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Recent years have seen growing interest in characterizing the properties of regional brain dynamics and their relationship to other features of brain structure and function. In particular, multiple studies have observed regional differences in the timescale over which activity fluctuates during periods of quiet rest. In the cerebral cortex, these timescales have been associated with both local circuit properties as well as patterns of inter-regional connectivity, including the extent to which each region exhibits widespread connectivity to other brain areas. In the current study, we build on prior observations of an association between connectivity and dynamics in the cerebral cortex by investigating the relationship between BOLD fMRI timescales and the modular organization of structural and functional brain networks. We characterize network community structure across multiple scales and find that longer timescales are associated with greater within-community functional connectivity and diverse structural connectivity. We also replicate prior observations of a positive correlation between timescales and structural connectivity degree. Finally, we find evidence for preferential functional connectivity between cortical areas with similar timescales. We replicate these findings in an independent dataset. These results contribute to our understanding of functional brain organization and structure-function relationships in the human brain, and support the notion that regional differences in cortical dynamics may in part reflect the topological role of each region within macroscale brain networks.

Coma and disorders of consciousness (DoC) are common manifestations of acute severe brain injuries. Research into their neuroanatomical basis can be traced from Hippocrates to the present day. Lesions causing DoC have traditionally been conceptualized as decreasing “alertness” from damage to the ascending arousal system, and/or, reducing level of “awareness” due to structural or functional impairment of large-scale brain networks. Within this framework, pharmacological and neuromodulatory interventions to promote recovery from DoC have hitherto met with limited success. This is partly due to inter-individual heterogeneity of brain injury patterns, and an incomplete understanding of brain network properties that characterize consciousness. Advances in multiscale computational modelling of brain dynamics have opened a unique opportunity to explore the causal mechanisms of brain activity at the biophysical level. These models can provide a novel approach for selection and optimization of potential interventions by simulation of brain network dynamics individualized for each patient. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) is a promising intervention tool for the noninvasive modulation of brain activity and behavior in neuroscience research and clinical settings. However, the resting‐state dynamic evolution of large‐scale functional brain networks following rTMS has rarely been investigated. Here, using resting‐state fMRI images collected from 23 healthy individuals before (baseline) and after 1 Hz rTMS of the left frontal (FRO) and occipital (OCC) lobes, we examined the different effects of rTMS on brain dynamics across the human cortex. By fitting a pairwise maximum entropy model (pMEM), we constructed an energy landscape for the baseline and poststimulus conditions by fitting a pMEM. We defined dominant brain states (local minima) in the energy landscape with synergistic activation and deactivation patterns of large‐scale functional networks. We calculated state dynamics including appearance probability, transitions and duration. The results showed that 1 Hz rTMS induced increased and decreased state probability, transitions and duration when delivered to the FRO and OCC targets, respectively. Most importantly, the shortest path and minimum cost between dominant brain states were altered after stimulation. The absolute sum of the costs from the source states to the destinations was lower after OCC stimulation than after FRO stimulation. In conclusion, our study characterized the dynamic trajectory of state transitions in the energy landscape and suggested that local rTMS can induce significant dynamic perturbation involving stimulated and distant functional networks, which aligns with the modern view of the dynamic and complex brain. Our results suggest low‐dimensional mapping of rTMS‐induced brain adaption, which will contribute to a broader and more effective application of rTMS in clinical settings. [ABSTRACT FROM AUTHOR]

The processes involved in encoding and decoding signals in the human brain are a continually studied topic, as neuronal information flow involves complex nonlinear dynamics. This study examines awake human intracranial electroencephalography (iEEG) data from normal brain regions to explore how biological sex influences these dynamics. The iEEG data were analyzed using permutation entropy and statistical complexity in the time domain and power spectrum calculations in the frequency domain. The Bandt and Pompe method was used to assess time series causality by associating probability distributions based on ordinal patterns with the signals. Due to the invasive nature of data acquisition, the study encountered limitations such as small sample sizes and potential sources of error. Nevertheless, the high spatial resolution of iEEG allows detailed analysis and comparison of specific brain regions. The results reveal differences between sexes in brain regions, observed through power spectrum, entropy, and complexity analyses. Significant differences were found in the left supramarginal gyrus, posterior cingulate, supplementary motor cortex, middle temporal gyrus, and right superior temporal gyrus. This study emphasizes the importance of considering sex as a biological variable in brain dynamics research, which is essential for improving the diagnosis and treatment of neurological and psychiatric disorders. [ABSTRACT FROM AUTHOR]

Background: Structural income inequality – the uneven income distribution across regions or countries – could affect brain structure and function, beyond individual differences. However, the impact of structural income inequality on the brain dynamics and the roles of demographics and cognition in these associations remains unexplored. Methods: Here, we assessed the impact of structural income inequality, as measured by the Gini coefficient on multiple EEG metrics, while considering the subject‐level effects of demographic (age, sex, education) and cognitive factors. Resting‐state EEG signals were collected from a diverse sample (countries = 10; healthy individuals = 1394 from Argentina, Brazil, Colombia, Chile, Cuba, Greece, Ireland, Italy, Turkey and United Kingdom). Complexity (fractal dimension, permutation entropy, Wiener entropy, spectral structure variability), power spectral and aperiodic components (1/f slope, knee, offset), as well as graph‐theoretic measures were analysed. Findings: Despite variability in samples, data collection methods, and EEG acquisition parameters, structural inequality systematically predicted electrophysiological brain dynamics, proving to be a more crucial determinant of brain dynamics than individual‐level factors. Complexity and aperiodic activity metrics captured better the effects of structural inequality on brain function. Following inequality, age and cognition emerged as the most influential predictors. The overall results provided convergent multimodal metrics of biologic embedding of structural income inequality characterised by less complex signals, increased random asynchronous neural activity, and reduced alpha and beta power, particularly over temporoposterior regions. Conclusion: These findings might challenge conventional neuroscience approaches that tend to overemphasise the influence of individual‐level factors, while neglecting structural factors. Results pave the way for neuroscience‐informed public policies aimed at tackling structural inequalities in diverse populations. [ABSTRACT FROM AUTHOR]

Abstract A main goal in neuroscience is to understand the computations carried out by neural populations that give animals their cognitive skills. Neural network models allow to formulate explicit hypotheses regarding the algorithms instantiated in the dynamics of a neural population, its firing statistics, and the underlying connectivity. Neural networks can be defined by a small set of parameters, carefully chosen to procure specific capabilities, or by a large set of free parameters, fitted with optimization algorithms that minimize a given loss function. In this work we alternatively propose a method to make a detailed adjustment of the network dynamics and firing statistic to better answer questions that link dynamics, structure, and function. Our algorithm—termed generalised Firing-to-Parameter (gFTP)—provides a way to construct binary recurrent neural networks whose dynamics strictly follows a user pre-specified transition graph that details the transitions between population firing states triggered by stimulus presentations. Our main contribution is a procedure that detects when a transition graph is not realisable in terms of a neural network, and makes the necessary modifications in order to obtain a new transition graph that is realisable and preserves all the information encoded in the transitions of the original graph. With a realisable transition graph, gFTP assigns values to the network firing states associated with each node in the graph, and finds the synaptic weight matrices by solving a set of linear separation problems. We test gFTP performance by constructing networks with random dynamics, continuous attractor-like dynamics that encode position in 2-dimensional space, and discrete attractor dynamics. We then show how gFTP can be employed as a tool to explore the link between structure, function, and the algorithms instantiated in the network dynamics.

