Search

Gamma oscillation regularity (GOR) indicates the synchronization of inhibitory interneurons, while the reactivity of cortico-cortical evoked potentials (CCEPs) is supposed to reflect local cortical excitability. Under the assumption that the early response of CCEP near the stimulation site also indicates excitatory activity primarily mediated by pyramidal cells, we aimed to visualize the cortical inhibitory and excitatory activities using GOR and CCEP in combination and to use them to predict the epileptogenic zone (EZ) in mesial temporal lobe epilepsy (MTLE). In five patients who underwent intracranial electrode implantation, GOR and CCEP reactivity in the vicinity of the stimulation site was quantified. The interictal GOR was calculated using multiscale entropy (MSE), the decrease of which was related to the enhanced GOR. These parameters were compared on an electrode-and-electrode basis, and spatially visualized on the brain surface. As a result, elevated GOR and CCEP reactivities, indicative of enhanced inhibitory and excitatory activities, were observed in the epileptogenic regions. Elevated CCEP reactivity was found to be localized to a restricted area centered on the seizure onset region, whereas GOR elevation was observed in a broader region surrounding it. Although these parameters independently predicted the EZ with high specificity, we combined the two to introduce a novel parameter, the excitatory and inhibitory (EI) index. The EI index predicted EZ with increased specificity compared with GOR or CCEP reactivity alone. Our results demonstrate that GOR and CCEP reactivity provided a quantitative visualization of the distribution of cortical inhibitory and excitatory activities and highlighted the relationship between the two parameters. The combination of GOR and CCEP reactivities are expected to serve as biomarkers for localizing the epileptogenic zone in MTLE from interictal intracranial electroencephalograms., Competing Interests: The authors declare that this study was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2024 Nagata, Kunii, Fujitani, Shimada and Saito.)

Introduction: Tai Chi has proved to be an effective therapy for balance performance and cognition. However, non-consistency exists in the results of the effect of Tai Chi training on standing balance control in older adults. This study aimed to use traditional and non-traditional methods to investigate the effect of Tai Chi on standing balance in older adults., Methods: Thirty-six Tai Chi practitioners (TC group) and thirty-six older adults with no Tai Chi practice (control group) were recruited in this study. A Nintendo Wii Balance Board was used to record the center of pressure (COP) during standing balance over 20 s in the condition of eyes closed with three repetitions. The wavelet analysis, multiscale entropy, recurrence quantification analysis, and traditional methods were used to evaluate the standing balance control in the anterior-posterior (AP) and mediolateral (ML) directions., Results: (1) Greater sway mean velocity in the AP direction and sway Path length were found in the TC group compared with the control group; (2) lower Very-low frequency band (0.10-0.39 Hz) and higher Moderate frequency band (1.56-6.25 Hz) in the AP and ML directions were found in the TC group compared with the control group; (3) greater complexity index (CI) and lower determinism (DET) in the AP and ML directions were observed in the TC group compared with control group; (4) greater path length linked with smaller Very-low frequency band in the AP and ML directions and higher Moderate frequency band in the AP direction in both groups; (5) greater path length linked with lower DET and higher CI in the AP direction only in the TC group., Conclusion: Long-term Tai Chi practice improved sensory reweighting (more reliance on the proprioception system and less reliance on the vestibular system) and complexity of standing balance control in older adults. In addition, greater sway velocity may be as an exploratory role in standing balance control of TC older adults, which correlated with greater complexity, but no such significant relationship in the control group. Therefore, the effects of Tai Chi practice on standing balance control in older adults may be attributed to the improvement of sensory reweighting and complexity rather than reduced sway velocity or amplitude., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cui, Hao, Tian, Yang, Wang and Lin.)

Background: Cognitive impairment disrupts postural control, particularly when standing while performing an unrelated cognitive task (i.e., dual-tasking). The temporal dynamics of standing postural sway are "complex," and such complexity may reflect the capacity of the postural control system to adapt to task demands. We aimed to characterize the impact of cognitive impairment on such sway complexity in older adults., Methods: Forty-nine older adult males (Alzheimer's disease (AD): n  = 21; mild cognitive impairment (MCI): n  = 13; cognitively-intact: n  = 15) completed two 60-s standing trials in each of single-task and visual-search dual-task conditions. In the dual-task condition, participants were instructed to count the frequency of a designated letter in a block of letters projected on screen. The sway complexity of center-of-pressure fluctuations in anterior-posterior (AP) and medial-lateral (ML) direction was quantified using multiscale entropy. The dual-task cost to complexity was obtained by calculating the percent change of complexity from single- to dual-task condition., Results: Repeated-measures ANOVAs revealed significant main effects of group ( F  > 4.8, p  < 0.01) and condition ( F  = 7.7, p  < 0.007) on both AP and ML sway complexity; and significant interaction between group and condition for ML sway complexity ( F  = 3.7, p  = 0.03). The AD group had the lowest dual-task ML complexity, as well as greater dual-task cost to ML ( p  = 0.03) compared to the other two groups. Visual-search task accuracy was correlated with ML sway complexity in the dual-task condition ( r  = 0.42, p  = 0.007), and the dual-task cost to ML sway complexity ( r  = 0.39, p  = 0.01) across all participants., Conclusion: AD-related cognitive impairment was associated with a greater relative reduction in postural sway complexity from single- to dual-tasking. Sway complexity appears to be sensitive to the impact of cognitive impairment on standing postural control., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Manor, McCarten, Wade and Jor’dan.)

