Epilepsy is a neurological disease characterized by epileptic seizures, which commonly manifest with pronounced frequency and amplitude changes in the EEG signal. In the case of focal seizures, initially localized pathological activity spreads from a so-called "onset zone" to a wider network of brain areas. Chimeras, defined as states of simultaneously occurring coherent and incoherent dynamics in symmetrically coupled networks are increasingly invoked for characterization of seizures. In particular, chimera-like states have been observed during the transition from a normal (asynchronous) to a seizure (synchronous) network state. However, chimeras in epilepsy have only been investigated with respect to the varying phases of oscillators. We propose a novel method to capture the characteristic pronounced changes in the recorded EEG amplitude during seizures by estimating chimera-like states directly from the signals in a frequency- and time-resolved manner. We test the method on a publicly available intracranial EEG dataset of 16 patients with focal epilepsy. We show that the proposed measure, titled Amplitude Entropy, is sensitive to the altered brain dynamics during seizure, demonstrating its significant increases during seizure as compared to before and after seizure. This finding is robust across patients, their seizures, and different frequency bands. In the future, Amplitude Entropy could serve not only as a feature for seizure detection, but also help in characterizing amplitude chimeras in other networked systems with characteristic amplitude dynamics.

• MeSH
• Adult MeSH
• Electroencephalography methods   MeSH
• Entropy MeSH
• Epilepsies, Partial * physiopathology   MeSH
• Humans MeSH
• Brain * physiopathology   MeSH
• Seizures * physiopathology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Membrane contact sites harbor a distinct set of proteins with varying biological functions, thereby emerging as hubs for localized signaling nanodomains underlying adequate cell function. Here, we will focus on mitochondria-associated endoplasmic reticulum membranes (MAMs), which serve as hotspots for Ca2+ signaling, redox regulation, lipid exchange, mitochondrial quality and unfolded protein response pathway. A network of MAM-resident proteins contributes to the structural integrity and adequate function of MAMs. Beyond endoplasmic reticulum (ER)-mitochondrial tethering proteins, MAMs contain several multi-protein complexes that mediate the transfer of or are influenced by Ca2+, reactive oxygen species and lipids. Particularly, IP3 receptors, intracellular Ca2+-release channels, and Sigma-1 receptors (S1Rs), ligand-operated chaperones, serve as important platforms that recruit different accessory proteins and intersect with these local signaling processes. Furthermore, many of these proteins are directly implicated in pathophysiological conditions, where their dysregulation or mutation is not only causing diseases such as cancer and neurodegeneration, but also rare genetic diseases, for example familial Parkinson's disease (PINK1, Parkin, DJ-1), familial Amyotrophic lateral sclerosis (TDP43), Wolfram syndrome1/2 (WFS1 and CISD2), Harel-Yoon syndrome (ATAD3A). In this review, we will discuss the current state-of-the-art regarding the molecular components, protein platforms and signaling networks underlying MAM integrity and function in cell function and how their dysregulation impacts MAMs, thereby driving pathogenesis and/or impacting disease burden. We will highlight how these insights can generate novel, potentially therapeutically relevant, strategies to tackle disease outcomes by improving the integrity of MAMs and the signaling processes occurring at these membrane contact sites.

