Neuronal Synchronization Research Articles

Distinct spatiotemporal patterns of neuronal functional connectivity in primary progressive aphasia variants.

Primary progressive aphasia is a syndrome characterized by progressive loss of language abilities with three main phenotypic clinical presentations, including logopenic, non-fluent/agrammatic, and semantic variants. Previous imaging studies have shown unique anatomic impacts within language networks in each variant. However, direct measures of spontaneous neuronal activity and functional integrity of these impacted neural networks in primary progressive aphasia are lacking. The aim of this study was to characterize the spatial and temporal patterns of resting state neuronal synchronizations in primary progressive aphasia syndromes. We hypothesized that resting state brain oscillations will show unique deficits within language network in each variant of primary progressive aphasia. We examined 39 patients with primary progressive aphasia including logopenic variant (n = 14, age = 61 ± 9 years), non-fluent/agrammatic variant (n = 12, age = 71 ± 8 years) and semantic variant (n = 13, age = 65 ± 7 years) using magnetoencephalographic imaging, compared to a control group that was matched in age and gender to each primary progressive aphasia subgroup (n = 20, age = 65 ± 5 years). Each patient underwent a complete clinical evaluation including a comprehensive battery of language tests. We examined the whole-brain resting state functional connectivity as measured by imaginary coherence in each patient group compared to the control cohort, in three frequency oscillation bands-delta-theta (2-8 Hz); alpha (8-12 Hz); beta (12-30 Hz). Each variant showed a distinct spatiotemporal pattern of altered functional connectivity compared to age-matched controls. Specifically, we found significant hyposynchrony of alpha and beta frequency within the left posterior temporal and occipital cortices in patients with the logopenic variant, within the left inferior frontal cortex in patients with the non-fluent/agrammatic variant, and within the left temporo-parietal junction in patients with the semantic variant. Patients with logopenic variant primary progressive aphasia also showed significant hypersynchrony of delta-theta frequency within bilateral medial frontal and posterior parietal cortices. Furthermore, region of interest-based analyses comparing the spatiotemporal patterns of variant-specific regions of interest identified in comparison to age-matched controls showed significant differences between primary progressive aphasia variants themselves. We also found distinct patterns of regional spectral power changes in each primary progressive aphasia variant, compared to age-matched controls. Our results demonstrate neurophysiological signatures of network-specific neuronal dysfunction in primary progressive aphasia variants. The unique spatiotemporal patterns of neuronal synchrony signify diverse neurophysiological disruptions and pathological underpinnings of the language network in each variant.

La naturaleza de la consciencia

La consciencia es un estado unificado de la mente, cualitativo y subjetivo. Una de cuyas formas más especiales es la autoconsciencia, que nos permite darnos cuenta de que nos damos cuenta y reflexionar sobre nuestros propios pensamientos (sección 1). Esta consciencia dota al ser humano de la capacidad para interpretar el mundo y responder a él. Así, gracias a los qualia, tenemos la capacidad de comportarnos circunstancialmente (sección 2). Es importante conocer los correlatos y las causas cerebrales que dan origen a la consciencia. Es en la corteza cerebral donde radica la capacidad de ser consciente. Problema de la unidad de percepción: sincronización de neuronas o integración funcional (sección 3). Sin embargo, el problema de la consciencia no consiste sólo en conocer su naturaleza (material), sino también en conocer cómo se produce la emergencia de la imaginación subjetiva, respuesta que actualmente no existe y que tampoco aportaría ninguna ventaja práctica a la especie (sección 4).

