1,013 research outputs found
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
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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 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 () 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} 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 -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
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