Minimum spanning tree analysis of EEG resting-state functional networks in schizophrenia.

Schizophrenia is a serious and complex mental disease, known to be associated with various subtle structural and functional deviations in the brain. Recently, increased attention is given to the analysis of brain-wide, global mechanisms, strongly altering the communication of long-distance brain areas in schizophrenia. Data of 32 patients with schizophrenia and 28 matched healthy control subjects were analyzed. Two minutes long 64-channel EEG recordings were registered during resting, eyes closed condition. Average connectivity strength was estimated with Weighted Phase Lag Index (wPLI) in lower frequencies: delta and theta, and Amplitude Envelope Correlation with leakage correction (AEC-c) in higher frequencies: alpha, beta, lower gamma and higher gamma. To analyze functional network topology Minimum Spanning Tree (MST) algorithms were applied. Results show that patients have weaker functional connectivity in delta and alpha frequency bands. Concerning network differences, the result of lower diameter, higher leaf number, and also higher maximum degree and maximum betweenness centrality in patients suggest a star-like, and more random network topology in patients with schizophrenia. Our findings are in accordance with some previous findings based on resting-state EEG (and fMRI) data, suggesting that MST network structure in schizophrenia is biased towards a less optimal, more centralized organization.

Combining detrended cross-correlation analysis with Riemannian geometry-based classification for improved brain-computer interface performance.

Riemannian geometry-based classification (RGBC) gained popularity in the field of brain-computer interfaces (BCIs) lately, due to its ability to deal with non-stationarities arising in electroencephalography (EEG) data. Domain adaptation, however, is most often performed on sample covariance matrices (SCMs) obtained from EEG data, and thus might not fully account for components affecting covariance estimation itself, such as regional trends. Detrended cross-correlation analysis (DCCA) can be utilized to estimate the covariance structure of such signals, yet it is computationally expensive in its original form. A recently proposed online implementation of DCCA, however, allows for its fast computation and thus makes it possible to employ DCCA in real-time applications. In this study we propose to replace the SCM with the DCCA matrix as input to RGBC and assess its effect on offline and online BCI performance. First we evaluated the proposed decoding pipeline offline on previously recorded EEG data from 18 individuals performing left and right hand motor imagery (MI), and benchmarked it against vanilla RGBC and popular MI-detection approaches. Subsequently, we recruited eight participants (with previous BCI experience) who operated an MI-based BCI (MI-BCI) online using the DCCA-enhanced Riemannian decoder. Finally, we tested the proposed method on a public, multi-class MI-BCI dataset. During offline evaluations the DCCA-based decoder consistently and significantly outperformed the other approaches. Online evaluation confirmed that the DCCA matrix could be computed in real-time even for 22-channel EEG, as well as subjects could control the MI-BCI with high command delivery (normalized Cohen's κ: 0.7409 ± 0.1515) and sample-wise MI detection (normalized Cohen's κ: 0.5200 ± 0.1610). Post-hoc analysis indicated characteristic connectivity patterns under both MI conditions, with stronger connectivity in the hemisphere contralateral to the MI task. Additionally, fractal scaling exponent of neural activity was found increased in the contralateral compared to the ipsilateral motor cortices (C4 and C3 for left and right MI, respectively) in both classes. Combining DCCA with Riemannian geometry-based decoding yields a robust and effective decoder, that not only improves upon the SCM-based approach but can also provide relevant information on the neurophysiological processes behind MI.

Transfer learning promotes acquisition of individual BCI skills.

Subject training is crucial for acquiring brain-computer interface (BCI) control. Typically, this requires collecting user-specific calibration data due to high inter-subject neural variability that limits the usability of generic decoders. However, calibration is cumbersome and may produce inadequate data for building decoders, especially with naïve subjects. Here, we show that a decoder trained on the data of a single expert is readily transferrable to inexperienced users via domain adaptation techniques allowing calibration-free BCI training. We introduce two real-time frameworks, (i) Generic Recentering (GR) through unsupervised adaptation and (ii) Personally Assisted Recentering (PAR) that extends GR by employing supervised recalibration of the decoder parameters. We evaluated our frameworks on 18 healthy naïve subjects over five online sessions, who operated a customary synchronous bar task with continuous feedback and a more challenging car racing game with asynchronous control and discrete feedback. We show that along with improved task-oriented BCI performance in both tasks, our frameworks promoted subjects' ability to acquire individual BCI skills, as the initial neurophysiological control features of an expert subject evolved and became subject specific. Furthermore, those features were task-specific and were learned in parallel as participants practiced the two tasks in every session. Contrary to previous findings implying that supervised methods lead to improved online BCI control, we observed that longitudinal training coupled with unsupervised domain matching (GR) achieved similar performance to supervised recalibration (PAR). Therefore, our presented frameworks facilitate calibration-free BCIs and have immediate implications for broader populations-such as patients with neurological pathologies-who might struggle to provide suitable initial calibration data.

