The biomedical sciences have recently undergone revolutionary change, due to the ability to digitize and store large data sets. In neuroscience, the data sources include measurements of neural activity measured using electrode arrays, EEG and MEG, brain imaging data from PET, fMRI, and optical imaging methods. Analysis, visualization, and management of these time series data sets is a growing field of research that has become increasingly important both for experimentalists and theorists interested in brain function. Written by investigators who have played an important role in developing the subject and in its pedagogical exposition, the current volume addresses the need for a textbook in this interdisciplinary area. The book is written for a broad spectrum of readers ranging from physical scientists, mathematicians, and statisticians wishing to educate themselves about neuroscience, to biologists who would like to learn time series analysis methods in particular and refresh their mathematical and statistical knowledge in general, through self-pedagogy. It may also be used as a supplement for a quantitative course in neurobiology or as a textbook for instruction on neural signal processing. The first part of the book contains a set of essays meant to provide conceptual background which are not technical and shall be generally accessible. Salient features include the adoption of an active perspective of the nervous system, an emphasis on function, and a brief survey of different theoretical accounts in neuroscience. The second part is the longest in the book, and contains a refresher course in mathematics and statistics leading up to time series analysis techniques. The third part contains applications of data analysis techniques to the range of data sources indicated above (also available as part of the Chronux data analysis platform from http://chronux.org), and the fourth part contains special topics.

(cont.) Whereas EEG/MEG record neural activity, fMRI reflects hemodynamic activity in the brain with high spatial resolution. We examine empirically the neurovascular coupling in simultaneously recorded MEG and diffuse optical imaging (DOI) data, which also reflects hemodynamic activity and is compatible with MEG recordings. Our results suggest that the neural activity and hemodynamic responses are aligned in space. However, the relationship between the temporal dynamics of the two types of signals is non-linear and varies from region to region. Based on these findings, we develop the fMRI-informed regional EEG/MEG source estimator (FIRE). This method is based on a generative model that encourages similar spatial patterns but allows for differences in time courses across imaging modalities. Our experiments with both Monte Carlo simulation and human fMRI-EEG/MEG data demonstrate that FIRE significantly reduces ambiguities in source localization and accurately captures the timing of activation in adjacent functional regions.

A long-standing objective of psychiatry has been the ability to both control and record the activity of precisely-defined populations of brain cells on the millisecond timescale most relevant for neural computation. Recent advances bring that goal increasingly near by leveraging the genetically-precise techniques of molecular biology with the high-speed, multiplexed command afforded by optical technologies to introduce and utilize light-sensitive neural activity control integrated with fast neural circuit imaging. In this thesis, I present exemplars of these technological advances and demonstrate their utility in illuminating the neural circuit basis of behaviors relevant to understanding psychiatric disease. I first show how fast neural circuit imaging may be integrated with optical neural control tools to develop insight into the role of genetically, developmentally, or projection defined populations of brain cells in mediating circuit-level physiological changes. I then demonstrate computational methods to analyze the resultant imaging data and apply fast circuit imaging to delineate links between hippocampal physiology and behavior in an animal model of depression. Finally, I present the development of a novel class of optically-activated, genetically-targetable control tools that permit optical control of G-protein coupled intracellular signaling; and the use of these molecular devices to determine causal roles of neuromodulatory inputs in reward processing. The development of these and similar optical modalities further improves the precision of questions addressable by the neuroscientist, and potentially the extent of disease treatable by the clinician.

This volume covers the latest developments in optical imaging of the brain which is becoming an increasingly important functional neuroimaging method. Optical intrinsic signals offer unrivaled temporal and spatial resolution of functional measurements of the exposed brain cortex in animals and humans. Near-infrared spectroscopy and imaging ap proaches permit the noninvasive functional assessment of the human brain at bedside. Main advantages of these optical techniques are the biochemical specificity of the meas urements and the potential of measuring correlates of intracellular and intravascular oxy genation simultaneously. Recent data indicate that one may also measure a more direct correlate of neuronal activity associated with changes in light scattering. In this volume, recent technical progress of the optical method is covered as well as the physiological basis of the measurements. In simultaneous studies, near-infrared spec troscopy measurements are directly compared to other functional methods, especially PET and fMRI and examples are given for new applications of the NIRS-method. Based on re sults obtained with optical methods and other functional techniques the latest in our under standing of the coupling of neuronal activity and cerebral blood flow response is reviewed. This is an important basis for a better understanding of all functional neuroi maging methods which rely on neurovascular coupling such as PET, SPET and fMRI. Fi nally the optical method is put into the perspective of presently available functional neuroimaging methods including fMRI, PET, MEG and EEG.

Optogenetics combines genetic engineering with optics to observe and control the function of cells using light, with clinical implications for restoration of vision and treatment of neurological diseases. As a new discipline much of the basic science and methods are currently under investigation and active development, thus there is a strong need for introductory literature in this field. This graduate level textbook provides an overview of the field of optogenetics in 5 concise chapters: Optogenetic tools, Applications in cellular systems, Mapping neuronal networks, Clinical applications and Restoration of vision and hearing. The concept and content was developed with top international researchers and students at a prestigious Dahlem Conference workshop.