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Brain electrical activity is largely composed of oscillations at characteristic frequencies. These rhythms are hierarchically organized and are thought to perform important pathological and physiological functions. The slow wave is a fundamental cortical rhythm that emerges in deep non-rapid eye movement sleep. In animals, the slow wave modulates delta, theta, spindle, alpha, beta, gamma and ripple oscillations, thus orchestrating brain electrical rhythms in sleep. While slow wave activity can enhance epileptic manifestations, it is also thought to underlie essential restorative processes and facilitate the consolidation of declarative memories. Animal studies show that slow wave activity is composed of rhythmically recurring phases of widespread, increased cortical cellular and synaptic activity, referred to as active- or up-state, followed by cellular and synaptic inactivation, referred to as silent- or down-state. However, its neural mechanisms in humans are poorly understood, since the traditional intracellular techniques used in animals are inappropriate for investigating the cellular and synaptic/transmembrane events in humans. To elucidate the intracortical neuronal mechanisms of slow wave activity in humans, novel, laminar multichannel microelectrodes were chronically implanted into the cortex of patients with drug-resistant focal epilepsy undergoing cortical mapping for seizure focus localization. Intracortical laminar local field potential gradient, multiple-unit and single-unit activities were recorded during slow wave sleep, related to simultaneous electrocorticography, and analysed with current source density and spectral methods. We found that slow wave activity in humans reflects a rhythmic oscillation between widespread cortical activation and silence. Cortical activation was demonstrated as increased wideband (0.3-200 Hz) spectral power including virtually all bands of cortical oscillations, increased multiple- and single-unit activity and powerful inward transmembrane currents, mainly localized to the supragranular layers. Neuronal firing in the up-state was sparse and the average discharge rate of single cells was less than expected from animal studies. Action potentials at up-state onset were synchronized within +/-10 ms across all cortical layers, suggesting that any layer could initiate firing at up-state onset. These findings provide strong direct experimental evidence that slow wave activity in humans is characterized by hyperpolarizing currents associated with suppressed cell firing, alternating with high levels of oscillatory synaptic/transmembrane activity associated with increased cell firing. Our results emphasize the major involvement of supragranular layers in the genesis of slow wave activity.

Here we critically review studies that used electroencephalography (EEG) or event-related potential (ERP) indices as a biomarker of Alzheimer's disease. In the first part we overview studies that relied on visual inspection of EEG traces and spectral characteristics of EEG. Second, we survey analysis methods motivated by dynamical systems theory (DST) as well as more recent network connectivity approaches. In the third part we review studies of sleep.  Next, we compare the utility of early and late ERP components in dementia research. In the section on mismatch negativity (MMN) studies we summarize their results and limitations and outline the emerging field of computational neurology. In the following we overview the use of EEG in the differential diagnosis of the most common neurocognitive disorders. Finally, we provide a summary of the state of the field and conclude that several promising EEG/ERP indices of synaptic neurotransmission are worth considering as potential biomarkers. Furthermore, we highlight some practical issues and discuss future challenges as well.

Alzheimer disease (AD) is the most frequent cause of major neurocognitive disorders with a huge economical and medical burden. Several studies pointed out that AD is associated with a high risk for developing epileptic seizures. The aims of our review were to evaluate and to summarize the current literature (ending in September 2015) of animal and human studies in the relation of AD and epileptic seizures. It seems likely that epileptic hyperexcitation could be partially responsible for the progression of AD due to the increased rate of amyloid deposition. Pathologic changes in animal models of AD are similar to those seen in human temporal lobe epilepsy. Antiepileptic treatment had a positive effect on cognitive function in animal and human studies. Because the detection of seizures in patients with cognitive decline is extremely difficult because of methodological problems, the true prevalence of seizures has remained unclear. Nonconvulsive seizures with no overt clinical symptoms may be frequent seizure types in AD. These are difficult to detect by clinical observation and with standard scalp electroencephalogram (EEG) methods. We propose that long-term EEG recording and video-EEG monitoring is necessary to prove the presence of epileptiform activity in demented patients.

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