Resting-state fractal brain connectivity is associated with impaired cognitive performance in healthy aging.

Aging affects cognitive functions even in the absence of ongoing pathologies. The neurophysiological basis of age-related cognitive decline (CD), however, is not completely understood. Alterations in both functional brain connectivity and in the fractal scaling of neuronal dynamics have been linked to aging and cognitive performance. Recently, fractal connectivity (FrC) has been proposed - combining the two concepts - for capturing long-term interactions among brain regions. FrC was shown to be influenced by increased mental workload; however, no prior studies investigated how resting-state FrC relates to cognitive performance and plausible CD in healthy aging. We recruited 19 healthy elderly (HE) and 24 young control (YC) participants, who underwent resting-state electroencephalography (EEG) measurements and comprehensive cognitive evaluation using 7 tests of the Cambridge Neurophysiological Test Automated Battery. FrC networks were reconstructed from EEG data using the recently introduced multiple-resampling cross-spectral analysis (MRCSA). Elderly individuals could be characterized with increased response latency and reduced performance in 4-4 tasks, respectively, with both reaction time and accuracy being affected in two tasks. Auto- and cross-spectral exponents - characterizing regional fractal dynamics and FrC, respectively, - were found reduced in HE when compared to YC over most of the cortex. Additionally, fractal scaling of frontoparietal connections expressed an inverse relationship with task performance in visual memory and sustained attention domains in elderly, but not in young individuals. Our results confirm that the fractal nature of brain connectivity - as captured by MRCSA - is affected in healthy aging. Furthermore, FrC appears as a sensitive neurophysiological marker of age-related CD.

Impaired Neurovascular Coupling and Increased Functional Connectivity in the Frontal Cortex Predict Age-Related Cognitive Dysfunction.

Impaired cerebrovascular function contributes to the genesis of age-related cognitive decline. In this study, the hypothesis is tested that impairments in neurovascular coupling (NVC) responses and brain network function predict cognitive dysfunction in older adults. Cerebromicrovascular and working memory function of healthy young (n = 21, 33.2±7.0 years) and aged (n = 30, 75.9±6.9 years) participants are assessed. To determine NVC responses and functional connectivity (FC) during a working memory (n-back) paradigm, oxy- and deoxyhemoglobin concentration changes from the frontal cortex using functional near-infrared spectroscopy are recorded. NVC responses are significantly impaired during the 2-back task in aged participants, while the frontal networks are characterized by higher local and global connection strength, and dynamic FC (p < 0.05). Both impaired NVC and increased FC correlate with age-related decline in accuracy during the 2-back task. These findings suggest that task-related brain states in older adults require stronger functional connections to compensate for the attenuated NVC responses associated with working memory load.

Fingerprints of decreased cognitive performance on fractal connectivity dynamics in healthy aging.

Analysis of brain functional connectivity (FC) could provide insight in how and why cognitive functions decline even in healthy aging (HA). Despite FC being established as fluctuating over time even in the resting state (RS), dynamic functional connectivity (DFC) studies involving healthy elderly individuals and assessing how these patterns relate to cognitive performance are yet scarce. In our recent study we showed that fractal temporal scaling of functional connections in RS is not only reduced in HA, but also predicts increased response latency and reduced task solving accuracy. However, in that work we did not address changes in the dynamics of fractal connectivity (FrC) strength itself and its plausible relationship with mental capabilities. Therefore, here we analyzed RS electroencephalography recordings of the same subject cohort as previously, consisting of 24 young and 19 healthy elderly individuals, who also completed 7 different cognitive tasks after data collection. Dynamic fractal connectivity (dFrC) analysis was carried out via sliding-window detrended cross-correlation analysis (DCCA). A machine learning method based on recursive feature elimination was employed to select the subset of connections most discriminative between the two age groups, identifying 56 connections that allowed for classifying participants with an accuracy surpassing 92%. Mean of DCCA was found generally increased, while temporal variability of FrC decreased in the elderly when compared to the young group. Finally, dFrC indices expressed an elaborate pattern of associations-assessed via Spearman correlation-with cognitive performance scores in both groups, linking fractal connectivity strength and variance to increased response latency and reduced accuracy in the elderly population. Our results provide further support for the relevance of FrC dynamics in understanding age-related cognitive decline and might help to identify potential targets for future intervention strategies.