326 Characterization of Synchronization Between Globus Pallidus Neurons and Motor Cortex in Parkinson's Disease

Abstract INTRODUCTION Excessive oscillatory neuronal synchronization throughout the basal ganglia thalamocortical motor loop is a hallmark of the Parkinsonian state. This may manifest as spike-spike correlations, coherence between field potentials, or spike-field interactions within or between structures in the circuit. Globus pallidus occupies a central role in basal ganglia processing, but neither internal (GPi) nor external (GPe) globus pallidus is monosynaptically connected to motor cortex. Understanding patterns of M1-pallidal synchronization will provide insight into the possible different roles of GPi and GPe stimulation, compared to STN stimulation, in ameliorating the excessive neuronal synchronization in PD. METHODS Using subdural electrodes and high resolution electrocorticography (ECoG) contacts temporarily placed over motor cortex during DBS implantation and microelectrode recordings, we evaluate the strength and topography of synchronization between pallidal neurons and cortical ECoG potentials in 16 PD patients. RESULTS >Recording from 59 GPe and 42 GPi cells with cortical ECoG field potentials demonstrated that 17% of GPe and 12% of GPi neurons showed significant interactions associated with cortical recording sites approximately 25 mm from midline. For those pairs with significant interactions, peak of the spike-triggered average potentials occurred within 100ms prior to spike time. GPe neurons showed maximum coherence with M1 in the beta (13-30 Hz) frequency range while GPi neurons had maximum coherence in the alpha (8-12 Hz) range. CONCLUSION Topography of significant M1-pallidal interactions is consistent with tractography findings showing more mesial areas of M1 to dominate cortical-basal ganglia anatomic connectivity. The observation that GPe stimulation is more “prokinetic” than GPi stimulation may be explained by the finding that GPe is more synchronized to the cortex in beta frequencies than GPi, as disruption of beta oscillation is important in ameliorating akinesia.

Early Correlated Network Activity in the Hippocampus: Its Putative Role in Shaping Neuronal Circuits

Synchronized neuronal activity occurring at different developmental stages in various brain structures represents a hallmark of developmental circuits. This activity, which differs in its specific patterns among animal species may play a crucial role in de novo formation and in shaping neuronal networks. In the rodent hippocampus in vitro, the so-called giant depolarizing potentials (GDPs) constitute a primordial form of neuronal synchrony preceding more organized forms of activity such as oscillations in the theta and gamma frequency range. GDPs are generated at the network level by the interaction of the neurotransmitters glutamate and GABA which, immediately after birth, exert both a depolarizing and excitatory action on their targets. GDPs are triggered by GABAergic interneurons, which in virtue of their extensive axonal branching operate as functional hubs to synchronize large ensembles of cells. Intrinsic bursting activity, driven by a persistent sodium conductance and facilitated by the low expression of Kv7.2 and Kv7.3 channel subunits, responsible for IM, exerts a permissive role in GDP generation. Here, we discuss how GDPs are generated in a probabilistic way when neuronal excitability within a local circuit reaches a certain threshold and how GDP-associated calcium transients act as coincident detectors for enhancing synaptic strength at emerging GABAergic and glutamatergic synapses. We discuss the possible in vivo correlate of this activity. Finally, we debate recent data showing how, in several animal models of neuropsychiatric disorders including autism, a GDPs dysfunction is associated to morphological alterations of neuronal circuits and behavioral deficits reminiscent of those observed in patients.

P366 Multimodal EEG/ECOG and fast optical signal measurements in interictal epileptic spikes

Objectives Although many studies in epilepsy have examined the synaptic mechanisms constituting the basis for most of the current principles of brain activity, relatively less studies have tried to characterize changes in the cellular environment that might predispose a network to pathologic synchronization. Methods In this study, near-infrared optical imaging was used with ECoG and EEG to investigate variations in the optical properties of cortical tissue directly associated with neuronal activity in 15 rats and 3 human epileptic patients. Time-frequency analysis was also used to track variations of (de) synchronization concomitantly with changes in optical signals during IES. Results Changes in Fast optical signals (FOS) occurred 320 ms before to 370 ms after the IES peak. These changes started before any changes in ECoG signal. In addition, time-frequency domain ECoG revealed an alternating decrease-increase-decrease in the ECoG spectral power (pointing to desynchronization-synchronization-desynchronization), which occurred concomitantly with an increase-decrease-increase in relative optical signal (pointing to shrinking-swelling-shrinking of the neuronal assembly) during the IES. Discussion These relationships between electrical and optical changes highlights the complexity of the interplay between the neuronal network activity and its environment around an IES. Conclusions These changes in the neuronal environment around IESs raise new questions about the mechanisms that provides the suitable conditions for the neuronal synchronization during IESs. Significance The multimodal-multiscale FOS-ECoG approach opens new avenues to better analyze the mechanisms of neuronal synchronization in the pathologic epileptic brain, which is applicable in clinic.