Mental fatigue (MF) jeopardizes performance and safety through a variety of cognitive impairments and according to the complexity loss theory, should represent "complexity loss" in electroencephalogram (EEG). However, the studies are few and inconsistent concerning the relationship between MF and loss of complexity, probably because of the susceptibility of brain waves to noise. In this study, MF was induced in thirteen male college students by a simulated flight task. Before and at the end of the task, spontaneous EEG and auditory steady-state response (ASSR) were recorded and instantaneous frequency variation (IFV) in alpha rhythm was extracted and analyzed by multiscale entropy (MSE) analysis. The results show that there were significant differences in IFV in alpha rhythm either from spontaneous EEG or from ASSR for all subjects. Therefore, the proposed method can be effective in revealing the complexity loss caused by MF in spontaneous EEG and ASSR, which may serve as a promising analyzing method to mark mild mental impairments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhai, Li, Zhou, Zhang, Luo, Tang and Xie.)

Background: Patients with generalized epilepsy who had lateralized EEG abnormalities after corpus callosotomy (CC) occasionally undergo subsequent surgeries to control intractable epilepsy., Objectives: This study evaluated retrospectively the combination of EEG multiscale entropy (MSE) and FDG-PET for identifying lateralization of the epileptogenic zone after CC., Methods: This study included 14 patients with pharmacoresistant epilepsy who underwent curative epilepsy surgery after CC. Interictal scalp EEG and FDG-PET obtained after CC were investigated to determine (1) whether the MSE calculated from the EEG and FDG-PET findings was lateralized to the surgical side, and (2) whether the lateralization was associated with seizure outcomes., Results: Seizure reduction rate was higher in patients with lateralized findings to the surgical side than those without (MSE: p < 0.05, FDG-PET: p < 0.05, both: p < 0.01). Seizure free rate was higher in patients with lateralized findings in both MSE and FDG-PET than in those without ( p < 0.05)., Conclusions: This study demonstrated that patients with lateralization of MSE and FDG-PET to the surgical side had better seizure outcomes. The combination of MSE and conventional FDG-PET may help to select surgical candidates for additional surgery after CC with good postoperative seizure outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kosugi, Iijima, Yokosako, Takayama, Kimura, Kaneko, Sumitomo, Saito, Nakagawa, Sato and Iwasaki.)

Background: The pathophysiology of depression in Parkinson's disease (PD) is not fully understood. Studies based upon functional MRI (fMRI) showed the alterations in the blood-oxygen-level-dependent (BOLD) fluctuations in multiple brain regions pertaining to depression in PD. However, large variance was observed across previous studies. Therefore, we conducted a meta-analysis to quantitatively evaluate the results in previous publications and completed an independent regions-of-interests (ROIs)-based analysis using our own data to validate the results of the meta-analysis., Methods: We searched PubMed, Embase, and Web of Science to identify fMRI studies in PD patients with depression. Using signed differential mapping (SDM) method, we performed a voxel-based meta-analysis. Then, a validation study by using multiscale entropy (MSE) in 28 PD patients with depression and 25 PD patients without depression was conducted. The fMRI scan was completed in anti-depression-medication-off state. The ROIs of the MSE analysis were the regions identified by the meta-analysis., Results: A total of 126 PD patients with depression and 153 PD patients without depression were included in meta-analysis. It was observed that the resting-state activities within the posterior cingulate gyrus, supplementary motor area (SMA), and cerebellum were altered in depressed patients. Then, in the validation study, these regions were used as ROIs. PD patients with depression had significantly lower MSE of the BOLD fluctuations in these regions (posterior cingulate gyrus: F = 0.856, p = 0.049; SMA: F = 0.914, p = 0.039; cerebellum: F = 0.227, p = 0.043)., Conclusion: Our study revealed that the altered BOLD activity in cingulate, SMA, and cerebellum of the brain were pertaining to depression in PD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Su, Cui, Liu, Chen, Fang, Ma, Zhou and Feng.)

Background: The autonomic nervous system (ANS) is crucial for acclimatization. Investigating the responses of acute exposure to a hypoxic environment may provide some knowledge of the cardiopulmonary system's adjustment mechanism. Objective : The present study investigates the longitudinal changes and recovery in heart rate variability (HRV) in a young healthy population when exposed to a simulated plateau environment. Methods : The study followed a strict experimental paradigm in which physiological signals were collected from 33 healthy college students (26 ± 2 years, 171 cm ± 7 cm, 64 ± 11 kg) using a medical-grade wearable device. The subjects were asked to sit in normoxic (approximately 101 kPa) and hypoxic (4,000 m above sea level, about 62 kPa) environments. The whole experimental process was divided into four stable resting measurement segments in chronological order to analyze the longitudinal changes of physical stress and recovery phases. Seventy-six time-domain, frequency-domain, and non-linear indicators characterizing rhythm variability were analyzed in the four groups. Results: Compared to normobaric normoxia, participants in hypobaric hypoxia had significantly lower HRV time-domain metrics, such as RMSSD, MeanNN, and MedianNN ( p  < 0.01), substantially higher frequency domain metrics such as LF/HF ratio ( p  < 0.05), significantly lower Poincaré plot parameters such as SD1/SD2 ratio and other Poincaré plot parameters are reduced considerably ( p  < 0.01), and Refined Composite Multi-Scale Entropy (RCMSE) curves are reduced significantly ( p  < 0.01). Conclusion: The present study shows that elevated heart rates, sympathetic activation, and reduced overall complexity were observed in healthy subjects exposed to a hypobaric and hypoxic environment. Moreover, the results indicated that Multiscale Entropy (MSE) analysis of RR interval series could characterize the degree of minor physiological changes. This novel index of HRV can better explain changes in the human ANS., Competing Interests: KL was employed by the company Beijing SensEcho Science & Technology Co., Ltd., Beijing, China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ma, Xu, Yan, Huang, Yan, Lan, Wang and Zhang.)

