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Changes of brain network dynamics reveal variations in macroscopic neural activity patterns in behavioral and cognitive aspects. Quantification and application of changed dynamics in brain functional connectivity networks may contribute to a better understanding of brain diseases, and ultimately provide better prognostic indicators or auxiliary diagnostic tools. At present, most studies are focused on the properties of brain functional connectivity network constructed by sliding window method. However, few studies have explored evidence-based brain network construction algorithms that reflect disease specificity. In this work, we first proposed a novel approach to characterize the spatiotemporal variability of dynamic functional connectivity networks based on electroencephalography (EEG) microstate, and then developed a classification framework for integrating spatiotemporal variability of brain networks to improve early Parkinson’s disease (PD) diagnostic performance. The experimental results indicated that compared with the brain network construction method based on conventional sliding window, the proposed method significantly improved the performance of early PD recognition, demonstrating that the dynamic spatiotemporal variability of microstate-based brain networks can reflect the pathological changes in the early PD brain. Furthermore, we observed that the spatiotemporal variability of early PD brain network has a specific distribution pattern in brain regions, which can be quantified as the degree of motor and cognitive impairment, respectively. Our work offers innovative methodological support for future research on brain network, and provides deeper insights into the spatiotemporal interaction patterns of brain activity and their variabilities in early PD.

Aberrant dynamic switches between internal brain states are believed to underlie motor dysfunction in Parkinson’s disease. Deep brain stimulation of the subthalamic nucleus is a well-established treatment for the motor symptoms of Parkinson’s disease, yet it remains poorly understood how subthalamic stimulation modulates the whole-brain intrinsic motor network state dynamics.To investigate this, we acquired resting-state functional magnetic resonance imaging time-series data from 27 medication-free patients with Parkinson’s disease (mean age: 64.8 years, standard deviation: 7.6) who had deep brain stimulation electrodes implanted in the subthalamic nucleus, in both on and off stimulation states. Sixteen matched healthy individuals were included as a control group. We adopted a powerful data-driven modelling approach, known as a hidden Markov model, to disclose the emergence of recurring activation patterns of interacting motor regions (whole-brain intrinsic motor network states) via the blood oxygen level-dependent signal detected in the resting-state functional magnetic resonance imaging time-series data from all participants. The estimated hidden Markov model disclosed the dynamics of distinct whole-brain motor network states, including frequency of occurrence, state duration, fractional coverage and their transition probabilities.Notably, the data-driven decoding of whole-brain intrinsic motor network states revealed that subthalamic stimulation reshaped functional network expression and stabilized state transitions. Moreover, subthalamic stimulation improved motor symptoms by modulating key trajectories of state transition within whole-brain intrinsic motor network states. This modulation mechanism of subthalamic stimulation was manifested in three significant effects: recovery, relieving and remodelling effects. Significantly, recovery effects correlated with improvements in tremor and posture symptoms induced by subthalamic stimulation (P < 0.05). Furthermore, subthalamic stimulation was found to restore a relatively low level of fluctuation of functional connectivity in all motor regions to a level closer to that of healthy participants. Also, changes in the fluctuation of functional connectivity between motor regions were associated with improvements in tremor and gait symptoms (P < 0.05).These findings fill a gap in our knowledge of the role of subthalamic stimulation at the level of neural activity, revealing the regulatory effects of subthalamic stimulation on whole-brain inherent motor network states in Parkinson’s disease. Our results provide mechanistic insight and explanation for how subthalamic stimulation modulates motor symptoms in Parkinson’s disease.

The human brain controls various cognitive functions via the functional coordination of multiple brain regions in an efficient and robust way. However, the relationship between consciousness state and the control mode of brain networks is poorly explored. Using multi-channel EEG, the present study aimed to characterize the abnormal control architecture of functional brain networks in the patients with disorders of consciousness (DOC). Resting state EEG data were collected from 40 DOC patients with different consciousness levels and 24 healthy subjects. Functional brain networks were constructed in five different EEG frequency bands and the broadband in the source level. Subsequently, a control architecture framework based on the minimum dominating set was applied to investigate the of control mode of functional brain networks for the subjects with different conscious states. Results showed that regardless of the consciousness levels, the functional networks of human brain operate in a distributed and overlapping control architecture different from that of random networks. Compared to the healthy controls, the patients have a higher control cost manifested by more minimum dominating nodes and increased degree of distributed control, especially in the alpha band. The ability to withstand network attack for the control architecture is positive correlated with the consciousness levels. The distributed of control increased correlation levels with Coma Recovery Scale-Revised score and improved separation between unresponsive wakefulness syndrome and minimal consciousness state. These findings may benefit our understanding of consciousness and provide potential biomarkers for the assessment of consciousness levels.