Epileptic interictal discharges are more frequent during NREM slow wave downstates.

Epileptiform activity in various but not all epilepsy and recording types and cerebral areas is more frequent in NREM sleep, and especially during sleep periods with high-amplitude EEG slow waves. Slow waves synchronize high-frequency oscillations: physiological activity from the theta through the gamma band usually appears during scalp-positive upstates while epileptiform activity occurs at transitory phases and the scalp-negative downstate. It has been proposed that interictal discharges (IIDs) are facilitated by the high degree of neuronal firing synchrony during slow wave transitory and downstates. This would suggest that their occurrence increases as a function of slow wave synchronization, indicated by greater amplitude, steeper slopes and higher EEG signal synchronization. We investigated the occurrence of IIDs during NREM sleep slow waves in epileptic patients undergoing presurgical electrophysiological monitoring. Intracranially registered IIDs preferentially occurred during the scalp-negative downstates of frontal scalp slow waves in all subjects. IID occurrence was more frequent during larger slow waves in the pooled sample and a subset of subjects. However, slow wave slope steepness and EEG signal synchronization between two frontal scalp channels was not significantly associated with IID occurrence. Our results indicate that IIDs indeed do not occur at the same slow wave phase as physiological rhythms, but contrary to previous hypotheses their occurrence is not strongly affected by EEG synchronization.

Computational Stimulation of the Basal Ganglia Neurons with Cost Effective Delayed Gaussian Waveforms.

Deep brain stimulation (DBS) has compelling results in the desynchronization of the basal ganglia neuronal activities and thus, is used in treating the motor symptoms of Parkinson's disease (PD). Accurate definition of DBS waveform parameters could avert tissue or electrode damage, increase the neuronal activity and reduce energy cost which will prolong the battery life, hence avoiding device replacement surgeries. This study considers the use of a charge balanced Gaussian waveform pattern as a method to disrupt the firing patterns of neuronal cell activity. A computational model was created to simulate ganglia cells and their interactions with thalamic neurons. From the model, we investigated the effects of modified DBS pulse shapes and proposed a delay period between the cathodic and anodic parts of the charge balanced Gaussian waveform to desynchronize the firing patterns of the GPe and GPi cells. The results of the proposed Gaussian waveform with delay outperformed that of rectangular DBS waveforms used in in-vivo experiments. The Gaussian Delay Gaussian (GDG) waveforms achieved lower number of misses in eliciting action potential while having a lower amplitude and shorter length of delay compared to numerous different pulse shapes. The amount of energy consumed in the basal ganglia network due to GDG waveforms was dropped by 22% in comparison with charge balanced Gaussian waveforms without any delay between the cathodic and anodic parts and was also 60% lower than a rectangular charged balanced pulse with a delay between the cathodic and anodic parts of the waveform. Furthermore, by defining a Synchronization Level metric, we observed that the GDG waveform was able to reduce the synchronization of GPi neurons more effectively than any other waveform. The promising results of GDG waveforms in terms of eliciting action potential, desynchronization of the basal ganglia neurons and reduction of energy consumption can potentially enhance the performance of DBS devices.

The atypical dopamine receptor agonist SKF 83959 enhances hippocampal and prefrontal cortical neuronal network activity in a rat model of cognitive dysfunction.

