Laminar analysis of slow wave activity in humans. Brain

Institute for Psychology, Hungarian Academy of Sciences, Budapest, Hungary.
Brain (Impact Factor: 9.2). 09/2010; 133(9):2814-29. DOI: 10.1093/brain/awq169
Source: PubMed


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.

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    • "Another potential limitation is that our data did not include multiunit activity recordings, thus preventing a direct observation of neuronal silence. However, previous studies in animals (Mukovski et al., 2007; Vyazovskiy et al., 2009) and humans (Cash et al., 2009; Csercsa et al., 2010; Nir et al., 2011) have provided solid evidence that the typical down-state characterized by sleep slow oscillations can be reliably detected based on spectral modulation in the high-frequency (20–100 Hz) range of the LFP signal. "
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    • "SW occur predominantly during stage 3 of NREM sleep. They are characterized as low frequency (<4 Hz) and high amplitude (>75 μV) waves, with each oscillation presenting a negative phase (or hyperpolarized phase) and a positive phase (or depolarized phase), both lasting hundreds of msec [8]. SW originate more frequently from the insula and the cingulate gyrus, and travel in an anteroposterior direction [9] [10]. "
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    • "This may imply that the N2 may be dominated by the same afferent input that drives the N1. The N2 also appears to reflect a cortical down-state followed by an up-state, a pattern that is similar to slow oscillations in slow wave sleep that engages multiple widespread brain areas in a complex regulatory process [Csercsa et al., 2010; Hangya et al., 2011]. According to this, the N1 component might be more suitable for analyzing direct cortico-cortical connections and the N2 reflects rather complex network topologies. "
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