Oscillatory synchronization in large-scale cortical networks predicts perception

Normal brain function requires the dynamic interaction of functionally specialized but widely distributed cortical regions. Long-range synchronization of oscillatory signals has been suggested to mediate these interactions within large-scale cortical networks, but direct evidence is sparse. Here we show that oscillatory synchronization is organized in such large-scale networks. We implemented an analysis approach that allows for imaging synchronized cortical networks and applied this technique to EEG recordings in humans. We identified two networks: beta-band synchronization (~20 Hz) in a fronto-parieto-occipital network and gamma-band synchronization (~80 Hz) in a centro-temporal network. Strong perceptual correlates support their functional relevance: the strength of synchronization within these networks predicted the subjects' perception of an ambiguous audiovisual stimulus as well as the integration of auditory and visual information. Our results provide evidence that oscillatory neuronal synchronization mediates neuronal communication within frequency-specific, large-scale cortical networks.     

Selective Modulation of Interhemispheric Functional Connectivity by HD-tACS Shapes Perception

Oscillatory neuronal synchronization between cortical areas has been suggested to constitute a flexible mechanism to coordinate information flow in the human cerebral cortex. However, it remains unclear whether synchronized neuronal activity merely represents an epiphenomenon or whether it is causally involved in the selective gating of information. Here, we combined bilateral high-density transcranial alternating current stimulation (HD-tACS) at 40 Hz with simultaneous electroencephalographic (EEG) recordings to study immediate electrophysiological effects during the selective entrainment of oscillatory gamma-band signatures. We found that interhemispheric functional connectivity was modulated in a predictable, phase-specific way: In-phase stimulation enhanced synchronization, anti-phase stimulation impaired functional coupling. Perceptual correlates of these connectivity changes were found in an ambiguous motion task, which strongly support the functional relevance of long-range neuronal coupling. Additionally, our results revealed a decrease in oscillatory alpha power in response to the entrainment of gamma band signatures. This finding provides causal evidence for the antagonistic role of alpha and gamma oscillations in the parieto-occipital cortex and confirms that the observed gamma band modulations were physiological in nature. Our results demonstrate that synchronized cortical network activity across several spatiotemporal scales is essential for conscious perception and cognition.     

Large-Scale Information Flow in Conscious and Unconscious States: an ECoG Study in Monkeys

Consciousness is an emergent property of the complex brain network. In order to understand how consciousness is constructed, neural interactions within this network must be elucidated. Previous studies have shown that specific neural interactions between the thalamus and frontoparietal cortices; frontal and parietal cortices; and parietal and temporal cortices are correlated with levels of consciousness. However, due to technical limitations, the network underlying consciousness has not been investigated in terms of large-scale interactions with high temporal and spectral resolution. In this study, we recorded neural activity with dense electrocorticogram (ECoG) arrays and used the spectral Granger causality to generate a more comprehensive network that relates to consciousness in monkeys. We found that neural interactions were significantly different between conscious and unconscious states in all combinations of cortical region pairs. Furthermore, the difference in neural interactions between conscious and unconscious states could be represented in 4 frequency-specific large-scale networks with unique interaction patterns: 2 networks were related to consciousness and showed peaks in alpha and beta bands, while the other 2 networks were related to unconsciousness and showed peaks in theta and gamma bands. Moreover, networks in the unconscious state were shared amongst 3 different unconscious conditions, which were induced either by ketamine and medetomidine, propofol, or sleep. Our results provide a novel picture that the difference between conscious and unconscious states is characterized by a switch in frequency-specific modes of large-scale communications across the entire cortex, rather than the cessation of interactions between specific cortical regions.     

Reentrant Processing in Intuitive Perception

The process of perception requires not only the brain''s receipt of sensory data but also the meaningful organization of that data in relation to the perceptual experience held in memory. Although it typically results in a conscious percept, the process of perception is not fully conscious. Research on the neural substrates of human visual perception has suggested that regions of limbic cortex, including the medial orbital frontal cortex (mOFC), may contribute to intuitive judgments about perceptual events, such as guessing whether an object might be present in a briefly presented fragmented drawing. Examining dense array measures of cortical electrical activity during a modified Waterloo Gestalt Closure Task, results show, as expected, that activity in medial orbital frontal electrical responses (about 250 ms) was associated with intuitive judgments. Activity in the right temporal-parietal-occipital (TPO) region was found to predict mOFC (∼150 ms) activity and, in turn, was subsequently influenced by the mOFC at a later time (∼300 ms). The initial perception of gist or meaning of a visual stimulus in limbic networks may thus yield reentrant input to the visual areas to influence continued development of the percept. Before perception is completed, the initial representation of gist may support intuitive judgments about the ongoing perceptual process.     

