrical stimulation of the brain is increasingly used to alleviate the symptoms of a range of neurological disorders and as a means to artificially inject information into neural circuits in neuroprosthetic applications. Machine learning has been proposed to find optimal stimulation settings autonomously. However, this approach is impeded by the...
Spontaneous activity in the absence of external input, including propagating waves of activity, is a robust feature of neuronal networks in vivo and in vitro. The neurophysiological and anatomical requirements for initiation and persistence of such activity, however, are poorly understood, as is their role in the function of neuronal networks. Comp...
Numerous studies suggest that biological neuronal networks self-organize towards a critical state with stable recruitment dynamics. Individual neurons would then statistically activate exactly one further neuron during activity cascades termed neuronal avalanches. Yet, it is unclear if and how this can be reconciled with the explosive recruitment d...
The spatial distribution of neurons and activity-dependent neurite outgrowth shape long-range interaction, recurrent local connectivity and the modularity in neuronal networks. We investigated how this mesoscale architecture develops by interaction of neurite outgrowth, cell migration and activity in cultured networks of rat cortical neurons and sh...
Epileptiform activity (EA) manifests in diverse patterns of hypersynchronous network activity. Fundamental research mostly addresses two extreme patterns, individual epileptiform spikes and seizures. We developed PEACOC to detect and classify a wide range of EA patterns in local field potentials. PEACOC delimits EA patterns as bursts of epileptifor...
Mesial temporal lobe epilepsy (MTLE), the most common form of focal epilepsy in adults, is often refractory to medication and associated with hippocampal sclerosis. Deep brain stimulation represents an alternative treatment option for drug-resistant patients who are ineligible for resective brain surgery. In clinical practice, closed-loop stimulati...
Mesial temporal lobe epilepsy (MTLE), the most common form of focal epilepsy in adults, is often refractory to medication and associated with hippocampal sclerosis. Deep brain stimulation represents an alternative treatment option for drug-resistant patients who are ineligible for resective brain surgery. In clinical practice, closed-loop stimulati...
Objective:
Recording and stimulating neuronal activity across different brain regions requires interfacing at multiple sites using dedicated tools while tissue reactions at the recording sites often prevent their successful long-term application. This implies the technological challenge of developing complex probe geometries while keeping the over...
Objective
Recording and stimulating neuronal activity across different brain regions requires interfacing at multiple sites using dedicated tools while tissue reactions at the recording sites often prevent their successful long-term application. This implies the technological challenge of developing complex probe geometries while keeping the overal...
Mesial temporal lobe epilepsy (MTLE) is the most common form of focal, pharmacoresistant epilepsy in adults and is often associated with hippocampal sclerosis. Here, we established the efficacy of optogenetic and electrical low-frequency stimulation (LFS) in interfering with seizure generation in a mouse model of MTLE. Specifically, we applied LFS...
A network consisting of excitatory and inhibitory (EI) neurons is a canonical model for understanding local cortical network activity. In this study, we extended the local circuit model and investigated how its dynamical landscape can be enriched when it interacts with another excitatory (E) population with long transmission delays. Through analysi...
Bioelectronic devices, interfacing neural tissue for therapeutic, diagnostic or rehabilitation purposes, rely on small electrode contacts in order to achieve highly sophisticated communication at the neural interface. Reliable recording and safe stimulation with small electrodes however are limited when conventional electrode metallizations are use...
Mesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsy in adults and is typically associated with hippocampal sclerosis and drug-resistant seizures. As an alternative to curative epilepsy surgery, brain stimulation evolves as a promising approach for seizure-interference. However, 35 particularly in MTLE with severe hippocam...
Mesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsy in adults and is typically associated with hippocampal sclerosis and drug-resistant seizures. As an alternative to curative epilepsy surgery, brain stimulation evolves as a promising approach for seizure-interference. However, particularly in MTLE with severe hippocampal...
Hypersynchronous network activity is the defining hallmark of epilepsy and manifests in a wide spectrum of phenomena, of which electrographic activity during seizures is only one extreme. The aim of this study was to differentiate between different types of epileptiform activity (EA) patterns and investigate their temporal succession and interactio...