Introduction: Fragile X syndrome (FXS) is a genetic disorder caused by a mutation of the fragile X mental retardation 1 gene ( FMR1 ). FXS is associated with neurophysiological abnormalities, including cortical hyperexcitability. Alterations in electroencephalogram (EEG) resting-state power spectral density (PSD) are well-defined in FXS and were found to be linked to neurodevelopmental delays. Whether non-linear dynamics of the brain signal are also altered remains to be studied. Methods: In this study, resting-state EEG power, including alpha peak frequency (APF) and theta/beta ratio (TBR), as well as signal complexity using multi-scale entropy (MSE) were compared between 26 FXS participants (ages 5-28 years), and 7 neurotypical (NT) controls with a similar age distribution. Subsequently a replication study was carried out, comparing our cohort to 19 FXS participants independently recorded at a different site. Results: PSD results confirmed the increased gamma, decreased alpha power and APF in FXS participants compared to NT controls. No alterations in TBR were found. Importantly, results revealed reduced signal complexity in FXS participants, specifically in higher scales, suggesting that altered signal complexity is sensitive to brain alterations in this population. The replication study mostly confirmed these results and suggested critical points of stagnation in the neurodevelopmental curve of FXS. Conclusion: Signal complexity is a powerful feature that can be added to the electrophysiological biomarkers of brain maturation in FXS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Proteau-Lemieux, Knoth, Agbogba, Côté, Barlahan Biag, Thurman, Martin, Bélanger, Rosenfelt, Tassone, Abbeduto, Jacquemont, Hagerman, Bolduc, Hessl, Schneider and Lippé.)

The mild cognitive impairment (MCI) stage plays an essential role in preventing the progression of older adults to Alzheimer's disease. In this study, neurofeedback training (NFT) is applied to improve MCI brain cognitive function. To assess the improvement effect, a novel algorithm called Weighted Multiple Multiscale Entropy (WMMSE) is proposed to extract and analyze the electroencephalogram (EEG) features of patients with MCI. To overcome the information loss problem of traditional multiscale entropy (MSE), WMMSE fully considered the correlation of the sequence and the contribution of each sequence to the total entropy. The experimental group composed of 39 patients with MCI was subjected to NFT for 10 days during two sessions. The control group included 21 patients with MCI without any intervention. The Lempel-Ziv complexity (LZC) was used for primary assessment, and WMMSE was used to accurately analyze the effect of NFT. The results show that the WMMSE values of F4, C3, C4, O1, and T5 channels post-NFT are higher compared with pre-NFT and significant differences ( P < 0.05). Moreover, the cognitive subscale of the Montreal Cognitive Assessment (MoCA) results shows that the post-NFT score is higher than the pre-NFT in the vast majority of the patients with MCI and significant differences ( P < 0.05). When compared with the control group, the WMMSE values of the experimental group increased in each channel. Therefore, the NFT intervention method contributes to brain cognitive functional recovery, and WMMSE can be used as a biomarker to evaluate the state of MCI brain cognitive function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Su, Li, Liu, Cui, Xie and Han.)

Alzheimer's disease (AD) is the most common form of dementia and is a progressive neurodegenerative disease that primarily develops in old age. In recent years, it has been reported that early diagnosis of AD and early intervention significantly delays disease progression. Hence, early diagnosis and intervention are emphasized. As a diagnostic index for AD patients, evaluating the complexity of the dependence of the electroencephalography (EEG) signal on the temporal scale of Alzheimer's disease (AD) patients is effective. Multiscale entropy analysis and multifractal analysis have been performed individually, and their usefulness as diagnostic indicators has been confirmed, but the complemental relationship between these analyses, which may enhance diagnostic accuracy, has not been investigated. We hypothesize that combining multiscale entropy and fractal analyses may add another dimension to understanding the alteration of EEG dynamics in AD. In this study, we performed both multiscale entropy and multifractal analyses on EEGs from AD patients and healthy subjects. We found that the classification accuracy was improved using both techniques. These findings suggest that the use of multiscale entropy analysis and multifractal analysis may lead to the development of AD diagnostic tools., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ando, Nobukawa, Kikuchi and Takahashi.)

