We present a new algorithm to efficiently simulate random models of large neural networks satisfying the property of time asynchrony. The model parameters (average firing rate, number of neurons, synaptic connection probability, and postsynaptic duration) are of the order of magnitude of a small mammalian brain or of human brain areas. Through the use of activity tracking and procedural connectivity (dynamical regeneration of synapses), computational and memory complexities of this algorithm are proved to be theoretically linear with the number of neurons. These results are experimentally validated by sequential simulations of millions of neurons and billions of synapses running in a few minutes using a single thread of an equivalent desktop computer.

We investigate several distribution-free dependence detection procedures, all based on a shuffling of the trials, from a statistical point of view. The mathematical justification of such procedures lies in the bootstrap principle and its approximation properties. In particular, we show that such a shuffling has mainly to be done on centered quantities—that is, quantities with zero mean under independence—to construct correct p -values, meaning that the corresponding tests control their false positive (FP) rate. Thanks to this study, we introduce a method, named permutation UE, which consists of a multiple testing procedure based on permutation of experimental trials and delayed coincidence count. Each involved single test of this procedure achieves the prescribed level, so that the corresponding multiple testing procedure controls the false discovery rate (FDR), and this with as few assumptions as possible on the underneath distribution, except independence and identical distribution across trials. The mathematical meaning of this assumption is discussed, and it is in particular argued that it does not mean what is commonly referred in neuroscience to as cross-trials stationarity. Some simulations show, moreover, that permutation UE outperforms the trial-shuffling of Pipa and Grün ( 2003 ) and the MTGAUE method of Tuleau-Malot et al. ( 2014 ) in terms of single levels and FDR, for a comparable amount of false negatives. Application to real data is also provided.

The unitary events (UE) method is one of the most popular and efficient methods used over the past decade to detect patterns of coincident joint spike activity among simultaneously recorded neurons. The detection of coincidences is usually based on binned coincidence count (Grün, 1996 ), which is known to be subject to loss in synchrony detection (Grün, Diesmann, Grammont, Riehle, & Aertsen, 1999 ). This defect has been corrected by the multiple shift coincidence count (Grün et al., 1999 ). The statistical properties of this count have not been further investigated until this work, the formula being more difficult to deal with than the original binned count. First, we propose a new notion of coincidence count, the delayed coincidence count, which is equal to the multiple shift coincidence count when discretized point processes are involved as models for the spike trains. Moreover, it generalizes this notion to nondiscretized point processes, allowing us to propose a new gaussian approximation of the count. Since unknown parameters are involved in the approximation, we perform a plug-in step, where unknown parameters are replaced by estimated ones, leading to a modification of the approximating distribution. Finally the method takes the multiplicity of the tests into account via a Benjamini and Hochberg approach (Benjamini & Hochberg, 1995 ), to guarantee a prescribed control of the false discovery rate. We compare our new method, MTGAUE (multiple tests based on a gaussian approximation of the unitary events) and the UE method proposed in Grün et al. ( 1999 ) over various simulations, showing that MTGAUE extends the validity of the previous method. In particular, MTGAUE is able to detect both profusion and lack of coincidences with respect to the independence case and is robust to changes in the underlying model. Furthermore MTGAUE is applied on real data.