Spike detection and sorting: combining algebraic differentiations with ICA

International audienceA new method for action potentials detection is proposed. The method is based on a numerical differentiation, as recently intro- duced from operational calculus. We show that it has good performance as compared to existing methods. We also combine the proposed method with ICA in order to obtain spike sorting

First-in-Human Phase I Study to Evaluate the Brain-Penetrant PI3K/mTOR Inhibitor GDC-0084 in Patients with Progressive or Recurrent High-Grade Glioma.

PurposeGDC-0084 is an oral, brain-penetrant small-molecule inhibitor of PI3K and mTOR. A first-in-human, phase I study was conducted in patients with recurrent high-grade glioma.Patients and methodsGDC-0084 was administered orally, once daily, to evaluate safety, pharmacokinetics (PK), and activity. Fluorodeoxyglucose-PET (FDG-PET) was performed to measure metabolic responses.ResultsForty-seven heavily pretreated patients enrolled in eight cohorts (2-65 mg). Dose-limiting toxicities included 1 case of grade 2 bradycardia and grade 3 myocardial ischemia (15 mg), grade 3 stomatitis (45 mg), and 2 cases of grade 3 mucosal inflammation (65 mg); the MTD was 45 mg/day. GDC-0084 demonstrated linear and dose-proportional PK, with a half-life (∼19 hours) supportive of once-daily dosing. At 45 mg/day, steady-state concentrations exceeded preclinical target concentrations producing antitumor activity in xenograft models. FDG-PET in 7 of 27 patients (26%) showed metabolic partial response. At doses ≥45 mg/day, a trend toward decreased median standardized uptake value in normal brain was observed, suggesting central nervous system penetration of drug. In two resection specimens, GDC-0084 was detected at similar levels in tumor and brain tissue, with a brain tissue/tumor-to-plasma ratio of >1 and >0.5 for total and free drug, respectively. Best overall response was stable disease in 19 patients (40%) and progressive disease in 26 patients (55%); 2 patients (4%) were nonevaluable.ConclusionsGDC-0084 demonstrated classic PI3K/mTOR-inhibitor related toxicities. FDG-PET and concentration data from brain tumor tissue suggest that GDC-0084 crossed the blood-brain barrier

Learning navigational maps through potentiation and modulation of hippocampal place cells

We analyze a model of navigational map formation based on correlation-based, temporally asymmetric potentiation and depression of synapses between hippocampal place cells. We show that synaptic modification during random exploration of an environment shifts the location encoded by place cell activity in such a way that it indicates the direction from any location to a fixed target avoiding walls and other obstacles. Multiple maps to different targets can be simultaneously stored if we introduce target-dependent modulation of place cell activity. Once maps to a number of target locations in a given environment have been stored, novel maps to previously unknown target locations are automatically constructed by interpolation between existing maps

Noise Induced Coherence in Neural Networks

We investigate numerically the dynamics of large networks of $N$ globally pulse-coupled integrate and fire neurons in a noise-induced synchronized state. The powerspectrum of an individual element within the network is shown to exhibit in the thermodynamic limit ($N\to \infty$) a broadband peak and an additional delta-function peak that is absent from the powerspectrum of an isolated element. The powerspectrum of the mean output signal only exhibits the delta-function peak. These results are explained analytically in an exactly soluble oscillator model with global phase coupling.Comment: 4 pages ReVTeX and 3 postscript figure

Cognitive navigation based on non-uniform Gabor space sampling, unsupervised growing networks, and reinforcement learning

We study spatial learning and navigation for autonomous agents. A state space representation is constructed by unsupervised Hebbian learning during exploration. As a result of learning, a representation of the continuous two-dimensional (2-D) manifold in the high-dimensional input space is found. The representation consists of a population of localized overlapping place fields covering the 2-D space densely and uniformly. This space coding is comparable to the representation provided by hippocampal place cells in rats. Place fields are learned by extracting spatio-temporal properties of the environment from sensory inputs. The visual scene is modeled using the responses of modified Gabor filters placed at the nodes of a sparse Log-polar graph. Visual sensory aliasing is eliminated by taking into account self-motion signals via path integration. This solves the hidden state problem and provides a suitable representation for applying reinforcement learning in continuous space for action selection. A temporal-difference prediction scheme is used to learn sensorimotor mappings to perform goal-oriented navigation. Population vector coding is employed to interpret ensemble neural activity. The model is validated on a mobile Khepera miniature robot

Generalized Rate-Code Model for Neuron Ensembles with Finite Populations

We have proposed a generalized Langevin-type rate-code model subjected to multiplicative noise, in order to study stationary and dynamical properties of an ensemble containing {\it finite} $N$ neurons. Calculations using the Fokker-Planck equation (FPE) have shown that owing to the multiplicative noise, our rate model yields various kinds of stationary non-Gaussian distributions such as gamma, inverse-Gaussian-like and log-normal-like distributions, which have been experimentally observed. Dynamical properties of the rate model have been studied with the use of the augmented moment method (AMM), which was previously proposed by the author with a macroscopic point of view for finite-unit stochastic systems. In the AMM, original $N$-dimensional stochastic differential equations (DEs) are transformed into three-dimensional deterministic DEs for means and fluctuations of local and global variables. Dynamical responses of the neuron ensemble to pulse and sinusoidal inputs calculated by the AMM are in good agreement with those obtained by direct simulation. The synchronization in the neuronal ensemble is discussed. Variabilities of the firing rate and of the interspike interval (ISI) are shown to increase with increasing the magnitude of multiplicative noise, which may be a conceivable origin of the observed large variability in cortical neurons.Comment: 19 pages, 9 figures, accepted in Phys. Rev. E after minor modification

The spike train statistics for consonant and dissonant musical accords

The simple system composed of three neural-like noisy elements is considered. Two of them (sensory neurons or sensors) are stimulated by noise and periodic signals with different ratio of frequencies, and the third one (interneuron) receives the output of these two sensors and noise. We propose the analytical approach to analysis of Interspike Intervals (ISI) statistics of the spike train generated by the interneuron. The ISI distributions of the sensory neurons are considered to be known. The frequencies of the input sinusoidal signals are in ratios, which are usual for music. We show that in the case of small integer ratios (musical consonance) the input pair of sinusoids results in the ISI distribution appropriate for more regular output spike train than in a case of large integer ratios (musical dissonance) of input frequencies. These effects are explained from the viewpoint of the proposed theory.Comment: 22 pages, 6 figure