Dynamical response properties of neocortical neuron ensembles: multiplicative versus additive noise.

To understand the mechanisms of fast information processing in the brain, it is necessary to determine how rapidly populations of neurons can respond to incoming stimuli in a noisy environment. Recently, it has been shown experimentally that an ensemble of neocortical neurons can track a time-varying input current in the presence of additive correlated noise very fast, up to frequencies of several hundred hertz. Modulations in the firing rate of presynaptic neuron populations affect, however, not only the mean but also the variance of the synaptic input to postsynaptic cells. It has been argued that such modulations of the noise intensity (multiplicative modulation) can be tracked much faster than modulations of the mean input current (additive modulation). Here, we compare the response characteristics of an ensemble of neocortical neurons for both modulation schemes. We injected sinusoidally modulated noisy currents (additive and multiplicative modulation) into layer V pyramidal neurons of the rat somatosensory cortex and measured the trial and ensemble-averaged spike responses for a wide range of stimulus frequencies. For both modulation paradigms, we observed low-pass behavior. The cutoff frequencies were markedly high, considerably higher than the average firing rates. We demonstrate that modulations in the variance can be tracked significantly faster than modulations in the mean input. Extremely fast stimuli (up to 1 kHz) can be reliably tracked, provided the stimulus amplitudes are sufficiently high.

FIND--a unified framework for neural data analysis.

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 analysis methods are complex and often lack reproducibility on the basis of published descriptions. To overcome this limitation we develop FIND (Finding Information in Neural Data) as a platform-independent, open source framework for the analysis of neuronal activity data based on Matlab (Mathworks). Here, we outline the structure of the FIND framework and describe its functionality, our measures of quality control, and the policies for developers and users. Within FIND we have developed a unified data import from various proprietary formats, simplifying standardized interfacing with tools for analysis and simulation. The toolbox FIND covers a steadily increasing number of tools. These analysis tools address various types of neural activity data, including discrete series of spike events, continuous time series and imaging data. Additionally, the toolbox provides solutions for the simulation of parallel stochastic point processes to model multi-channel spiking activity. We illustrate two examples of complex analyses with FIND tools: First, we present a time-resolved characterization of the spiking irregularity in an in vivo extracellular recording from a mushroom-body extrinsic neuron in the honeybee during odor stimulation. Second, we describe layer specific input dynamics in the rat primary visual cortex in vivo in response to visual flash stimulation on the basis of multi-channel spiking activity.

G-Node: an integrated tool-sharing platform to support cellular and systems neurophysiology in the age of global neuroinformatics.

The global scale of neuroinformatics offers unprecedented opportunities for scientific collaborations between and among experimental and theoretical neuroscientists. To fully harvest these possibilities, a set of coordinated activities is required that will improve three key ingredients of neuroscientific research: data access, data storage, and data analysis, together with supporting activities for teaching and training. Focusing on the development of tools aiming at neurophysiological data, the newly established German Neuroinformatics Node (G-Node) aims at addressing these aspects as part of the International Neuroinformatics Coordination Facility (INCF). Based on its technical and scientific scope, the Node could play a substantial role for cellular and systems neurophysiology as well as for the neuroscience community at large.

Detecting epileptic seizures in long-term human EEG: a new approach to automatic online and real-time detection and classification of polymorphic seizure patterns.

Epileptic seizures can cause a variety of temporary changes in perception and behavior. In the human EEG they are reflected by multiple ictal patterns, where epileptic seizures typically become apparent as characteristic, usually rhythmic signals, often coinciding with or even preceding the earliest observable changes in behavior. Their detection at the earliest observable onset of ictal patterns in the EEG can, thus, be used to start more-detailed diagnostic procedures during seizures and to differentiate epileptic seizures from other conditions with seizure-like symptoms. Recently, warning and intervention systems triggered by the detection of ictal EEG patterns have attracted increasing interest. Since the workload involved in the detection of seizures by human experts is quite formidable, several attempts have been made to develop automatic seizure detection systems. So far, however, none of these found widespread application. Here, we present a novel procedure for generic, online, and real-time automatic detection of multimorphologic ictal-patterns in the human long-term EEG and its validation in continuous, routine clinical EEG recordings from 57 patients with a duration of approximately 43 hours and additional 1,360 hours of seizure-free EEG data for the estimation of the false alarm rates. We analyzed 91 seizures (37 focal, 54 secondarily generalized) representing the six most common ictal morphologies (alpha, beta, theta, and delta- rhythmic activity, amplitude depression, and polyspikes). We found that taking the seizure morphology into account plays a crucial role in increasing the detection performance of the system. Moreover, besides enabling a reliable (mean false alarm rate<0.5/h, for specific ictal morphologies<0.25/h), early and accurate detection (average correct detection rate>96%) within the first few seconds of ictal patterns in the EEG, this procedure facilitates the automatic categorization of the prevalent seizure morphologies without the necessity to adapt the proposed system to specific patients.

Short-term changes in bilateral hippocampal coherence precede epileptiform events.

The mesial temporal lobe epilepsy syndrome (MTLE) is the most common form of focal epilepsies. MTLE patients usually respond very little to pharmacological therapy and surgical resection of temporal brain areas is mandatory. Finding less invasive therapies than resection of the sclerotic hippocampus requires knowledge of the network structures and dynamics involved in seizure generation. Investigation of the time interval immediately preceding seizure onset would help in understanding the initiation mechanisms of the seizure proper and, thereby, possibly improve therapeutical options. Here, we employed the in vivo intrahippocampal kainate model in mice, which is characterized by unilateral histological changes, resembling hippocampal sclerosis observed in human MTLE, and recurrent focal seizures. In these epileptic mice, population spikes occurred during epileptiform events (EEs) in the ipsilateral, histologically changed hippocampus, but also concomitantly in the contralateral, intact hippocampus. We studied synchronization processes between the ipsilateral, sclerotic hippocampus and the contralateral hippocampus immediately preceding the onset of EEs. We show that coherence between the two hippocampi decreased consistently and reliably for all EEs at 8 to 12 s before their onset at high frequencies (>100 Hz), without changes in power in these bands. This early decoupling of the two hippocampi indicates the time range for cellular and network mechanisms leading to increased excitability and/or synchronicity in the tissue and thus ultimately to epileptic seizures.