Urinary Biomarkers of Oxidative Stress in Aging: Implications for Prediction of Accelerated Biological Age in Prospective Cohort Studies.

Background: Aging is a major risk factor for a range of chronic diseases. Oxidative stress theory of aging has been previously proposed as one of the mechanisms responsible for the age-related decline in organ/tissue function and the development of age-related diseases. Urine contains rich biological information on the health status of every major organ system and can be an important noninvasive source for biomarkers of systemic oxidative stress in aging. Aims: The objective of this cross-sectional study was to validate a novel panel of urinary oxidative stress biomarkers. Methods: Nucleic acid oxidation adducts and oxidative damage markers of lipids and proteins were assessed in urine samples from nondiabetic and currently nonsmoking subjects (n = 198) across different ages (20 to 89 years old). Urinary parameters and chronological age were correlated then the biological age of enrolled individuals was determined from the urinary oxidative stress markers using the algorithm of Klemera and Doubal. Results: Our findings showed that 8-oxo-7,8-deoxyguanosine (8-oxoG), 8-oxo-7,8-dihydroguanosine (8-OHdG), and dityrosine (DTyr) positively correlated with chronological age, while the level of an F2-isoprostane (iPF2 α-VI) correlated negatively with age. We found that 8-oxoG, DTyr, and iPF2 α-VI were significantly higher among accelerated agers compared to nonaccelerated agers and that a decision tree model could successfully identify accelerated agers with an accuracy of >92%. Discussion. Our results indicate that 8-oxoG and iPF2 α-VI levels in the urine reveal biological aging. Conclusion: Assessing urinary biomarkers of oxidative stress may be an important approach for the evaluation of biological age by identifying individuals at accelerated risk for the development of age-related diseases.

Real-Time Algorithm for Detrended Cross-Correlation Analysis of Long-Range Coupled Processes.

Assessing power-law cross-correlations between a pair - or among a set - of processes is of great significance in diverse fields of analyses ranging from neuroscience to financial markets. In most cases such analyses are computationally expensive and thus carried out offline once the entire signal is obtained. However, many applications - such as mental state monitoring or financial forecasting - call for fast algorithms capable of estimating scale-free coupling in real time. Detrended cross-correlation analysis (DCCA), a generalization of the detrended fluctuation analysis (DFA) to the bivariate domain, has been introduced as a method designed to quantify power-law cross-correlations between a pair of non-stationary signals. Later, in analogy with the Pearson cross-correlation coefficient, DCCA was adapted to the detrended cross-correlation coefficient (DCCC), however as of now no online algorithms were provided for either of these analysis techniques. Here we introduce a new formula for obtaining the scaling functions in real time for DCCA. Moreover, the formula can be generalized via matrix notation to obtain the scaling relationship between not only a pair of signals, but also all possible pairs among a set of signals at the same time. This includes parallel estimation of the DFA scaling function of each individual process as well, thus allowing also for real-time acquisition of DCCC. The proposed algorithm matches its offline variants in precision, while being substantially more efficient in terms of execution time. We demonstrate that the method can be utilized for mental state monitoring on multi-channel electroencephalographic recordings obtained in eyes-closed and eyes-open resting conditions.

Multiple-Resampling Cross-Spectral Analysis: An Unbiased Tool for Estimating Fractal Connectivity With an Application to Neurophysiological Signals.

