title: Laminar analysis of slow wave activity in humans.
abstract: 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.
authors.affiliation: Institute for Psychology, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Richárd
authors.initials: R
authors.lastname: Csercsa
authors.forename: Balázs
authors.initials: B
authors.lastname: Dombovári
authors.forename: Dániel
authors.initials: D
authors.lastname: Fabó
authors.forename: Lucia
authors.initials: L
authors.lastname: Wittner
authors.forename: Loránd
authors.initials: L
authors.lastname: Eross
authors.forename: László
authors.initials: L
authors.lastname: Entz
authors.forename: András
authors.initials: A
authors.lastname: Sólyom
authors.forename: György
authors.initials: G
authors.lastname: Rásonyi
authors.forename: Anna
authors.initials: A
authors.lastname: Szucs
authors.forename: Anna
authors.initials: A
authors.lastname: Kelemen
authors.forename: Rita
authors.initials: R
authors.lastname: Jakus
authors.forename: Vera
authors.initials: V
authors.lastname: Juhos
authors.forename: László
authors.initials: L
authors.lastname: Grand
authors.forename: Andor
authors.initials: A
authors.lastname: Magony
authors.forename: Péter
authors.initials: P
authors.lastname: Halász
authors.forename: Tamás F
authors.initials: TF
authors.lastname: Freund
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Maglóczky
authors.forename: Sydney S
authors.initials: SS
authors.lastname: Cash
authors.forename: László
authors.initials: L
authors.lastname: Papp
authors.forename: György
authors.initials: G
authors.lastname: Karmos
authors.forename: Eric
authors.initials: E
authors.lastname: Halgren
authors.forename: István
authors.initials: I
authors.lastname: Ulbert
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000166:cytology / Q000502:physiology* / Q000503:physiopathology; D001931:Brain Mapping; D004569:Electroencephalography; D004594:Electrophysiology / Q000379:methods; D004827:Epilepsy / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D009474:Neurons / Q000502:physiology; D010507:Periodicity; D013057:Spectrum Analysis / Q000379:methods*