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.

In vivo validation of the electronic depth control probes

“…More specifically, we found that the LFP is rhythmic at about 1 Hz; its depth profile well corresponds to previous findings, where the LFP inversion was taking place in layer III corresponding to a depth about 300 -500 μ m below the cortical surface [2,3,16]. We have also shown that the bimodality of the oscillation using MUA measures can be reliably characterized, which is also in correspondence with the basic properties of SWA and previous findings.…”

“…The up-state LFP is positive on the brain surface and negative in deeper layers; it contains nested higher-frequency oscillations (e.g., 5 -100 Hz) accompanied by cell firing. The down-state LFP is negative on the brain surface and inverts to positivity in the deeper layers, and contains no spectral or cellular firing activity [2,3,16].…”

“…According to previous studies, extracting the envelope of the MUA helps identifying state transitions [3]. To extract the MUA envelope, first the wide band signals were band-pass filtered (500 -5000 Hz, 24 dB/octave, zero phase shift) and rectified ( Figure 3 A).…”

“…By using the time stamps of the down-to up-state transition as a reference point, the average spatial, temporal, and spectral patterns of the SWA were calculated to relate our measurements to the findings of other results using different probes [2,3,16].…”

Intracranial neuronal ensemble recordings and analysis in epilepsy

“…Thalamocortical unit activity underlies the generation of slow oscillation, one of the most important brain processes participating in generation of sleep (Crunelli et al, 2015). Slow wave activity in humans showed alternating neuronal excitation and inhibition patterns identified previously in animal models as upstates and downstates Csercsa et al, 2010;Nobili et al, 2012;Peyrache et al, 2012;Staba, C. L. Wilson, Bragin, Fried and Engel, 2002a). …”