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In Fast Oscillations in Cortical Circuits, the authors use a combination of electrophysiological and computer modeling techniques to analyze how large networks of neurons can produce both epileptic seizures and functionally relevant synchronized oscillations.
This book first reviews the case that brain oscillations not only are important for cognition, as long suspected, but also play a part in the expression of signs and symptoms of neuropsychiatric disorders. The cellular mechanisms of many of the clinically relevant oscillations have been studied by the authors and their colleagues, using in vitro slice methods as well as detailed computer simulations. A surprising insight is that gap junctions between principal neurons play an absolutely critical role in so many types of oscillation in neuronal populations; oscillations are not just the result of properties of individual neurons and their synaptic connections. Furthermore, the way in which gap junctions produce oscillations in the cortex is novel, involving as it does global properties of networks, rather than just the time constants of membrane currents. This insight has implications for therapeutics as well as for our understanding of normal brain functions.
The present Thesis addressed different questions concerning spontaneous oscillatory activity in the cerebral cortex, including functional comparative studies, studies of mechanisms generating this activity and the evaluation of alterations in a model of mental disability. The main technique used for this work is the recording of electrophysiological extracellular Local Field Potential signals, which mainly respond to the activity of local populations of neurons. This type of recordings was obtained both in brain slices and in vivo and was used in combination with other techniques. Single Unit recordings, which evaluate the firing properties of a single neuron, were also obtained in combination of LFP in some of the studies. In the first study, we aimed to disclose the role of persistent sodium current in controlling cortical oscillatory activity, either in the generation and maintenance of UP states in slow oscillations and the control of fast beta-gamma oscillations. Here, we saw that blocking this current with phenytoin provoked the elongation of UP states and increased firing rate of the network, while the generation of new UP states was prevented. In another study, we performed a comparison of the oscillatory activity along different cortical areas in vivo. Here, prefrontal cortex showed special features compared to primary areas, including increased firing rate and gamma oscillations, and firing patterns of single units. This study also included a measurement of the speed of propagation of UP states, because prefrontal cortex was found to present a reduced Coefficient of Variation of UP state duration, compatible with being an area of wave generation. Thus, we aimed to demonstrate a main pattern of propagation of slow waves from frontal areas to posterior areas, as previously described in humans. Finally, we performed a study of the functional and anatomical alterations in the cortical network underlying cognitive deficits in a transgenic model of Down syndrome, TgDyrk1A mice. This work was performed in two cortical areas: prefrontal and primary somatosensory cortex. In our study of prefrontal cortex, TgDyrk1A mice presented alterations in oscillatory activity that were compatible with as more inhibited network, such as decreased firing rate, decreased gamma oscillations and a slower speed of propagation. This unbalance between excitation and inhibition was later demonstrated at anatomical level, and may explain our findings of altered behavior in cognitive tasks that involved prefrontal cortex such as the puzzle box. In our study in somatosensory cortex, thalamocortical evoked potentials showed increased cortical inhibition. Although that, oscillatory activity, either in parameters of Slow waves or beta-gamma frequencies, remained unchanged, suggesting the existence of compensatory mechanisms. From the work of this Thesis, we demonstrated some mechanistic aspects that control the emergence of rhythmic patterns from cortical circuits, with a striking role on the mechanisms which control excitability or cortical connectivity that underlies oscillations. First, this study presents de dependence of slow and fast rhythms on an intrinsic mechanism of neurons that governs cortical oscillations which is the persistent sodium current. Secondly, here is presented the role of cortical excitability in the expression of those rhythms across different cortical areas. And finally, this study shows the changes in cortical network function in a model of Down syndrome by means of analyzing oscillatory activity, as this represents a network activity and reflects the altered cellular and connectivity elements which are critical for the expression of cortical rhythms. These findings can all be understood within frame of altered balance between excitation and inhibition.
Jasper's Basic Mechanisms, Fourth Edition, is the newest most ambitious and now clinically relevant publishing project to build on the four-decade legacy of the Jasper's series. In keeping with the original goal of searching for "a better understanding of the epilepsies and rational methods of prevention and treatment.", the book represents an encyclopedic compendium neurobiological mechanisms of seizures, epileptogenesis, epilepsy genetics and comordid conditions. Of practical importance to the clinician, and new to this edition are disease mechanisms of genetic epilepsies and therapeutic approaches, ranging from novel antiepileptic drug targets to cell and gene therapies.