• MeSH
• Endoplasmic Reticulum * metabolism   pathology   MeSH
• Intracellular Membranes * metabolism   MeSH
• Humans MeSH
• Mitochondrial Membranes metabolism   MeSH
• Mitochondria * metabolism   pathology   MeSH
• Neoplasms * metabolism   pathology   therapy   genetics   MeSH
• Neurodegenerative Diseases * metabolism   pathology   therapy   genetics   MeSH
• Sigma-1 Receptor MeSH
• Receptors, sigma metabolism   MeSH
• Unfolded Protein Response MeSH
• Calcium Signaling MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Brain imaging studies in complex regional pain syndrome (CRPS) have found mixed evidence for functional and structural changes in CRPS. In this cross-sectional study, we evaluated two patient cohorts from different centers and examined functional connectivity (rsFC) in 51 CRPS patients and 50 matched controls. rsFC was compared in predefined ROI pairs, but also in non-hypothesis driven analyses. Resting state (rs)fMRI changes in default mode network (DMN) and the degree rank order disruption index (kD) were additionally evaluated. Finally, imaging parameters were correlated with clinical severity and somatosensory function. Among predefined pairs, we found only weakly to moderately lower functional connectivity between the right nucleus accumbens and bilateral ventromedial prefrontal cortex in the infra-slow oscillations (ISO) band. The unconstrained ROI-to-ROI analysis revealed lower rsFC between the periaqueductal gray matter (PAG) and left anterior insula, and higher rsFC between the right sensorimotor thalamus and nucleus accumbens. In the correlation analysis, pain was positively associated with insulo-prefrontal rsFC, whereas sensorimotor thalamo-cortical rsFC was positively associated with tactile spatial resolution of the affected side. In contrast to previous reports, we found no group differences for kD or rsFC in the DMN, but detected overall lower data quality in patients. In summary, while some of the previous results were not replicated despite the larger sample size, novel findings from two independent cohorts point to potential down-regulated antinociceptive modulation by the PAG and increased connectivity within the reward system as pathophysiological mechanisms in CRPS. However, in light of the detected systematic differences in data quality between patients and healthy subjects, validity of rsFC abnormalities in CRPS should be carefully scrutinized in future replication studies.

• MeSH
• Default Mode Network diagnostic imaging   physiopathology   MeSH
• Adult MeSH
• Complex Regional Pain Syndromes * physiopathology   diagnostic imaging   MeSH
• Connectome methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Brain physiopathology   diagnostic imaging   MeSH
• Nerve Net physiopathology   diagnostic imaging   MeSH
• Cross-Sectional Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Antagonistic activity of brain networks likely plays a fundamental role in how the brain optimizes its performance by efficient allocation of computational resources. A prominent example involves externally/internally oriented attention tasks, implicating two anticorrelated, intrinsic brain networks: the default mode network (DMN) and the dorsal attention network (DAN). To elucidate electrophysiological underpinnings and causal interplay during attention switching, we recorded intracranial EEG (iEEG) from 25 epilepsy patients with electrode contacts localized in the DMN and DAN. We show antagonistic network dynamics of activation-related changes in high-frequency (> 50 Hz) and low-frequency (< 30 Hz) power. The temporal profile of information flow between the networks estimated by functional connectivity suggests that the activated network inhibits the other one, gating its activity by increasing the amplitude of the low-frequency oscillations. Insights about inter-network communication may have profound implications for various brain disorders in which these dynamics are compromised.

• MeSH
• Adult MeSH
• Electroencephalography MeSH
• Electrophysiological Phenomena MeSH
• Epilepsy physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Brain * physiology   physiopathology   MeSH
• Nerve Net * physiology   MeSH
• Attention * physiology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Despite advances in understanding the cellular and molecular processes underlying memory and cognition, and recent successful modulation of cognitive performance in brain disorders, the neurophysiological mechanisms remain underexplored. High frequency oscillations beyond the classic electroencephalogram spectrum have emerged as a potential neural correlate of fundamental cognitive processes. High frequency oscillations are detected in the human mesial temporal lobe and neocortical intracranial recordings spanning gamma/epsilon (60-150 Hz), ripple (80-250 Hz) and higher frequency ranges. Separate from other non-oscillatory activities, these brief electrophysiological oscillations of distinct duration, frequency and amplitude are thought to be generated by coordinated spiking of neuronal ensembles within volumes as small as a single cortical column. Although the exact origins, mechanisms and physiological roles in health and disease remain elusive, they have been associated with human memory consolidation and cognitive processing. Recent studies suggest their involvement in encoding and recall of episodic memory with a possible role in the formation and reactivation of memory traces. High frequency oscillations are detected during encoding, throughout maintenance, and right before recall of remembered items, meeting a basic definition for an engram activity. The temporal coordination of high frequency oscillations reactivated across cortical and subcortical neural networks is ideally suited for integrating multimodal memory representations, which can be replayed and consolidated during states of wakefulness and sleep. High frequency oscillations have been shown to reflect coordinated bursts of neuronal assembly firing and offer a promising substrate for tracking and modulation of the hypothetical electrophysiological engram.

