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Highlights • The functional characterization of callosal connections is informed by anatomical data. • Callosal connections play a conditional driving role depending on the brain state and behavioral demands. • Callosal connections play a modulatory function, in addition to a driving role. • The corpus callosum participates in learning and interhemispheric transfer of sensorimotor habits. • The corpus callosum contributes to language processing and cognitive functions., The brain operates through the synaptic interaction of distant neurons within flexible, often heterogeneous, distributed systems. Histological studies have detailed the connections between distant neurons, but their functional characterization deserves further exploration. Studies performed on the corpus callosum in animals and humans are unique in that they capitalize on results obtained from several neuroscience disciplines. Such data inspire a new interpretation of the function of callosal connections and delineate a novel road map, thus paving the way toward a general theory of cortico-cortical connectivity. Here we suggest that callosal axons can drive their post-synaptic targets preferentially when coupled to other inputs endowing the cortical network with a high degree of conditionality. This might depend on several factors, such as their pattern of convergence-divergence, the excitatory and inhibitory operation mode, the range of conduction velocities, the variety of homotopic and heterotopic projections and, finally, the state-dependency of their firing. We propose that, in addition to direct stimulation of post-synaptic targets, callosal axons often play a conditional driving or modulatory role, which depends on task contingencies, as documented by several recent studies.

The alpha rhythm (AR) represents a fundamental oscillatory mechanism that controls information flow in the brain via rhythmic changes in neuronal excitability. AR is generated in the thalamus and neocortex and coordinated by the cortico-cortical and thalamo-cortical circuits. Human AR recorded by electroencephalogram (EEG) typically consists of a high-frequency occipito-parietal component (ARC1) and a low-frequency occipito-temporal component (ARC2). The selectivity of their responses to space versus object cognition tasks links ARC1 to the dorsal processing stream and ARC2 to the ventral stream. AR changes are the most pronounced EEG phenomena in the aging human brain. Both components slow down with aging and their sources shift in the anterior-inferior direction, but ARC1 evolves faster than ARC2. This causes a spatial and frequency overlap, leading to the transformation of the multicomponent AR into a single-component AR with age. Understanding these processes is essential for monitoring normal aging and neurodegenerative processes in the human brain.

Heterogeneity of the posterior alpha rhythm (AR) is a widely assumed but rarely tested phenomenon. We decomposed the posterior AR in the cortical source space with a 3-way PARAFAC technique, taking into account the spatial, frequency, and temporal aspects of mid-density EEG. We found a multicomponent AR structure in 90% of a group of 29 healthy adults. The typical resting-state structure consisted of a high-frequency occipito-parietal component of the AR (ARC1) and a low-frequency occipito-temporal component (ARC2), characterized by individual dynamics in time. In a few cases, we found a 3-component structure, with two ARC1s and one ARC2. The AR structures were stable in their frequency and spatial features over weeks to months, thus representing individual EEG alpha phenotypes. Cortical topography, individual stability, and similarity to the primate AR organization link ARC1 to the dorsal visual stream and ARC2 to the ventral one. Understanding how many and what kind of posterior AR components contribute to the EEG is essential for clinical neuroscience as an objective basis for AR segmentation and for interpreting AR dynamics under various conditions, both normal and pathological, which can selectively affect individual components.

In humans, spatial integration develops slowly, continuing through childhood into adolescence. On the assumption that this protracted course depends on the formation of networks with slowly developing top-down connections, we compared effective connectivity in the visual cortex between 13 children (age 7-13) and 14 adults (age 21-42) using a passive perceptual task. The subjects were scanned while viewing bilateral gratings, which either obeyed Gestalt grouping rules [colinear gratings (CG)] or violated them [non-colinear gratings (NG)]. The regions of interest for dynamic causal modeling were determined from activations in functional MRI contrasts stimuli > background and CG > NG. They were symmetrically located in V1 and V3v areas of both hemispheres. We studied a common model, which contained reciprocal intrinsic and modulatory connections between these regions. An analysis of effective connectivity showed that top-down modulatory effects generated at an extrastriate level and interhemispheric modulatory effects between primary visual areas (all inhibitory) are significantly weaker in children than in adults, suggesting that the formation of feedback and interhemispheric effective connections continues into adolescence. These results are consistent with a model in which spatial integration at an extrastriate level results in top-down messages to the primary visual areas, where they are supplemented by lateral (interhemispheric) messages, making perceptual encoding more efficient and less redundant. Abnormal formation of top-down inhibitory connections can lead to the reduction of habituation observed in migraine patients.

