Alzheimer's Disease (AD) is irreversible. Mild cognitive impairment (MCI) is the first symptomatic stage of AD. Distinguishing MCI patients from healthy controls (HCs) through appropriate techniques is critical for early therapeutic interventions and prolonging patients' health. In this study, we explored characteristic indicators for MCI through dimension reduction of brain networks. After the brains (100 HCs and 100 MCIs from ADNI dataset) were partitioned into 360 parcels, one-dimension time series was extracted from diffusion and resting-state functional magnetic resonance imaging (MRI) data using network dimension-reduction techniques. Power-spectrum was then employed to transform the time series into frequency domain, to find characteristic indicators for MCI. Statistical tests indicate that the indicators (mean square frequency, and center frequency) estimated with brain network reductions could differentiate MCIs from HCs more significantly, compared with those of BOLD time series of specific AD-related subregions (hippocampus, and parieto-temporal subregions). Power-spectrum of one-dimension time series extracted with network reductions might be a viable method for distinguishing MCI progression stages. This approach could potentially facilitate earlier and more precise differentiation between MCIs and HCs, showing future clinical applicability.
Abstract Background Parkinson’s disease (PD) is a progressive neurodegenerative disease that usually happens to elderly people, with a wide range of motor and dementia symptoms. An objective and convenient biomarker for PD detection is extremely valuable, especially one that could be acquired non-invasively and low-costly. To this end, this study used resting-state scalp electroencephalography (EEG) signals to explore dynamic functional-connectivity (dFC) states between each pair of EEG recording channels, without source localization. Methods dFC refers to synchronization patterns over time between each pair of EEG channels. First, five frequency bands were extracted from EEG signals with fourth-order Butterworth bandpass filter, including delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (8–30 Hz) and gamma (30–50 Hz). Then, after non-random joint fluctuation was measured with weighted symbolic mutual information (wSMI) algorithm, whole-brain dynamic channelwise dFC states were estimated, and classified with k-means clustering. At last, FC state occurrences were calculated, and ANOVA analyses were performed for each state. Two open-source resting-state EEG data sets (https://doi.org/10.18112/openneuro.ds002778.v1.0.4: 32 channels, 16 health controls and 15 PD subjects. https://doi.org/10.18112/openneuro.ds003490.v1.1.0: 64 channels, 25 health controls and 25 PD subjects) were used to test our methods. Results Significant changes in proportions of various dFC states within beta frequency-band were consistently observed in these both data sets (p value < 0.05). Conclusions Our findings suggest that channelwise dFC states within beta frequency-band directly extracted from resting-state scalp–EEG recordings could potentially serve as a biomarker of PD.
While 7T diffusion magnetic resonance imaging (dMRI) has high spatial resolution, its diffusion imaging quality is usually affected by signal loss due to B1 inhomogeneity, T2 decay, susceptibility, and chemical shift. In contrast, 3T dMRI has relative higher diffusion angular resolution, but lower spatial resolution. Combination of 3T and 7T dMRI, thus, may provide more detailed and accurate information about the voxel-wise fiber orientations to better understand the structural brain connectivity. However, this topic has not yet been thoroughly explored until now. In this study, we explored the feasibility of fusing 3T and 7T dMRI data to extract voxel-wise quantitative parameters at higher spatial resolution. After 3T and 7T dMRI data was preprocessed, respectively, 3T dMRI volumes were coregistered into 7T dMRI space. Then, 7T dMRI data was harmonized to the coregistered 3T dMRI B0 (b = 0) images. Last, harmonized 7T dMRI data was fused with 3T dMRI data according to four fusion rules proposed in this study. We employed high-quality 3T and 7T dMRI datasets (N = 24) from the Human Connectome Project to test our algorithms. The diffusion tensors (DTs) and orientation distribution functions (ODFs) estimated from the 3T-7T fused dMRI volumes were statistically analyzed. More voxels containing multiple fiber populations were found from the fused dMRI data than from 7T dMRI data set. Moreover, extra fiber directions were extracted in temporal brain regions from the fused dMRI data at Otsu’s thresholds of quantitative anisotropy, but could not be extracted from 7T dMRI dataset. This study provides novel algorithms to fuse intra-subject 3T and 7T dMRI data for extracting more detailed information of voxel-wise quantitative parameters, and a new perspective to build more accurate structural brain networks.
