Chapters included in Section 2 review the changes in neuronal network function that enable a brain to become epileptic and generate seizure activity. In Chapter 6, Kaila et al. describe functionally excitatory synaptic and non-synaptic modes of GABA_A receptor signaling that promote focal seizure generation and provide a rationale for the loss of efficacy of GABA_A receptor enhancing antiseizure medications in controlling seizures, while Zhang et al., in Chapter 7, focus on the role of connexins and pannexins in epileptic disorders, a topic that may have potential therapeutic applications in the near future. Chapters 8–11 (which are contributed by de Curtis et al., Chang et al., Evstratova et al., and Lévesque et al., respectively) address from different perspectives, including optogenetic stimulation procedures, the transition, development, and termination of focal seizures in different areas of the limbic system.

In Chapter 12, Tropani et al. discuss how seizures are related to cognitive deficits via the generation of theta (around 8 Hz) oscillations, and propose that they play a role for “inhibition” of cognitive networks during the interictal period, while in Chapter 13, de la Prida and Gotman review the importance of high-frequency oscillations (ranging between 80 and 500 Hz) as electrophysiological markers of epileptogenic regions. The influence of long-range changes in excitability on seizures is then addressed in Chapters 14 and 15. In the first of these two chapters, Frauscher and Timofeev review the bidirectional interactions occurring between sleep and epilepsy, while in the second, Baud et al. discuss the existence of cycles in the epileptic brain activity that operate over diverse timescales, ranging from circadian to circannual.

In Chapter 16 Merricks and Shevon review the history, technology, and scientific contributions of single neuron recordings obtained from epilepsy patients undergoing therapeutic surgical procedures; these studies have also proven to be invaluable for validating research data obtained from animal or computational models. The latter topic is then addressed in Chapter 17 by González et al., who modeled the role of ion concentration dynamics on seizure initiation, progression, and termination, as well as in Chapter 18, by Sheheitli et al., who use mathematical approaches to simulate and classify diverse types of seizure onset/offset patterns into 16 different “dynamotypes.” Moreover, in Chapter 19, Gnatkovsky and Schindler report on the state of the art of computational electroencephalogram analysis.

The last three chapter of Section 2 address the topic of generalized absence seizures. In Chapter 20, Lőrincz et al. addressed the changes in intrinsic membrane currents and network mechanisms within both cortico-thalamic and cortico-basal ganglia-thalamic circuits contributing to absence seizure generation. In Chapter 21, Meyer and Maheshwari report on the dynamics of cortical neurons imaged during spontaneous spike-wave seizures in genetic mouse models, and the reduced excitability of parvalbumin-positive inhibitory interneurons in the corticothalamic circuit as a mechanism for absence seizure generation. Finally, in Chapter 22, Cho and Paz describe key structural, synaptic, cellular, and biophysical elements underlying thalamic rhythmogenesis, and discuss how perturbations of these properties in rodent genetic models ultimately generate or facilitate seizures.

Most of the chapters included in this section of the fifth edition of Jasper’s Basic Mechanisms of the Epilepsies present novel technical approaches and reflect a multicellular view to outline fundamental brain abnormalities in epileptic disorders. In contrast with the last edition published in 2012, where the major focus was directed toward the role of specific channel or receptor malfunction, here, the emphasis has shifted to the dynamic behavior of network and brain systems that mediate the generation of seizures in focal and generalized epileptic disorders.