Hyperventilation (HV) is an activation technique performed during clinical practices to trigger epileptiform activities, supporting the neurophysiological evaluation of patients with epilepsy. Although the role of HV has often been questioned, especially in the case of focal epilepsy, no studies have ever assessed how cortical structures respond to such a maneuver via intracranial EEG recordings. This work aims to fill this gap by evaluating the HV effects on the Stereo-EEG (SEEG) signals from a cohort of 10 patients with drug-resistant focal epilepsy. We extracted multiple quantitative metrics from the SEEG signals and compared the results obtained during HV, awake status, non-REM sleep, and seizure onset. Our findings show that the cortical connectivity, estimated via the phase transfer entropy (PTE) algorithm, strongly increases during the HV maneuver, similar to non-REM sleep. The opposite effect is observed during seizure onset, as ictal transitions involve the desynchronization of the brain structures within the epileptogenic zone. We conclude that HV promotes a conductive environment that may facilitate the propagation of epileptiform activities but is not sufficient to trigger seizures in focal epilepsy. [ABSTRACT FROM AUTHOR]

A main goal in neuroscience is to understand the computations carried out by neural populations that give animals their cognitive skills. Neural network models allow to formulate explicit hypotheses regarding the algorithms instantiated in the dynamics of a neural population, its firing statistics, and the underlying connectivity. Neural networks can be defined by a small set of parameters, carefully chosen to procure specific capabilities, or by a large set of free parameters, fitted with optimization algorithms that minimize a given loss function. In this work we alternatively propose a method to make a detailed adjustment of the network dynamics and firing statistic to better answer questions that link dynamics, structure, and function. Our algorithm—termed generalised Firing-to-Parameter (gFTP)—provides a way to construct binary recurrent neural networks whose dynamics strictly follows a user pre-specified transition graph that details the transitions between population firing states triggered by stimulus presentations. Our main contribution is a procedure that detects when a transition graph is not realisable in terms of a neural network, and makes the necessary modifications in order to obtain a new transition graph that is realisable and preserves all the information encoded in the transitions of the original graph. With a realisable transition graph, gFTP assigns values to the network firing states associated with each node in the graph, and finds the synaptic weight matrices by solving a set of linear separation problems. We test gFTP performance by constructing networks with random dynamics, continuous attractor-like dynamics that encode position in 2-dimensional space, and discrete attractor dynamics. We then show how gFTP can be employed as a tool to explore the link between structure, function, and the algorithms instantiated in the network dynamics. [ABSTRACT FROM AUTHOR]

A good theory of mathematical beauty is more practical than any current observation, as new predictions about physical reality can be self-consistently verified. This belief applies to the current status of understanding deep neural networks including large language models and even the biological intelligence. Toy models provide a metaphor of physical reality, allowing mathematically formulating the reality (i.e., the so-called theory), which can be updated as more conjectures are justified or refuted. One does not need to present all details in a model, but rather, more abstract models are constructed, as complex systems such as the brains or deep networks have many sloppy dimensions but much less sti dimensions that strongly impact macroscopic observables. This type of bottom-up mechanistic modeling is still promising in the modern era of understanding the natural or artificial intelligence. Here, we shed light on eight challenges in developing theory of intelligence following this theoretical paradigm. Theses challenges are representation learning, generalization, adversarial robustness, continual learning, causal learning, internal model of the brain, next-token prediction, and the mechanics of subjective experience. [ABSTRACT FROM AUTHOR]

Scale-free brain activity, linked with learning, the integration of different time scales, and the formation of mental models, is correlated with a metastable cognitive basis. The spectral slope, a key aspect of scale-free dynamics, was proposed as a potential indicator to distinguish between different sleep stages. Studies suggest that brain networks maintain a consistent scale-free structure across wakefulness, anesthesia, and recovery. Although differences in anesthetic sensitivity between the sexes are recognized, these variations are not evident in clinical electroencephalographic recordings of the cortex. Recently, changes in the slope of the power law exponent of neural activity were found to correlate with changes in Rényi entropy, an extended concept of Shannon's information entropy. These findings establish quantifiers as a promising tool for the study of scale-free dynamics in the brain. Our study presents a novel visual representation called the Rényi entropy-complexity causality space, which encapsulates complexity, permutation entropy, and the Rényi parameter q. The main goal of this study is to define this space for classical dynamical systems within theoretical bounds. In addition, the study aims to investigate how well different time series mimicking scale-free activity can be discriminated. Finally, this tool is used to detect dynamic features in intracranial electroencephalography (iEEG) signals. To achieve these goals, the study implementse the Bandt and Pompe method for ordinal patterns. In this process, each signal is associated with a probability distribution, and the causal measures of Rényi entropy and complexity are computed based on the parameter q. This method is a valuable tool for analyzing simulated time series. It effectively distinguishes elements of correlated noise and provides a straightforwardmeans of examining differences in behaviors, characteristics, and classifications. For the iEEG experimental data, the REM state showed a greater number of significant sex-based differences, while the supramarginal gyrus region showed themost variation across differentmodes and analyzes. Exploring scale-free brain activity with this framework could provide valuable insights into cognition and neurological disorders. The results may have implications for understanding differences in brain function between the sexes and their possible relevance to neurological disorders. [ABSTRACT FROM AUTHOR]

Background Although dopaminergic disturbances are well-known in schizophrenia, the understanding of dopamine-related brain dynamics remains limited. This study investigates the dynamic coactivation patterns (CAPs) associated with the substantia nigra (SN), a key dopaminergic nucleus, in first-episode treatment-naïve patients with schizophrenia (FES). Methods Resting-state fMRI data were collected from 84 FES and 94 healthy controls (HCs). Frame-wise clustering was implemented to generate CAPs related to SN activation or deactivation. Connectome features of each CAP were derived using an edge-centric method. The occurrence for each CAP and the balance ratio for antagonistic CAPs were calculated and compared between two groups, and correlations between temporal dynamic metrics and symptom burdens were explored. Results Functional reconfigurations in CAPs exhibited significant differences between the activation and deactivation states of SN. During SN activation, FES more frequently recruited a CAP characterized by activated default network, language network, control network, and the caudate, compared to HCs (F = 8.54, FDR- p = 0.030). Moreover, FES displayed a tilted balance towards a CAP featuring SN-coactivation with the control network, caudate, and thalamus, as opposed to its antagonistic CAP (F = 7.48, FDR- p = 0.030). During SN deactivation, FES exhibited increased recruitment of a CAP with activated visual and dorsal attention networks but decreased recruitment of its opposing CAP (F = 6.58, FDR- p = 0.034). Conclusion Our results suggest that neuroregulatory dysfunction in dopaminergic pathways involving SN potentially mediates aberrant time-varying functional reorganizations in schizophrenia. This finding enriches the dopamine hypothesis of schizophrenia from the perspective of brain dynamics. [ABSTRACT FROM AUTHOR]