Investigating scale-free (i.e., fractal) functional connectivity in the brain has recently attracted increasing attention. Although numerous methods have been developed to assess the fractal nature of functional coupling, these typically ignore that neurophysiological signals are assemblies of broadband, arrhythmic activities as well as oscillatory activities at characteristic frequencies such as the alpha waves. While contribution of such rhythmic components may bias estimates of fractal connectivity, they are also likely to represent neural activity and coupling emerging from distinct mechanisms. Irregular-resampling auto-spectral analysis (IRASA) was recently introduced as a tool to separate fractal and oscillatory components in the power spectrum of neurophysiological signals by statistically summarizing the power spectra obtained when resampling the original signal by several non-integer factors. Here we introduce multiple-resampling cross-spectral analysis (MRCSA) as an extension of IRASA from the univariate to the bivariate case, namely, to separate the fractal component of the cross-spectrum between two simultaneously recorded neural signals by applying the same principle. MRCSA does not only provide a theoretically unbiased estimate of the fractal cross-spectrum (and thus its spectral exponent) but also allows for computing the proportion of scale-free coupling between brain regions. As a demonstration, we apply MRCSA to human electroencephalographic recordings obtained in a word generation paradigm. We show that the cross-spectral exponent as well as the proportion of fractal coupling increases almost uniformly over the cortex during the rest-task transition, likely reflecting neural desynchronization. Our results indicate that MRCSA can be a valuable tool for scale-free connectivity studies in characterizing various cognitive states, while it also can be generalized to other applications outside the field of neuroscience.

Scale-Free Functional Brain Networks Exhibit Increased Connectivity, Are More Integrated and Less Segregated in Patients with Parkinson's Disease following Dopaminergic Treatment.

Dopaminergic treatment (DT), the standard therapy for Parkinson's disease (PD), alters the dynamics of functional brain networks at specific time scales. Here, we explore the scale-free functional connectivity (FC) in the PD population and how it is affected by DT. We analyzed the electroencephalogram of: (i) 15 PD patients during DT (ON) and after DT washout (OFF) and (ii) 16 healthy control individuals (HC). We estimated FC using bivariate focus-based multifractal analysis, which evaluated the long-term memory (H(2)) and multifractal strength (ΔH15) of the connections. Subsequent analysis yielded network metrics (node degree, clustering coefficient and path length) based on FC estimated by H(2) or ΔH15. Cognitive performance was assessed by the Mini Mental State Examination (MMSE) and the North American Adult Reading Test (NAART). The node degrees of the ΔH15 networks were significantly higher in ON, compared to OFF and HC, while clustering coefficient and path length significantly decreased. No alterations were observed in the H(2) networks. Significant positive correlations were also found between the metrics of H(2) networks and NAART scores in the HC group. These results demonstrate that DT alters the multifractal coupled dynamics in the brain, warranting the investigation of scale-free FC in clinical and pharmacological studies.

Multifractal Functional Connectivity Analysis of Electroencephalogram Reveals Reorganization of Brain Networks in a Visual Pattern Recognition Paradigm.

The human brain consists of anatomically distant neuronal assemblies that are interconnected via a myriad of synapses. This anatomical network provides the neurophysiological wiring framework for functional connectivity (FC), which is essential for higher-order brain functions. While several studies have explored the scale-specific FC, the scale-free (i.e., multifractal) aspect of brain connectivity remains largely neglected. Here we examined the brain reorganization during a visual pattern recognition paradigm, using bivariate focus-based multifractal (BFMF) analysis. For this study, 58 young, healthy volunteers were recruited. Before the task, 3-3 min of resting EEG was recorded in eyes-closed (EC) and eyes-open (EO) states, respectively. The subsequent part of the measurement protocol consisted of 30 visual pattern recognition trials of 3 difficulty levels graded as Easy, Medium, and Hard. Multifractal FC was estimated with BFMF analysis of preprocessed EEG signals yielding two generalized Hurst exponent-based multifractal connectivity endpoint parameters, H(2) and ΔH 15; with the former indicating the long-term cross-correlation between two brain regions, while the latter captures the degree of multifractality of their functional coupling. Accordingly, H(2) and ΔH 15 networks were constructed for every participant and state, and they were characterized by their weighted local and global node degrees. Then, we investigated the between- and within-state variability of multifractal FC, as well as the relationship between global node degree and task performance captured in average success rate and reaction time. Multifractal FC increased when visual pattern recognition was administered with no differences regarding difficulty level. The observed regional heterogeneity was greater for ΔH 15 networks compared to H(2) networks. These results show that reorganization of scale-free coupled dynamics takes place during visual pattern recognition independent of difficulty level. Additionally, the observed regional variability illustrates that multifractal FC is region-specific both during rest and task. Our findings indicate that investigating multifractal FC under various conditions - such as mental workload in healthy and potentially in diseased populations - is a promising direction for future research.

