J. Matias Palva

New vistas for α-frequency band oscillations

The amplitude of α-frequency band (8–14Hz) activity in the human electroencephalogram is suppressed by eye opening, visual stimuli and visual scanning, whereas it is enhanced during internal tasks, such as mental calculation and working memory. α-Frequency band oscillations have hence been thought to reflect idling or inhibition of task-irrelevant cortical areas. However, recent data on α-amplitude and, in particular, α-phase dynamics posit a direct and active role for α-frequency band rhythmicity in the mechanisms of attention and consciousness. We propose that simultaneous α-, β- (14–30Hz) and γ- (30–70Hz) frequency band oscillations are required for unified cognitive operations, and hypothesize that cross-frequency phase synchrony between α, β and γ oscillations coordinates the selection and maintenance of neuronal object representations during working memory, perception and consciousness.

Long-Range Temporal Correlations and Scaling Behavior in Human Brain Oscillations

The human brain spontaneously generates neural oscillations with a large variability in frequency, amplitude, duration, and recurrence. Little, however, is known about the long-term spatiotemporal structure of the complex patterns of ongoing activity. A central unresolved issue is whether fluctuations in oscillatory activity reflect a memory of the dynamics of the system for more than a few seconds. We investigated the temporal correlations of network oscillations in the normal human brain at time scales ranging from a few seconds to several minutes. Ongoing activity during eyes-open and eyes-closed conditions was recorded with simultaneous magnetoencephalography and electroencephalography. Here we show that amplitude fluctuations of 10 and 20 Hz oscillations are correlated over thousands of oscillation cycles. Our analyses also indicated that these amplitude fluctuations obey power-law scaling behavior. The scaling exponents were highly invariant across subjects. We propose that the large variability, the long-range correlations, and the power-law scaling behavior of spontaneous oscillations find a unifying explanation within the theory of self-organized criticality, which offers a general mechanism for the emergence of correlations and complex dynamics in stochastic multiunit systems. The demonstrated scaling laws pose novel quantitative constraints on computational models of network oscillations. We argue that critical-state dynamics of spontaneous oscillations may lend neural networks capable of quick reorganization during processing demands.

Early Neural Correlates of Conscious Somatosensory Perception

The cortical processing of consciously perceived and unperceived somatosensory stimuli is thought to be identical during the first 100-120 ms after stimulus onset. Thereafter, the electrophysiological correlates of conscious perception have been shown to be reflected in the N1 component of the evoked response as well as in later (>200 ms) nonstimulus-locked γ-band (28-50 Hz) oscillatory activity. To evaluate more specifically the time course and correlation of neuronal oscillations with conscious perception, we recorded neuromagnetic responses to threshold-intensity somatosensory stimuli. We show here that cortical broadband activities phase locked to the subsequently perceived stimuli in somatosensory, frontal, and parietal regions as early as 30-70 ms from stimulus onset, whereas the phase locking to the unperceived stimuli was weak and primarily restricted to somatosensory regions. Such stimulus locking also preceded the perceived stimuli, indicating that the phase of ongoing cortical activities biases subsequent perception. Furthermore, the data show that the stimulus locking was present in the θ- (4-8 Hz), α- (8-14 Hz), β- (14-28 Hz), and γ- (28-40 Hz) frequency bands, of which the widespread α-band component was dominant for the consciously perceived stimuli but virtually unobservable for the unperceived stimuli. Our results show that the neural correlates of conscious perception are already found during the earliest stages of cortical processing from 30 to 150 ms after stimulus onset and suggest that α-frequency-band oscillations have a role in the neural mechanisms of sensory awareness.

Neuronal long-range temporal correlations and avalanche dynamics are correlated with behavioral scaling laws

Scale-free fluctuations are ubiquitous in behavioral performance and neuronal activity. In time scales from seconds to hundreds of seconds, psychophysical dynamics and the amplitude fluctuations of neuronal oscillations are governed by power-law-form long-range temporal correlations (LRTCs). In millisecond time scales, neuronal activity comprises cascade-like neuronal avalanches that exhibit power-law size and lifetime distributions. However, it remains unknown whether these neuronal scaling laws are correlated with those characterizing behavioral performance or whether neuronal LRTCs and avalanches are related. Here, we show that the neuronal scaling laws are strongly correlated both with each other and with behavioral scaling laws. We used source reconstructed magneto- and electroencephalographic recordings to characterize the dynamics of ongoing cortical activity. We found robust power-law scaling in neuronal LRTCs and avalanches in resting-state data and during the performance of audiovisual threshold stimulus detection tasks. The LRTC scaling exponents of the behavioral performance fluctuations were correlated with those of concurrent neuronal avalanches and LRTCs in anatomically identified brain systems. The behavioral exponents also were correlated with neuronal scaling laws derived from a resting-state condition and with a similar anatomical topography. Finally, despite the difference in time scales, the scaling exponents of neuronal LRTCs and avalanches were strongly correlated during both rest and task performance. Thus, long and short time-scale neuronal dynamics are related and functionally significant at the behavioral level. These data suggest that the temporal structures of human cognitive fluctuations and behavioral variability stem from the scaling laws of individual and intrinsic brain dynamics.