Objective: Intractable epilepsy and uncontrolled seizures could affect cardiac function and the autonomic nerve system with a negative impact on children's growth. The aim of this study was to investigate the variability and complexity of cardiac autonomic function in pre-school children with pediatric intractable epilepsy (PIE). Methods: Twenty four-hour Holter electrocardiograms (ECGs) from 93 patients and 46 healthy control subjects aged 3-6 years were analyzed by the methods of traditional heart rate variability (HRV), multiscale entropy (MSE), and Kurths-Wessel symbolization entropy (KWSE). Receiver operating characteristic (ROC) curve analysis was used to estimate the overall discrimination ability. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) models were also analyzed. Results: Pre-school children with PIE had significantly lower HRV measurements than healthy controls in time (Mean&#95;RR, SDRR, RMSSD, pNN50) and frequency (VLF, LF, HF, LF/HF, TP) domains. For the MSE analysis, area 1&#95;5 in awake state was lower, and areas 6&#95;15 and 6&#95;20 in sleep state were higher in PIE with a significant statistical difference. KWSE in the PIE group was also inferior to that in healthy controls. In ROC curve analysis, pNN50 had the greatest discriminatory power for PIE. Based on both NRI and IDI models, the combination of MSE indices (wake: area1&#95;5 and sleep: area6&#95;20) and KWSE (m = 2, τ = 1, α = 0.16) with traditional HRV measures had greater discriminatory power than any of the single HRV measures. Significance: Impaired HRV and complexity were found in pre-school children with PIE. HRV, MSE, and KWSE could discriminate patients with PIE from subjects with normal cardiac complexity. These findings suggested that the MSE and KWSE methods may be helpful for assessing and understanding heart rate dynamics in younger children with epilepsy., Competing Interests: HH and LL reported personal fees from Beijing Pins Medical Co., outside the submitted work. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Cheng, Deng, Wang, Qin, Fang, Yuan, Hao, Jiang, Liao, Yin, Chen, Zou, Li, Gao, Shu, Huang, Gao, Liang and Li.)

Background: Older adults with hypertension often had diminished walking performance. The underlying mechanism through which hypertension affects walking performance, however, has not been fully understood. We here measured the complexity of the continuous systolic (SBP) and diastolic (DBP) blood pressure fluctuation, grade of white matter lesions (WMLs), and cognitive function and used structural equation modeling (SEM) to examine the interrelationships between hypertension, BP complexity, WMLs, cognitive function, and walking speed in single- and dual-task conditions. Methods: A total of 152 older adults with age > 60 years (90 hypertensive and 62 normotensive participants) completed one MRI scan of brain structure, a finger BP assessment of at least 10 min, Mini-Mental State Examination (MMSE) to assess cognitive function, and 10-meter walking tests in single (i.e., normal walking) and dual tasks (i.e., walking while performing a serial subtraction of three from a random three-digit number). The grade of WMLs was assessed using the total score of Fazekas scale; the complexity of SBP and DBP was measured using multiscale entropy (MSE), and the walking performance was assessed by walking speed in single- and dual-task conditions. Results: As compared to normotensives, hypertensive older adults had significantly slower walking speed, lower complexity of SBP and DBP, greater grade of WMLs, and poorer cognitive function ( p < 0.03). Those with lower BP complexity (β > 0.31, p < 0.003), greater WML grade (β < -0.39, p < 0.0002), and/or poorer cognitive function (β < -0.39, p < 0.0001) had slower walking speed in single- and/or dual-task conditions. The SEM model demonstrated significant total effects of hypertension on walking speed, and such effects were mediated by BP complexity only, or BP complexity, WML grade, and cognitive function together. Conclusion: This study demonstrates the cross-sectional association between the complexity of continuous beat-to-beat BP fluctuation, WML grade, cognitive function, and walking speed in hypertensive and normotensive older adults, revealing a potential mechanism that hypertension may affect walking performance in older adults through diminished BP complexity, increased WML grade, and decreased cognitive function, and BP complexity is an important factor for such effects. Future longitudinal studies are warranted to confirm the findings in this study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jiang, Cai, Zhao, Gao, Peng, Zhang, Deng, Fu, Qin, Chang, Manor and Zhou.)

We review the literature to argue the importance of the occurrence of crucial events in the dynamics of physiological processes. Crucial events are interpreted as short time intervals of turbulence, and the time distance between two consecutive crucial events is a waiting time distribution density with an inverse power law (IPL) index μ, with μ < 3 generating non-stationary behavior. The non-stationary condition is characterized by two regimes of the IPL index: (a) perennial non-stationarity, with 1 < μ < 2 and (b) slow evolution toward the stationary regime, with 2 < μ < 3. Human heartbeats and brain dynamics belong to the latter regime, with healthy physiological processes tending to be closer to the border with the perennial non-stationary regime with μ = 2. The complexity of cognitive tasks is associated with the mental effort required to address a difficult task, which leads to an increase of μ with increasing task difficulty. On this basis we explore the conjecture that disease evolution leads the IPL index μ moving from the healthy condition μ = 2 toward the border with Gaussian statistics with μ = 3, as the disease progresses. Examining heart rate time series of patients affected by diabetes-induced autonomic neuropathy of varying severity, we find that the progression of cardiac autonomic neuropathy (CAN) indeed shifts μ from the border with perennial variability, μ = 2, to the border with Gaussian statistics, μ = 3 and provides a novel, sensitive index for assessing disease progression. We find that at the Gaussian border, the dynamical complexity of crucial events is replaced by Gaussian fluctuation with long-time memory., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jelinek, Tuladhar, Culbreth, Bohara, Cornforth, West and Grigolini.)