The exploration of functional resting-state brain developmental parameters and measures can help to improve scientific, psychological, and medical applications. The present work focussed on both traditional approaches, such as topographical power analyses at the signal space level, and advanced approaches, such as the exploration of age-related dynamics of source space data. The results confirmed the expectation that the third life decade would show a kind of stability in oscillatory signal and source-space-related parameters. However, from a source dynamics perspective, different frequency ranges appear to develop quite differently, as reflected in age-related sequential network communication profiles. Among other discoveries, the left anterior cingulate source location could be shown to reduce bi-directional network communication in the lower alpha band, whereas it differentiated its uni- and bidirectional communication dynamics to sub-cortical and posterior brain locations. Higher alpha oscillations enhanced communication dynamics between the thalamus and particularly frontal areas. In conclusion, resting-state data appear to be, at least in part, functionally reorganized in the default mode network, while quantitative measures, such as topographical power and regional source activity, did not correlate with age in the third life decade. In line with other authors, we suggest the further development of a multi-perspective approach in biosignal analyses. [ABSTRACT FROM AUTHOR]

• Avalanche transition matrices are used to investigate the spatio-temporal spreading of neuronal avalanches in ALS; • ALS patients present higher values of the nodal strength in both cortical and sub-cortical brain areas, as compared to controls; • The nodal strength directly correlates with disease duration, corroborating the clinical relevance of brain dynamics. To test the hypothesis that patients affected by Amyotrophic Lateral Sclerosis (ALS) show an altered spatio-temporal spreading of neuronal avalanches in the brain, and that this may related to the clinical picture. We obtained the source-reconstructed magnetoencephalography (MEG) signals from thirty-six ALS patients and forty-two healthy controls. Then, we used the construct of the avalanche transition matrix (ATM) and the corresponding network parameter nodal strength to quantify the changes in each region, since this parameter provides key information about which brain regions are mostly involved in the spreading avalanches. ALS patients presented higher values of the nodal strength in both cortical and sub-cortical brain areas. This parameter correlated directly with disease duration. In this work, we provide a deeper characterization of neuronal avalanches propagation in ALS, describing their spatio-temporal trajectories and identifying the brain regions most likely to be involved in the process. This makes it possible to recognize the brain areas that take part in the pathogenic mechanisms of ALS. Furthermore, the nodal strength of the involved regions correlates directly with disease duration. Our results corroborate the clinical relevance of aperiodic, fast large-scale brain activity as a biomarker of microscopic changes induced by neurophysiological processes. [ABSTRACT FROM AUTHOR]

Perturbations of consciousness arise from the interplay of brain network architecture, dynamics, and neuromodulation , providing the opportunity to interrogate the effects of these elements on behaviour and cognition. Fundamental building blocks of brain function can be identified through the lenses of space, time, and information. Each lens reveals similarities and differences across pathological and pharmacological perturbations of consciousness, in humans and across different species. Anaesthesia and brain injury can induce unconsciousness via different mechanisms, but exhibit shared neural signatures across space, time, and information. During loss of consciousness, the brain's ability to explore functional patterns beyond the dictates of anatomy may become constrained. The effects of psychedelics may involve decoupling of brain structure and function across spatial and temporal scales. Disentangling how cognitive functions emerge from the interplay of brain dynamics and network architecture is among the major challenges that neuroscientists face. Pharmacological and pathological perturbations of consciousness provide a lens to investigate these complex challenges. Here, we review how recent advances about consciousness and the brain's functional organisation have been driven by a common denominator: decomposing brain function into fundamental constituents of time, space, and information. Whereas unconsciousness increases structure–function coupling across scales, psychedelics may decouple brain function from structure. Convergent effects also emerge: anaesthetics, psychedelics, and disorders of consciousness can exhibit similar reconfigurations of the brain's unimodal–transmodal functional axis. Decomposition approaches reveal the potential to translate discoveries across species, with computational modelling providing a path towards mechanistic integration. [ABSTRACT FROM AUTHOR]

Abstract Background Structural income inequality – the uneven income distribution across regions or countries – could affect brain structure and function, beyond individual differences. However, the impact of structural income inequality on the brain dynamics and the roles of demographics and cognition in these associations remains unexplored. Methods Here, we assessed the impact of structural income inequality, as measured by the Gini coefficient on multiple EEG metrics, while considering the subject‐level effects of demographic (age, sex, education) and cognitive factors. Resting‐state EEG signals were collected from a diverse sample (countries = 10; healthy individuals = 1394 from Argentina, Brazil, Colombia, Chile, Cuba, Greece, Ireland, Italy, Turkey and United Kingdom). Complexity (fractal dimension, permutation entropy, Wiener entropy, spectral structure variability), power spectral and aperiodic components (1/f slope, knee, offset), as well as graph‐theoretic measures were analysed. Findings Despite variability in samples, data collection methods, and EEG acquisition parameters, structural inequality systematically predicted electrophysiological brain dynamics, proving to be a more crucial determinant of brain dynamics than individual‐level factors. Complexity and aperiodic activity metrics captured better the effects of structural inequality on brain function. Following inequality, age and cognition emerged as the most influential predictors. The overall results provided convergent multimodal metrics of biologic embedding of structural income inequality characterised by less complex signals, increased random asynchronous neural activity, and reduced alpha and beta power, particularly over temporoposterior regions. Conclusion These findings might challenge conventional neuroscience approaches that tend to overemphasise the influence of individual‐level factors, while neglecting structural factors. Results pave the way for neuroscience‐informed public policies aimed at tackling structural inequalities in diverse populations.

Abstract Background Objective and quantifiable markers are crucial for developing novel therapeutics for mental disorders by 1) stratifying clinically similar patients with different underlying neurobiological deficits and 2) objectively tracking disease trajectory and treatment response. Schizophrenia is often confounded with other psychiatric disorders, especially bipolar disorder, if based on cross-sectional symptoms. Awake and sleep EEG have shown promise in identifying neurophysiological differences as biomarkers for schizophrenia. However, most previous studies, while useful, were conducted in European and American populations, had small sample sizes, and utilized varying analytic methods, limiting comprehensive analyses or generalizability to diverse human populations. Furthermore, the extent to which wake and sleep neurophysiology metrics correlate with each other and with symptom severity or cognitive impairment remains unresolved. Moreover, how these neurophysiological markers compare across psychiatric conditions is not well characterized. The utility of biomarkers in clinical trials and practice would be significantly advanced by well-powered transdiagnostic studies. The Global Research Initiative on the Neurophysiology of Schizophrenia (GRINS) project aims to address these questions through a large, multi-center cohort study involving East Asian populations. To promote transparency and reproducibility, we describe the protocol for the GRINS project. Methods The research procedure consists of an initial screening interview followed by three subsequent sessions: an introductory interview, an evaluation visit, and an overnight neurophysiological recording session. Data from multiple domains, including demographic and clinical characteristics, behavioral performance (cognitive tasks, motor sequence tasks), and neurophysiological metrics (both awake and sleep electroencephalography), are collected by research groups specialized in each domain. Conclusion Pilot results from the GRINS project demonstrate the feasibility of this study protocol and highlight the importance of such research, as well as its potential to study a broader range of patients with psychiatric conditions. Through GRINS, we are generating a valuable dataset across multiple domains to identify neurophysiological markers of schizophrenia individually and in combination. By applying this protocol to related mental disorders often confounded with each other, we can gather information that offers insight into the neurophysiological characteristics and underlying mechanisms of these severe conditions, informing objective diagnosis, stratification for clinical research, and ultimately, the development of better-targeted treatment matching in the clinic.

Relating brain activity to cognition and behavior is the primary goal of cognitive neuroscience. Neuroscientists are increasingly summarizing the brain dynamics that underlie cognition and behavior in terms of brain states. Brain states have traditionally been defined as specific spatial patterns of activity or functional connectivity. We propose that brain states should be conceptualized as waves – recurring patterns of activity that sequentially propagate with different delay times. This definition emphasizes both the spatial and temporal patterns of brain activity. There is ample evidence of wave-like activity in the brain at multiple scales and levels. This emerging literature supports the broader adoption of a wave perspective of brain activity. Specifically, a brain state can be described as a set of recurring, sequential patterns of propagating brain activity, namely a wave. We examine a collective body of experimental work investigating wave-like properties. Based on these works, we consider brain states as waves using a scale-agnostic framework across time and space. Emphasis is placed on the sequentiality and periodicity associated with brain activity. We conclude by discussing the implications, prospects, and experimental opportunities of this framework. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a common neurodegenerative dementia, characterized by abnormal dynamic functional connectivity (DFC). Traditional DFC analysis, assuming linear brain dynamics, may neglect the complexity of the brain's nonlinear interactions. Energy landscape analysis offers a holistic, nonlinear perspective to investigate brain network attractor dynamics, which was applied to resting-state fMRI data for AD in this study. Methods: This study utilized resting-state fMRI data from 60 individuals, comparing 30 Alzheimer's patients with 30 controls, from the Alzheimer's Disease Neuroimaging Initiative. Energy landscape analysis was applied to the data to characterize the aberrant brain network dynamics of AD patients. Results: The AD group stayed in the co-activation state for less time than the healthy control (HC) group, and a positive correlation was identified between the transition frequency of the co-activation state and behavior performance. Furthermore, the AD group showed a higher occurrence frequency and transition frequency of the cognitive control state and sensory integration state than the HC group. The transition between the two states was positively correlated with behavior performance. Conclusion: The results suggest that the co-activation state could be important to cognitive processing and that the AD group possibly raised cognitive ability by increasing the occurrence and transition between the impaired cognitive control and sensory integration states. [ABSTRACT FROM AUTHOR]

In the 19th century, the discovery of general anesthesia revolutionized medical care. In the 21st century, anesthetics have become indispensable tools to study consciousness. Here, I review key aspects of the relationship between anesthesia and the neurobiology of consciousness, including interfaces of sleep and anesthetic mechanisms, anesthesia and primary sensory processing, the effects of anesthetics on large-scale functional brain networks, and mechanisms of arousal from anesthesia. I discuss the implications of the data derived from the anesthetized state for the science of consciousness and then conclude with outstanding questions, reflections, and future directions. In the 19th century, the discovery of general anesthesia revolutionized medical care. In the 21st century, anesthetics have become indispensable tools to study consciousness. Here, I review key aspects of the relationship between anesthesia and the neurobiology of consciousness, including interfaces between sleep and anesthetic mechanisms, anesthesia and primary sensory processing, the effects of anesthetics on large-scale functional brain networks, and mechanisms of arousal from anesthesia. I discuss the implications of data derived from the anesthetized state for the science of consciousness, then conclude with outstanding questions, reflections, and future directions. [ABSTRACT FROM AUTHOR]

Empirical evidence indicates that conscious states, distinguished by the presence of phenomenal qualities, are closely linked to synchronized neural activity patterns whose dynamical characteristics can be attributed to self- organized criticality and phase transitions. These findings imply that insight into the mechanism by which the brain controls phase transitions will provide a deeper understanding of the fundamental mechanism by which the brain manages to transcend the threshold of consciousness. This article aims to show that the initiation of phase transitions and the formation of synchronized activity patterns is due to the coupling of the brain to the zero-point field (ZPF), which plays a central role in quantum electrodynamics (QED). The ZPF stands for the presence of ubiquitous vacuum fluctuations of the electromagnetic field, represented by a spectrum of normal modes. With reference to QED- based model calculations, the details of the coupling mechanism are revealed, suggesting that critical brain dynamics is governed by the resonant interaction of the ZPF with the most abundant neurotransmitter glutamate. The pyramidal neurons in the cortical microcolumns turn out to be ideally suited to control this interaction. A direct consequence of resonant glutamate-ZPF coupling is the amplification of specific ZPF modes, which leads us to conclude that the ZPF is the key to the understanding of consciousness and that the distinctive feature of neurophysiological processes associated with conscious experience consists in modulating the ZPF. Postulating that the ZPF is an inherently sentient field and assuming that the spectrum of phenomenal qualities is represented by the normal modes of the ZPF, the significance of resonant glutamate-ZPF interaction for the formation of conscious states becomes apparent in that the amplification of specific ZPF modes is inextricably linked with the excitation of specific phenomenal qualities. This theory of consciousness, according to which phenomenal states arise through resonant amplification of zero-point modes, is given the acronym TRAZE. An experimental setup is specified that can be used to test a corollary of the theory, namely, the prediction that normally occurring conscious perceptions are absent under experimental conditions in which resonant glutamate-ZPF coupling is disrupted. [ABSTRACT FROM AUTHOR]

Previous neuroimaging studies have offered unique insights about the spatial organization of activations and deactivations across the brain; however, these were not powered to explore the exact timing of events at the subsecond scale combined with a precise anatomical source of information at the level of individual brains. As a result, we know little about the order of engagement across different brain regions during a given cognitive task. Using experimental arithmetic tasks as a prototype for human-unique symbolic processing, we recorded directly across 10,076 brain sites in 85 human subjects (52% female) using the intracranial electroencephalography. Our data revealed a remarkably distributed change of activity in almost half of the sampled sites. In each activated brain region, we found juxtaposed neuronal populations preferentially responsive to either the target or control conditions, arranged in an anatomically orderly manner. Notably, an orderly successive activation of a set of brain regions--anatomically consistent across subjects--was observed in individual brains. The temporal order of activations across these sites was replicable across subjects and trials. Moreover, the degree of functional connectivity between the sites decreased as a function of temporal distance between regions, suggesting that the information is partially leaked or transformed along the processing chain. Our study complements prior imaging studies by providing hitherto unknown information about the timing of events in the brain during arithmetic processing. Such findings can be a basis for developing mechanistic computational models of human-specific cognitive symbolic systems. [ABSTRACT FROM AUTHOR]

Scale-free brain activity, linked with learning, the integration of different time scales, and the formation of mental models, is correlated with a metastable cognitive basis. The spectral slope, a key aspect of scale-free dynamics, was proposed as a potential indicator to distinguish between different sleep stages. Studies suggest that brain networks maintain a consistent scale-free structure across wakefulness, anesthesia, and recovery. Although differences in anesthetic sensitivity between the sexes are recognized, these variations are not evident in clinical electroencephalographic recordings of the cortex. Recently, changes in the slope of the power law exponent of neural activity were found to correlate with changes in Rényi entropy, an extended concept of Shannon's information entropy. These findings establish quantifiers as a promising tool for the study of scale-free dynamics in the brain. Our study presents a novel visual representation called the Rényi entropy-complexity causality space, which encapsulates complexity, permutation entropy, and the Rényi parameter q. The main goal of this study is to define this space for classical dynamical systems within theoretical bounds. In addition, the study aims to investigate how well different time series mimicking scale-free activity can be discriminated. Finally, this tool is used to detect dynamic features in intracranial electroencephalography (iEEG) signals. To achieve these goals, the study implementse the Bandt and Pompe method for ordinal patterns. In this process, each signal is associated with a probability distribution, and the causal measures of Rényi entropy and complexity are computed based on the parameter q. This method is a valuable tool for analyzing simulated time series. It effectively distinguishes elements of correlated noise and provides a straightforward means of examining differences in behaviors, characteristics, and classifications. For the iEEG experimental data, the REM state showed a greater number of significant sex-based differences, while the supramarginal gyrus region showed the most variation across different modes and analyzes. Exploring scale-free brain activity with this framework could provide valuable insights into cognition and neurological disorders. The results may have implications for understanding differences in brain function between the sexes and their possible relevance to neurological disorders.

Diversity in brain health is influenced by individual differences in demographics and cognition. However, most studies on brain health and diseases have typically controlled for these factors rather than explored their potential to predict brain signals. Here, we assessed the role of individual differences in demographics (age, sex, and education; n = 1298) and cognition (n = 725) as predictors of different metrics usually used in case-control studies. These included power spectrum and aperiodic (1/f slope, knee, offset) metrics, as well as complexity (fractal dimension estimation, permutation entropy, Wiener entropy, spectral structure variability) and connectivity (graph-theoretic mutual information, conditional mutual information, organizational information) from the source space resting-state EEG activity in a diverse sample from the global south and north populations. Brain-phenotype models were computed using EEG metrics reflecting local activity (power spectrum and aperiodic components) and brain dynamics and interactions (complexity and graph-theoretic measures). Electrophysiological brain dynamics were modulated by individual differences despite the varied methods of data acquisition and assessments across multiple centers, indicating that results were unlikely to be accounted for by methodological discrepancies. Variations in brain signals were mainly influenced by age and cognition, while education and sex exhibited less importance. Power spectrum activity and graph-theoretic measures were the most sensitive in capturing individual differences. Older age, poorer cognition, and being male were associated with reduced alpha power, whereas older age and less education were associated with reduced network integration and segregation. Findings suggest that basic individual differences impact core metrics of brain function that are used in standard case-control studies. Considering individual variability and diversity in global settings would contribute to a more tailored understanding of brain function.

• Representing brain anatomy, dynamics and function as a network is now becoming standard in neuroscience. A network is a deceptively simple structure, in essence, a collection of units and relations between them, but with a plethora of characteristic properties which can be extracted from the relation pattern. • Endowing a system with a network structure does not necessarily entail that this system actually works as a network and that the properties of the associated network are those of the underlying system. • It is therefore essential to evaluate the extent to which a network representation, particularly at system-level scales, can reveal fundamental aspects of brain dynamics, whether it can produce specific brain phenomenology, and ultimately whether it genuinely documents the way the brain carries out the functions it is supposed to fulfil, the extent to which they show robustness with respect to the way they are equipped with a network structure or the way in which the structure is parsed when analysing it. • Addressing these issues involves answering the following related questions: are network properties telling us something more than pure connectivity? Is there a scale at which we can consider that the collection of nodes and their connections starts being a network? What aspects of brain activity genuinely behave as a network? What aspects of known brain phenomenology can be ascribed to its network structure? Are there genuine topology-driven neural phenomena? Is there some network-based equivalent of dys connection syndromes? In fine, how much of brain physics network structure can (correctly) represent? Can network theory help highlighting as yet unknown phenomenology? What are the minimal ingredients a network structure should incorporate to reflect/highlight properties of brain physics? • We first discuss the meaning of networkness and the general conditions under which a complex system has genuine network structure. We then review ways in which neural systems can meaningfully be equipped with a network structure in different domains and at various spatial and temporal scales and analyse some implications for neural systems' dynamics of equipping a neural system with a network structure. Graph theory is now becoming a standard tool in system-level neuroscience. However, endowing observed brain anatomy and dynamics with a complex network structure does not entail that the brain actually works as a network. Asking whether the brain behaves as a network means asking whether network properties count. From the viewpoint of neurophysiology and, possibly, of brain physics, the most substantial issues a network structure may be instrumental in addressing relate to the influence of network properties on brain dynamics and to whether these properties ultimately explain some aspects of brain function. Here, we address the dynamical implications of complex network, examining which aspects and scales of brain activity may be understood to genuinely behave as a network. To do so, we first define the meaning of networkness , and analyse some of its implications. We then examine ways in which brain anatomy and dynamics can be endowed with a network structure and discuss possible ways in which network structure may be shown to represent a genuine organisational principle of brain activity, rather than just a convenient description of its anatomy and dynamics. [ABSTRACT FROM AUTHOR]

Global neural dynamics emerge from multi-scale brain structures, with nodes dynamically communicating to form transient ensembles that may represent neural information. Neural activity can be measured empirically at scales spanning proteins and subcellular domains to neuronal assemblies or whole-brain networks connected through tracts, but it has remained challenging to bridge knowledge between empirically tractable scales. Multi-scale models of brain function have begun to directly link the emergence of global brain dynamics in conscious and unconscious brain states with microscopic changes at the level of cells. In particular, adaptive exponential integrate-and-fire (AdEx) mean-field models representing statistical properties of local populations of neurons have been connected following human tractography data to represent multi-scale neural phenomena in simulations using The Virtual Brain (TVB). While mean-field models can be run on personal computers for short simulations, or in parallel on high-performance computing (HPC) architectures for longer simulations and parameter scans, the computational burden remains red heavy and vast areas of the parameter space remain unexplored. In this work, we report that our HPC framework, a modular set of methods used here to implement the TVB-AdEx model for the graphics processing unit (GPU) and analyze emergent dynamics, notably accelerates simulations and substantially reduces computational resource requirements. The framework preserves the stability and robustness of the TVB-AdEx model, thus facilitating a finer-resolution exploration of vast parameter spaces as well as longer simulations that were previously near impossible to perform. Comparing our GPU implementations of the TVB-AdEx framework with previous implementations using central processing units (CPUs), we first show correspondence of the resulting simulated time-series data from GPU and CPU instantiations. Next, the similarity of parameter combinations, giving rise to patterns of functional connectivity, between brain regions is demonstrated. By varying global coupling together with spike-frequency adaptation, we next replicate previous results indicating inter-dependence of these parameters in inducing transitions between dynamics associated with conscious and unconscious brain states. Upon further exploring parameter space, we report a nonlinear interplay between the spike-frequency adaptation and subthreshold adaptation, as well as previously unappreciated interactions between the global coupling, adaptation, and propagation velocity of action potentials along the human connectome. Given that simulation and analysis toolkits are made public as open-source packages, this framework serves as a template onto which other models can be easily scripted. Further, personalized data-sets can be used for for the creation of red virtual brain twins toward facilitating more precise approaches to the study of epilepsy, sleep, anesthesia, and disorders of consciousness. These results thus represent potentially impactful, publicly available methods for simulating and analyzing human brain states. [ABSTRACT FROM AUTHOR]

Introduction: The complexity of brain signals may hold clues to understand brainbased disorders. Sample entropy, an index that captures the predictability of a signal, is a promising tool to measure signal complexity. However, measurement of sample entropy from fMRI signals has its challenges, and numerous questions regarding preprocessing and parameter selection require research to advance the potential impact of this method. For one example, entropy may be highly sensitive to the effects of motion, yet standard approaches to addressing motion (e.g., scrubbing) may be unsuitable for entropy measurement. For another, the parameters used to calculate entropy need to be defined by the properties of data being analyzed, an issue that has frequently been ignored in fMRI research. The current work sought to rigorously address these issues and to create methods that could be used to advance this field. Methods: We developed and tested a novel windowing approach to select and concatenate (ignoring connecting volumes) low-motion windows in fMRI data to reduce the impact of motion on sample entropy estimates. We created utilities (implementing autoregressive models and a grid search function) to facilitate selection of the matching length m parameter and the error tolerance r parameter. We developed an approach to apply these methods at every grayordinate of the brain, creating a whole-brain dense entropy map. These methods and tools have been integrated into a publicly available R package ("powseR"). We demonstrate these methods using data from the ABCD study. After applying the windowing procedure to allow sample entropy calculation on the lowest-motion windows from runs 1 and 2 (combined) and those from runs 3 and 4 (combined), we identified the optimal m and r parameters for these data. To confirm the impact of the windowing procedure, we compared entropy values and their relationship with motion when entropy was calculated using the full set of data vs. those calculated using the windowing procedure. We then assessed reproducibility of sample entropy calculations using the windowed procedure by calculating the intraclass correlation between the earlier and later entropy measurements at every grayordinate. Results: When applying these optimized methods to the ABCD data (from the subset of individuals who had enough windows of continuous "usable" volumes), we found that the novel windowing procedure successfully mitigated the large inverse correlation between entropy values and head motion seen when using a standard approach. Furthermore, using the windowed approach, entropy values calculated early in the scan (runs 1 and 2) are largely reproducible when measured later in the scan (runs 3 and 4), although there is some regional variability in reproducibility. Discussion: We developed an optimized approach to measuring sample entropy that addresses concerns about motion and that can be applied across datasets through user-identified adaptations that allow the method to be tailored to the dataset at hand. We offer preliminary results regarding reproducibility. We also include recommendations for fMRI data acquisition to optimize sample entropy measurement and considerations for the field. [ABSTRACT FROM AUTHOR]

Matrix factorization in the context of dual numbers has found applications, in recent years, in fields such as kinematics and computer graphics. In this paper, we develop an efficient approach for handling large-scale data low-rank approximation problems using the UTV decomposition of dual matrices (DUTV). Theoretically, we propose an explicit expression for the DUTV and provide necessary and sufficient conditions for its existence. During this process, we also discovered that the general low-rank model for dual matrices can be solved by the Sylvester equation. In numerical experiments, the DUTV algorithm outperforms the dual matrix SVD algorithm in terms of speed and maintains effective performance in wave recognition. Subsequently, we utilize the DUTV algorithm to validate brain functional circuits in large-scale task-state functional magnetic resonance imaging data. Successfully identifying three types of wave signals, the DUTV method provides substantial empirical evidence for cognitive neuroscience theories. [ABSTRACT FROM AUTHOR]

Studying states and state transitions in the brain is challenging due to nonlinear, complex dynamics. In this research, we analyze the brain's response to non-invasive perturbations. Perturbation techniques offier a powerful method for studying complex dynamics, though their translation to human brain data is under-explored. This method involves applying small inputs, in this case via photic stimulation, to a system and measuring its response. Sensitivity to perturbations can forewarn a state transition. Therefore, biomarkers of the brain's perturbation response or "cortical excitability" could be used to indicate seizure transitions. However, perturbing the brain often involves invasive intracranial surgeries or expensive equipment such as transcranial magnetic stimulation (TMS) which is only accessible to a minority of patient groups, or animal model studies. Photic stimulation is a widely used diagnostic technique in epilepsy that can be used as a non-invasive perturbation paradigm to probe brain dynamics during routine electroencephalography (EEG) studies in humans. This involves changing the frequency of strobing light, sometimes triggering a photo-paroxysmal response (PPR), which is an electrographic event that can be studied as a state transition to a seizure state. We investigate alterations in the response to these perturbations in patients with genetic generalized epilepsy (GGE), with (n = 10) and without (n = 10) PPR, and patients with psychogenic non-epileptic seizures (PNES; n = 10), compared to resting controls (n = 10). Metrics of EEG time-series data were evaluated as biomarkers of the perturbation response including variance, autocorrelation, and phase-based synchrony measures. We observed considerable differences in all group biomarker distributions during stimulation compared to controls. In particular, variance and autocorrelation demonstrated greater changes in epochs close to PPR transitions compared to earlier stimulation epochs. Comparison of PPR and spontaneous seizure morphology found them indistinguishable, suggesting PPR is a valid proxy for seizure dynamics. Also, as expected, posterior channels demonstrated the greatest change in synchrony measures, possibly reflecting underlying PPR pathophysiologic mechanisms. We clearly demonstrate observable changes at a group level in cortical excitability in epilepsy patients as a response to perturbation in EEG data. Our work re-frames photic stimulation as a non-invasive perturbation paradigm capable of inducing measurable changes to brain dynamics. [ABSTRACT FROM AUTHOR]

Matrix factorizations in dual number algebra, a hypercomplex number system, have been applied to kinematics, spatial mechanisms, and other fields recently. We develop an approach to identify spatiotemporal patterns in the brain such as traveling waves using the singular value decomposition (SVD) of dual matrices in this paper. Theoretically, we propose the compact dual singular value decomposition (CDSVD) of dual complex matrices with explicit expressions as well as a necessary and sufficient condition for its existence. Furthermore, based on the CDSVD, we report on the optimal solution to the best rank-k approximation under a newly defined quasi-metric in the dual complex number system. The CDSVD is also related to the dual Moore--Penrose generalized inverse. Numerically, comparisons with other available algorithms are conducted, which indicate less computational costs of our proposed CDSVD. In addition, the infinitesimal part of the CDSVD can identify the true rank of the original matrix from the noise-added matrix, but the classical SVD cannot. Next, we employ experiments on simulated time-series data and a road monitoring video to demonstrate the beneficial effect of the infinitesimal parts of dual matrices in spatiotemporal pattern identification. Finally, we apply this approach to the large-scale brain functional magnetic resonance imaging data, identify three kinds of traveling waves, and further validate the consistency between our analytical results and the current knowledge of cerebral cortex function. [ABSTRACT FROM AUTHOR]

Empirical evidence indicates that conscious states, distinguished by the presence of phenomenal qualities, are closely linked to synchronized neural activity patterns whose dynamical characteristics can be attributed to self-organized criticality and phase transitions. These findings imply that insight into the mechanism by which the brain controls phase transitions will provide a deeper understanding of the fundamental mechanism by which the brain manages to transcend the threshold of consciousness. This article aims to show that the initiation of phase transitions and the formation of synchronized activity patterns is due to the coupling of the brain to the zero-point field (ZPF), which plays a central role in quantum electrodynamics (QED). The ZPF stands for the presence of ubiquitous vacuum fluctuations of the electromagnetic field, represented by a spectrum of normal modes. With reference to QED-based model calculations, the details of the coupling mechanism are revealed, suggesting that critical brain dynamics is governed by the resonant interaction of the ZPF with the most abundant neurotransmitter glutamate. The pyramidal neurons in the cortical microcolumns turn out to be ideally suited to control this interaction. A direct consequence of resonant glutamate-ZPF coupling is the amplification of specific ZPF modes, which leads us to conclude that the ZPF is the key to the understanding of consciousness and that the distinctive feature of neurophysiological processes associated with conscious experience consists in modulating the ZPF. Postulating that the ZPF is an inherently sentient field and assuming that the spectrum of phenomenal qualities is represented by the normal modes of the ZPF, the significance of resonant glutamate-ZPF interaction for the formation of conscious states becomes apparent in that the amplification of specific ZPF modes is inextricably linked with the excitation of specific phenomenal qualities. This theory of consciousness, according to which phenomenal states arise through resonant amplification of zero-point modes, is given the acronym TRAZE. An experimental setup is specified that can be used to test a corollary of the theory, namely, the prediction that normally occurring conscious perceptions are absent under experimental conditions in which resonant glutamate-ZPF coupling is disrupted.

Hyperventilation (HV) is an activation technique performed during clinical practices to trigger epileptiform activities, supporting the neurophysiological evaluation of patients with epilepsy. Although the role of HV has often been questioned, especially in the case of focal epilepsy, no studies have ever assessed how cortical structures respond to such a maneuver via intracranial EEG recordings. This work aims to fill this gap by evaluating the HV effects on the Stereo-EEG (SEEG) signals from a cohort of 10 patients with drug-resistant focal epilepsy. We extracted multiple quantitative metrics from the SEEG signals and compared the results obtained during HV, awake status, non-REM sleep, and seizure onset. Our findings show that the cortical connectivity, estimated via the phase transfer entropy (PTE) algorithm, strongly increases during the HV maneuver, similar to non-REM sleep. The opposite effect is observed during seizure onset, as ictal transitions involve the desynchronization of the brain structures within the epileptogenic zone. We conclude that HV promotes a conductive environment that may facilitate the propagation of epileptiform activities but is not sufficient to trigger seizures in focal epilepsy.

IntroductionThe complexity of brain signals may hold clues to understand brain-based disorders. Sample entropy, an index that captures the predictability of a signal, is a promising tool to measure signal complexity. However, measurement of sample entropy from fMRI signals has its challenges, and numerous questions regarding preprocessing and parameter selection require research to advance the potential impact of this method. For one example, entropy may be highly sensitive to the effects of motion, yet standard approaches to addressing motion (e.g., scrubbing) may be unsuitable for entropy measurement. For another, the parameters used to calculate entropy need to be defined by the properties of data being analyzed, an issue that has frequently been ignored in fMRI research. The current work sought to rigorously address these issues and to create methods that could be used to advance this field.MethodsWe developed and tested a novel windowing approach to select and concatenate (ignoring connecting volumes) low-motion windows in fMRI data to reduce the impact of motion on sample entropy estimates. We created utilities (implementing autoregressive models and a grid search function) to facilitate selection of the matching length m parameter and the error tolerance r parameter. We developed an approach to apply these methods at every grayordinate of the brain, creating a whole-brain dense entropy map. These methods and tools have been integrated into a publicly available R package (“powseR”). We demonstrate these methods using data from the ABCD study. After applying the windowing procedure to allow sample entropy calculation on the lowest-motion windows from runs 1 and 2 (combined) and those from runs 3 and 4 (combined), we identified the optimal m and r parameters for these data. To confirm the impact of the windowing procedure, we compared entropy values and their relationship with motion when entropy was calculated using the full set of data vs. those calculated using the windowing procedure. We then assessed reproducibility of sample entropy calculations using the windowed procedure by calculating the intraclass correlation between the earlier and later entropy measurements at every grayordinate.ResultsWhen applying these optimized methods to the ABCD data (from the subset of individuals who had enough windows of continuous “usable” volumes), we found that the novel windowing procedure successfully mitigated the large inverse correlation between entropy values and head motion seen when using a standard approach. Furthermore, using the windowed approach, entropy values calculated early in the scan (runs 1 and 2) are largely reproducible when measured later in the scan (runs 3 and 4), although there is some regional variability in reproducibility.DiscussionWe developed an optimized approach to measuring sample entropy that addresses concerns about motion and that can be applied across datasets through user-identified adaptations that allow the method to be tailored to the dataset at hand. We offer preliminary results regarding reproducibility. We also include recommendations for fMRI data acquisition to optimize sample entropy measurement and considerations for the field.

Epilepsy is one of the most diffused neurological disorders, affecting 50 million people worldwide. Around 30% of patients have drug-resistant epilepsy (DRE), defined as failure of at least two tolerated antiseizure medications (ASMs) to achieve sustained seizure freedom. Brain surgery is an effective therapeutic approach in this group, hinging on the accurate localization of the epileptic focus. The latter task is complex and requires multimodal investigation methods. Epilepsy is also a network disorder and represents one of the best application scenarios of methods leveraging brain functional organization at large scales. Connectivity analysis represents a promising tool for improving surgical assessment, enabling better identification of candidates who could benefit the most from epilepsy surgery. The scalp electroencephalography (EEG) is the most relevant tool to characterize epileptic activity. The EEG has benefited significantly from technological advancement across the last decades. Firstly, electrical source imaging (ESI) allows the reconstruction of electrical activity detected by EEG at the cortex level; secondly, functional connectivity (FC) allows the assessment of functional dependencies across brain areas. The EEG has therefore expanded potential applications in the localization and characterization of the epileptogenic network for surgical planning. As the translation of these methods in clinical practice is little discussed in the literature, we reviewed the investigations using EEG-derived FC. We showed that the FC-informed identification of the epileptic networks improves the localization precision in focal epilepsy. We discussed the heterogeneity in the results and methodology preventing prompt research-to-clinic translation. We finally provided practical suggestions for promoting the applicability of FC-based research in real clinical practice, looking for future research.