Altered Oscillation and Synchronization of Default-Mode Network Activity in Mild Alzheimer’s Disease Compared to Mild Cognitive Impairment: An Electrophysiological Study

Some researchers have suggested that the default mode network (DMN) plays an important role in the pathological mechanisms of Alzheimer’s disease (AD). To examine whether the cortical activities in DMN regions show significant difference between mild AD from mild cognitive impairment (MCI), electrophysiological responses were analyzed from 21 mild Alzheimer’s disease (AD) and 21 mild cognitive impairment (MCI) patients during an eyes closed, resting-state condition. The spectral power and functional connectivity of the DMN were estimated using a minimum norm estimate (MNE) combined with fast Fourier transform and imaginary coherence analysis. Our results indicated that source-based EEG maps of resting-state activity showed alterations of cortical spectral power in mild AD when compared to MCI. These alterations are characteristic of attenuated alpha or beta activities in the DMN, as are enhanced delta or theta activities in the medial temporal, inferior parietal, posterior cingulate cortex and precuneus. With regard to altered synchronization in AD, altered functional interconnections were observed as specific connectivity patterns of connection hubs in the precuneus, posterior cingulate cortex, anterior cingulate cortex and medial temporal regions. Moreover, posterior theta and alpha power and altered connectivity in the medial temporal lobe correlated significantly with scores obtained on the Mini-Mental State Examination (MMSE). In conclusion, EEG is a useful tool for investigating the DMN in the brain and differentiating early stage AD and MCI patients. This is a promising finding; however, further large-scale studies are needed.     

Neural synchrony in brain disorders: relevance for cognitive dysfunctions and pathophysiology

Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, novel methods of time series analysis have been developed for the examination of task- and performance-related oscillatory activity and its synchronization. Studies employing these advanced techniques revealed that synchronization of oscillatory responses in the beta- and gamma-band is involved in a variety of cognitive functions, such as perceptual grouping, attention-dependent stimulus selection, routing of signals across distributed cortical networks, sensory-motor integration, working memory, and perceptual awareness. Here, we review evidence that certain brain disorders, such as schizophrenia, epilepsy, autism, Alzheimer's disease, and Parkinson's are associated with abnormal neural synchronization. The data suggest close correlations between abnormalities in neuronal synchronization and cognitive dysfunctions, emphasizing the importance of temporal coordination. Thus, focused search for abnormalities in temporal patterning may be of considerable clinical relevance.     

Experimental and theoretical approaches to conscious processing

Recent experimental studies and theoretical models have begun to address the challenge of establishing a causal link between subjective conscious experience and measurable neuronal activity. The present review focuses on the well-delimited issue of how an external or internal piece of information goes beyond nonconscious processing and gains access to conscious processing, a transition characterized by the existence of a reportable subjective experience. Converging neuroimaging and neurophysiological data, acquired during minimal experimental contrasts between conscious and nonconscious processing, point to objective neural measures of conscious access: late amplification of relevant sensory activity, long-distance cortico-cortical synchronization at beta and gamma frequencies, and "ignition" of a large-scale prefronto-parietal network. We compare these findings to current theoretical models of conscious processing, including the Global Neuronal Workspace (GNW) model according to which conscious access occurs when incoming information is made globally available to multiple brain systems through a network of neurons with long-range axons densely distributed in prefrontal, parieto-temporal, and cingulate cortices. The clinical implications of these results for general anesthesia, coma, vegetative state, and schizophrenia are discussed.     

Dynamic Changes in Phase-Amplitude Coupling Facilitate Spatial Attention Control in Fronto-Parietal Cortex

Attention is a core cognitive mechanism that allows the brain to allocate limited resources depending on current task demands. A number of frontal and posterior parietal cortical areas, referred to collectively as the fronto-parietal attentional control network, are engaged during attentional allocation in both humans and non-human primates. Numerous studies have examined this network in the human brain using various neuroimaging and scalp electrophysiological techniques. However, little is known about how these frontal and parietal areas interact dynamically to produce behavior on a fine temporal (sub-second) and spatial (sub-centimeter) scale. We addressed how human fronto-parietal regions control visuospatial attention on a fine spatiotemporal scale by recording electrocorticography (ECoG) signals measured directly from subdural electrode arrays that were implanted in patients undergoing intracranial monitoring for localization of epileptic foci. Subjects (n = 8) performed a spatial-cuing task, in which they allocated visuospatial attention to either the right or left visual field and detected the appearance of a target. We found increases in high gamma (HG) power (70–250 Hz) time-locked to trial onset that remained elevated throughout the attentional allocation period over frontal, parietal, and visual areas. These HG power increases were modulated by the phase of the ongoing delta/theta (2–5 Hz) oscillation during attentional allocation. Critically, we found that the strength of this delta/theta phase-HG amplitude coupling predicted reaction times to detected targets on a trial-by-trial basis. These results highlight the role of delta/theta phase-HG amplitude coupling as a mechanism for sub-second facilitation and coordination within human fronto-parietal cortex that is guided by momentary attentional demands.     