Alpha rhythm (AR) changes are the most pronounced electroencephalogram phenomenon in the aging brain. We analyzed them based on the inherent AR structure obtained by parallel factor analysis decomposition in the cortical source space. AR showed a stable multicomponent structure in 78% of sixty 20- to 81-year-old healthy adults. Typically, it consists of 2 components. The distribution of the higher frequency occipito-parietal component widens with age, with its maximum moving from BA18/19 to BA37. The low-frequency component originating from the occipito-temporal regions in young adults also moves anteriorly with age, while maintaining its maximum within BA37. Both components slow down by 1 Hz over the adult lifespan. The multicomponent AR is more common in younger subjects, whereas a single-component AR in older subjects. This uneven occurrence as well as the increasing spatial and frequency overlaps between components suggest transformation of the multicomponent AR into the single-component AR with age. A detailed knowledge of AR component structure would be useful to monitor age-related neurodegenerative processes in humans.

Introduction Interindividual variations in regional structural properties covary across the brain, thus forming networks that change as a result of aging and accompanying neurological conditions. The alterations of superficial white matter (SWM) in Alzheimer's disease (AD) are of special interest, since they follow the AD-specific pattern characterized by the strongest neurodegeneration of the medial temporal lobe and association cortices. Methods Here, we present an SWM network analysis in comparison with SWM topography based on the myelin content quantified with magnetization transfer ratio (MTR) for 39 areas in each hemisphere in 15 AD patients and 15 controls. The networks are represented by graphs, in which nodes correspond to the areas, and edges denote statistical associations between them. Results In both groups, the networks were characterized by asymmetrically distributed edges (predominantly in the left hemisphere). The AD-related differences were also leftward. The edges lost due to AD tended to connect nodes in the temporal lobe to other lobes or nodes within or between the latter lobes. The newly gained edges were mostly confined to the temporal and paralimbic regions, which manifest demyelination of SWM already in mild AD. Conclusion This pattern suggests that the AD pathological process coordinates SWM demyelination in the temporal and paralimbic regions, but not elsewhere. A comparison of the MTR maps with MTR-based networks shows that although, in general, the changes in network architecture in AD recapitulate the topography of (de)myelination, some aspects of structural covariance (including the interhemispheric asymmetry of networks) have no immediate reflection in the myelination pattern.

Synchronization behavior of electroencephalographic (EEG) signals is important for decoding information processing in the human brain. Modern multichannel EEG allows a transition from traditional measurements of synchronization in pairs of EEG signals to whole-brain synchronization maps. The latter can be based on bivariate measures (BM) via averaging over pair-wise values or, alternatively, on multivariate measures (MM), which directly ascribe a single value to the synchronization in a group. In order to compare BM versus MM, we applied nine different estimators to simulated multivariate time series with known parameters and to real EEGs. We found widespread correlations between BM and MM, which were almost frequency-independent for all the measures except coherence. The analysis of the behavior of synchronization measures in simulated settings with variable coupling strength, connection probability, and parameter mismatch showed that some of them, including S-estimator, S-Renyi, omega, and coherence, are more sensitive to linear interdependences, while others, like mutual information and phase locking value, are more responsive to nonlinear effects. One must consider these properties together with the fact that MM are computationally less expensive and, therefore, more efficient for the large-scale data sets than BM while choosing a synchronization measure for EEG analysis.

Alzheimer's disease (AD) disrupts functional connectivity in distributed cortical networks. We analyzed changes in the S-estimator, a measure of multivariate intraregional synchronization, in electroencephalogram (EEG) source space in 15 mild AD patients versus 15 age-matched controls to evaluate its potential as a marker of AD progression. All participants underwent 2 clinical evaluations and 2 EEG recording sessions on diagnosis and after a year. The main effect of AD was hyposynchronization in the medial temporal and frontal regions and relative hypersynchronization in posterior cingulate, precuneus, cuneus, and parietotemporal cortices. However, the S-estimator did not change over time in either group. This result motivated an analysis of rapidly progressing AD versus slow-progressing patients. Rapidly progressing AD patients showed a significant reduction in synchronization with time, manifest in left frontotemporal cortex. Thus, the evolution of source EEG synchronization over time is correlated with the rate of disease progression and should be considered as a cost-effective AD biomarker. (c) 2013 Elsevier Inc. All rights reserved.