Currently, structural connectivity (SC) strength is usually non-invasively estimated as streamline density or connection probability, via tractography based on diffusion magnetic resonance imaging (dMRI). However, nonnegligible tracking biases are still unavoidably introduced into SC strength computation, thus affecting exploration of anatomical mechanism underlying functional interactions. Here, we refined SC strength from empirical functional connectivity (FC) by combining neural computational model and deep-learning techniques. First, the neural computation model (Generic2dOscillator) was employed to generate simulated FCs from dMRI-tracked SCs. Then, these two kinds of connectivity matrices were used as samples to train generative adversarial network (GAN) incorporating graph attention (GAT). Last, empirical FCs were fed to the trained GAN to infer SCs. Global topological metrics of the predicted SCs have better consistency, no matter whether brains were parcellated into 62 or 132 subregions. More reasonable SC strength was obtained for the specific structural connections that are prone to tracking bias. These findings help us in understanding of the brain’s white matter organization, and in integrating dMRI and fMRI images to study coupling relationship between SC and FC networks.
Brain magnetic resonance imaging (MRI) is crucial for diagnosing and understanding neurological disorders, but inherent limitations hinder the visualization of fine details in brain structures. The emergence of super-resolution techniques, especially deep-learning methods, has improved imaging quality of MRI, by increasing MRI spatial resolution. At present, deep-learning algorithms mostly performed super-resolution on 2D MRI images. However, considering 3D nature of MRI, 3D models are more suitable for brain MRI super-resolution. To achieve finer brain structural details, this study proposes a 3D brain MRI super-resolution method based on diffusion model (3D-SRDM), which is a fast and easily trainable neural network for the generation of high-resolution brain MRI images. In our 3D-SRDM model, the self-attention module in U-Net is replaced with 3D spatial attention mechanism. The network structure of 3D-SRDM is optimized to reduce training parameters. Moreover, accelerated sampling from denoising diffusion implicit model is also incorporated to reduce time consumption. By these optimizations, compared with original diffusion model, the proposed model can achieve about 10- and 5-fold speed increase at 4x and 8x super-resolution of 3D brain MRI volumes, respectively, almost without affecting image quality. Thus, 3D-SRDM has potential application value in efficiently generating high-resolution 3D brain MRI images, thus facilitating the doctors' diagnosis.
In vivo revealing how brain subregions are structurally connected during neonatal period via diffusion magnetic resonance imaging (dMRI) is critical for understanding brain development and pediatric mental disorders. However, even if preprocess was performed on dMRI images including denoising, eddy and motion correction, and unring, residual artifacts still affect the construction of brain structural networks. In this study, nonlocal estimation of multispectral magnitudes (NESMA) was extended to further smooth the preprocessed brain dMRI images of 46 healthy infants from the developing Human Connectome Project (dHCP). The proposed method smoothed dMRI images by exploiting similar multispectral diffusion-weighted signal pattern and the signal redundance among 3D patches. After structural connectivity networks were constructed from the smoothed dMRI images, network-level and nodal topological measures were estimated. While characteristic path length remained unchanged, significantly higher global efficiency, average clustering coefficient, and transitivity were observed in the infant structural networks built from NESMA-smoothed dMRI images. Additionally, more brain subregions with clustering coefficient > = 0.035 and local efficiency > = 0.05 were identified. In summary, higher efficiency was observed in the structural connectivity networks of healthy infants. Nonlocal estimation of multispectral diffusion-weighted volumes has nonnegligible effect on topological analysis of infant brain structural networks. The code for this algorithm is publicly available at https://github.com/freedom1979/NESMA-dMRI .
At present, the incidence of Parkinson's disease (PD) is gradually increasing. This seriously affects the quality of life of patients, and the burden of diagnosis and treatment is increasing. However, the disease is difficult to intervene in early stage as early monitoring means are limited. Aiming to find an effective biomarker of PD, this work extracted correlation between each pair of electroencephalogram (EEG) channels for each frequency band using weighted symbolic mutual information and k-means clustering. The results showed that State1 of Beta frequency band ( P = 0.034) and State5 of Gamma frequency band ( P = 0.010) could be used to differentiate health controls and off-medication Parkinson's disease patients. These findings indicated that there were significant differences in the resting channel-wise correlation states between PD patients and healthy subjects. However, no significant differences were found between PD-on and PD-off patients, and between PD-on patients and healthy controls. This may provide a clinical diagnosis reference for Parkinson's disease.