Deficits in neuronal network synchrony in hippocampus and prefrontal cortex have been widely demonstrated in disorders of cognitive dysfunction, including schizophrenia and Alzheimer's disease. The atypical dopamine agonist SKF 83959 has been shown to increase brain-derived neurotrophic factor signalling and suppress activity of glycogen synthase kinase-3 in PFC, two processes important to learning and memory. The purpose of this study was to therefore evaluate the impact of SKF 83959 on oscillatory deficits in methylazoxymethanol acetate (MAM) rat model of schizophrenia. To achieve this, local field potentials were recorded simultaneously from the hippocampus and prefrontal cortex of anesthetized rats at 15 and 90min following both acute and repeated administration of SKF 83959 (0.4mg/kg). In MAM rats, but not controls, repeated SKF 83959 treatment increased signal amplitude in hippocampus and enhanced the spectral power of low frequency delta and theta oscillations in this region. In PFC, SKF 83959 increased delta, theta and gamma spectral power. Increased HIP-PFC theta coherence was also evident following acute and repeated SKF 83959. In apparent contradiction to these oscillatory effects, in MAM rats, SKF 83959 inhibited spatial learning and induced a significant increase in thigmotactic behaviour. These findings have uncovered a previously unknown role for SKF 83959 in the positive regulation of hippocampal-prefrontal cortical oscillatory network activity. As SKF 83959 is known to have affinity for a number of receptors, delineating the receptor mechanisms that mediate the positive drug effects on neuronal oscillations could have significant future implications in disorders associated with cognitive dysfunction.

Extensive astrocyte synchronization advances neuronal coupling in slow wave activity in vivo

Slow wave activity (SWA) is a characteristic brain oscillation in sleep and quiet wakefulness. Although the cell types contributing to SWA genesis are not yet identified, the principal role of neurons in the emergence of this essential cognitive mechanism has not been questioned. To address the possibility of astrocytic involvement in SWA, we used a transgenic rat line expressing a calcium sensitive fluorescent protein in both astrocytes and interneurons and simultaneously imaged astrocytic and neuronal activity in vivo. Here we demonstrate, for the first time, that the astrocyte network display synchronized recurrent activity in vivo coupled to UP states measured by field recording and neuronal calcium imaging. Furthermore, we present evidence that extensive synchronization of the astrocytic network precedes the spatial build-up of neuronal synchronization. The earlier extensive recruitment of astrocytes in the synchronized activity is reinforced by the observation that neurons surrounded by active astrocytes are more likely to join SWA, suggesting causality. Further supporting this notion, we demonstrate that blockade of astrocytic gap junctional communication or inhibition of astrocytic Ca2+ transients reduces the ratio of both astrocytes and neurons involved in SWA. These in vivo findings conclusively suggest a causal role of the astrocytic syncytium in SWA generation.

Autaptic effects on synchrony of neurons coupled by electrical synapses

In this paper, we numerically study the effects of a special synapse known as autapse on synchronization of population of Morris-Lecar (ML) neurons coupled by electrical synapses. Several configurations of the ML neuronal populations such as a pair or a ring or a globally coupled network with and without autapses are examined. While most of the papers on the autaptic effects on synchronization have used networks of neurons of same spiking rate, we use the network of neurons of different spiking rates. We find that the optimal autaptic coupling strength and the autaptic time delay enhance synchronization in our neural networks. We use the phase response curve analysis to explain the enhanced synchronization by autapses. Our findings reveal the important relationship between the intraneuronal feedback loop and the interneuronal coupling.

Enhancement of synchronized activity between hippocampal CA1 neurons during initial storage of associative fear memory.

Learning and memory storage requires neuronal plasticity induced in the hippocampus and other related brain areas, and this process is thought to rely on synchronized activity in neural networks. We used paired whole-cell recording in vivo to examine the synchronized activity that was induced in hippocampal CA1 neurons by associative fear learning. We found that both membrane potential synchronization and spike synchronization of CA1 neurons could be transiently enhanced after task learning, as observed on day 1 but not day 5. On day 1 after learning, CA1 neurons showed a decrease in firing threshold and rise times of suprathreshold membrane potential changes as well as an increase in spontaneous firing rates, possibly contributing to the enhancement of spike synchronization. The transient enhancement of CA1 neuronal synchronization may play important roles in the induction of neuronal plasticity for initial storage and consolidation of associative memory. The hippocampus is critical for memory acquisition and consolidation. This function requires activity- and experience-induced neuronal plasticity. It is known that neuronal plasticity is largely dependent on synchronized activity. As has been well characterized, repetitive correlated activity of presynaptic and postsynaptic neurons can lead to long-term modifications at their synapses. Studies on network activity have also suggested that memory processing in the hippocampus may involve learning-induced changes of neuronal synchronization, as observed in vivo between hippocampal CA3 and CA1 networks as well as between the rhinal cortex and the hippocampus. However, further investigation of learning-induced synchronized activity in the hippocampus is needed for a full understanding of hippocampal memory processing. In this study, by performing paired whole-cell recording in vivo on CA1 pyramidal cells (PCs) in anaesthetized adult rats, we examined CA1 neuronal synchronization before and after associative fear learning. We first found in naive animals that there was a low level of membrane potential (MP) synchronization and spike synchronization of CA1 PCs. In conditioned animals, we found a significant enhancement of both MP synchronization and spike synchronization, as observed on day 1 after learning, and this enhancement was transient and not observed on day 5. Accompanying learning-induced synchronized activity was a decreased firing threshold and rise time of suprathreshold MP changes as well as an increased spontaneous firing rate, possibly contributing to the enhanced spike synchronization. The transiently enhanced CA1 neuronal synchronization may have important roles in generating neuronal plasticity for hippocampal storage and consolidation of associative memory traces.

