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.

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.

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.

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.

Model-based evaluation of the microhemodynamic effects of PEGylated HBOC molecules in the rat brain cortex: a laser speckle imaging study.

Hemoglobin-based oxygen carriers (HBOCs) were developed with the aim of substituting transfusions in emergency events. However, they exhibit adverse events, such as nitric oxide (NO) scavenging, vasoactivity, enhanced platelet aggregation, presently hampering their clinical application. The impact of two prototypical PEGylated HBOCs, Euro-PEG-Hb and PEG-HbO2, endowed by different oxygen affinities and hydrodynamic volumes, was assessed on the cerebrocortical parenchymal microhemodynamics, and extravasation through the blood-brain-barrier (BBB) by laser speckle contrast imaging (LSCI) method and near-infrared (NIR) imaging, respectively. By evaluating voxel-wise cerebrocortical red blood cell velocity, non-invasively for its mean kernel-wise value ( v ¯ RBC ), and model-derived kernel-wise predictions for microregional tissue hematocrit, THt, and fractional change in hematocrit-corrected vascular resistance, R', as measures of potential adverse effects (enhanced platelet aggregation and vasoactivity, respectively) we found i) no significant difference between tested HBOCs in the systemic and microregional parameters, and in the relative spatial dispersion of THt, and R' as additional measures of HBOC-related adverse effects, and ii) no extravasation through BBB by Euro-PEG-Hb. We conclude that Euro-PEG-Hb does not exhibit adverse effects in the brain microcirculation that could be directly attributed to NO scavenging.

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.

Engineering tyrosine residues into hemoglobin enhances heme reduction, decreases oxidative stress and increases vascular retention of a hemoglobin based blood substitute.

Hemoglobin (Hb)-based oxygen carriers (HBOC) are modified extracellular proteins, designed to replace or augment the oxygen-carrying capacity of erythrocytes. However, clinical results have generally been disappointing due to adverse side effects, in part linked to the intrinsic oxidative toxicity of Hb. Previously a redox-active tyrosine residue was engineered into the Hb ß subunit (ßF41Y) to facilitate electron transfer between endogenous antioxidants such as ascorbate and the oxidative ferryl heme species, converting the highly oxidizing ferryl species into the less reactive ferric (met) form. We inserted different single tyrosine mutations into the α and ß subunits of Hb to determine if this effect of ßF41Y was unique. Every mutation that was inserted within electron transfer range of the protein surface and the heme increased the rate of ferryl reduction. However, surprisingly, three of the mutations (ßT84Y, αL91Y and ßF85Y) also increased the rate of ascorbate reduction of ferric(met) Hb to ferrous(oxy) Hb. The rate enhancement was most evident at ascorbate concentrations equivalent to that found in plasma (< 100 µM), suggesting that it might be of benefit in decreasing oxidative stress in vivo. The most promising mutant (ßT84Y) was stable with no increase in autoxidation or heme loss. A decrease in membrane damage following Hb addition to HEK cells correlated with the ability of ßT84Y to maintain the protein in its oxygenated form. When PEGylated and injected into mice, ßT84Y was shown to have an increased vascular half time compared to wild type PEGylated Hb. ßT84Y represents a new class of mutations with the ability to enhance reduction of both ferryl and ferric Hb, and thus has potential to decrease adverse side effects as one component of a final HBOC product.

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.

Impact of Healthy Aging on Multifractal Hemodynamic Fluctuations in the Human Prefrontal Cortex.

