Computational Neuroscience in Epilepsy

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.

Contributors

Foreword

Rise of the Machines – On the Threshold of a New Era in Epilepsy Research

Introduction: Applications and Emerging Concepts of Computational

Neuroscience in Epilepsy Research

Part I Computational Modeling Techniques and Databases in Epilepsy Research

1 Simulation of Large Networks: Technique and Progress

2 The Neuron Simulation Environment in Epilepsy Research

3 The CoCoDat Database: Systematically Organizing and Selecting Quantitative Data on Single Neurons and Microcircuitry

4 Validating Models of Epilepsy

5 Using NeuroConstruct to Develop and Modify Biologically Detailed 3D Neuronal Network Models in Health and Disease

6 Computational Neuroanatomy of the Rat Hippocampus: Implications and Applications to Epilepsy

Part II Epilepsy and Altered Network Topology

7 Modeling Circuit Alterations in Epilepsy: A Focus on Mossy Cell Loss and Mossy Fiber Sprouting in the Dentate Gyrus

8 Functional Consequences of Transformed Network Topology in Hippocampal Sclerosis

9 Multiple-Scale Hierarchical Connectivity of Cortical Networks Limits the Spread of Activity

Part III Destabilization of Neuronal Networks

10 Computer Simulations of Sodium Channel Mutations that Cause Generalized Epilepsy with Febrile Seizures Plus

11 Gain Modulation and Stability in Neural Networks

12 Neocortical Epileptiform Activity in Neuronal Models with Biophysically Realistic Ion Channels

13 Corticothalamic Feedback: A Key to Explain Absence Seizures

14 Mechanisms of Graded Persistent Activity: Implications for Epilepsy

15 Small Networks, Large Networks, Experiment and Theory – Can We Bring Them Together with Oscillations, Heterogeneity and Inhibition?

Part IV Homeostasis and Epilepsy

16 Stability and Plasticity in Neuronal and Network Dynamics

17 Homeostatic Plasticity and Post-Traumatic Epileptogenesis

Part V Mechanisms of Synchronization

18 Synchronization in Hybrid Neuronal Networks

19 Complex Synaptic Dynamics of GABAergic Networks of the Hippocampus

20 Experimental and Theoretical Analyses of Synchrony in Feedforward Networks

21 Modulation of Synchrony by Interneurons: Insights from Attentional Modulation of Responses in the Visual Cortex

Part VI Interictal to Ictal Transitions

22 Cellular and Network Mechanisms of Oscillations Preceding and Perhaps Initiating Epileptic Discharges

23 Transition to Ictal Activity in Temporal Lobe Epilepsy: Insights from Macroscopic Models

24 Unified Modeling and Analysis of Primary Generalized Seizures

25 A Neuronal Network Model of Corticothalamic Oscillations: The Emergence of Epileptiform Absence Seizures

26 Extracellular Potassium Dynamics and Epileptogenesis

27 Slow Waves Associated with Seizure Activity

Part VII Seizure Dynamics

28 Dynamics of Epileptic Seizures during Evolution and Propagation

29 Are Correlation Dimension and Lyapunov Exponents Useful Tools for Prediction of Epileptic Seizures?

30 Towards a Dynamics of Seizure Mechanics

Part VIII Towards Computer-Aided Therapy

31 Principles and Practice of Computer-Aided Drug Design as Applied to the Discovery of Antiepileptic Agents

32 Computation Applied to Clinical Epilepsy and Antiepileptic Devices

33 Microelectrode-based Epilepsy Therapy: A Hybrid Neural Prosthesis Incorporating Seizure Prediction and Intervention with Biomimetic Maintenance of Normal Hippocampal Function

Index

Basic neuroscientists, clinical neuroscientists, epileptologists, neurologists, biophysicists, computational modelers, engineers, as well as graduate students, postdocs, and professors.