Sleep deprivation alters task-related changes in functional connectivity of the frontal cortex: A near-infrared spectroscopy study.

Sleep deprivation (SD) is known to be associated with decreased cognitive performance; however, the underlying mechanisms are poorly understood. As interactions between distinct brain regions depend on mental state, functional brain networks established by these connections typically show a reorganization during task. Hence, analysis of functional connectivity (FC) could reveal the task-related change in the examined frontal brain networks. Our objective was to assess the impact of SD on static FC in the prefrontal and motor cortices and find whether changes in FC correlate with changes in neuropsychological scores. Healthy young male individuals (n = 10, 27.6 ± 3.7 years of age) participated in the study. A battery of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and 48 channel functional near-infrared spectroscopy (fNIRS) measurements were performed before and after 24 hr of SD. Network metrics were obtained by graph theoretical analysis using the fNIRS records in resting state and during finger-tapping sessions. During task, SD resulted in a significantly smaller decrease in the number and strength of functional connections (characterizing FC) in the frontal cortex. Changes in the global connection strengths correlated with decreased performance in the paired association learning test. These results indicate a global impact of SD on functional brain networks in the frontal lobes.

Corrigendum: Two-Tiered Response of Cardiorespiratory-Cerebrovascular Network to Orthostatic Challenge.

[This corrects the article DOI: 10.3389/fphys.2021.622569.].

Two-Tiered Response of Cardiorespiratory-Cerebrovascular Network to Orthostatic Challenge.

Dynamic interdependencies within and between physiological systems and subsystems are key for homeostatic mechanisms to establish an optimal state of the organism. These interactions mediate regulatory responses elicited by various perturbations, such as the high-pressure baroreflex and cerebral autoregulation, alleviating the impact of orthostatic stress on cerebral hemodynamics and oxygenation. The aim of this study was to evaluate the responsiveness of the cardiorespiratory-cerebrovascular networks by capturing linear and nonlinear interdependencies to postural changes. Ten young healthy adults participated in our study. Non-invasive measurements of arterial blood pressure (from that cardiac cycle durations were derived), breath-to-breath interval, cerebral blood flow velocity (BFV, recorded by transcranial Doppler sonography), and cerebral hemodynamics (HbT, total hemoglobin content monitored by near-infrared spectroscopy) were performed for 30-min in resting state, followed by a 1-min stand-up and a 1-min sit-down period. During preprocessing, noise was filtered and the contribution of arterial blood pressure was regressed from BFV and HbT signals. Cardiorespiratory-cerebrovascular networks were reconstructed by computing pair-wise Pearson-correlation or mutual information between the resampled signals to capture their linear and/or nonlinear interdependencies, respectively. The interdependencies between cardiac, respiratory, and cerebrovascular dynamics showed a marked weakening after standing up persisting throughout the sit-down period, which could mainly be attributed to strikingly attenuated nonlinear coupling. To summarize, we found that postural changes induced topological changes in the cardiorespiratory-cerebrovascular network. The dissolution of nonlinear networks suggests that the complexity of key homeostatic mechanisms maintaining cerebral hemodynamics and oxygenation is indeed sensitive to physiological perturbations such as orthostatic stress.

Separating scale-free and oscillatory components of neural activity in schizophrenia.