Fluctuations in resting-state cerebral hemodynamics show scale-free behavior over two distinct scaling ranges. Changes in such bimodal (multi) fractal pattern give insight to altered cerebrovascular or neural function. Our main goal was to assess the distribution of local scale-free properties characterizing cerebral hemodynamics and to disentangle the influence of aging on these multifractal parameters. To this end, we obtained extended resting-state records (N = 214) of oxyhemoglobin (HbO), deoxyhemoglobin (HbR) and total hemoglobin (HbT) concentration time series with continuous-wave near-infrared spectroscopy technology from the brain cortex. 52 healthy volunteers were enrolled in this study: 24 young (30.6 ± 8.2 years), and 28 elderly (60.5 ± 12.0 years) subjects. Using screening tests on power-law, multifractal noise, and shuffled data sets we evaluated the presence of true multifractal hemodynamics reflecting long-range correlation (LRC). Subsequently, scaling-range adaptive bimodal signal summation conversion (SSC) was performed based on standard deviation (σ) of signal windows across a range of temporal scales (s). Building on moments of different order (q) of the measure, σ(s), multifractal SSC yielded generalized Hurst exponent function, H(q), and singularity spectrum, D(h) separately for a fast and slow component (the latter dominating the highest temporal scales). Parameters were calculated reflecting the estimated measure at s = N (focus), degree of LRC [Hurst exponent, H(2) and maximal Hölder exponent, hmax] and measuring strength of multifractality [full-width-half-maximum of D(h) and ΔH15 = H(-15)-H(15)]. Correlation-based signal improvement (CBSI) enhanced our signal in terms of interpreting changes due to neural activity or local/systemic hemodynamic influences. We characterized the HbO-HbR relationship with the aid of fractal scale-wise correlation coefficient, rσ(s) and SSC-based multifractal covariance analysis. In the majority of subjects, cerebral hemodynamic fluctuations proved bimodal multifractal. In case of slow component of raw HbT, hmax, and H(2) were lower in the young group explained by a significantly increased rσ(s) among elderly at high temporal scales. Regarding the fast component of CBSI-pretreated HbT and that of HbO-HbR covariance, hmax, and focus were decreased in the elderly group. These observations suggest an attenuation of neurovascular coupling reflected by a decreased autocorrelation of the neuronal component concomitant with an accompanying increased autocorrelation of the non-neuronal component in the elderly group.

Multifractal dynamics of resting-state functional connectivity in the prefrontal cortex.

Brain function is organized as a network of functional connections between different neuronal populations with connection strengths dynamically changing in time and space. Studies investigating functional connectivity (FC) usually follow a static approach when describing FC by considering the connectivity strengths constant, however a dynamic approach seems more reasonable, as this way the spatio-temporal dynamics of the underlying system can also be captured. OBJECTIVE: The scale-free, i.e. fractal nature of neural dynamics is an inherent property of the nervous system. The aim of this study was to determine if dynamic functional connectivity (DFC) in the prefrontal cortex shows not only scale-free but indeed multifractal dynamics. APPROACH: Functional near-infrared spectroscopy (fNIRS) was used to monitor resting-state brain activity in young healthy volunteers. Sliding window correlation (SWC) analysis and graph theory approach were utilized to capture the functional connection networks for every time point, whose topology was subsequently characterized with three network metrics-Density, Clustering Coefficient and Efficiency-each capturing a different aspect of the given network. The temporal structuring of the obtained network metric time series was then described by multifractal time series analysis. MAIN RESULTS: We found the DFC in the prefrontal cortex fluctuating according to scale-free, specifically multifractal dynamics. Moreover, different topological properties of the network showed different multifractal characteristics. All the results were reproducible in all window sizes used in the SWC analysis, however we found that the actual values of the given multifractal properties depended significantly on the window size. SIGNIFICANCE: Our results may well be another indication of a self-organized critical state underlying resting-state brain activity. The proposed analysis of functional brain dynamics can also open new perspectives for future clinical applications.

Increased prefrontal cortex connectivity during cognitive challenge assessed by fNIRS imaging.

In this study, functional near-infrared spectroscopy (fNIRS) and the graph theory approach were used to access the functional connectivity (FC) of the prefrontal cortex (PFC) in a resting state and during increased mental workload. For this very purpose, a pattern recognition-based test was developed, which elicited a strong response throughout the PFC during the test condition. FC parameters obtained during stimulation were found increased compared to those in a resting state after correlation based signal improvement (CBSI), which can attenuate those components of fNIRS signals which are unrelated to neural activity. These results indicate that the cognitive challenge increased the FC in the PFC and suggests a great potential in investigating FC in various cognitive states.