Eugenio Rodriguez

The brainweb: phase synchronization and large-scale integration.

The emergence of a unified cognitive moment relies on the coordination of scattered mosaics of functionally specialized brain regions. Here we review the mechanisms of large-scale integration that counterbalance the distributed anatomical and functional organization of brain activity to enable the emergence of coherent behaviour and cognition. Although the mechanisms involved in large-scale integration are still largely unknown, we argue that the most plausible candidate is the formation of dynamic links mediated by synchrony over multiple frequency bands.

Measuring phase synchrony in brain signals

This article presents, for the first time, a practical method for the direct quantification of frequency‐specific synchronization (i.e., transient phase‐locking) between two neuroelectric signals. The motivation for its development is to be able to examine the role of neural synchronies as a putative mechanism for long‐range neural integration during cognitive tasks. The method, called phase‐locking statistics (PLS), measures the significance of the phase covariance between two signals with a reasonable time‐resolution (<100 ms). Unlike the more traditional method of spectral coherence, PLS separates the phase and amplitude components and can be directly interpreted in the framework of neural integration. To validate synchrony values against background fluctuations, PLS uses surrogate data and thus makes no a priori assumptions on the nature of the experimental data. We also apply PLS to investigate intracortical recordings from an epileptic patient performing a visual discrimination task. We find large‐scale synchronies in the gamma band (45 Hz), e.g., between hippocampus and frontal gyrus, and local synchronies, within a limbic region, a few cm apart. We argue that whereas long‐scale effects do reflect cognitive processing, short‐scale synchronies are likely to be due to volume conduction. We discuss ways to separate such conduction effects from true signal synchrony. Hum Brain Mapping 8:194–208, 1999.

Perception's shadow: long-distance synchronization of human brain activity

Transient periods of synchronization of oscillating neuronal discharges in the frequency range 30–80 Hz (gamma oscillations) have been proposed to act as an integrative mechanism that may bring a widely distributed set of neurons together into a coherent ensemble that underlies a cognitive act. Results of several experiments in animals provide support for this idea (see, for example, refs 4,5,6,7,8,9,10). In humans, gamma oscillations have been described both on the scalp (measured by electroencephalography and magnetoencephalography) and in intracortical recordings, but no direct participation of synchrony in a cognitive task has been demonstrated so far. Here we record electrical brain activity from subjects who are viewing ambiguous visual stimuli (perceived either as faces or as meaningless shapes). We show for the first time, to our knowledge, that only face perception induces a long-distance pattern of synchronization, corresponding to the moment of perception itself and to the ensuing motor response. A period of strong desynchronization marks the transition between the moment of perception and the motor response. We suggest that this desynchronization reflects a process of active uncoupling of the underlying neural ensembles that is necessary to proceed from one cognitive state to another.

Comparison of Hilbert transform and wavelet methods for the analysis of neuronal synchrony

The quantification of phase synchrony between neuronal signals is of crucial importance for the study of large-scale interactions in the brain. Two methods have been used to date in neuroscience, based on two distinct approaches which permit a direct estimation of the instantaneous phase of a signal [Phys. Rev. Lett. 81 (1998) 3291; Human Brain Mapping 8 (1999) 194]. The phase is either estimated by using the analytic concept of Hilbert transform or, alternatively, by convolution with a complex wavelet. In both methods the stability of the instantaneous phase over a window of time requires quantification by means of various statistical dependence parameters (standard deviation, Shannon entropy or mutual information). The purpose of this paper is to conduct a direct comparison between these two methods on three signal sets: (1) neural models; (2) intracranial signals from epileptic patients; and (3) scalp EEG recordings. Levels of synchrony that can be considered as reliable are estimated by using the technique of surrogate data. Our results demonstrate that the differences between the methods are minor, and we conclude that they are fundamentally equivalent for the study of neuroelectrical signals. This offers a common language and framework that can be used for future research in the area of synchronization.

Synchronization of Neural Activity across Cortical Areas Correlates with Conscious Perception

Subliminal stimuli can be deeply processed and activate similar brain areas as consciously perceived stimuli. This raises the question which signatures of neural activity critically differentiate conscious from unconscious processing. Transient synchronization of neural activity has been proposed as a neural correlate of conscious perception. Here we test this proposal by comparing the electrophysiological responses related to the processing of visible and invisible words in a delayed matching to sample task. Both perceived and nonperceived words caused a similar increase of local (gamma) oscillations in the EEG, but only perceived words induced a transient long-distance synchronization of gamma oscillations across widely separated regions of the brain. After this transient period of temporal coordination, the electrographic signatures of conscious and unconscious processes continue to diverge. Only words reported as perceived induced (1) enhanced theta oscillations over frontal regions during the maintenance interval, (2) an increase of the P300 component of the event-related potential, and (3) an increase in power and phase synchrony of gamma oscillations before the anticipated presentation of the test word. We propose that the critical process mediating the access to conscious perception is the early transient global increase of phase synchrony of oscillatory activity in the gamma frequency range.

