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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Available from: Anna Kelemen, Oct 04, 2015
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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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    ABSTRACT: During non-rapid eye movement (NREM) sleep (stage N3), when consciousness fades, cortico-cortical interactions are impaired while neurons are still active and reactive. Why is this? We compared cortico-cortical evoked-potentials recorded during wakefulness and NREM by means of time-frequency analysis and phase-locking measures in 8 epileptic patients undergoing intra-cerebral stimulations/recordings for clinical evaluation. We observed that, while during wakefulness electrical stimulation triggers a chain of deterministic phase-locked activations in its cortical targets, during NREM the same input induces a slow wave associated with an OFF-period (suppression of power>20Hz), possibly reflecting a neuronal down-state. Crucially, after the OFF-period, cortical activity resumes to wakefulness-like levels, but the deterministic effects of the initial input are lost, as indicated by a sharp drop of phase-locked activity. These findings suggest that the intrinsic tendency of cortical neurons to fall into a down-state after a transient activation (i.e. bistability) prevents the emergence of stable patterns of causal interactions among cortical areas during NREM. Besides sleep, the same basic neurophysiological dynamics may play a role in pathological conditions in which thalmo-cortical information integration and consciousness are impaired in spite of preserved neuronal activity. Copyright © 2015. Published by Elsevier Inc.
    NeuroImage 03/2015; 6. DOI:10.1016/j.neuroimage.2015.02.056 · 6.36 Impact Factor
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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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    ABSTRACT: Sleep complaints are common after mild traumatic brain injury (mTBI). While recent findings suggest that sleep macro-architecture is preserved in mTBI, features of non-rapid eye movement (NREM) sleep micro-architecture including electroencephalography (EEG) spectral power, slow waves (SW), and sleep spindles could be affected. This study aimed to compare NREM sleep in mTBI and healthy controls, and explore whether NREM sleep characteristics correlate with sleep complaints in these groups. Thirty-four mTBI participants (mean age: 34.2 ± 11.9 yrs; post-injury delay: 10.5 ± 10.4 weeks) and 29 age-matched controls (mean age: 32.4 ± 8.2 yrs) were recruited for two consecutive nights of polysomnographic (PSG) recording. Spectral power was computed and SW and spindles were automatically detected in three derivations (F3, C3, O1) for the first three sleep cycles. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). mTBI participants reported significant poorer sleep quality than controls on the PSQI and showed significant increases in beta power during NREM sleep at the occipital derivation only. Conversely, no group differences were found in SW and spindle characteristics. Interestingly, changes in NREM sleep characteristics were not associated with mTBI estimation of sleep quality. Compared to controls, mTBI were found to have enhanced NREM beta power. However, these changes were not found to be associated with the subjective evaluation of sleep. While increases in beta bands during NREM sleep may be attributable to the occurrence of a brain injury, they could also be related to the presence of pain and anxiety as suggested in one prior study. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.
    Sleep Medicine 01/2015; DOI:10.1016/j.sleep.2014.12.002 · 3.15 Impact Factor
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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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    ABSTRACT: The role of cortical connectivity in brain function and pathology is increasingly being recognized. While in vivo magnetic resonance imaging studies have provided important insights into anatomical and functional connectivity, these methodologies are limited in their ability to detect electrophysiological activity and the causal relationships that underlie effective connectivity. Here, we describe results of cortico-cortical evoked potential (CCEP) mapping using single pulse electrical stimulation in 25 patients undergoing seizure monitoring with subdural electrode arrays. Mapping was performed by stimulating adjacent electrode pairs and recording CCEPs from the remainder of the electrode array. CCEPs reliably revealed functional networks and showed an inverse relationship to distance between sites. Coregistration to Brodmann areas (BA) permitted group analysis. Connections were frequently directional with 43% of early responses and 50% of late responses of connections reflecting relative dominance of incoming or outgoing connections. The most consistent connections were seen as outgoing from motor cortex, BA6–BA9, somatosensory (SS) cortex, anterior cingulate cortex, and Broca's area. Network topology revealed motor, SS, and premotor cortices along with BA9 and BA10 and language areas to serve as hubs for cortical connections. BA20 and BA39 demonstrated the most consistent dominance of outdegree connections, while BA5, BA7, auditory cortex, and anterior cingulum demonstrated relatively greater indegree. This multicenter, large-scale, directional study of local and long-range cortical connectivity using direct recordings from awake, humans will aid the interpretation of noninvasive functional connectome studies. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 07/2014; 35(12). DOI:10.1002/hbm.22581 · 5.97 Impact Factor
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