• MeSH
• Electroencephalography MeSH
• Cognition * physiology   MeSH
• Humans MeSH
• Brain physiology   MeSH
• Brain Waves physiology   MeSH
• Memory physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

High-frequency oscillations (HFOs) represent an electrographic biomarker of endogenous epileptogenicity and seizure-generating tissue that proved clinically useful in presurgical planning and delineating the resection area. In the neocortex, the clinical observations on HFOs are not sufficiently supported by experimental studies stemming from a lack of realistic neocortical epilepsy models that could provide an explanation of the pathophysiological substrates of neocortical HFOs. In this study, we explored pathological epileptiform network phenomena, particularly HFOs, in a highly realistic murine model of neocortical epilepsy due to focal cortical dysplasia (FCD) type II. FCD was induced in mice by the expression of the human pathogenic mTOR gene mutation during embryonic stages of brain development. Electrographic recordings from multiple cortical regions in freely moving animals with FCD and epilepsy demonstrated that the FCD lesion generates HFOs from all frequency ranges, i.e., gamma, ripples, and fast ripples up to 800 Hz. Gamma-ripples were recorded almost exclusively in FCD animals, while fast ripples occurred in controls as well, although at a lower rate. Gamma-ripple activity is particularly valuable for localizing the FCD lesion, surpassing the utility of fast ripples that were also observed in control animals, although at significantly lower rates. Propagating HFOs occurred outside the FCD, and the contralateral cortex also generated HFOs independently of the FCD, pointing to a wider FCD network dysfunction. Optogenetic activation of neurons carrying mTOR mutation and expressing Channelrhodopsin-2 evoked fast ripple oscillations that displayed spectral and morphological profiles analogous to spontaneous oscillations. This study brings experimental evidence that FCD type II generates pathological HFOs across all frequency bands and provides information about the spatiotemporal properties of each HFO subtype in FCD. The study shows that mutated neurons represent a functionally interconnected and active component of the FCD network, as they can induce interictal epileptiform phenomena and HFOs.

• MeSH
• Electroencephalography MeSH
• Epilepsy * MeSH
• Focal Cortical Dysplasia * MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Mice MeSH
• TOR Serine-Threonine Kinases MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Sepsis-associated encephalopathy (SAE) is a frequent severe complication of sepsis and the systemic inflammatory response syndrome, associated with high mortality and long-term neurologic consequences in surviving patients. One of the main clinical signs of SAE are discontinuous sleep periods that are fragmented by frequent awakenings. Although this brain state fragmentation strongly impacts the functionality of the nervous and other systems, its underlying network mechanisms are still poorly understood. In this work, we therefore aim to characterize the properties and dynamics of brain oscillatory states in response to SAE in an acute rat model of sepsis induced by high-dose lipopolysaccharide (LPS; 10 mg/kg). To focus on intrinsically generated brain state dynamics, we used a urethane model that spares oscillatory activity in rapid eye movement (REM)-like and nonrapid eye movement (NREM)-like sleep states. Intraperitoneal LPS injection led to a robust instability of both oscillatory states resulting in several folds more state transitions. We identified opposing shifts in low-frequency oscillations (1-9 Hz) in REM and NREM-like states under influence of LPS. This resulted in increased similarity between both states. Moreover, the state-space jitter in both states increased as well, pointing to higher within-state instability. The reduction of interstate spectral distances in 2-D state space, combined with increased within-state jitter might represent a key factor in changing the energy landscape of brain oscillatory state attractors, and hence lead to altered sleep architecture. Their emergence during sepsis might point to a mechanism underlying severe sleep fragmentation as described both in sepsis patients and SAE animal models.