Functional connectivity (FC) is among the most informative features derived from EEG. However, the most straightforward sensor-space analysis of FC is unreliable owing to volume conductance effects. An alternative-source-space analysis of FC-is optimal for high- and mid-density EEG (hdEEG, mdEEG); however, it is questionable for widely used low-density EEG (ldEEG) because of inadequate surface sampling. Here, using simulations, we investigate the performance of the two source FC methods, the inverse-based source FC (ISFC) and the cortical partial coherence (CPC). To examine the effects of localization errors of the inverse method on the FC estimation, we simulated an oscillatory source with varying locations and SNRs. To compare the FC estimations by the two methods, we simulated two synchronized sources with varying between-source distance and SNR. The simulations were implemented for hdEEG, mdEEG, and ldEEG. We showed that the performance of both methods deteriorates for deep sources owing to their inaccurate localization and smoothing. The accuracy of both methods improves with the increasing between-source distance. The best ISFC performance was achieved using hd/mdEEG, while the best CPC performance was observed with ldEEG. In conclusion, with hdEEG, ISFC outperforms CPC and therefore should be the preferred method. In the studies based on ldEEG, the CPC is a method of choice.

We consider electroencephalograms (EEGs) of healthy individuals and compare the properties of the brain functional networks found through two methods: unpartialized and partialized cross-correlations. The networks obtained by partial correlations are fundamentally different from those constructed through unpartial correlations in terms of graph metrics. In particular, they have completely different connection efficiency, clustering coefficient, assortativity, degree variability, and synchronization properties. Unpartial correlations are simple to compute and they can be easily applied to large-scale systems, yet they cannot prevent the prediction of non-direct edges. In contrast, partial correlations, which are often expensive to compute, reduce predicting such edges. We suggest combining these alternative methods in order to have complementary information on brain functional networks.

Alzheimer's disease (AD) is likely to disrupt the synchronization of the bioelectrical processes in the distributed cortical networks underlying cognition. We analyze the surface topography of the multivariate phase synchronization (MPS) of multichannel EEG in 17 patients (Clinical Dementia Rating (CDR) Scale: 0.5-1; Functional Assessment Staging (FAST): 3-4) compared to 17 controls by applying a combination of global and regional MPS measures to the resting EEG. In early AD, whole-head mapping reveals a specific landscape of synchronization characterized by a decrease in MPS over the fronto-temporal region and an increase over the temporo-parieto-occipital region predominantly of the left hemisphere. These features manifest themselves through the EEG delta beta bands and discriminate patients from controls with an accuracy of up to 94%. Moreover, the abnormal MPS in both anterior and posterior clusters correlates with the Mini Mental State Examination score, binding regional EEG synchronization to cognitive decline in AD patients. The MPS technique reveals that the EEG phenotype of early AD is relevant to the clinical picture and may ultimately become its sensitive and specific biomarker. (C) 2008 Elsevier Inc. All rights reserved.

Functional networks in the human brain have been investigated using electrophysiological methods (EEG/MEG, LFP, and MUA) and steady-state paradigms that apply periodic luminance or contrast modulation to drive cortical networks. We have used this approach with fMRI to characterize a cortical network driven by a checkerboard reversing at a fixed frequency. We found that the fMRI signals in voxels located in occipital cortex were increased by checkerboard reversal at frequencies ranging from 3 to 14 Hz. In contrast, the response of a cluster of voxels centered on basal medial frontal cortex depended strongly on the reversal frequency, consistently exhibiting a peak in the response for specific reversal frequencies between 3 and 5 Hz in each subject. The fMRI signals at the frontal voxels were positively correlated indicating a homogeneous cluster. Some of the occipital voxels were positively correlated to the frontal voxels apparently forming a large-scale functional network. Other occipital voxels were negatively correlated to the frontal voxels, suggesting a functionally distinct network. The results provide preliminary fMRI evidence that during visual stimulation, input frequency can be varied to engage different functional networks.