Slow endogenous activity transients and developmental expression of K + -Cl ) cotransporter 2 in the immature human cortex

Spontaneous transients of correlated activity are a characteristic feature of immature brain structures, where they are thought to be crucial for the establishment of precise neuronal connectivity. Studies on experimental animals have shown that this kind of early activity in cortical structures is composed of long‐lasting, intermittent network events, which undergo a developmental decline that is closely paralleled by the maturation of GABAergic inhibition. In order to examine whether similar events occur in the immature human cortex, we performed direct current‐coupled electroencephalography (EEG) recordings from sleeping preterm babies. We show now that much of the preterm EEG activity is confined to spontaneous, slow activity transients. These transients are characterized by a large voltage deflection that nests prominent oscillatory activity in several frequency bands covering the whole frequency spectrum of the preterm EEG (<0.1–30 Hz). The slow voltage deflections had an amplitude of up to 800 µV. Most of these ‘giant’ events originated in the temporo‐occipital areas, with a maximum rate of about 8/min, and their occurrence as well as amplitude showed a decline by the time of normal birth. In age‐matched fetal brain tissue, this decrease in the spontaneous activity transients was associated with a developmental up‐regulation of the neuronal chloride extruder K+–Cl− cotransporter 2, a crucial molecule for the generation of inhibitory GABAergic Cl– currents. Our work indicates that slow endogenous activity transients in the immature human neocortex are mostly confined to the prenatal stage and appear to be terminated in parallel with the maturation of functional GABAergic inhibition.

Carbonic Anhydrase Isoform VII Acts as a Molecular Switch in the Development of Synchronous Gamma-Frequency Firing of Hippocampal CA1 Pyramidal Cells

Identification of the molecular mechanisms that enable synchronous firing of CA1 pyramidal neurons is central to the understanding of the functional properties of this major hippocampal output pathway. Using microfluorescence measurements of intraneuronal pH, in situ hybridization, as well as intracellular, extracellular, and K+-sensitive microelectrode recordings, we show now that the capability for synchronous gamma-frequency (20–80 Hz) firing in response to high-frequency stimulation (HFS) emerges abruptly in the rat hippocampus at approximately postnatal day 12. This was attributable to a steep developmental upregulation of intrapyramidal carbonic anhydrase isoform VII, which acts as a key molecule in the generation of HFS-induced tonic GABAergic excitation. These results point to a crucial role for the developmental expression of intrapyramidal carbonic anhydrase VII activity in shaping integrative functions, long-term plasticity and susceptibility to epileptogenesis.

Stimulus-induced change in long-range temporal correlations and scaling behaviour of sensorimotor oscillations

The human brain spontaneously generates large‐scale network oscillations at around 10 and 20 Hz. The amplitude envelope of these oscillations fluctuates intermittently and was recently reported to exhibit power‐law decay of the autocorrelation for hundreds of seconds. This indicates that the underlying networks are in a dynamic state resembling the self‐organized critical state known to exist in many complex systems. Based on the mechanism of how correlations emerge in these systems, we hypothesized that the physiological basis of long‐range power‐law correlations is the buildup of a memory of past activity by a continuous modification of the networks functional connectivity by the ongoing oscillations. In this framework, exogenous perturbations of ongoing oscillations would degrade or abolish this dynamic network memory. We investigated the sensitivity of the temporal correlations in sensorimotor 10‐ and 20‐Hz oscillations to median nerve stimulation that is known to have immediate effects on ongoing oscillations. Our results show that the amplitude fluctuations of these oscillations were effectively modulated by the somatosensory stimuli but still exhibited long‐range temporal correlations and power‐law scaling behaviour. The magnitude of the temporal correlations was, however, attenuated and the power‐law exponents were decreased. This implies that the stimuli indeed degraded the networks memory of its past.

Gamma Oscillations Underlie the Maintenance of Feature-Specific Information and the Contents of Visual Working Memory

Visual working memory (VWM) sustains information online as integrated object representations. Neuronal mechanisms supporting the maintenance of feature-specific information have remained unidentified. Synchronized oscillations in the gamma band (30-120 Hz) characterize VWM retention and predict task performance, but whether these oscillations are specific to memorized features and VWM contents or underlie general executive VWM functions is not known. In the present study, we investigated whether gamma oscillations reflect the maintenance of feature-specific information in VWM. Concurrent magneto- and electroencephalography was recorded while subjects memorized different object features or feature conjunctions in identical VWM experiments. Using a data-driven source analysis approach, we show that the strength, load-dependence, and source topographies of gamma oscillations in the visual cortex differentiate these memorized features. Load-dependence of gamma oscillations in feature-specific visual and prefrontal areas also predicts VWM accuracy. Furthermore, corroborating the hypothesis that gamma oscillations support the perceptual binding of feature-specific neuronal assemblies, we also show that VWM for color-location conjunctions is associated with stronger gamma oscillations than that for these features separately. Gamma oscillations hence support the maintenance of feature-specific information and reflect VWM contents. The results also suggest that gamma oscillations contribute to feature binding in the formation of memory representations.

Bistability breaks-off deterministic responses to intracortical stimulation during non-REM sleep

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 thalamo-cortical information integration and consciousness are impaired in spite of preserved neuronal activity.

Cross-frequency synchronization connects networks of fast and slow oscillations during visual working memory maintenance

Neuronal activity in sensory and fronto-parietal (FP) areas underlies the representation and attentional control, respectively, of sensory information maintained in visual working memory (VWM). Within these regions, beta/gamma phase-synchronization supports the integration of sensory functions, while synchronization in theta/alpha bands supports the regulation of attentional functions. A key challenge is to understand which mechanisms integrate neuronal processing across these distinct frequencies and thereby the sensory and attentional functions. We investigated whether such integration could be achieved by cross-frequency phase synchrony (CFS). Using concurrent magneto- and electroencephalography, we found that CFS was load-dependently enhanced between theta and alpha–gamma and between alpha and beta-gamma oscillations during VWM maintenance among visual, FP, and dorsal attention (DA) systems. CFS also connected the hubs of within-frequency-synchronized networks and its strength predicted individual VWM capacity. We propose that CFS integrates processing among synchronized neuronal networks from theta to gamma frequencies to link sensory and attentional functions. DOI: http://dx.doi.org/10.7554/eLife.13451.001