Altered Rolandic Gamma-Band Activation Associated with Motor Impairment and Ictal Network Desynchronization in Childhood Epilepsy

Epilepsy is associated with an abnormal expression of neural oscillations and their synchronization across brain regions. Oscillatory brain activation and synchronization also play an important role in cognition, perception and motor control. Childhood epilepsy is associated with a variety of cognitive and motor deficits, but the relationship between altered functional brain responses in various frequency ranges and functional impairment in these children remains poorly understood. We investigated functional magnetoencephalographic (MEG) responses from motor cortex in multiple functionally relevant frequency bands following median nerve stimulation in twelve children with epilepsy, including four children with motor impairments. We demonstrated that children with motor impairments exhibit an excessive gamma-band response from Rolandic cortex, and that the magnitude of this Rolandic gamma response is negatively associated with motor function. Abnormal responses from motor cortex were also associated with ictal desynchronization of oscillations within Rolandic cortex measured using intracranial EEG (iEEG). These results provide the evidence that ictal disruption of motor networks is associated with an altered functional response from motor cortex, which is in turn associated with motor impairment.     

Theta band zero-lag long-range cortical synchronization via hippocampal dynamical relaying

Growing evidence suggests that synchronization among distributed neuronal networks underlie functional integration in the brain. Neural synchronization is typically revealed by a consistent phase delay between neural responses generated in two separated sources. But the influence of a third neuronal assembly in that synchrony pattern remains largely unexplored. We investigate here the potential role of the hippocampus in determining cortico-cortical theta synchronization in different behavioral states during motor quiescent and while animals actively explore the environment. To achieve this goal, the two states were modeled with a recurrent network involving the hippocampus, as a relay element, and two distant neocortical sites. We found that cortico-cortical neural coupling accompanied higher hippocampal theta oscillations in both behavioral states, although the highest level of synchronization between cortical regions emerged during motor exploration. Local field potentials recorded from the same brain regions qualitatively confirm these findings in the two behavioral states. These results suggest that zero-lag long-range cortico-cortical synchronization is likely mediated by hippocampal theta oscillations in lower mammals as a function of cognitive demands and motor acts.     

Spatially constrained adaptive rewiring in cortical networks creates spatially modular small world architectures

A modular small-world topology in functional and anatomical networks of the cortex is eminently suitable as an information processing architecture. This structure was shown in model studies to arise adaptively; it emerges through rewiring of network connections according to patterns of synchrony in ongoing oscillatory neural activity. However, in order to improve the applicability of such models to the cortex, spatial characteristics of cortical connectivity need to be respected, which were previously neglected. For this purpose we consider networks endowed with a metric by embedding them into a physical space. We provide an adaptive rewiring model with a spatial distance function and a corresponding spatially local rewiring bias. The spatially constrained adaptive rewiring principle is able to steer the evolving network topology to small world status, even more consistently so than without spatial constraints. Locally biased adaptive rewiring results in a spatial layout of the connectivity structure, in which topologically segregated modules correspond to spatially segregated regions, and these regions are linked by long-range connections. The principle of locally biased adaptive rewiring, thus, may explain both the topological connectivity structure and spatial distribution of connections between neuronal units in a large-scale cortical architecture.     

Enhanced cortical excitability in grapheme-color synesthesia and its modulation

Synesthesia is an unusual condition characterized by the over-binding of two or more features and the concomitant automatic and conscious experience of atypical, ancillary images or perceptions. Previous research suggests that synesthetes display enhanced modality-specific perceptual processing, but it remains unclear whether enhanced processing contributes to conscious awareness of color photisms. In three experiments, we investigated whether grapheme-color synesthesia is characterized by enhanced cortical excitability in primary visual cortex and the role played by this hyperexcitability in the expression of synesthesia. Using transcranial magnetic stimulation, we show that synesthetes display 3-fold lower phosphene thresholds than controls during stimulation of the primary visual cortex. We next used transcranial direct current stimulation to discriminate between two competing hypotheses of the role of hyperexcitability in the expression of synesthesia. We demonstrate that synesthesia can be selectively augmented with cathodal stimulation and attenuated with anodal stimulation of primary visual cortex. A control task revealed that the effect of the brain stimulation was specific to the experience of synesthesia. These results indicate that hyperexcitability acts as a source of noise in visual cortex that influences the availability of the neuronal signals underlying conscious awareness of synesthetic photisms.     