INTRODUCTION: Alterations in narrow-band spectral power of electroencephalography (EEG) recordings are commonly reported in patients with schizophrenia (SZ). It is well established however that electrophysiological signals comprise a broadband scale-free (or fractal) component generated by mechanisms different from those producing oscillatory neural activity. Despite this known feature, it has not yet been investigated if spectral abnormalities found in SZ could be attributed to scale-free or oscillatory brain function. METHODS: In this study, we analyzed resting-state EEG recordings of 14 SZ patients and 14 healthy controls. Scale-free and oscillatory components of the power spectral density (PSD) were separated, and band-limited power (BLP) of the original (mixed) PSD, as well as its fractal and oscillatory components, was estimated in five frequency bands. The scaling property of the fractal component was characterized by its spectral exponent in two distinct frequency ranges (1-13 and 13-30 Hz). RESULTS: Analysis of the mixed PSD revealed a decrease of BLP in the delta band in SZ over the central regions; however, this difference could be attributed almost exclusively to a shift of power toward higher frequencies in the fractal component. Broadband neural activity expressed a true bimodal nature in all except frontal regions. Furthermore, both low- and high-range spectral exponents exhibited a characteristic topology over the cortex in both groups. CONCLUSION: Our results imply strong functional significance of scale-free neural activity in SZ and suggest that abnormalities in PSD may emerge from alterations of the fractal and not only the oscillatory components of neural activity.

Decreased connection density and modularity of functional brain networks during n-back working memory paradigm.

INTRODUCTION: Investigating how the brain adapts to increased mental workload through large-scale functional reorganization appears as an important research question. Functional connectivity (FC) aims at capturing how disparate regions of the brain dynamically interact, while graph theory provides tools for the topological characterization of the reconstructed functional networks. Although numerous studies investigated how FC is altered in response to increased working memory (WM) demand, current results are still contradictory as few studies confirmed the robustness of these findings in a low-density setting. METHODS: In this study, we utilized the n-back WM paradigm, in which subjects were presented stimuli (single digits) sequentially, and their task was to decide for each given stimulus if it matched the one presented n-times earlier. Electroencephalography recordings were performed under a control (0-back) and two task conditions of varying difficulty (2- and 3-back). We captured the characteristic connectivity patterns for each difficulty level by performing FC analysis and described the reconstructed functional networks with various graph theoretical measures. RESULTS: We found a substantial decrease in FC when transitioning from the 0- to the 2- or 3-back conditions, however, no differences relating to task difficulty were identified. The observed changes in brain network topology could be attributed to the dissociation of two (frontal and occipitotemporal) functional modules that were only present during the control condition. Furthermore, behavioral and performance measures showed both positive and negative correlations to connectivity indices, although only in the higher frequency bands. CONCLUSION: The marked decrease in FC may be due to temporarily abandoned connections that are redundant or irrelevant in solving the specific task. Our results indicate that FC analysis is a robust tool for investigating the response of the brain to increased cognitive workload.

Multifractal and Entropy-Based Analysis of Delta Band Neural Activity Reveals Altered Functional Connectivity Dynamics in Schizophrenia.

Dynamic functional connectivity (DFC) was established in the past decade as a potent approach to reveal non-trivial, time-varying properties of neural interactions - such as their multifractality or information content -, that otherwise remain hidden from conventional static methods. Several neuropsychiatric disorders were shown to be associated with altered DFC, with schizophrenia (SZ) being one of the most intensely studied among such conditions. Here we analyzed resting-state electroencephalography recordings of 14 SZ patients and 14 age- and gender-matched healthy controls (HC). We reconstructed dynamic functional networks from delta band (0.5-4 Hz) neural activity and captured their spatiotemporal dynamics in various global network topological measures. The acquired network measure time series were made subject to dynamic analyses including multifractal analysis and entropy estimation. Besides group-level comparisons, we built a classifier to explore the potential of DFC features in classifying individual cases. We found stronger delta-band connectivity, as well as increased variance of DFC in SZ patients. Surrogate data testing verified the true multifractal nature of DFC in SZ, with patients expressing stronger long-range autocorrelation and degree of multifractality when compared to controls. Entropy analysis indicated reduced temporal complexity of DFC in SZ. When using these indices as features, an overall cross-validation accuracy surpassing 89% could be achieved in classifying individual cases. Our results imply that dynamic features of DFC such as its multifractal properties and entropy are potent markers of altered neural dynamics in SZ and carry significant potential not only in better understanding its pathophysiology but also in improving its diagnosis. The proposed framework is readily applicable for neuropsychiatric disorders other than schizophrenia.

Scale-Free Coupled Dynamics in Brain Networks Captured by Bivariate Focus-Based Multifractal Analysis.

While most connectivity studies investigate functional connectivity (FC) in a scale-dependent manner, coupled neural processes may also exhibit broadband dynamics, manifesting as power-law scaling of their measures of interdependence. Here we introduce the bivariate focus-based multifractal (BFMF) analysis as a robust tool for capturing such scale-free relations and use resting-state electroencephalography (EEG) recordings of 12 subjects to demonstrate its performance in reconstructing physiological networks. BFMF was employed to characterize broadband FC between 62 cortical regions in a pairwise manner, with all investigated connections being tested for true bivariate multifractality. EEG channels were also grouped to represent the activity of six resting-state networks (RSNs) in the brain, thus allowing for the analysis of within- and between- RSNs connectivity, separately. Most connections featured true bivariate multifractality, which could be attributed to the genuine scale-free coupling of neural dynamics. Bivariate multifractality showed a characteristic topology over the cortex that was highly concordant among subjects. Long-term autocorrelation was higher in within-RSNs, while the degree of multifractality was generally found stronger in between-RSNs connections. These results offer statistical evidence of the bivariate multifractal nature of functional coupling in the brain and validate BFMF as a robust method to capture such scale-independent coupled dynamics.

Multifractal and entropy analysis of resting-state electroencephalography reveals spatial organization in local dynamic functional connectivity.

Functional connectivity of the brain fluctuates even in resting-state condition. It has been reported recently that fluctuations of global functional network topology and those of individual connections between brain regions expressed multifractal scaling. To expand on these findings, in this study we investigated if multifractality was indeed an inherent property of dynamic functional connectivity (DFC) on the regional level as well. Furthermore, we explored if local DFC showed region-specific differences in its multifractal and entropy-related features. DFC analyses were performed on 62-channel, resting-state electroencephalography recordings of twelve young, healthy subjects. Surrogate data testing verified the true multifractal nature of regional DFC that could be attributed to the presumed nonlinear nature of the underlying processes. Moreover, we found a characteristic spatial distribution of local connectivity dynamics, in that frontal and occipital regions showed stronger long-range correlation and higher degree of multifractality, whereas the highest values of entropy were found over the central and temporal regions. The revealed topology reflected well the underlying resting-state network organization of the brain. The presented results and the proposed analysis framework could improve our understanding on how resting-state brain activity is spatio-temporally organized and may provide potential biomarkers for future clinical research.

Multifractal Dynamic Functional Connectivity in the Resting-State Brain.

Assessing the functional connectivity (FC) of the brain has proven valuable in enhancing our understanding of brain function. Recent developments in the field demonstrated that FC fluctuates even in the resting state, which has not been taken into account by the widely applied static approaches introduced earlier. In a recent study using functional near-infrared spectroscopy (fNIRS) global dynamic functional connectivity (DFC) has also been found to fluctuate according to scale-free i.e., fractal dynamics evidencing the true multifractal (MF) nature of DFC in the human prefrontal cortex. Expanding on these findings, we performed electroencephalography (EEG) measurements in 14 regions over the whole cortex of 24 healthy, young adult subjects in eyes open (EO) and eyes closed (EC) states. We applied dynamic graph theoretical analysis to capture DFC by computing the pairwise time-dependent synchronization between brain regions and subsequently calculating the following dynamic graph topological measures: Density, Clustering Coefficient, and Efficiency. We characterized the dynamic nature of these global network metrics as well as local individual connections in the networks using focus-based multifractal time series analysis in all traditional EEG frequency bands. Global network topological measures were found fluctuating-albeit at different extent-according to true multifractal nature in all frequency bands. Moreover, the monofractal Hurst exponent was found higher during EC than EO in the alpha and beta bands. Individual connections showed a characteristic topology in their fractal properties, with higher autocorrelation owing to short-distance connections-especially those in the frontal and pre-frontal cortex-while long-distance connections linking the occipital to the frontal and pre-frontal areas expressed lower values. The same topology was found with connection-wise multifractality in all but delta band connections, where the very opposite pattern appeared. This resulted in a positive correlation between global autocorrelation and connection-wise multifractality in the higher frequency bands, while a strong anticorrelation in the delta band. The proposed analytical tools allow for capturing the fine details of functional connectivity dynamics that are evidently present in DFC, with the presented results implying that multifractality is indeed an inherent property of both global and local DFC.