To characterize the effects of Alzheimer's disease (AD) on cortical functional connectivity in perception, we analyzed interhemispheric lagged synchronization (ILS) in the source space of high-density EEG recorded in aged controls and patients with amnestic mild cognitive impairment (aMCI) or AD while they viewed collinear and noncollinear bilateral moving gratings. Beta-band ILS was lower in aMCI and AD compared with controls in a large region centered on BA39. As previously reported, in young adults, collinear iso-oriented gratings versus noncollinear gratings synchronizes EEG reflecting perceptual grouping. Only aged controls showed the expected beta-band ILS increase originating in the dorsal visual stream (BA18). The aMCI group only showed a theta-band increase in an adjacent region (BA19). In AD patients, there was no ILS increase. Regression analysis revealed that the posterior callosal area and EEG slowing predict reduction of beta but not emergence of theta ILS response. Considering that we found no between-group differences in resting ILS, perception-related EEG appears to be more sensitive to AD effects, including ILS signs of neurodegeneration and compensation.

The early visual system processes different spatial frequencies (SFs) separately. To examine where in the brain the scale-specific information is integrated, we mapped the neural assemblies engaged in interhemispheric coupling with electroencephalographic (EEG) coherence and blood-oxygen-level dependent (BOLD) signal. During similar EEG and functional magnetic resonance imaging (fMRI) experiments, our subjects viewed centrally presented bilateral gratings of different SF (0.25–8.0 cpd), which either obeyed Gestalt grouping rules (iso-oriented, IG) or violated them (orthogonally oriented, OG). The IG stimuli (0.5–4.0 cpd) synchronized EEG at discrete beta frequencies (beta1, beta2) and increased BOLD (0.5 and 2.0 cpd tested) in ventral (around collateral sulcus) and dorsal (parieto-occipital fissure) regions compared with OG. At both SF, the beta1 coherence correlated with the ventral activations, whereas the beta2 coherence correlated with the dorsal ones. Thus distributed neural substrates mediated interhemispheric integration at single SF. The relative impact of the ventral versus dorsal networks was modulated by the SF of the stimulus.

In one of two patients (MS and FJ) with bilateral, early-onset lesion of the primary visual cortex, Kiper et al. (2002) observed a considerable degree of functional recovery. To clarify the physiological mechanisms involved in the recovery, we used fMRI and quantitative EEG to study both patients. The fMRI investigations indicated that in both patients, isolated islands of the primary visual cortex are functioning, in the right hemisphere in MS and in the left in FJ. The functional recovery observed in MS roughly correlated with the functional maturation of interhemispheric connections and might reflect the role of corticocortical connectivity in visual perception. The functionality of interhemispheric connections was assessed by analyzing the changes in occipital inter-hemispheric coherence of EEG signals (ICoh) evoked by moving gratings. In the patient MS, this ICoh response was present at 7:11 y and was more mature at 9:2 y. In the more visually mpaired patient, FJ, a consistent increase in ICoh to visual stimuli could not be obtained, possibly because of the later occurrence of the lesion.

Background Psychogenic non-epileptic seizures (PNES) are involuntary paroxysmal events that are unaccompanied by epileptiform EEG discharges. We hypothesised that PNES are a disorder of distributed brain networks resulting from their functional disconnection.The disconnection may underlie a dissociation mechanism that weakens the influence of unconsciously presented traumatising information but exerts maladaptive effects leading to episodic failures of behavioural control manifested by psychogenic ‘seizures’. Methods To test this hypothesis, we compared functional connectivity (FC) derived from resting state high-density EEGs of 18 patients with PNES and 18 age-matched and gender-matched controls. To this end, the EEGs were transformed into source space using the local autoregressive average inverse solution. FC was estimated with a multivariate measure of lagged synchronisation in the θ, α and β frequency bands for 66 brain sites clustered into 18 regions. A multiple comparison permutation test was applied to deduce significant between-group differences in inter-regional and intraregional FC. Results The significant effect of PNES—a decrease in lagged FC between the basal ganglia and limbic, prefrontal, temporal, parietal and occipital regions—was found in the α band. Conclusion We believe that this finding reveals a possible neurobiological substrate of PNES, which explains both attenuation of the effect of potentially disturbing mental representations and the occurrence of PNES episodes. By improving understanding of the aetiology of this condition, our results suggest a potential refinement of diagnostic criteria and management principles.

