Spatial encoding in primate hippocampus during free navigation.

The hippocampus comprises two neural signals-place cells and θ oscillations-that contribute to facets of spatial navigation. Although their complementary relationship has been well established in rodents, their respective contributions in the primate brain during free navigation remains unclear. Here, we recorded neural activity in the hippocampus of freely moving marmosets as they naturally explored a spatial environment to more explicitly investigate this issue. We report place cells in marmoset hippocampus during free navigation that exhibit remarkable parallels to analogous neurons in other mammalian species. Although θ oscillations were prevalent in the marmoset hippocampus, the patterns of activity were notably different than in other taxa. This local field potential oscillation occurred in short bouts (approximately .4 s)-rather than continuously-and was neither significantly modulated by locomotion nor consistently coupled to place-cell activity. These findings suggest that the relationship between place-cell activity and θ oscillations in primate hippocampus during free navigation differs substantially from rodents and paint an intriguing comparative picture regarding the neural basis of spatial navigation across mammals

Graph analysis of functional brain networks: practical issues in translational neuroscience

The brain can be regarded as a network: a connected system where nodes, or units, represent different specialized regions and links, or connections, represent communication pathways. From a functional perspective communication is coded by temporal dependence between the activities of different brain areas. In the last decade, the abstract representation of the brain as a graph has allowed to visualize functional brain networks and describe their non-trivial topological properties in a compact and objective way. Nowadays, the use of graph analysis in translational neuroscience has become essential to quantify brain dysfunctions in terms of aberrant reconfiguration of functional brain networks. Despite its evident impact, graph analysis of functional brain networks is not a simple toolbox that can be blindly applied to brain signals. On the one hand, it requires a know-how of all the methodological steps of the processing pipeline that manipulates the input brain signals and extract the functional network properties. On the other hand, a knowledge of the neural phenomenon under study is required to perform physiological-relevant analysis. The aim of this review is to provide practical indications to make sense of brain network analysis and contrast counterproductive attitudes

Conditional network measures using multivariate partial coherence analysis for spike train data with application to multi-electrode array recordings

This thesis proposes a novel approach for functional connectivity studies of neuronal signal recordings based on statistical signal processing analysis in the frequency domain using Multivariate Partial Coherence (MVPC) combined with network theory measures. MVPC is applied to spike trains signals to make inferences about the underlying network structure. The presence of connections between single unit spike trains is estimated using both coherence and MVPC analysis. Scalability of MVPC analysis is investigated through application to simulated spike train data with up to 100 simultaneous spike trains generated from a network of excitatory and inhibitory cortical neurons. Stable MVPC estimates were obtained with up to 198 predictors in partial coherence estimates, using a combination of simulated cortical neuron data and additional Poisson spike train predictors. MVPC provides higher order partial coherence analysis for multi-channel spike trains signals, removing effects of common influences in pairwise connectivity estimates. Network measures applied to binary and weighted adjacency measures derived from coherence and partial coherence are compared to determine the differences in unconditional and conditional networks of spike train interactions. A combination of MVPC analysis along with network theory analysis provides a systematic approach for multi-channel spike train signals. The proposed method is applied to simulated and multi-electrode array (MEA) spike train data. The MEA data consists of 19 single unit channels recorded from a study of connectivity in a model of kainic acid (KA) induced epileptiform activity for mesial temporal lobe epilepsy (mTLE) in a rat. The network theory analysis uses basic measures on both conditional and unconditional network, which highlights the differences in network structure and characteristics between the two representations. Complex analysis on conditional networks is useful in describing the properties of integration and segregation in the network

Point process modeling and estimation: advances in the analysis of dynamic neural spiking data