The importance of timing in segregated theta phase-coupling for cognitive performance

Functional cortical circuits for central executive functions have been shown to emerge by theta (~6 Hz) phase-coupling of distant cortical areas. It has been repeatedly shown that frontoparietal theta coupling at ~0° relative phase is associated with recognition, encoding, short-term retention, and planning; however, a causal link has not been demonstrated so far. Here we used transcranial alternating current stimulation simultaneously applied at 6 Hz over left prefrontal and parietal cortices with a relative 0° ("synchronized" condition) or 180° ("desynchronized" condition) phase difference or a placebo stimulation condition, whereas healthy subjects performed a delayed letter discrimination task. We show that exogenously induced frontoparietal theta synchronization significantly improves visual memory-matching reaction times as compared to placebo stimulation. In contrast, exogenously induced frontoparietal theta desynchronization deteriorates performance. The present findings provide for the first time evidence of causality of theta phase-coupling of distant cortical areas for cognitive performance in healthy humans. Moreover, the results demonstrate the suitability of transcranial alternating current stimulation to artificially induce coupling or decoupling of behaviorally relevant brain rhythms between segregated cortical regions.     

Early cortical specialization for face-to-face communication in human infants

This study examined the brain bases of early human social cognitive abilities. Specifically, we investigated whether cortical regions implicated in adults' perception of facial communication signals are functionally active in early human development. Four-month-old infants watched two kinds of dynamic scenarios in which a face either established mutual gaze or averted its gaze, both of which were followed by an eyebrow raise with accompanying smile. Haemodynamic responses were measured by near-infrared spectroscopy, permitting spatial localization of brain activation (experiment 1), and gamma-band oscillatory brain activity was analysed from electroencephalography to provide temporal information about the underlying cortical processes (experiment 2). The results revealed that perceiving facial communication signals activates areas in the infant temporal and prefrontal cortex that correspond to the brain regions implicated in these processes in adults. In addition, mutual gaze itself, and the eyebrow raise with accompanying smile in the context of mutual gaze, produce similar cortical activations. This pattern of results suggests an early specialization of the cortical network involved in the perception of facial communication cues, which is essential for infants' interactions with, and learning from, others.     

Compensating for synaptic loss in Alzheimer’s disease

Confirming that synaptic loss is directly related to cognitive deficit in Alzheimer’s disease (AD) has been the focus of many studies. Compensation mechanisms counteract synaptic loss and prevent the catastrophic amnesia induced by synaptic loss via maintaining the activity levels of neural circuits. Here we investigate the interplay between various synaptic degeneration and compensation mechanisms, and abnormal cortical oscillations based on a large-scale network model consisting of 100,000 neurons exhibiting several cortical firing patterns, 8.5 million synapses, short-term plasticity, axonal delays and receptor kinetics. The structure of the model is inspired by the anatomy of the cerebral cortex. The results of the modelling study suggest that cortical oscillations respond differently to compensation mechanisms. Local compensation preserves the baseline activity of theta (5–7 Hz) and alpha (8–12 Hz) oscillations whereas delta (1–4 Hz) and beta (13–30 Hz) oscillations are maintained via global compensation. Applying compensation mechanisms independently shows greater effects than combining both compensation mechanisms in one model and applying them in parallel. Consequently, it can be speculated that enhancing local compensation might recover the neural processes and cognitive functions that are associated with theta and alpha oscillations whereas inducing global compensation might contribute to the repair of neural (cognitive) processes which are associated with delta and beta band activity. Compensation mechanisms may vary across cortical regions and the activation of inappropriate compensation mechanism in a particular region may fail to recover network dynamics and/or induce secondary pathological changes in the network.     