• MeSH
• Electroencephalography methods   MeSH
• Hippocampus MeSH
• Kinetics MeSH
• Rats MeSH
• Lipopolysaccharides * MeSH
• Sepsis * complications   MeSH
• Sleep, REM physiology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Working memory is a cognitive process that involves short-term active maintenance, flexible updating, and processing of goal- or task-relevant information. All frequency bands are involved in working memory. The activities of the theta and gamma frequency bands in the frontoparietal network are highly involved in working memory processes; theta oscillations play a role in the temporal organization of working memory items, and gamma oscillations influence the maintenance of information in working memory. Transcranial alternating current stimulation (tACS) results in frequency-specific modulation of endogenous oscillations and has shown promising results in cognitive neuroscience. The electrophysiological and behavioral changes induced by the modulation of endogenous gamma frequency in the prefrontal cortex using tACS have not been extensively studied in the context of working memory. Therefore, we aimed to investigate the effects of frontal gamma-tACS on working memory outcomes. We hypothesized that a 10-min gamma tACS administered over the frontal cortex would significantly improve working memory outcomes. Young healthy participants performed Luck-Vogel cognitive behavioral tasks with simultaneous pre- and post-intervention EEG recording (Sham versus 40 Hz tACS). Data from forty-one participants: sham (15 participants) and tACS (26 participants), were used for the statistical and behavioral analysis. The relative changes in behavioral outcomes and EEG due to the intervention were analyzed. The results show that tACS caused an increase in the power spectral density in the high beta and low gamma EEG bands and a decrease in left-right coherence. On the other hand, tACS had no significant effect on success rates and response times. Conclusion: 10 min of frontal 40 Hz tACS was not sufficient to produce detectable behavioral effects on working memory, whereas electrophysiological changes were evident. The limitations of the current stimulation protocol and future directions are discussed in detail in the following sections.

• Publication type
• Journal Article MeSH

The phenomenon of déjà vu (DV) has intrigued scientists for decades, yet its neurophysiological underpinnings remain elusive. Brain regions have been identified in which morphometry differs between healthy individuals according to the frequency of their DV experiences. This study built upon these findings by assessing if and how neural activity in these and other brain regions also differ with respect to DV experience. Resting-state fMRI was performed on 68 healthy volunteers, 44 of whom reported DV experiences (DV group) and 24 who did not (NDV group). Using multivariate analyses, we then assessed the (fractional) amplitude of low-frequency fluctuations (fALFF/ALFF), a metric that is believed to index brain tissue excitability, for five discrete frequency bands within sets of brain regions implicated in DV and those comprising the default mode network (DMN). Analyses revealed significantly lower values of fALFF/ALFF for specific frequency bands in the DV relative to the NDV group, particularly within mesiotemporal structures, bilateral putamina, right caudatum, bilateral superior frontal cortices, left lateral parietal cortex, dorsal and ventral medial prefrontal cortex, and the posterior cingulate cortex. The pattern of differences in fALFF/ALFF measures between the brains of individuals who have experienced DV and those who have not provides new neurophysiological insights into this phenomenon, including the potential role of the DMN. We suggest that the erroneous feeling of familiarity arises from a temporary disruption of cortico-subcortical circuitry together with the upregulation of cortical excitability.

• MeSH
• Emotions MeSH
• Humans MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Brain Mapping methods   MeSH
• Brain diagnostic imaging   MeSH
• Brain Waves * physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The relationship between network structure and dynamics is one of the most extensively investigated problems in the theory of complex systems of recent years. Understanding this relationship is of relevance to a range of disciplines-from neuroscience to geomorphology. A major strategy of investigating this relationship is the quantitative comparison of a representation of network architecture (structural connectivity, SC) with a (network) representation of the dynamics (functional connectivity, FC). Here, we show that one can distinguish two classes of functional connectivity-one based on simultaneous activity (co-activity) of nodes, the other based on sequential activity of nodes. We delineate these two classes in different categories of dynamical processes-excitations, regular and chaotic oscillators-and provide examples for SC/FC correlations of both classes in each of these models. We expand the theoretical view of the SC/FC relationships, with conceptual instances of the SC and the two classes of FC for various application scenarios in geomorphology, ecology, systems biology, neuroscience and socio-ecological systems. Seeing the organisation of dynamical processes in a network either as governed by co-activity or by sequential activity allows us to bring some order in the myriad of observations relating structure and function of complex networks.

• MeSH
• Ecology * MeSH
• Ecosystem * MeSH
• Brain MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH