Excitatory and inhibitory (EI) interactions shape network activity. However, little is known about the EI interactions in pathological conditions such as epilepsy. To investigate EI interactions during seizure-like events (SLEs), we performed simultaneous dual and triple whole cell and extracellular recordings in pyramidal cells and oriens interneurons in rat hippocampal CA1. We describe a novel pattern of interleaving EI activity during spontaneous in vitro SLEs generated by the potassium channel blocker 4-aminopyridine in the presence of decreased magnesium. Interneuron activity was increased during interictal periods. During ictal discharges interneurons entered into long-lasting depolarization block (DB) with suppression of spike generation; simultaneously, pyramidal cells produced spike trains with increased frequency (6–14 Hz) and correlation. After this period of runaway excitation, interneuron postictal spiking resumed and pyramidal cells became progressively quiescent. We performed correlation measures of cell-pair interactions using either the spikes alone or the subthreshold postsynaptic interspike signals. EE spike correlation was notably increased during interneuron DB, whereas subthreshold EE correlation decreased. EI spike correlations increased at the end of SLEs, whereas II subthreshold correlations increased during DB. Our findings underscore the importance of complex cell-type–specific neuronal interactions in the formation of seizure patterns.

The pathological phenomena of seizures and spreading depression have long been considered separate physiological events in the brain. By incorporating conservation of particles and charge, and accounting for the energy required to restore ionic gradients, we extend the classic Hodgkin–Huxley formalism to uncover a unification of neuronal membrane dynamics. By examining the dynamics as a function of potassium and oxygen, we now account for a wide range of neuronal activities, from spikes to seizures, spreading depression (whether high potassium or hypoxia induced), mixed seizure and spreading depression states, and the terminal anoxic “wave of death.” Such a unified framework demonstrates that all of these dynamics lie along a continuum of the repertoire of the neuron membrane. Our results demonstrate that unified frameworks for neuronal dynamics are feasible, can be achieved using existing biological structures and universal physical conservation principles, and may be of substantial importance in enabling our understanding of brain activity and in the control of pathological states.

Observability and controllability are essential concepts to the design of predictive observer models and feedback controllers of networked systems. For example, noncontrollable mathematical models of real systems have subspaces that influence model behavior, but cannot be controlled by an input. Such subspaces can be difficult to determine in complex nonlinear networks. Since almost all of the present theory was developed for linear networks without symmetries, here we present a numerical and group representational framework, to quantify the observability and controllability of nonlinear networks with explicit symmetries that shows the connection between symmetries and nonlinear measures of observability and controllability. We numerically observe and theoretically predict that not all symmetries have the same effect on network observation and control. Our analysis shows that the presence of symmetry in a network may decrease observability and controllability, although networks containing only rotational symmetries remain controllable and observable. These results alter our view of the nature of observability and controllability in complex networks, change our understanding of structural controllability, and affect the design of mathematical models to observe and control such networks.

Background and significance The third Sustainable Development Goal for child health, which aims to end preventable deaths of newborns and children less than 5 years of age by 2030, cannot be met without substantial reduction of infection-specific neonatal mortality in the developing world. Neonatal infections are estimated to account for 26% of annual neonatal deaths, with mortality rates highest in sub-Saharan Africa (SSA). Reliable and comprehensive estimates of the incidence and aetiology surrounding neonatal sepsis in SSA remain incompletely available. We estimate the economic burden of neonatal sepsis in SSA. Methods Data available through global health agencies and in the medical literature were used to determine population demographics in SSA, as well as to determine the incidence, disease burden, mortality and resulting disabilities associated with neonatal sepsis. The disability-adjusted life years (DALY) associated with successful treatment or prevention of neonatal sepsis in SSA for 1 year were calculated. The value of a statistical life (VSL) methodology was estimated to evaluate the economic burden of untreated neonatal sepsis in SSA. Results We conservatively estimate that 5.29–8.73 million DALYs are lost annually in SSA due to neonatal sepsis. Corresponding VSL estimates predict an annual economic burden ranging from $10 billion to $469 billion. Conclusions Our results highlight and quantify the scope of the public health and economic burden posed by neonatal sepsis in SSA. We quantify the substantial potential impact of more successful treatment and prevention strategies, and we highlight the need for greater investment in strategies to characterise, diagnose, prevent and manage neonatal sepsis and its long-term sequelae in SSA.

The spatiotemporal structure of brain oscillations are important in understanding neural function. We analyze oscillatory episodes from isotropic preparations from the middle layers of a mammalian cortex which display irregular and chaotic spatiotemporal wave activity, within which spontaneously emerge spiral and plane waves. The dimensionality of these dynamics shows a consistent decrease during the middle of these episodes, regardless of the presence of simple spiral or plane waves. It is important to define the relevant biological order parameters which govern these dynamical bifurcations.