Studying states and state transitions in the brain is challenging due to nonlinear, complex dynamics. In this research, we analyze the brain's response to non-invasive perturbations. Perturbation techniques offer a powerful method for studying complex dynamics, though their translation to human brain data is under-explored. This method involves applying small inputs, in this case via photic stimulation, to a system and measuring its response. Sensitivity to perturbations can forewarn a state transition. Therefore, biomarkers of the brain's perturbation response or “cortical excitability” could be used to indicate seizure transitions. However, perturbing the brain often involves invasive intracranial surgeries or expensive equipment such as transcranial magnetic stimulation (TMS) which is only accessible to a minority of patient groups, or animal model studies. Photic stimulation is a widely used diagnostic technique in epilepsy that can be used as a non-invasive perturbation paradigm to probe brain dynamics during routine electroencephalography (EEG) studies in humans. This involves changing the frequency of strobing light, sometimes triggering a photo-paroxysmal response (PPR), which is an electrographic event that can be studied as a state transition to a seizure state. We investigate alterations in the response to these perturbations in patients with genetic generalized epilepsy (GGE), with (n = 10) and without (n = 10) PPR, and patients with psychogenic non-epileptic seizures (PNES; n = 10), compared to resting controls (n = 10). Metrics of EEG time-series data were evaluated as biomarkers of the perturbation response including variance, autocorrelation, and phase-based synchrony measures. We observed considerable differences in all group biomarker distributions during stimulation compared to controls. In particular, variance and autocorrelation demonstrated greater changes in epochs close to PPR transitions compared to earlier stimulation epochs. Comparison of PPR and spontaneous seizure morphology found them indistinguishable, suggesting PPR is a valid proxy for seizure dynamics. Also, as expected, posterior channels demonstrated the greatest change in synchrony measures, possibly reflecting underlying PPR pathophysiologic mechanisms. We clearly demonstrate observable changes at a group level in cortical excitability in epilepsy patients as a response to perturbation in EEG data. Our work re-frames photic stimulation as a non-invasive perturbation paradigm capable of inducing measurable changes to brain dynamics.

Fibromyalgia has been characterized by augmented cross-network functional communication between the brain’s sensorimotor, default mode, and attentional (salience/ventral and dorsal) networks. However, the underlying mechanisms of these aberrant communication patterns are unknown. In this study, we sought to understand large-scale topographic patterns at instantaneous timepoints, known as coactivation patterns (CAPs). We found that a sustained pressure pain challenge temporally modulated the occurrence of CAPs. Using proton magnetic resonance spectroscopy, we found that greater basal excitatory over inhibitory neurotransmitter levels within the anterior insula orchestrated higher cross-network connectivity between the anterior insula and the default mode network through lower occurrence of a CAP encompassing the attentional networks during sustained pain. Moreover, we found that hyperalgesia in fibromyalgia was mediated through increased occurrence of a CAP encompassing the sensorimotor network during sustained pain. In conclusion, this study elucidates the role of momentary large-scale topographic brain patterns in shaping noxious information in patients with fibromyalgia, while laying the groundwork for using precise spatiotemporal dynamics of the brain for the potential development of therapeutics. [ABSTRACT FROM AUTHOR]

Fundamental tensions exist between formal-logical approaches and cognitive approaches to linguistic meaning. The divergence arises from the fundamental differences in nature and form between formal/mathematical structures of natural language meaning and their cognitive representations. While the former are abstract and logical categories of representations, the latter are ultimately embodied and grounded in sensory-motor systems of the brain. This article aims to motivate a unifying theory/formalism of linguistic meaning from a general biologically integrative perspective in the context of current theorizing in linguistics, neurobiology and cognitive sciences on human language meaning within which two divergent approaches for the mathematical and cognitive aspects of linguistic meaning exist. The tensions can be somewhat neutralized if formalmathematical structures and cognitive representations of natural language meaning can be shown to have representational duality and unity in brain dynamics. This work shows a broad outline of one, if not the only one, path toward this vision. [ABSTRACT FROM AUTHOR]

Functional connectivity has been used as a framework to investigate widespread brain interactions underlying cognitive deficits in mild cognitive impairment (MCI). However, many functional connectivity metrics focus on the average of the periodic activities, disregarding the aperiodic bursts of activity (i.e., the neuronal avalanches) characterizing the large-scale dynamic activities of the brain. Here, we apply the recently described avalanche transition matrix framework to source-reconstructed magnetoencephalography signals in a cohort of 32 MCI patients and 32 healthy controls to describe the spatio-temporal features of neuronal avalanches and explore their topological properties. Our results showed that MCI patients showed a more centralized network (as assessed by higher values of the degree divergence and leaf fraction) as compared to healthy controls. Furthermore, we found that the degree divergence (in the theta band) was predictive of hippocampal memory impairment. These findings highlight the role of the changes of aperiodic bursts in clinical conditions and may contribute to a more thorough phenotypical assessment of patients. [ABSTRACT FROM AUTHOR]

Recent neurobiological models on language suggest that auditory sentence comprehension is supported by a coordinated temporal interplay within a left-dominant brain network, including the posterior inferior frontal gyrus (pIFG), posterior superior temporal gyrus and sulcus (pSTG/STS), and angular gyrus (AG). Here, we probed the timing and causal relevance of the interplay between these regions by means of concurrent transcranial magnetic stimulation and electroencephalography (TMSEEG). Our TMS-EEG experiments reveal region- and time-specific causal evidence for a bidirectional information flow from left pSTG/STS to left pIFG and back during auditory sentence processing. Adapting a condition-and-perturb approach, our findings further suggest that the left pSTG/STS can be supported by the left AG in a statedependent manner. [ABSTRACT FROM AUTHOR]

While external stimulation can reliably trigger neuronal activity, cerebral processes can operate independently from the environment. In this study, we conceptualize autogenous cerebral processes (ACPs) as intrinsic operations of the brain that exist on multiple scales and can influence or shape stimulus responses, behavior, homeostasis, and the physiological state of an organism. We further propose that the field should consider exploring to what extent perception, arousal, behavior, or movement, as well as other cognitive functions previously investigated mainly regarding their stimulus-response dynamics, are ACP-driven. [ABSTRACT FROM AUTHOR]

Background: Sex differences impact Alzheimer's disease (AD) neuropathology, but cell-to-network level dysfunctions in the prodromal phase are unclear. Alterations in hippocampal excitation-inhibition balance (EIB) have recently been linked to early AD pathology. Objective: Examine how AD risk factors (age, APOEɛ4, amyloid-β) relate to hippocampal EIB in cognitively normal males and females using connectome-level measures. Methods: Individuals from the OASIS-3 cohort (age 42–95) were studied (N = 437), with a subset aged 65+ undergoing neuropsychological testing (N = 231). Results: In absence of AD risk factors (APOEɛ4/Aβ+), whole-brain EIB decreases with age more significantly in males than females (p = 0.021, β= –0.007). Regression modeling including APOEɛ4 allele carriers (Aβ–) yielded a significant positive AGE-by-APOE interaction in the right hippocampus for females only (p = 0.013, β= 0.014), persisting with inclusion of Aβ+ individuals (p = 0.012, β= 0.014). Partial correlation analyses of neuropsychological testing showed significant associations with EIB in females: positive correlations between right hippocampal EIB with categorical fluency and whole-brain EIB with the Trail Making Test (p < 0.05). Conclusions: Sex differences in EIB emerge during normal aging and progresses differently with AD risk. Results suggest APOEɛ4 disrupts hippocampal balance more than amyloid in females. Increased excitation correlates positively with neuropsychological performance in the female group, suggesting a duality in terms of potential beneficial effects prior to cognitive impairment. This underscores the translational relevance of APOEɛ4 related hyperexcitation in females, potentially informing therapeutic targets or early interventions to mitigate AD progression in this vulnerable population. [ABSTRACT FROM AUTHOR]