A common interest of scientists in many fields is to understand the relationship between the dynamics of a physical system and the occurrences of discrete events within such physical system. Seismologists study the connection between mechanical vibrations of the Earth and the occurrences of earthquakes so that future earthquakes can be better predicted. Astrophysicists study the association between the oscillating energy of celestial regions and the emission of photons to learn the Universe's various objects and their interactions. Neuroscientists study the link between behavior and the millisecond-timescale spike patterns of neurons to understand higher brain functions. Such relationships can often be formulated within the framework of state-space models with point process observations. The basic idea is that the dynamics of the physical systems are driven by the dynamics of some stochastic state variables and the discrete events we observe in an interval are noisy observations with distributions determined by the state variables. This thesis proposes several new methodological developments that advance the framework of state-space models with point process observations at the intersection of statistics and neuroscience. In particular, we develop new methods 1) to characterize the rhythmic spiking activity using history-dependent structure, 2) to model population spike activity using marked point process models, 3) to allow for real-time decision making, and 4) to take into account the need for dimensionality reduction for high-dimensional state and observation processes. We applied these methods to a novel problem of tracking rhythmic dynamics in the spiking of neurons in the subthalamic nucleus of Parkinson's patients with the goal of optimizing placement of deep brain stimulation electrodes. We developed a decoding algorithm that can make decision in real-time (for example, to stimulate the neurons or not) based on various sources of information present in population spiking data. Lastly, we proposed a general three-step paradigm that allows us to relate behavioral outcomes of various tasks to simultaneously recorded neural activity across multiple brain areas, which is a step towards closed-loop therapies for psychological diseases using real-time neural stimulation. These methods are suitable for real-time implementation for content-based feedback experiments

Modeling and Analysis of Neural Spike Trains

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Development of new tools and germplasms for improvement of wheat resistance to Fusarium head blight

Doctor of PhilosophyDepartment of AgronomyGuihua BaiXiaomao LinWheat Fusarium head blight (FHB) is a devastating disease of wheat worldwide, which can significantly reduce grain yield and quality. Although the application of fungicides can reduce FHB damage, growing FHB resistant wheat is the most effective and eco-friendly approach to reduce the losses. To develop locally adapted FHB-resistant hard winter wheat germplasm, we transferred three major QTLs: Fhb1, Qfhs.ifa-5A, and Qfhb.rwg-5A.2 into two hard winter wheat cultivars, ‘Everest’ and ‘Overland’, using marker-assisted backcrossing and multiplex restriction amplicon sequencing (MRASeq). Ten ‘Overland’ background lines and nine ‘Everest’ background lines with better FHB resistance, recurrent parent similar agronomic traits were selected. They can be used as FHB resistant bridge parents for hard winter wheat breeding. To identify native FHB resistant sources, a population of 201 U.S. breeding lines and cultivars were genotyped using 90K wheat SNP arrays and phenotyped for the percentage of symptomatic spikelets (PSS), Fusarium damaged kernels (FDK) and deoxynivalenol (DON), a toxin produced by the pathogen. Genome-wide association studies (GWAS) identified significant trait associations with single nucleotide polymorphisms (SNPs) on chromosomes 1A, 1D, 2B, 3A, 3B, 4A, 5B and 5D. These marker-trait associations (MTAs) were significant for at least two of the three traits or a single trait in at least two experiments. To accelerate the evaluation of the FDK, we developed an algorithm that can separate FDK from healthy kernels with an accuracy of 90% based on color differences using image processing and unsupervised machine learning methods. Discovery and creation of the new FHB resistant germplasms and development of the fast FDK phenotyping algorithm will accelerate the improvement of U.S. hard winter wheat cultivars for FHB resistance

Non-linear dimensionality reduction on extracellular waveforms reveals cell type diversity in premotor cortex

Cortical circuits are thought to contain a large number of cell types that coordinate to produce behavior. Current in vivo methods rely on clustering of specified features of extracellular waveforms to identify putative cell types, but these capture only a small amount of variation. Here, we develop a new method (WaveMAP) that combines non-linear dimensionality reduction with graph clustering to identify putative cell types. We apply WaveMAP to extracellular waveforms recorded from dorsal premotor cortex of macaque monkeys performing a decision-making task. Using WaveMAP, we robustly establish eight waveform clusters and show that these clusters recapitulate previously identified narrow- and broad-spiking types while revealing previously unknown diversity within these subtypes. The eight clusters exhibited distinct laminar distributions, characteristic firing rate patterns, and decision-related dynamics. Such insights were weaker when using feature-based approaches. WaveMAP therefore provides a more nuanced understanding of the dynamics of cell types in cortical circuits.https://elifesciences.org/articles/67490Published versio

Hidden Markov Models

Hidden Markov Models (HMMs), although known for decades, have made a big career nowadays and are still in state of development. This book presents theoretical issues and a variety of HMMs applications in speech recognition and synthesis, medicine, neurosciences, computational biology, bioinformatics, seismology, environment protection and engineering. I hope that the reader will find this book useful and helpful for their own research