The mesoscale architecture of neuronal networks strongly influences the initiation of spontaneous activity and its pathways of propagation. Spontaneous activity has been studied extensively in networks of cultured cortical neurons that generate complex yet reproducible patterns of synchronous bursting events that resemble the activity dynamics in d...
In mesial temporal lobe epilepsy (mTLE) an initial precipitating injury can trigger aberrant wiring of neuronal circuits causing seizure activity. While circuit reorganization is known to be largely activity-dependent, the interactions between neuronal activity and synaptic plasticity during the development of mTLE remain poorly understood. Therefo...
A network consisting of excitatory and inhibitory (EI) neurons is a canonical model for understanding cortical network activity. In this study, we extend the EI network model and investigate how its dynamical landscape can be enriched when it interacts with another excitatory (E) population with transmission delays. Through analysis and simulations...
Objective:
Optogenetic modulation of neural activity is a ubiquitous tool for basic investigation of brain circuits. While the majority of optogenetic paradigms rely on short light pulses to evoke synchronized activity of optically sensitized cells, many neurobiological processes are associated with slow local field potential (LFP) oscillations. T...
Targeted interaction with networks in the brain is of immense therapeutic relevance. The highly dynamic nature of neuronal networks and changes with progressive diseases create an urgent need for closed-loop control. Without adequate mathematical models of such complex networks, however, it remains unclear how tractable control problems can be form...
Mesial temporal lobe epilepsy is characterized by focal, recurrent spontaneous seizures, sclerosis and granule cell dispersion in the hippocampal formation. Changes in theta rhythm properties have been correlated with the severity of hippocampal restructuring and were suggested as a cause of memory deficits accompanying epilepsy. For severe scleros...
Penetrating neural probes comprising arrays of microelectrodes are commonly used to monitor local field potentials and multi-unit activity in animal brain over time frames of weeks. To correlate these recorded signals to specific tissue areas, histological analysis is performed after the experimental endpoint. Even if the lesion of the penetrating...
Penetrating neural probes comprising arrays of microelectrodes are commonly used to monitor local field potentials and multi-unit activity in animal brain over time frames of weeks. To correlate these recorded signals to specific tissue areas, histological analysis is performed after the experimental endpoint. Even if the lesion of the penetrating...
Summary of T2 metrics.Quantitative values of T2 measurements are listed for individual mice (saline-injected: N12, NP13, NP17, NP28, NP29; kainate-injected: NP10, NP11, NP14, NP25, NP26, NP27, NP31, NP34) and longitudinal time points (pre, 1d, 4d, 8d, 16d, 31d following injection).DOI:
http://dx.doi.org/10.7554/eLife.25742.007
Summary of 1H-MR metrics.Quantitative values of 1H-MR spectroscopy are listed for individual mice (saline-injected: N12, NP13, NP17, NP28, NP29; kainate-injected: NP10, NP11, NP14, NP25, NP26, NP27, NP31, NP34) and longitudinal time points (pre, 1d, 4d, 8d, 16d, 31d following injection).DOI:
http://dx.doi.org/10.7554/eLife.25742.010
Summary of DWI metrics.Quantitative values of DWI measurements are listed for individual mice (saline-injected: N12, NP13, NP17, NP28, NP29; kainate-injected: NP10, NP11, NP14, NP25, NP26, NP27, NP31, NP34) and longitudinal time points (pre, 1d, 4d, 8d, 16d, 31d following injection).DOI:
http://dx.doi.org/10.7554/eLife.25742.013
Summary of dorsoventral diffusivity metrics.Quantitative values of dorsoventral diffusivity (dvD) measurements are listed for individual mice (saline-injected: N12, NP13, NP17, NP28, NP29; kainate-injected: NP10, NP11, NP14, NP25, NP26, NP27, NP31, NP34) and longitudinal time points (pre, 1d, 4d, 8d, 16d, 31d following injection).DOI:
http://dx.doi...
Quantitative summary of statistically tested parameters.
The table displays all results statistical tests performed (right column) for each parameter (left column). The reference to the corresponding figure is given in the middle column. CI, confidence interval; n, number of animals; n*, number of sections; n°, number of recordings.
DOI:
http://dx....