We report on the case of a 20-year-old man with bilateral parasagittal parieto-occipital polymicrogyria and epilepsy. Functional magnetic resonance imaging responses to reversing checkerboard and interhemispheric electroencephalogram coherence changes to moving gratings were investigated. Results of both studies indicate that the polymicrogyric cortex was activated by visual stimuli, suggesting preserved function in the dysplastic area.

The preclinical Alzheimer's disease (AD) - amnestic mild cognitive impairment (MCI) - is manifested by phenotypes classified into exclusively memory (single-domain) MCI (sMCI) and multiple-domain MCI (mMCI). We suggest that typical MCI-to-AD progression occurs through the sMCI-to-mMCI sequence as a result of the extension of initial pathological processes. To support this hypothesis, we assess myelin content with a Magnetization Transfer Ratio (MTR) in 21 sMCI and 21 mMCI patients and in 42 age-, sex-, and education-matched controls. A conjunction analysis revealed MTR reduction shared by sMCI and mMCI groups in the medial temporal lobe and posterior structures including white matter (WM: splenium, posterior corona radiata) and gray matter (GM: hippocampus; parahippocampal and lingual gyri). A disjunction analysis showed the spread of demyelination to prefrontal WM and insula GM in executive mMCI. Our findings suggest that demyelination starts in the structures affected by neurofibrillary pathology; its presence correlates with the clinical picture and indicates the method of MCI-to-AD progression. In vivo staging of preclinical AD can be developed in terms of WM/GM demyelination.

Recently graph theory and complex networks have been widely used as a mean to model functionality of the brain. Among different neuroimaging techniques available for constructing the brain functional networks, electroencephalography (EEG) with its high temporal resolution is a useful instrument of the analysis of functional interdependencies between different brain regions. Alzheimer's disease (AD) is a neurodegenerative disease, which leads to substantial cognitive decline, and eventually, dementia in aged people. To achieve a deeper insight into the behavior of functional cerebral networks in AD, here we study their synchronizability in 17 newly diagnosed AD patients compared to 17 healthy control subjects at no-task, eyes-closed condition. The cross-correlation of artifact-free EEGs was used to construct brain functional networks. The extracted networks were then tested for their synchronization properties by calculating the eigenratio of the Laplacian matrix of the connection graph, i.e., the largest eigenvalue divided by the second smallest one. In AD patients, we found an increase in the eigenratio, i.e., a decrease in the synchronizability of brain networks across delta, alpha, beta, and gamma EEG frequencies within the wide range of network costs. The finding indicates the destruction of functional brain networks in early AD.

Abnormalities in the topology of brain networks may be an important feature and etiological factor for psychogenic non-epileptic seizures (PNES). To explore this possibility, we applied a graph theoretical approach to functional networks based on resting state EEGs from 13 PNES patients and 13 age- and gender-matched controls. The networks were extracted from Laplacian-transformed time-series by a cross-correlation method. PNES patients showed close to normal local and global connectivity and small-world structure, estimated with clustering coefficient, modularity, global efficiency, and small-worldness metrics, respectively. Yet the number of PNES attacks per month correlated with a weakness of local connectedness and a skewed balance between local and global connectedness quantified with small-worldness, all in EEG alpha band. In beta band, patients demonstrated above-normal resiliency, measured with assortativity coefficient, which also correlated with the frequency of PNES attacks. This interictal EEG phenotype may help improve differentiation between PNES and epilepsy. The results also suggest that local connectivity could be a target for therapeutic interventions in PNES. Selective modulation (strengthening) of local connectivity might improve the skewed balance between local and global connectivity and so prevent PNES events.