Objective. Parkinson’s disease (PD) is one of the most common neurodegenerative diseases, and early diagnosis is crucial to delay disease progression. The diagnosis of early PD has always been a difficult clinical problem due to the lack of reliable biomarkers. Electroencephalogram (EEG) is the most common clinical detection method, and studies have attempted to discover the EEG spectrum characteristics of early PD, but the reported conclusions are not uniform due to the heterogeneity of early PD patients. There is an urgent need for a more advanced algorithm to extract spectrum characteristics from EEG to satisfy the personalized requirements. Approach. The structured power spectral density with spatial distribution was used as the input of convolutional neural network (CNN). A visualization technique called gradient-weighted class activation mapping was used to extract the optimal frequency bands for identifying early PD. Based on the model visualization, we proposed a novel quantitative index of spectral characteristics, spatial-mapping relative power (SRP), to detect personalized abnormalities in the spatial spectral characteristics of EEG in early PD. Main results. We demonstrated the feasibility of applying CNN to identify the patients with early PD with an accuracy of 99.87% ± 0.03%. The models indicated the characteristic frequency bands (high-delta (3.5–4.5 Hz) and low-alpha (7.5–11 Hz) frequency bands) that are used to identify the early PD. The SRP of these two characteristic bands in early PD patients was significantly higher than that in the control group, and the abnormalities were consistent at the group and individual levels. Significance. This study provides a novel personalized detection algorithm based on deep learning to reveal the optimal frequency bands for identifying early PD and obtain the spatial frequency characteristics of early PD. The findings of this study will provide an effective reference for the auxiliary diagnosis of early PD in clinical practice.

The subthalamic nucleus (STN) and globus pallidus internus (GPi) are the two most common and effective target brain areas for deep brain stimulation (DBS) treatment of advanced Parkinson's disease. Although DBS has been shown to restore functional neural circuits of this disorder, the changes in topological organization associated with active DBS of each target remain unknown. To investigate this, we acquired resting-state functional magnetic resonance imaging (fMRI) data from 34 medication-free patients with Parkinson's disease that had DBS electrodes implanted in either the subthalamic nucleus or internal globus pallidus (n = 17 each), in both ON and OFF DBS states. Sixteen age-matched healthy individuals were used as a control group. We evaluated the regional information processing capacity and transmission efficiency of brain networks with and without stimulation, and recorded how stimulation restructured the brain network topology of patients with Parkinson's disease. For both targets, the variation of local efficiency in motor brain regions was significantly correlated (p0.05) with improvement rate of the Uniform Parkinson's Disease Rating Scale-III scores, with comparable improvements in motor function for the two targets. However, non-motor brain regions showed changes in topological organization during active stimulation that were target-specific. Namely, targeting the STN decreased the information transmission of association, limbic and paralimbic regions, including the inferior frontal gyrus angle, insula, temporal pole, superior occipital gyri, and posterior cingulate, as evidenced by the simultaneous decrease of clustering coefficient and local efficiency. GPi-DBS had a similar effect on the caudate and lenticular nuclei, but enhanced information transmission in the cingulate gyrus. These effects were not present in the DBS-OFF state for GPi-DBS, but persisted for STN-DBS. Our results demonstrate that DBS to the STN and GPi induce distinct brain network topology reconstruction patterns, providing innovative theoretical evidence for deciphering the mechanism through which DBS affects disparate targets in the human brain.