ELife digest
Roughly one percent of people in the world suffer from epilepsy, a disorder in which individuals experience seizures due to abnormal electrical activity in the brain. Seizures can vary from brief episodes of amnesia or déjà-vu to convulsions and loss of consciousness. In adults, the most common form of epilepsy is known as temporal lob...
Granule cell dispersion (GCD) represents a pathological widening of the granule cell layer in the dentate gyrus and it is frequently observed in patients with mesial temporal lobe epilepsy (MTLE). Recent studies in human MTLE specimens and in animal epilepsy models have shown that a decreased expression and functional inactivation of the extracellu...
The hippocampus is reciprocally connected with the entorhinal cortex. Although several studies emphasized a role for the entorhinal cortex in mesial temporal lobe epilepsy (MTLE), it remains uncertain whether its synaptic connections with the hippocampus are altered. To address this question, we traced hippocampo-entorhinal and entorhino-hippocampa...
Neuronal diseases, such as Epilepsy and Parkinson’s disease, are commonly investigated in animal models by recording neurons extracellularly with microelectrode arrays, for example in the hippocampus, over long periods. Subsequent histology is used to correlate the recorded signals to the recording area or neuron type and the status of the neuronal...
Motivation Electrical stimulation of the brain is increasingly used as a strategy to alleviate the symptoms of a range of neurological disorders, and as a possible means to artificially inject information into neural circuits, e.g. towards bidirectional neural prostheses [1]. Conventionally, stimulation of neuronal networks explicitly or implicitly...
Dentate granule cells and the hippocampal CA2 region are resistant to cell loss associated with mesial temporal lobe epilepsy (MTLE). It is known that granule cells undergo mossy fiber sprouting in the dentate gyrus which contributes to a recurrent, proepileptogenic circuitry in the hippocampus. Here we show that mossy fiber sprouting also targets...
Penetrating microelectrode probes offer the opportunity to precisely monitor neuronal signals over several months. After the experimental end point, histological methods are used to analyze the tissue and to correlate recorded signals to histological findings. However, accurate retroactive tracing of the position of individual microelectrodes is cu...
Variable responses of neuronal networks to repeated sensory or electrical stimuli reflect the interaction of the stimulus' response with ongoing activity in the brain and its modulation by adaptive mechanisms such as cognitive context, network state or cellular excitability and synaptic transmission capability. Here, we focus on reliability, length...
Purpose:
Temporal lobe epilepsy is often accompanied by neuron loss and rewiring in the hippocampus. We hypothesized that the interaction of subnetworks of the entorhinal-hippocampal loop between epileptic events should show significant signatures of these pathologic changes.
Methods:
We combined simultaneous recording of local field potentials...
Cultured neuronal networks are an interesting experimental model in which neurons are freed from cortical architecture and plated on microelectrode arrays (MEA). Present in their dynamics are periods of strongly synchronized spiking by the network, termed 'bursting', whose role is not understood but dominates network dynamics and, due to its resist...
Structural changes in the hippocampal network associated with mesial temporal lobe epilepsy (MTLE) very likely contribute to seizure susceptibility. These changes should not only be reflected in epileptic seizures but also affect ongoing brain activity.
Recent findings in mice suggest that the theta and gamma rhythms in ongoing activity are indeed...
The emergence of spontaneous bursting events in developing neuronal networks likely depends on the evolving network connectivity. Theoretical models have shown that hierarchical network structures embedding clusters of strongly inter-connected neurons are optimal for initiating and sustaining spontaneous activity [1]. It is conceivable that activit...
Dissociated cortical cultures grown on microelectrode arrays (MEA) have been established as a useful biological model in the analysis of network dynamics. Their network dynamics are dominated by periods of strongly synchronized spiking, termed 'bursting', whose role is currently not understood. It has been demonstrated that bursts have different mo...
In this work we study the excitatory AMPA, and NMDA, and inhibitory GABA A receptor mediated dynamical changes in neuronal networks of neonatal rat cortex in vitro. Extracellular network-wide activity was recorded with 59 planar electrodes simultaneously under different pharmacological conditions. We analyzed the changes of overall network activity...
Recent studies using feedforward Echo State Networks (ESN) demonstrate that reservoir stability can be strongly affected by reservoir substructures, such as clusters. Here, we evaluate the impact of including feedback on clustered ESNs and assert that certain cluster configurations extend the permissible range of spectral radius values. We also rep...