Visual short-term memory (VSTM) is an important cognitive function that acts as a temporary storage for visual information. Previous studies have shown that VSTM capacity can be modulated by the location of one's hands, where hand proximity enhances neural processing and memory of nearby visual stimuli. The present study used traditional event-related potentials (ERP) along with multiscale entropy (MSE) analysis to shed light on the neural mechanism(s) behind such near-hand effect. Participants' electroencephalogram (EEG) data were recorded as they performed a VSTM task with their hands either proximal or distal to the display. ERP analysis showed altered memory processing in the 400-700 ms time window during memory retrieval period. Importantly, MSE analysis also showed significant EEG difference between hand proximal and distal conditions between scales 10 to 20, and such difference is clustered around the right parietal cortex - a region that is involved in VSTM processing and bimodal hand-eye integration. The implications of higher MSE time scale in the parietal cortex are discussed in the context of signal complexity and its possible relation to cognitive processing. To our knowledge, this study provides the first investigation using MSE to characterize the temporal characteristics and signal complexity behind the effect of hand proximity., (Copyright © 2020 Tseng and Lo.)

Recent empirical evidence reveals that creative idea generation builds upon an interplay of multiple neural networks. Measures of temporal complexity yield important information about the underlying mechanisms of these co-activated neural networks. A few neurophysiological studies investigated brain signal complexity (BSC) during the production of creative verbal associations and resting states, aiming to relate it with creative task performance. However, it is unknown whether the complexity of brain signals can distinguish between productions of typical and original verbal associations. In the present study, we investigated verbal creativity with multiscale entropy (MSE) of electroencephalography (EEG) signals, which quantifies complexity over multiple timescales, capturing unique dynamic features of neural networks. MSE was measured in verbal divergent thinking (DT) states while emphasizing on producing either typical verbal associations or original verbal associations. We hypothesized that MSE differentiates between brain states characterizing the production of typical and original associations and is a sensitive neural marker of individual differences in producing original associations. Results from a sample of N = 92 young adults revealed slightly higher average MSE for original as compared with typical association production in small and medium timescales at frontal electrodes and slightly higher average MSE for typical association production in higher timescales at parietal electrodes. However, measurement models failed to uncover specificity of individual differences as MSE in typical vs. original associations was perfectly correlated. Hence, individuals with higher MSE in original association condition also exhibit higher MSE during the production of typical associations. The difference between typical and original association MSE was not significantly associated with human-rated originality of the verbal associations. In sum, we conclude that MSE is a potential marker of creative verbal association states, but replications and extensions are needed, especially with respect to the brain-behavior relationships., (Copyright © 2020 Kaur, Ouyang, Sommer, Weiss, Zhou and Hildebrandt.)

The role of attentional focusing in motor tasks has been highlighted frequently. The "internal-external" dimension has emerged, but also the spatial distance between body and attended location. In two experiments, an extended attentional focus paradigm was introduced to investigate distality effects of attentional foci on balance performance. First, the distality of the coordinates of the point of focus was varied between a proximal and distal position on an artificial tool attached to the body. Second, the distance of the displayed effect on the wall was varied between a 2.5 and 5 m condition. Subjects were instructed to focus on controlling either a proximal or distal spot on a tool attached to their head, represented by two laser pointers. Subsequently, they needed to visually track their own body-movement effect of one of the laser pointers at a wall while completing various single leg stance tasks. Center of pressure (COP) sway was analyzed using a linear method (classic sway variables) as well as a non-linear method (multiscale entropy). In addition, laser trajectories were videotaped and served as additional performance outcome measure. Experiment 1 revealed differences in balance performance under proximal compared to distal attentional focus conditions. Moreover, experiment 2 yielded differences in balance-related sway measures and laser data between the 2.5 and 5 m condition of the visually observable movement effect. In conclusion, varying the distality of the point of focus between proximal and distal impacted balance performance. However, this effect was not consistent across all balance tasks. Relevantly, the distality of the movement effect shows a significant effect on balance plus laser performance with advantages in more distal conditions. This research emphasizes the importance of the spatial distality of movement effects for human behavior., (Copyright © 2020 Kupper, Roemer, Jusko and Zentgraf.)

The irregularity and uncertainty of neurophysiologic signals across different time scales can be regarded as neural complexity, which is related to the adaptability of the nervous system and the information processing between neurons. We recently reported general loss of brain complexity, as measured by multiscale sample entropy (MSE), at pain-related regions in females with primary dysmenorrhea (PDM). However, it is unclear whether this loss of brain complexity is associated with inter-subject genetic variations. Brain-derived neurotrophic factor (BDNF) is a widely expressed neurotrophin in the brain and is crucial to neural plasticity. The BDNF Val66Met single-nucleotide polymorphism (SNP) is associated with mood, stress, and pain conditions. Therefore, we aimed to examine the interactions of BDNF Val66Met polymorphism and long-term menstrual pain experience on brain complexity. We genotyped BDNF Val66Met SNP in 80 PDM females (20 Val/Val, 31 Val/Met, 29 Met/Met) and 76 healthy female controls (25 Val/Val, 36 Val/Met, 15 Met/Met). MSE analysis was applied to neural source activity estimated from resting-state magnetoencephalography (MEG) signals during pain-free state. We found that brain complexity alterations were associated with the interactions of BDNF Val66Met polymorphism and menstrual pain experience. In healthy female controls, Met carriers (Val/Met and Met/Met) demonstrated lower brain complexity than Val/Val homozygotes in extensive brain regions, suggesting a possible protective role of Val/Val homozygosity in brain complexity. However, after experiencing long-term menstrual pain, the complexity differences between different genotypes in healthy controls were greatly diminished in PDM females, especially in the limbic system, including the hippocampus and amygdala. Our results suggest that pain experience preponderantly affects the effect of BDNF Val66Met polymorphism on brain complexity. The results of the present study also highlight the potential utilization of resting-state brain complexity for the development of new therapeutic strategies in patients with chronic pain.