UNLABELLED Glutathione (GSH) dysregulation at the gene, protein, and functional levels has been observed in schizophrenia patients. Together with disease-like anomalies in GSH deficit experimental models, it suggests that such redox dysregulation can play a critical role in altering neural connectivity and synchronization, and thus possibly causing schizophrenia symptoms. To determine whether increased GSH levels would modulate EEG synchronization, N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients in a randomized, double-blind, crossover protocol for 60 days, followed by placebo for another 60 days (or vice versa). We analyzed whole-head topography of the multivariate phase synchronization (MPS) for 128-channel resting-state EEGs that were recorded at the onset, at the point of crossover, and at the end of the protocol. In this proof of concept study, the treatment with NAC significantly increased MPS compared to placebo over the left parieto-temporal, the right temporal, and the bilateral prefrontal regions. These changes were robust both at the group and at the individual level. Although MPS increase was observed in the absence of clinical improvement at a group level, it correlated with individual change estimated by Liddle's disorganization scale. Therefore, significant changes in EEG synchronization induced by NAC administration may precede clinically detectable improvement, highlighting its possible utility as a biomarker of treatment efficacy. TRIAL REGISTRATION ClinicalTrials.gov NCT01506765.

Objective Psychogenic non-epileptic seizures (PNES) are paroxysmal events that, in contrast to epileptic seizures, are related to psychological causes without the presence of epileptiform EEG changes. Recent models suggest a multifactorial basis for PNES. A potentially paramount, but currently poorly understood factor is the interplay between psychiatric features and a specific vulnerability of the brain leading to a clinical picture that resembles epilepsy. Hypothesising that functional cerebral network abnormalities may predispose to the clinical phenotype, the authors undertook a characterisation of the functional connectivity in PNES patients. Methods The authors analysed the whole-head surface topography of multivariate phase synchronisation (MPS) in interictal high-density EEG of 13 PNES patients as compared with 13 age- and sex-matched controls. MPS mapping reduces the wealth of dynamic data obtained from high-density EEG to easily readable synchronisation maps, which provide an unbiased overview of any changes in functional connectivity associated with distributed cortical abnormalities. The authors computed MPS maps for both Laplacian and common-average-reference EEGs. Results In a between-group comparison, only patchy, non-uniform changes in MPS survived conservative statistical testing. However, against the background of these unimpressive group results, the authors found widespread inverse correlations between individual PNES frequency and MPS within the prefrontal and parietal cortices. Interpretation PNES appears to be associated with decreased prefrontal and parietal synchronisation, possibly reflecting dysfunction of networks within these regions.

Schizophrenia is often considered as a dysconnection syndrome in which, abnormal interactions between large-scale functional brain networks result in cognitive and perceptual deficits. In this article we apply the graph theoretic measures to brain functional networks based on the resting EEGs of fourteen schizophrenic patients in comparison with those of fourteen matched control subjects. The networks were extracted from common-average-referenced EEG time-series through partial and unpartial cross-correlation methods. Unpartial correlation detects functional connectivity based on direct and/or indirect links, while partial correlation allows one to ignore indirect links. We quantified the network properties with the graph metrics, including mall-worldness, vulnerability, modularity, assortativity, and synchronizability. The schizophrenic patients showed method-specific and frequency-specific changes especially pronounced for modularity, assortativity, and synchronizability measures. However, the differences between schizophrenia patients and normal controls in terms of graph theory metrics were stronger for the unpartial correlation method.

The interhemispheric asymmetries that originate from connectivity-related structuring of the cortex are compromised in schizophrenia (SZ). Under the assumption that such abnormalities affect functional connectivity, we analyzed its correlate-EEG synchronization-in SZ patients and matched controls. We applied multivariate synchronization measures based on Laplacian EEG and tuned to various spatial scales. Compared to the controls who had rightward asymmetry at a local level (EEG power), rightward anterior and leftward posterior asymmetries at an intraregional level (1st and 2nd order S-estimator), and rightward global asymmetry (hemispheric S-estimator), SZ patients showed generally attenuated asymmetry, the effect being strongest for intraregional synchronization in the alpha and beta bands. The abnormalities of asymmetry increased with the duration of the disease and correlated with the negative symptoms. We discuss the tentative links between these findings and gross anatomical asymmetries, including the cerebral torque and gyrification pattern, in normal subjects and SZ patients.