Acknowledgements [1] Golshani, P., Goncalves, J. T., Khoshkhoo, S., Mostany, R., Smirnakis, S., and Portera-Cailliau, C. (2009). Internally mediated developmental desynchronization of neocortical network activity. J. Neurosci. 29 (35), 10890-10899.
[2] Shahaf, G., Eytan, D., Gal, A., Kermany, E., Lyakhov, V., Zrenner, C., and Marom, S. (2008). Orde...
Acknowledgements (1) Shatz, C. J. (1996). Emergence of order in visual system development. J Physiol Paris. 90(3-4):141-50.
(2) Meister, M., Wong, R. O., Baylor, D. A., Shatz, C. J. (1991). Synchronous bursts of action potentials in ganglion cells of the developing mammalian retina. Science 17;252(5008):939-43.
(3) Kaiser, M., and Hilgetag, C. C. (...
Acknowledgements Jimbo, Y., Kanawa, A., Parodi, P., and Torre, V. (2000). The dynamics of a neuronal culture of dissociated cortical neurons of neonatal rats. Biol. Cybern. 83, 1-20.
Legrand, J.-C., Darbon, P., and Streit, J. (2004). Contributions of NMDA receptors to network recruitment and rhythm generation in spinal cord cultures. Eur. J. Neuros...
The toxicity of chemicals on brain development is of major concern. A predictive in vitro test for potential developmental neurotoxicity (DNT) needs to be an inexpensive, quick, standardized and predictive alternative to present in vivo methods. Here, we combine endpoints based on attachment, proliferation, differentiation and electrophysiological...
Acknowledgements Froriep, U.P., Kumar, A., Häussler, U., Cosandier-Rimélé, D., Haas, C. A., and Egert, U. (2010). The relation of entorhinal cortex and dentate gyrus in a model of temporal lobe epilepsy, FENS Abstr. 5, 015.14.
Herwik, S., Kisban, S., Aarts, A.A.A., Seidl, K., Girardeau, G., Benchenane, K., Zugaro, M.B., Wiener, S.I., Paul, O., Nev...
Derivation of the steady state firing rate R*.
(0.03 MB PDF)
Derivation of the nullcline of the model.
(0.03 MB PDF)
Recently evidence has accumulated that many neural networks exhibit self-organized criticality. In this state, activity is similar across temporal scales and this is beneficial with respect to information flow. If subcritical, activity can die out, if supercritical epileptiform patterns may occur. Little is known about how developing networks will...
The complexity of biological neural networks does not allow to directly relate their biophysical properties to the dynamics of their electrical activity. We present a reservoir computing approach for functionally identifying a biological neural network, i.e. for building an artificial system that is functionally equivalent to the reference biologic...
Self-organized criticality (SOC) [1] was first described inneuronal cell cultures by Beggs and Plenz [2]. Neuronalnetworks being in a critical state produce avalanche-likedischarges that are power-law distributed. The assessmentof avalanches in neuronal networks is a new way of look-ing at neuronal activities apart from bursts, synchroniza-tion etc...
We use a planar, CMOS-based microelectrode array (MEA) featuring 3,150 metal electrodes per mm<sup>2</sup> and 126 recording channels to record spatially highly resolved extracellular action potentials (EAPs) from Purkinje cells (PCs) in acute cerebellar slices. An Independent-Component-Analysis-based (ICA) spike sorter is used to reveal EAPs of si...
A high-density planar microelectrode system (HD-MEA), based on complementary metal-oxide-semi-conductor (CMOS) microelectronics technology has been used for in vitro recordings of extracellular potentials. At the same time, subcelllular lateral resolution and high temporal resolution (sampling at 20 kHz) of cellular electrical activity have been ac...
There is an enduring quest for technologies that provide – temporally and spatially – highly resolved information on electric neuronal or cardiac activity in functional tissues or cell cultures. Here, we present a planar high-density, low-noise microelectrode system realized in microelectronics technology that features 11,011 microelectrodes (3,150...
The complexity of neurophysiology data has increased tremendously over the last years, especially due to the widespread availability of multi-channel recording techniques. With adequate computing power the current limit for computational neuroscience is the effort and time it takes for scientists to translate their ideas into working code. Advanced...