Alzheimer's disease (AD) is characterized by progressive deterioration of brain function among elderly people. Studies revealed aberrant correlations in spontaneous blood oxygen level-dependent (BOLD) signals in resting-state functional magnetic resonance imaging (rs-fMRI) over a wide range of temporal scales. However, the study of the temporal dynamics of BOLD signals in subjects with AD and mild cognitive impairment (MCI) remains largely unexplored. Multiscale entropy (MSE) analysis is a method for estimating the complexity of finite time series over multiple time scales. In this research, we applied MSE analysis to investigate the abnormal complexity of BOLD signals using the rs-fMRI data from the Alzheimer's disease neuroimaging initiative (ADNI) database. There were 30 normal controls (NCs), 33 early MCI (EMCI), 32 late MCI (LMCI), and 29 AD patients. Following preprocessing of the BOLD signals, whole-brain MSE maps across six time scales were generated using the Complexity Toolbox. One-way analysis of variance (ANOVA) analysis on the MSE maps of four groups revealed significant differences in the thalamus, insula, lingual gyrus and inferior occipital gyrus, superior frontal gyrus and olfactory cortex, supramarginal gyrus, superior temporal gyrus, and middle temporal gyrus on multiple time scales. Compared with the NC group, MCI and AD patients had significant reductions in the complexity of BOLD signals and AD patients demonstrated lower complexity than that of the MCI subjects. Additionally, the complexity of BOLD signals from the regions of interest (ROIs) was found to be significantly associated with cognitive decline in patient groups on multiple time scales. Consequently, the complexity or MSE of BOLD signals may provide an imaging biomarker of cognitive impairments in MCI and AD.

While geriatric patients have a high likelihood of requiring anesthesia, they carry an increased risk for adverse cognitive outcomes from its use. Previous work suggests this could be mitigated by better intraoperative monitoring using indexes defined by several processed electroencephalogram (EEG) measures. Unfortunately, inconsistencies between patients and anesthetic agents in current analysis techniques have limited the adoption of EEG as standard of care. In attempts to identify new analyses that discriminate clinically-relevant anesthesia timepoints, we tested 1/ f frequency scaling as well as measures of complexity from nonlinear dynamics. Specifically, we tested whether analyses that characterize time-delayed embeddings, correlation dimension (CD), phase-space geometric analysis, and multiscale entropy (MSE) capture loss-of-consciousness changes in EEG activity. We performed these analyses on EEG activity collected from a traditionally hard-to-monitor patient population: geriatric patients on beta-adrenergic blockade who were anesthetized using a combination of fentanyl and propofol. We compared these analyses to traditional frequency-derived measures to test how well they discriminated EEG states before and after loss of response to verbal stimuli. We found spectral changes similar to those reported previously during loss of response. We also found significant changes in 1/ f frequency scaling. Additionally, we found that our phase-space geometric characterization of time-delayed embeddings showed significant differences before and after loss of response, as did measures of MSE. Our results suggest that our new spectral and complexity measures are capable of capturing subtle differences in EEG activity with anesthesia administration-differences which future work may reveal to improve geriatric patient monitoring.

Methods from non-linear dynamics have enhanced understanding of functional dysregulation in various diseases but received less attention in diabetes. This retrospective cross-sectional study evaluates and compares relationships between indices of non-linear dynamics and traditional glycemic variability, and their potential application in diabetes control. Continuous glucose monitoring provided data for 177 subjects with type 1 ( n = 22), type 2 diabetes ( n = 143), and 12 non-diabetic subjects. Each time series comprised 576 glucose values. We calculated Poincaré plot measures (SD1, SD2), shape (SFE) and area of the fitting ellipse (AFE), multiscale entropy (MSE) index, and detrended fluctuation exponents ( α1, α2 ). The glycemic variability metrics were the coefficient of variation (%CV) and standard deviation. Time of glucose readings in the target range (TIR) defined the quality of glycemic control. The Poincaré plot indices and α exponents were higher ( p < 0.05) in type 1 than in the type 2 diabetes; SD1 (mmol/l): 1.64 ± 0.39 vs. 0.94 ± 0.35, SD2 (mmol/l): 4.06 ± 0.99 vs. 2.12 ± 1.04, AFE (mmol 2 /l 2 ): 21.71 ± 9.82 vs. 7.25 ± 5.92, and α1: 1.94 ± 0.12 vs. 1.75 ± 0.12, α2 : 1.38 ± 0.11 vs. 1.30 ± 0.15. The MSE index decreased consistently from the non-diabetic to the type 1 diabetic group (5.31 ± 1.10 vs. 3.29 ± 0.83, p < 0.001); higher indices correlated with lower %CV values ( r = -0.313, p < 0.001). In a subgroup of type 1 diabetes patients, insulin pump therapy significantly decreased SD1 (-0.85 mmol/l), SD2 (-1.90 mmol/l), and AFE (-16.59 mmol 2 /l 2 ), concomitantly with %CV (-15.60). The MSE index declined from 3.09 ± 0.94 to 1.93 ± 0.40 ( p = 0.001), whereas the exponents α1 and α2 did not. On multivariate regression analyses, SD1, SD2, SFE, and AFE emerged as dominant predictors of TIR ( β = -0.78, -1.00, -0.29, and -0.58) but %CV as a minor one, though α1 and MSE failed. In the regression models, including SFE, AFE, and α2 ( β = -0.32), %CV was not a significant predictor. Poincaré plot descriptors provide additional information to conventional variability metrics and may complement assessment of glycemia, but complexity measures produce mixed results.