Neurovascular EGFL7 regulates adult neurogenesis in the subventricular zone and thereby affects olfactory perception

Adult neural stem cells reside in a specialized niche in the subventricular zone (SVZ). Throughout life they give rise to adult-born neurons in the olfactory bulb (OB), thus contributing to neural plasticity and pattern discrimination. Here, we show that the neurovascular protein EGFL7 is secreted by endothelial cells and neural stem cells (NSCs) of the SVZ to shape the vascular stem-cell niche. Loss of EGFL7 causes an accumulation of activated NSCs, which display enhanced activity and re-entry into the cell cycle. EGFL7 pushes activated NSCs towards quiescence and neuronal progeny towards differentiation. This is achieved by promoting Dll4-induced Notch signalling at the blood vessel-stem cell interface. Fewer inhibitory neurons form in the OB of EGFL7-knockout mice, which increases the absolute signal conducted from the mitral cell layer of the OB but decreases neuronal network synchronicity. Consequently, EGFL7-knockout mice display severe physiological defects in olfactory behaviour and perception.

Abnormal Resting-State Connectivity in a Substantia Nigra-Related Striato-Thalamo-Cortical Network in a Large Sample of First-Episode Drug-Naïve Patients With Schizophrenia.

The dopamine hypothesis is one of the most influential theories of the neurobiological background of schizophrenia (SCZ). However, direct evidence for abnormal dopamine-related subcortical-cortical circuitry disconnectivity is still lacking. The aim of this study was therefore to test dopamine-related substantia nigra (SN)-based striato-thalamo-cortical resting-state functional connectivity (FC) in SCZ. Based on our a priori hypothesis, we analyzed a large sample resting-state functional magnetic resonance imaging (fMRI) dataset from first-episode drug-naïve SCZ patients (n = 112) and healthy controls (n = 82) using the SN as the seed region for an investigation of striato-thalamo-cortical FC. This was done in the standard band of slow frequency oscillations and then in its subfrequency bands (Slow4 and Slow5). Results: The analysis showed in SCZ: (1) reciprocal functional hypo-connectivity between SN and striatum, with differential patterns for Slow5 and Slow4; (2) functional hypo-connectivity between striatum and thalamus, as well as functional hyper-connectivity between thalamus and sensorimotor cortical areas, specifically in Slow4; (3) correlation of thalamo-sensorimotor functional hyper-connectivity with psychopathological symptoms. Conclusions: We demonstrate abnormal dopamine-related SN-based striato-thalamo-cortical FC in slow frequency oscillations in first-episode drug-naive SCZ. This suggests that altered dopaminergic function in the SN leads to abnormal neuronal synchronization (as indexed by FC) within subcortical-cortical circuitry, complementing the dopamine hypothesis in SCZ on the regional level of resting-state activity.

Modeling of inter-neuronal coupling medium and its impact on neuronal synchronization.