Individual differences in perceptual switching rates; the role of occipital alpha and frontal theta band activity

Prolonged presentation of visually ambiguous figures leads to perceptual switching. Individual switching rates show great variability. The present study compares individuals with high versus low switching rates by investigating human scalp electroencephalogram and blink rates. Eight subjects viewed the Necker cube continuously and responded to perceptual switching by pressing a button. Frequent switchers showed characteristic occipital alpha and frontal theta band activity prior to a switch, whereas infrequent switchers did not. The alpha activity was specific to switching, the theta activity was generic to perceptual processing conditions. A negative correlation was observed between perceptual switching and blink rates. These results suggest that the ability to concentrate attentional effort on the task is responsible for the differences in perceptual switching rates     

Converging Intracranial Markers of Conscious Access

We compared conscious and nonconscious processing of briefly flashed words using a visual masking procedure while recording intracranial electroencephalogram (iEEG) in ten patients. Nonconscious processing of masked words was observed in multiple cortical areas, mostly within an early time window (<300 ms), accompanied by induced gamma-band activity, but without coherent long-distance neural activity, suggesting a quickly dissipating feedforward wave. In contrast, conscious processing of unmasked words was characterized by the convergence of four distinct neurophysiological markers: sustained voltage changes, particularly in prefrontal cortex, large increases in spectral power in the gamma band, increases in long-distance phase synchrony in the beta range, and increases in long-range Granger causality. We argue that all of those measures provide distinct windows into the same distributed state of conscious processing. These results have a direct impact on current theoretical discussions concerning the neural correlates of conscious access.     

Precisely timed oculomotor and parietal EEG activity in perceptual switching

Blinks and saccades cause transient interruptions of visual input. To investigate how such effects influence our perceptual state, we analyzed the time courses of blink and saccade rates in relation to perceptual switching in the Necker cube. Both time courses of blink and saccade rates showed peaks at different moments along the switching process. A peak in blinking rate appeared 1,000 ms prior to the switching responses. Blinks occurring around this peak were associated with subsequent switching to the preferred interpretation of the Necker cube. Saccade rates showed a peak 150 ms prior to the switching response. The direction of saccades around this peak was predictive of the perceived orientation of the Necker cube afterwards. Peak blinks were followed and peak saccades were preceded by transient parietal theta band activity indicating the changing of the perceptual interpretation. Precisely-timed blinks, therefore, can initiate perceptual switching, and precisely-timed saccades can facilitate an ongoing change of interpretation.     

Synchronous and asynchronous bursting states: role of intrinsic neural dynamics

Brain signals such as local field potentials often display gamma-band oscillations (30-70 Hz) in a variety of cognitive tasks. These oscillatory activities possibly reflect synchronization of cell assemblies that are engaged in a cognitive function. A type of pyramidal neurons, i.e., chattering neurons, show fast rhythmic bursting (FRB) in the gamma frequency range, and may play an active role in generating the gamma-band oscillations in the cerebral cortex. Our previous phase response analyses have revealed that the synchronization between the coupled bursting neurons significantly depends on the bursting mode that is defined as the number of spikes in each burst. Namely, a network of neurons bursting through a Ca(2+)-dependent mechanism exhibited sharp transitions between synchronous and asynchronous firing states when the neurons exchanged the bursting mode between singlet, doublet and so on. However, whether a broad class of bursting neuron models commonly show such a network behavior remains unclear. Here, we analyze the mechanism underlying this network behavior using a mathematically tractable neuron model. Then we extend our results to a multi-compartment version of the NaP current-based neuron model and prove a similar tight relationship between the bursting mode changes and the network state changes in this model. Thus, the synchronization behavior couples tightly to the bursting mode in a wide class of networks of bursting neurons.     

Bistable percepts in the brain: FMRI contrasts monocular pattern rivalry and binocular rivalry

The neural correlates of binocular rivalry have been actively debated in recent years, and are of considerable interest as they may shed light on mechanisms of conscious awareness. In a related phenomenon, monocular rivalry, a composite image is shown to both eyes. The subject experiences perceptual alternations in which the two stimulus components alternate in clarity or salience. The experience is similar to perceptual alternations in binocular rivalry, although the reduction in visibility of the suppressed component is greater for binocular rivalry, especially at higher stimulus contrasts. We used fMRI at 3T to image activity in visual cortex while subjects perceived either monocular or binocular rivalry, or a matched non-rivalrous control condition. The stimulus patterns were left/right oblique gratings with the luminance contrast set at 9%, 18% or 36%. Compared to a blank screen, both binocular and monocular rivalry showed a U-shaped function of activation as a function of stimulus contrast, i.e. higher activity for most areas at 9% and 36%. The sites of cortical activation for monocular rivalry included occipital pole (V1, V2, V3), ventral temporal, and superior parietal cortex. The additional areas for binocular rivalry included lateral occipital regions, as well as inferior parietal cortex close to the temporoparietal junction (TPJ). In particular, higher-tier areas MT+ and V3A were more active for binocular than monocular rivalry for all contrasts. In comparison, activation in V2 and V3 was reduced for binocular compared to monocular rivalry at the higher contrasts that evoked stronger binocular perceptual suppression, indicating that the effects of suppression are not limited to interocular suppression in V1.