The infant brain shows rapid neural network development that considerably influences cognitive and behavioral abilities in later life. Reportedly, this neural development process can be indexed by estimating neural signal complexity. However, the precise developmental trajectory of brain signal complexity during infancy remains elusive. This study was conducted to ascertain the trajectory of magnetoencephalography (MEG) signal complexity from 2 months to 3 years of age in five infants using multiscale entropy (MSE), which captures signal complexity at multiple temporal scales. Analyses revealed scale-dependent developmental trajectories. Specifically, signal complexity predominantly increased from 5 to 15 months of age at higher temporal scales, whereas the complexity at lower temporal scales was constant across age, except in one infant who showed decreased complexity. Despite a small sample size limiting this study's power, this is the first report of a longitudinal investigation of changes in brain signal complexity during early infancy and is unique in its application of MSE analysis of longitudinal MEG data during infancy. The results of this pilot study may serve to further our understanding of the longitudinal changes in the neural dynamics of the developing infant brain.

Complexity analysis of resting-state blood oxygen level-dependent (BOLD) signals using entropy methods has attracted considerable attention. However, investigation on the bias of entropy estimates in resting-state functional magnetic resonance imaging (fMRI) signals and a general strategy for selecting entropy parameters is lacking. In this paper, we present a minimizing error approach to reduce the bias of sample entropy (SampEn) and multiscale entropy (MSE) in resting-state fMRI data. The strategy explored a range of parameters that minimized the relative error of SampEn of BOLD signals in cerebrospinal fluids where minimal physiologic information was present, and applied these parameters to calculate SampEn of BOLD signals in gray matter regions. We examined the effect of various parameters on the results of SampEn and MSE analyses of a large normal aging adult cohort (354 healthy subjects aged 21-89 years). The results showed that a tradeoff between pattern length m and tolerance factor r was necessary to maintain the accuracy of SampEn estimates. Furthermore, an increased relative error of SampEn was associated with an increased coefficient of variation in voxel-wise statistics. Overall, the parameters m = 1 and r = 0.20-0.45 provided reliable MSE estimates in short resting-state fMRI signals. For a single-scale SampEn analysis, a wide range of parameters was available with data lengths of at least 97 time points. This study provides a minimization error strategy for future studies on the non-linear analysis of resting-state fMRI signals to account for the bias of entropy estimates.

Background: Impaired motor control is one of the most common symptoms of multiple system atrophy (MSA). It arises from dysfunction of the cerebellum and its connected neural networks, including the primary motor cortex (M1), and is associated with altered spontaneous (i.e., resting-state) brain network activity. Non-invasive repetitive transcranial magnetic stimulation (rTMS) selectively facilitates the excitability of supraspinal networks. Repeated rTMS sessions have been shown to induce long-term changes to both resting-state brain dynamics and behavior in several neurodegenerative diseases. Here, we hypothesized that a multi-session rTMS intervention would improve motor control in patients with MSA, and that such improvements would correlate with changes in resting-state brain activity. Methods: Nine participants with MSA received daily sessions of 5 Hz rTMS for 5 days. rTMS targeted both the cerebellum and the bilateral M1. Before and within 3 days after the intervention, motor control was assessed by the motor item of the Unified Multiple System Atrophy Rating Scale (UMSARS). Resting-state brain activity was recorded by blood-oxygen-level dependency (BOLD) functional magnetic resonance imaging. The "complexity" of resting-state brain activity fluctuations was quantified within seven well-known functional cortical networks using multiscale entropy, a technique that estimates the degree of irregularity of the BOLD time-series across multiple scales of time. Results: The rTMS intervention was well-attended and was not associated with any adverse events. Average motor scores were lower (i.e., better performance) following the rTMS intervention as compared to baseline ( t 8 = 2.3, p = 0.003). Seven of nine participants exhibited such pre-to-post intervention improvements. A trend toward an increase in resting-state complexity was observed within the motor network ( t 8 = 1.86, p = 0.07). Participants who exhibited greater increases in motor network resting-state complexity demonstrated greater improvement in motor control ( r 2 = 0.72, p = 0.004). Conclusion: This pilot study demonstrated that a five-session rTMS intervention targeting the cerebellum and bilateral M1 is feasible and safe for those with MSA. More definitive, well-controlled trials are warranted to confirm our preliminary results that rTMS may alleviate the severity of motor dysfunction and modulate the multiscale dynamics of motor network brain activity.

Pulse oximetry is routinely used for monitoring patients' oxygen saturation levels with little regard to the variability of this physiological variable. There are few published studies on oxygen saturation variability (OSV), with none describing the variability and its pattern in a healthy adult population. The aim of this study was to characterize the pattern of OSV using several parameters; the regularity (sample entropy analysis), the self-similarity [detrended fluctuation analysis (DFA)] and the complexity [multiscale entropy (MSE) analysis]. Secondly, to determine if there were any changes that occur with age. The study population consisted of 36 individuals. The "young" population consisted of 20 individuals [Mean (±1 SD) age = 21.0 (±1.36 years)] and the "old" population consisted of 16 individuals [Mean (±1 SD) age = 50.0 (±10.4 years)]. Through DFA analysis, OSV was shown to exhibit fractal-like patterns. The sample entropy revealed the variability to be more regular than heart rate variability and respiratory rate variability. There was also a significant inverse correlation between mean oxygen saturation and sample entropy in healthy individuals. Additionally, the MSE analysis described a complex fluctuation pattern, which was reduced with age ( p < 0.05). These findings suggest partial "uncoupling" of the cardio-respiratory control system that occurs with aging. Overall, this study has characterized OSV using pre-existing tools. We have showed that entropy analysis of pulse oximetry signals carries information about body oxygenation. This may have the potential to be used in clinical practice to detect differences in diseased patient subsets.