In this paper, modeling of the coupling medium between two neurons, the effects of the model parameters on the synchronization of those neurons, and compensation of coupling strength deficiency in synchronization are studied. Our study exploits the inter-neuronal coupling medium and investigates its intrinsic properties in order to get insight into neuronal-information transmittance and, there from, brain-information processing. A novel electrical model of the coupling medium that represents a well-known RLC circuit attributable to the coupling medium’s intrinsic resistive, inductive, and capacitive properties is derived. Surprisingly, the integration of such properties reveals the existence of a natural three-term control strategy, referred to in the literature as the proportional integral derivative (PID) controller, which can be responsible for synchronization between two neurons. Consequently, brain-information processing can rely on a large number of PID controllers based on the coupling medium properties responsible for the coherent behavior of neurons in a neural network. Herein, the effects of the coupling model (or natural PID controller) parameters are studied and, further, a supervisory mechanism is proposed that follows a learning and adaptation policy based on the particle swarm optimization algorithm for compensation of the coupling strength deficiency.

Enhanced Neuronal Synchrony During Skilled Reaching at High Altitude.

Enhanced Neuronal Synchrony During Skilled Reaching at High Altitude.

Unified principles of thalamo-cortical processing: the neural switch.

It has been reported that cross-frequency interactions may play an important role in local processing within thalamus and neocortex, as well as information transfer between subcortical and cortico-cortical brain regions. Strong commonalities in rhythmic network properties have been observed across recording techniques and task demands, but strong neuroscientific theories to situate such observations within a unified framework with direct relevance to explain neuropathologies remain scarce. Based on a comprehensive review of animal and human literature, we probe and introduce a neurophysiological framework to explain how coordinated cross-frequency and interregional oscillatory cortical dynamics underlie typical and atypical brain activation, and the formation of distributed functional ensembles supporting cortical networks underpinning perception and cognition. We propose that local regional activation by an external stimulus via a sensory pathway entails (1) attenuated alpha (8-14Hz) and increased theta (4-8Hz) and gamma (30-50Hz) oscillatory activity, and (2) increased interactions among theta and gamma rhythms. These local dynamics also mediate the integration of activated neural populations into large-scale functional assemblies through neuronal synchronization. This comprehensive perspective into the animal and human literature indicates a further thinking beyond synchrony and connectivity and the readiness for more hypothesis-driven research and modeling toward unified principles of thalamo-cortical processing. We further introduced such a possible framework: "The ATG switch". We also discussed evidence that alpha-theta-gamma dynamics emerging from thalamocortical interactions may be implicated and disrupted in numerous neurological and neuropsychiatric conditions.

Status epilepticus in dogs and cats, part 1: etiopathogenesis, epidemiology, and diagnosis.

To review current knowledge of the etiopathogenesis, diagnosis, and consequences of status epilepticus (SE) in veterinary patients. Human and veterinary literature, including clinical and laboratory research and reviews. Status epilepticus is a common emergency in dogs and cats, and may be the first manifestation of a seizure disorder. It results from the failure of termination of an isolated seizure. Multiple factors are involved in SE, including initiation and maintenance of neuronal excitability, neuronal network synchronization, and brain microenvironmental contributions to ictogenesis. Underlying etiologies of epilepsy and SE in dogs and cats are generally classified as genetic (idiopathic), structural-metabolic, or unknown. Diagnosis of convulsive SE is usually made based on historical information and the nature of the seizures. Patient specific variables, such as the history, age of seizure onset, and physical and interictal neurological examination findings can help hone the rule out list, and are used to guide selection and prioritization of diagnostic tests. Electroencephalographic monitoring is routinely used in people to diagnose SE and guide patient care decisions, but is infrequently performed in veterinary medicine. Nonconvulsive status epilepticus has been recognized in veterinary patients; routine electroencephalography would aid in the diagnosis of this phenomenon in dogs and cats. Status epilepticus is a medical emergency that can result in life-threatening complications involving the brain and systemic organs. Status epilepticus often requires comprehensive diagnostic testing, treatment with multiple anticonvulsant agents, and intensive supportive care.