In schizophrenia patients, glutathione dysregulation at the gene, protein and functional levels, leads to N-methyl-D-aspartate (NMDA) receptor hypofunction. These patients also exhibit deficits in auditory sensory processing that manifests as impaired mismatch negativity (MMN), which is an auditory evoked potential (AEP) component related to NMDA receptor function. N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients to determine whether increased levels of brain glutathione would improve MMN and by extension NMDA function. A randomized, double-blind, cross-over protocol was conducted, entailing the administration of NAC (2 g/day) for 60 days and then placebo for another 60 days (or vice versa). 128-channel AEPs were recorded during a frequency oddball discrimination task at protocol onset, at the point of cross-over, and at the end of the study. At the onset of the protocol, the MMN of patients was significantly impaired compared to sex- and age- matched healthy controls (p=0.003), without any evidence of concomitant P300 component deficits. Treatment with NAC significantly improved MMN generation compared with placebo (p=0.025) without any measurable effects on the P300 component. MMN improvement was observed in the absence of robust changes in assessments of clinical severity, though the latter was observed in a larger and more prolonged clinical study. This pattern suggests that MMN enhancement may precede changes to indices of clinical severity, highlighting the possible utility AEPs as a biomarker of treatment efficacy. The improvement of this functional marker may indicate an important pathway towards new therapeutic strategies that target glutathione dysregulation in schizophrenia.

Perception, motion, and cognition involve the formation of cooperative neuronal assemblies distributed over the cerebral cortex. It remains to explore what characterizes the assemblies, their location, and the structural substrate of assembly formation. In this EEG/fMRI study, we describe the response of the visual areas of the two hemispheres in subjects who viewed bilateral iso-oriented (IG) or orthogonally-oriented (OG) moving gratings projected in the two hemifields. The IG stimulus synchronized activity across the hemispheres, as shown by an increased EEG coherence. The increase was restricted to the occipital electrodes and to the beta band. Compared with OG, IG increased the BOLD signal in a restricted territory corresponding to area VP/V4. Within this territory, a linear relation was found between the increased interhemispheric EEG coherence and BOLD. Thus, the increased BOLD localized a trans-hemispheric, synchronous neuronal assembly probably achieved by a callosal cortico-cortical connection. This assembly might reflect an early stage of perceptual grouping since the IG stimulus conforms to Gestalt psychology principles of collinearity and common fate.

Cortical computation involves the formation of cooperative neuronal assemblies characterized by synchronous oscillatory activity. A traditional method for the identification of synchronous neuronal assemblies has been the coherence analysis of EEG signals. Here, we suggest a new method called S estimator, whereby cortical synchrony is defined from the embedding dimension in a state-space. We first validated the method on clusters of chaotic coupled oscillators and compared its performance to that of other methods for assessing synchronization. Then nine adult subjects were studied with high-density EEG recordings, while they viewed in the two hemifields (hence with separate hemispheres) identical sinusoidal gratings either arranged collinearly and moving together, or orthogonally oriented and moving at 90 degrees . The estimated synchronization increased with the collinear gratings over a cluster of occipital electrodes spanning both hemispheres, whereas over temporo-parietal regions of both hemispheres, it decreased with the same stimulus and it increased with the orthogonal gratings. Separate calculations for different EEG frequencies showed that the occipital clusters involved synchronization in the beta band and the temporal clusters in the alpha band. The gamma band appeared to be insensitive to stimulus diversity. Different stimulus configurations, therefore, appear to cause a complex rearrangement of synchronous neuronal assemblies distributed over the cortex, in particular over the visual cortex.

Visual corpus callosum (CC) preferentially interconnects neurons selective for similar stimulus orientation near the representations of the vertical meridian. These properties allow studying the CC functionality with EEG coherence analysis. Iso-oriented and orthogonally-oriented gratings were presented to the two hemifields, either close to the vertical meridian or far from it. In animals with intact CC, and in man, interhemispheric coherence (ICoh) increased only with iso-oriented gratings presented near or crossing the vertical meridian. The increase was localized to occipital electrodes and was specific for the beta-gamma frequency band. Visual-stimulus induced changes in ICoh were studied in patients with early pathologies of the visual areas. From a girl with abnormal vision and severe bilateral lesion of the primary visual areas at 3 weeks, after premature birth at 30 weeks, we obtained no ICoh response until 9 years. In control children visual stimulation increased occipital ICoh at 6-7 years. From a young man having suffered similar lesions when he was 9 months older than the girl, no consistent increase in ICoh could be obtained. In a 14-year-old girl with congenital visual agnosia, no visible lesions, but with a temporal-occipital epileptic focus, ICoh responses were evoked both by iso-oriented, and by orthogonally-oriented gratings. In a young man with bilateral parieto-occipital microgyria extending into the calcarine sulcus, visual stimuli increased ICoh as in normal individuals, but the response was weaker. These cases are discussed in terms of development of CC connections and point to a variety of plastic changes in the cortical connectivity of children.