To explore the abnormal brain activity of early Parkinson’s disease with mild cognitive impairment (ePD-MCI) patients, the study analyzed the dynamic fluctuation of electroencephalogram (EEG) signals and the dynamic change of information communication between EEG signals of ePD-MCI patients. In this study, we recorded resting-state EEG signals of 30 ePD-MCI patients and 37 early Parkinson’s disease without mild cognitive impairment (ePD-nMCI) patients. First, we analyzed the difference of the complexity of EEG signals between the two groups. And we found that the complexity in the ePD-MCI group was significantly higher than that in the ePD-nMCI group. Then, by analyzing the dynamic functional network (DFN) topology based on the optimal sliding-window, we found that the temporal correlation coefficients of ePD-MCI patients were lower in the delta and theta bands than those in the ePD-nMCI patients. The temporal characteristic path length of ePD-MCI patients in the alpha band was higher than that of ePD-nMCI patients. In the theta and alpha bands, the temporal small world degrees of ePD-MCI patients were lower than that of patients with ePD-nMCI. In addition, the functional connectivity strength of ePD-MCI patients affected by cognitive impairment was weaker than that of ePD-nMCI patients, and the stability of dynamic functional connectivity network was decreased. This finding may serve as a biomarker to identify ePD-MCI and contribute to the early intervention treatment of ePD-MCI.

Highlights • We have found that PD can be characterized by unique spatial microstate different from healthy controls, which may be related to the brain dysfunction in PD. • The drug-free patients with PD show abnormal brain dynamics revealed by the regular changes of temporal microstate features in early PD and such temporal dynamics in microstates are correlated with motor function and cognition of the subjects. • The obtained results may deepen our understanding of the brain dysfunction caused by PD, and obtain some quantifiable signatures to provide an auxiliary reference for the early diagnosis of PD., The clinical diagnosis of Parkinson's disease (PD) is very difficult, especially in the early stage of the disease, because there is no physiological indicator that can be referenced. Drug-free patients with early PD are characterized by clinical symptoms such as impaired motor function and cognitive decline, which was caused by the dysfunction of brain's dynamic activities. The indicators of brain dysfunction in patients with PD at an early unmedicated condition may provide a valuable basis for the diagnosis of early PD and later treatment. In order to find the spatiotemporal characteristic markers of brain dysfunction in PD, the resting-state EEG microstate analysis is used to explore the transient state of the whole brain of 23 drug-free patients with PD on the sub-second timescale compared to 23 healthy controls. EEG microstates reflect a transiently stable brain topological structure with spatiotemporal characteristics, and the spatial characteristic microstate classes and temporal parameters provide insight into the brain's functional activities in PD patients. The further exploration was to explore the relation between temporal microstate parameters and significant clinical symptoms to determine whether these parameters could be used as a basis for clinically assisted diagnosis. Therefore, we used a general linear model (GLM) to explore the relevance of microstate parameters to clinical scales and multiple patient attributes, and the Wilcoxon rank sum test was used to quantify the linear relation between influencing factors and microstate parameters. Results of microstate analysis revealed that there was an unique spatial microstate different from healthy controls in PD, and several other typical microstates had significant differences compared with the normal control group, and these differences were reflected in the microstate parameters, such as longer durations and more occurrences of one class of microstates in PD compared with healthy controls. Furthermore, correlation analysis showed that there was a significant correlation between multiple microstate classes’ parameters and significant clinical symptoms, including impaired motor function and cognitive decline. These results indicate that we have found multiple quantifiable feature tags that reflect brain dysfunction in the early stage of PD. Importantly, such temporal dynamics in microstates are correlated with clinical scales which represent the motor function and recognize level. The obtained results may deepen our understanding of the brain dysfunction caused by PD, and obtain some quantifiable signatures to provide an auxiliary reference for the early diagnosis of PD.

The rapid increase in the number of people with Alzheimer's disease (AD) represents one of the major challenges to the health and social care systems. Early detection of AD makes it possible for patients to access appropriate services and to benefit from new therapies and treatments. The objective of the study reported in this paper is to develop the method of complexity characterization of EEG in AD patients in its early stages. In this paper, we propose the fractional permutation entropy (FPE) to analyze 16-channels electroencephalograph (EEG) signals from 15 AD groups and 15 age-matched control groups. FPE is a modified method based on the permutation entropy (PE), which can be used as a measurement to analyze the complexity of the EEG signals. Firstly, the simulation analysis of FPE was performed and the results show that FPE could effectively evaluate the complexity of time series. Then we calculated the FPE of real EEG series to detect the complexity abnormalities in AD. It is demonstrated that the FPE of AD patients is significantly decreased in alpha band at most EEG channels. Thus, it suggests that FPE may become a probably useful tool to analyze the complexity abnormalities of AD and some other neurologic disorders.