Spontaneous signals in neuroimaging data may provide information on cortical health in disease and aging, but the relative sensitivity of different approaches is unknown. In the present study, we compared different but complementary indicators of neural dynamics in resting-state MEG and BOLD fMRI, and their relationship with blood flow. Participants included patients with post-stroke aphasia, age-matched controls, and young adults. The complexity of brain activity at rest was quantified in MEG using spectral analysis and multiscale entropy (MSE) measures, whereas BOLD variability was quantified as the standard deviation (SDBOLD), mean squared successive difference (MSSD), and sample entropy of the BOLD time series. We sought to assess the utility of signal variability and complexity measures as markers of age-related changes in healthy adults and perilesional dysfunction in chronic stroke. The results indicate that reduced BOLD variability is a robust finding in aging, whereas MEG measures are more sensitive to the cortical abnormalities associated with stroke. Furthermore, reduced complexity of MEG signals in perilesional tissue were correlated with hypoperfusion as assessed with arterial spin labeling (ASL), while no such relationship was apparent with BOLD variability. These findings suggest that MEG signal complexity offers a sensitive index of neural dysfunction in perilesional tissue in chronic stroke, and that these effects are clearly distinguishable from those associated with healthy aging.

The objective assessment of psychological traits of healthy subjects and psychiatric patients has been growing interest in clinical and bioengineering research fields during the last decade. Several experimental evidences strongly suggest that a link between Autonomic Nervous System (ANS) dynamics and specific dimensions such as anxiety, social phobia, stress, and emotional regulation might exist. Nevertheless, an extensive investigation on a wide range of psycho-cognitive scales and ANS non-invasive markers gathered from standard and non-linear analysis still needs to be addressed. In this study, we analyzed the discerning and correlation capabilities of a comprehensive set of ANS features and psycho-cognitive scales in 29 non-pathological subjects monitored during resting conditions. In particular, the state of the art of standard and non-linear analysis was performed on Heart Rate Variability, InterBreath Interval series, and InterBeat Respiration series, which were considered as monovariate and multivariate measurements. Experimental results show that each ANS feature is linked to specific psychological traits. Moreover, non-linear analysis outperforms the psychological assessment with respect to standard analysis. Considering that the current clinical practice relies only on subjective scores from interviews and questionnaires, this study provides objective tools for the assessment of psychological dimensions.

Autism spectrum disorders (ASD) are heterogeneous neurodevelopmental disorders that are reportedly characterized by aberrant neural networks. Recently developed multiscale entropy analysis (MSE) can characterize the complexity inherent in electroencephalography (EEG) dynamics over multiple temporal scales in the dynamics of neural networks. We encountered an 18-year-old man with ASD whose refractory catatonic obsessive-compulsive symptoms were improved dramatically after electroconvulsive therapy (ECT). In this clinical case study, we strove to clarify the neurophysiological mechanism of ECT in ASD by assessing EEG complexity using MSE. Along with ECT, the frontocentral region showed decreased EEG complexity at higher temporal scales, whereas the occipital region expressed an increase at lower temporal scales. Furthermore, these changes were associated with clinical improvement associated with the elevation of brain-derived neurotrophic factor, which is a molecular hypothesis of ECT, playing key roles in ASD pathogenesis. Changes in EEG complexity in a region-specific and temporal scale-specific manner that we found might reflect atypical EEG dynamics in ASD. Although MSE is not a direct approach to measuring neural connectivity and the results are from only a single case, they might reflect specific aberrant neural network activity and the therapeutic neurophysiological mechanism of ECT in ASD.

An emerging field of research focused on fluctuations in brain signals has provided evidence that the complexity of those signals, as measured by entropy, conveys important information about network dynamics (e.g., local and distributed processing). While much research has focused on how neural complexity differs in populations with different age groups or clinical disorders, substantially less research has focused on the basic understanding of neural complexity in populations with young and healthy brain states. The present study used resting-state fMRI data from the Human Connectome Project (Van Essen et al., 2013) to test the extent that neural complexity in the BOLD signal, as measured by multiscale entropy (1) would differ from random noise, (2) would differ between four major resting-state networks previously associated with higher-order cognition, and (3) would be associated with the strength and extent of functional connectivity-a complementary method of estimating information processing. We found that complexity in the BOLD signal exhibited different patterns of complexity from white, pink, and red noise and that neural complexity was differentially expressed between resting-state networks, including the default mode, cingulo-opercular, left and right frontoparietal networks. Lastly, neural complexity across all networks was negatively associated with functional connectivity at fine scales, but was positively associated with functional connectivity at coarse scales. The present study is the first to characterize neural complexity in BOLD signals at a high temporal resolution and across different networks and might help clarify the inconsistencies between neural complexity and functional connectivity, thus informing the mechanisms underlying neural complexity.