Reference EPFL-CONF-160719doi:10.1016/j.ijpsycho.2008.05.550View record in Web of Science Record created on 2010-11-30, modified on 2017-05-12

The EEG inter- and intrahemispheric coherences (ICoh and HCoh) in the theta, alpha and beta bands were studied in an acallosal group (ACCG) of five children and a normal group of 30 sex- and age-matched children (NG) during resting and tapping conditions. Being functionally deficient, tapping in the ACCG was characterized by increased intertap intervals and variability (in right-hand tapping) and by variability together with decreased synchronization (in bimanual tapping). In the ACCG, frontal, central and parietal ICohs were shown to be smaller, while temporal ICohs were larger under all conditions (see also Koeda, T., Knyazeva, M., Jonkman, J., Njiokiktjien, C., De Sonneville, L., Vildavsky, V., 1995. The resting EEG in acallosal children: compensatory left hemisphere mechanisms? Electroencephalogr. Clin. Neurophysiol. 95, 397-407). The effect was most pronounced in the EEG beta band. The sagittal HCohs, including fronto-central, fronto-parietal, and centro-parietal HCohs within both hemispheres, were larger in the ACCG, whereas temporal HCoh (fronto-temporal, centro-temporal, parieto-temporal and occipito-temporal) were smaller, suggesting rearrangement of intracortical activity associated with callosal agenesis. Tapping induced an increase in ICoh and HCoh between frontal, central and parietal areas in the NG, and weak enhancement only in the left temporal HCoh in the ACCG. The beta band, the most reactive band in the NG, was 'silent' in the ACCG, suggesting deviant cortical function during motor activity as well.

Resting EEG interhemispheric and interhemispheric coherences (ICoh and HCoh) in the theta, alpha and beta bands were studied in 7 patients with agenesis of the corpus callosum (5 children, aged 10–14 years, and 2 adults) and 2 groups of sex- and age-matched normal children and adults (42 subjects). In patients the ICohs (F3/F4, C3/C4, P3/P4, O1/O2) were lower than in the normal sample. The ICoh decrease, corresponding with the completeness of commissural agenesis, showed the essential role of the corpus callosum in interhemispheric EEG synchronization. A remarkable new fact was found, namely lower right hemisphere HCoh in the acallosal patients in comparison to the normals, suggesting reduced connectivity of the right hemisphere. It is assumed that the deviant HCoh patterns in the patients, most pronounced in the beta band, are indicative of compensatory left hemisphere mechanisms, accounting for a specific brain plasticity phenomenon in acallosal subjects.

Assuming selective vulnerability of short association U-fibers in early Alzheimer's disease (AD), we quantified demyelination of the surface white matter (dSWM) with magnetization transfer ratio (MTR) in 15 patients (Clinical Dementia Rating Scale [CDR] 0.5-1; Functional Assessment Staging [FAST]: 3-4) compared with 15 controls. MTRs were computed for 39 areas in each hemisphere. We found a bilateral MTR decrease in the temporal, cingulate, parietal, and prefrontal areas. With linear discriminant analysis, we successfully classified all the participants with 3 variates including the cuneus, parahippocampal, and superior temporal regions of the left hemisphere. The pattern of dSWM changed with the age of AD onset. In early onset patients, we found bilateral posterior demyelination spreading to the temporal areas in the left hemisphere. The late onset patients showed a distributed bilateral pattern with the temporal and cingulate areas strongly affected. A correlation with Mini Mental State Examination (MMSE), Lexis, and memory tests revealed the dSWM impact on cognition. A specific landscape of dSWM in early AD shows the potential of MTR imaging as an in vivo biomarker superior to currently used techniques.