The purpose of this work is to review recent findings highlighting the mechanisms and functions of the neuronal oscillations that structure brain activity across the sleep-wake cycle. An increasing number of studies conducted in humans and animals, and using a variety of techniques ranging from intracellular recording to functional neuroimaging, has provided important insight into the mechanisms and functional properties of these brain rhythms. Studies of these rhythms are fundamental not only for basic neuroscience, but also for clinical neuroscience. At the basic science level, neuronal oscillations shape the interactions between different areas of the brain and profoundly impact neural responses to the environment, thereby mediating the processing of information in the brain. At the clinical level, brain oscillations are affected in numerous neurological conditions and might provide useful biomarkers that inform about patients’ evolution and vulnerability. During sleep, these brain rhythms could provide functional support to internal states that govern the basic maintenance of local circuit and systemic interactions. During wake, the rhythmicity of cortical and subcortical circuits have been linked with sensory processing, cognitive operations, and preparation for action. This book will attempt to link together these sleep and wake functional roles at the level of neuroimaging and electroencephalographic measures, local field potentials, and even at the cellular level. ​
Epilepsy is a neurological disorder that affects millions of patients worldwide and arises from the concurrent action of multiple pathophysiological processes. The power of mathematical analysis and computational modeling is increasingly utilized in basic and clinical epilepsy research to better understand the relative importance of the multi-faceted, seizure-related changes taking place in the brain during an epileptic seizure. This groundbreaking book is designed to synthesize the current ideas and future directions of the emerging discipline of computational epilepsy research. Chapters address relevant basic questions (e.g., neuronal gain control) as well as long-standing, critically important clinical challenges (e.g., seizure prediction). Computational Neuroscience in Epilepsy should be of high interest to a wide range of readers, including undergraduate and graduate students, postdoctoral fellows and faculty working in the fields of basic or clinical neuroscience, epilepsy research, computational modeling and bioengineering. - Covers a wide range of topics from molecular to seizure predictions and brain implants to control seizures - Contributors are top experts at the forefront of computational epilepsy research - Chapter contents are highly relevant to both basic and clinical epilepsy researchers
This elegant book presents current evidence on the organization of the mammalian cerebral cortex. The focus on synapses and their function provides the basis for understanding how this critical part of the brain could work. Dr. White and his colleague Dr. Keller have collated an impressive mass of material. This makes the crucial information accessible and coherent. Dr. White pioneered an area of investigation that to most others, and occasionally to himself, seemed a bottomless pit of painstaking at tention to detail for the identification and enumeration of cortical syn apses. I do not recall that he or anyone else suspected, when he began to publish his now classic papers, that the work would be central to an accelerating convergence of information and ideas from neurobiology and computer science, especially artificial intelligence (AI) (Rumelhart and McClelland, 1986). The brain is the principal organ responsible for the adaptive capacities of animals. What has impressed students of biology, of medicine, and, to an extent, of philosophy is the correlation between the prominence of the cerebral cortex and the adaptive "complexity" of a particular spe cies. Most agree that the cortex is what sets Homo sapiens apart from other species quantitatively and qualitatively (Rakic, 1988). This is summarized in the first chapter.
Studies of mechanisms in the brain that allow complicated things to happen in a coordinated fashion have produced some of the most spectacular discoveries in neuroscience. This book provides eloquent support for the idea that spontaneous neuron activity, far from being mere noise, is actually the source of our cognitive abilities. It takes a fresh look at the coevolution of structure and function in the mammalian brain, illustrating how self-emerged oscillatory timing is the brain's fundamental organizer of neuronal information. The small-world-like connectivity of the cerebral cortex allows for global computation on multiple spatial and temporal scales. The perpetual interactions among the multiple network oscillators keep cortical systems in a highly sensitive "metastable" state and provide energy-efficient synchronizing mechanisms via weak links. In a sequence of "cycles," György Buzsáki guides the reader from the physics of oscillations through neuronal assembly organization to complex cognitive processing and memory storage. His clear, fluid writing-accessible to any reader with some scientific knowledge-is supplemented by extensive footnotes and references that make it just as gratifying and instructive a read for the specialist. The coherent view of a single author who has been at the forefront of research in this exciting field, this volume is essential reading for anyone interested in our rapidly evolving understanding of the brain.