Dysfunctional Long-Range Coordination of Neural Activity during Gestalt Perception in Schizophrenia

Recent theoretical and empirical research on schizophrenia converges on the notion that core aspects of the pathophysiology of the disorder may arise from a dysfunction in the coordination of distributed neural activity. Synchronization of neural responses in the β-band (15–30 Hz) and γ-band range (30–80 Hz) has been implicated as a possible neural substrate for dysfunctional coordination in schizophrenia. To test this hypothesis, we examined the electroencephalography (EEG) activity in 19 patients with a Diagnostic and Statistical Manual of Mental Disorder, edition IV criteria, diagnosis of schizophrenia and 19 healthy control subjects during a Gestalt perception task. EEG data were analyzed for phase synchrony and induced spectral power as an index of neural synchronization. Schizophrenia patients were impaired significantly in the detection of images that required the grouping of stimulus elements into coherent object representations. This deficit was accompanied by longer reaction times in schizophrenia patients. Deficits in Gestalt perception in schizophrenia patients were associated with reduced phase synchrony in the β-band (20–30 Hz), whereas induced spectral power in the γ-band (40–70 Hz) was mainly intact. Our findings suggest that schizophrenia patients are impaired in the long-range synchronization of neural responses, which may reflect a core deficit in the coordination of neural activity and underlie the specific cognitive dysfunctions associated with the disorder.

Neural synchrony and the development of cortical networks

Recent data indicate that the synchronisation of oscillatory activity is relevant for the development of cortical circuits as demonstrated by the involvement of neural synchrony in synaptic plasticity and changes in the frequency and synchronisation of neural oscillations during development. Analyses of resting-state and task-related neural synchrony indicate that gamma-oscillations emerge during early childhood and precise temporal coordination through neural synchrony continues to mature until early adulthood. The late maturation of neural synchrony is compatible with changes in the myelination of cortico-cortical connections and with late development of GABAergic neurotransmission. These findings highlight the role of neural synchrony for normal brain development as well as its potential importance for understanding neurodevelopmental disorders, such as autism spectrum disorders (ASDs) and schizophrenia.

Cortical Oscillatory Activity Is Critical for Working Memory as Revealed by Deficits in Early-Onset Schizophrenia

Impairments in working memory (WM) are a core cognitive deficit in schizophrenia. Neurophysiological models suggest that deficits during WM maintenance in schizophrenia may be explained by abnormalities in the GABAergic system, which will lead to deficits in high-frequency oscillations. However, it is not yet clear which of the three WM phases (encoding, maintenance, retrieval) are affected by dysfunctional oscillatory activity. We investigated the relationship between impairments in oscillatory activity in a broad frequency range (3–100 Hz) and WM load in the different phases of WM in 14 patients with early-onset schizophrenia and 14 matched control participants using a delayed matching to sample paradigm. During encoding, successful memorization was predicted by evoked theta, alpha, and beta oscillatory activity in controls. Patients showed severe reductions in the evoked activity in these frequency bands. During early WM maintenance, patients showed a comparable WM load-dependent increase in induced alpha and gamma activity to controls. In contrast, during the later maintenance phase, patients showed a shift in the peak of induced gamma activity to the lower WM load conditions. Finally, induced theta and gamma activity were reduced in patients during retrieval. Our findings suggest that the WM deficit in schizophrenia is associated with impaired oscillatory activity during all phases of the task and that the cortical storage system reaches its capacity limit at lower loads. Inability to maintain oscillatory activity in specific frequency bands could thus result in the information overload that may underlie both cognitive deficits and psychopathological symptoms of schizophrenia.

The development of neural synchrony reflects late maturation and restructuring of functional networks in humans

Brain development is characterized by maturational processes that span the period from childhood through adolescence to adulthood, but little is known whether and how developmental processes differ during these phases. We analyzed the development of functional networks by measuring neural synchrony in EEG recordings during a Gestalt perception task in 68 participants ranging in age from 6 to 21 years. Until early adolescence, developmental improvements in cognitive performance were accompanied by increases in neural synchrony. This developmental phase was followed by an unexpected decrease in neural synchrony that occurred during late adolescence and was associated with reduced performance. After this period of destabilization, we observed a reorganization of synchronization patterns that was accompanied by pronounced increases in gamma-band power and in theta and beta phase synchrony. These findings provide evidence for the relationship between neural synchrony and late brain development that has important implications for the understanding of adolescence as a critical period of brain maturation.

STUDYING SINGLE-TRIALS OF PHASE SYNCHRONOUS ACTIVITY IN THE BRAIN

This paper introduces a new method, single-trial phase locking statistics (S-PLS) to estimate phase locking in single trials of brain signals between two electrodes. The possibility of studying single trials removes an important limitation in the study of long-range synchrony in brain signals. S-PLS is closely related to our previous method, phase locking statistics (PLS) that estimates phase locking over a set of trials. The S-PLS method is described in detail and applied to human surface recordings during the task of face-recognition. We compare these results with those provided by PLS and show that they are qualitatively very similar, although S-PLS provides better discrimination of synchronic episodes.