Closed-loop deep brain stimulation by pulsatile delayed feedback with increased gap between pulse phases

Computationally it was shown that desynchronizing delayed feedback stimulation methods are effective closed-loop techniques for the control of synchronization in ensembles of interacting oscillators. We here computationally design stimulation signals for electrical stimulation of neuronal tissue that preserve the desynchronizing delayed feedback characteristics and comply with mandatory charge deposit-related safety requirements. For this, the amplitude of the high-frequency (HF) train of biphasic charge-balanced pulses used by the standard HF deep brain stimulation (DBS) is modulated by the smooth feedback signals. In this way we combine the desynchronizing delayed feedback approach with the HF DBS technique. We show that such a pulsatile delayed feedback stimulation can effectively and robustly desynchronize a network of model neurons comprising subthalamic nucleus and globus pallidus external and suggest this approach for desynchronizing closed-loop DBS. Intriguingly, an interphase gap introduced between the recharging phases of the charge-balanced biphasic pulses can significantly improve the stimulation-induced desynchronization and reduce the amount of the administered stimulation. In view of the recent experimental and clinical studies indicating a superiority of the closed-loop DBS to open-loop HF DBS, our results may contribute to a further development of effective stimulation methods for the treatment of neurological disorders characterized by abnormal neuronal synchronization.

Neuronal oscillations and synchronicity associated with gamma-hydroxybutyrate during resting-state in healthy male volunteers.

Gamma-hydroxybutyrate (GHB) is a putative neurotransmitter, a drug of abuse, an anesthetic agent, and a treatment for neuropsychiatric disorders. In previous electroencephalography (EEG) studies, GHB was shown to induce an electrophysiological pattern of "paradoxical EEG-behavioral dissociation" characterized by increased delta and theta oscillations usually associated with sleep during awake states. However, no detailed source localization of these alterations and no connectivity analyses have been performed yet. We tested the effects of GHB (20 and 35mg/kg, p.o.) on current source density (CSD), lagged phase synchronization (LPS), and global omega complexity (GOC) of neuronal oscillations in a randomized, double-blind, placebo-controlled, balanced cross-over study in 19 healthy, male participants using exact low-resolution electromagnetic tomography (eLORETA) of resting-state high-density EEG recordings. Compared to placebo, GHB increased CSD of theta oscillations (5-7Hz) in the posterior cingulate cortex (PCC) and alpha1 (8-10Hz) oscillations in the anterior cingulate cortex. Higher blood plasma values were associated with higher LPS values of delta (2-4Hz) oscillations between the PCC and the right inferior parietal lobulus. Additionally, GHB decreased GOC of alpha1 oscillations. These findings indicate that alterations in neuronal oscillations in the PCC mediate the psychotropic effects of GHB. Theta oscillations emerging from the PCC in combination with stability of functional connectivity within the default mode network might explain the GHB-related "paradoxical EEG-behavioral dissociation." Our findings related to GOC suggest a reduced number of relatively independent neuronal processes, an effect that has also been demonstrated for other anesthetic agents.

Network modeling of resting state connectivity points towards the bottom up theories of schizophrenia

The dysconnectivity theory of schizophrenia proposes that schizophrenia symptoms arise from abnormalities in neuronal synchrony. Resting-state Functional Connectivity (FC) techniques allow us to highlight synchronization of large-scale networks, the Resting-state Networks (RNs). A large body of work suggests that disruption of RN synchronization could give rise to specific schizophrenia symptoms. The present study aimed to explore within- and between-network FC strength of 34 RNs in 29 patients suffering from schizophrenia, and their relationships with schizophrenia symptoms. Resting-state data were analyzed using independent component analysis and dual-regression techniques. Our results showed that both within-RN and between-RN FC were disrupted in patients with schizophrenia, with a global trend toward weaker FC. This decrease affected more particularly visual, auditory and crossmodal binding networks. These alterations were correlated with negative symptoms, positive symptoms and hallucinations, indicating abnormalities in visual processing and crossmodal binding in schizophrenia. Moreover, we stressed an anomalous synchronization between a visual network and a network thought to be engaged in mental imaging processes, correlated with delusions and hallucinations. Altogether, our results supported the assumption that some schizophrenia symptoms may be related to low-order sensory alterations impacting higher-order cognitive processes, i.e. the “bottom-up” hypothesis of schizophrenia symptoms.