Due to high computational requirements, deep-learning decoders for motor imaginary (MI) electroencephalography (EEG) signals are usually implemented on bulky and heavy computing devices that are inconvenient for physical actions. To date, the application of deep-learning techniques in independent portable brain-computer-interface (BCI) devices has not been extensively explored. In this study, we proposed a high-accuracy MI EEG decoder by incorporating spatial-attention mechanism into convolution neural network (CNN), and deployed it on fully integrated single-chip microcontroller unit (MCU). After the CNN model was trained on workstation computer using GigaDB MI datasets (52 subjects), its parameters were then extracted and converted to build deep-learning architecture interpreter on MCU. For comparison, EEG-Inception model was also trained using the same dataset, and was deployed on MCU. The results indicate that our deep-learning model can independently decode imaginary left-/right-hand motions. The mean accuracy of the proposed compact CNN reaches 96.75 ± 2.41
Super-resolution of brain magnetic resonance imaging (MRI) generates high resolution brain images as opposed to low-resolution ones, thus providing more detailed anatomical information for diagnosis of neurodegenerative diseases. Although denoising diffusion probabilistic model (DDPM) has displayed remarkable performance in super-resolution of face and natural images, its application to producing high-resolution brain MRI images has not been explored. This study proposed a new deep-learning super-resolution framework for brain MRI images based on DDPM, via incorporating self-attention mechanism into DDPM. The main improvements are as follows: (a) Only one input channel is preserved. (b) The number of baseline channels is reduced from 64 to 32, to improve training speed. (c) Self-attention mechanism is added to 32 x 32, 16 x 16, and 8 x 8 resolution layers rather than only to 16 x 16 layer. (d) Feature-wise affine transformation is added to residual block. Experimental results on open T1-and diffusion-weighted brain MRI datasets show that our DDPM model outperformed the state-of-the-art super-resolution methods. In terms of learned perceptual image patch similarity (LPIPS) metric, the proposed DDPM model achieved the least distortion of generated super-resolution brain MRI images. This framework can also be conveniently used to reconstruct high-resolution MRI images of other body parts such as spinal and knee in future.
Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely employed to examine brain functional connectivity (FC) alterations in various neurological disorders. At present, various computational methods have been proposed to estimate connectivity strength between different brain regions, as the edge weight of FC networks. However, little is known about which model is more sensitive to Alzheimer's disease (AD) progression. This study comparatively characterized topological properties of rs-FC networks constructed with Pearson correlation (PC), dynamic time warping (DTW), and group information guided independent component analysis (GIG-ICA), aimed at investigating the sensitivity and effectivity of these methods in differentiating AD stages. A total of 54 subjects from Alzheimer's Disease Neuroimaging Initiative (ANDI) database, divided into healthy control (HC), mild cognition impairment (MCI), and AD groups, were included in this study. Network-level (global efficiency and characteristic path length) and nodal (clustering coefficient) metrics were used to capture groupwise difference across HC, MCI, and AD groups. The results showed that almost no significant differences were found according to global efficiency and characteristic path length. However, in terms of clustering coefficient, 52 brain parcels sensitive to AD progression were identified in rs-FC networks built with GIG-ICA, much more than PC (6 parcels) and DTW (3 parcels). This indicates that GIG-ICA is more sensitive to AD progression than PC and DTW. The findings also confirmed that the AD-linked FC alterations mostly appeared in temporal, cingulate, and angular areas, which might contribute to clinical diagnosis of AD. Overall, this study provides insights into the topological properties of rs-FC networks over AD progression, suggesting that FC strength estimation of FC networks cannot be neglected in AD-related graph analysis.
Magnetic coupling resonance wireless power transfer can efficiently provide energy to intracranial implants under safety constraints, and is the main way to power fully implantable brain–computer interface systems. However, the existing maximum efficiency tracking wireless power transfer system is aimed at optimizing the overall system efficiency, but the efficiency of the secondary side is not optimized. Moreover, the parameters of the transmitter and the receiver change nonlinearly in the power control process, and the efficiency tracking mainly depends on wireless communication. The heat dissipation caused by the unoptimized receiver efficiency and the wireless communication delay in power control will inevitably affect neural activity and even cause damage, thus affecting the results of neuroscience research. Here, a linear-power-regulated wireless power transfer method is proposed to realize the linear change of the received power regulation and optimize the receiver efficiency, and a miniaturized linear-power-regulated wireless power transfer system is developed. With the received power control, the efficiency of the receiver is increased to more than 80%, which can significantly reduce the heating of fully implantable microsystems. The linear change of the received power regulation makes the reflected impedance in the transmitter change linearly, which will help to reduce the dependence on wireless communication and improve biological safety in received power control applications.
Normative aging and Alzheimer’s disease (AD) propagation alter anatomical connections among brain parcels. However, the interaction between the trajectories of age- and AD-linked alterations in the topology of the structural brain network is not well understood. In this study, diffusion-weighted magnetic resonance imaging (MRI) datasets of 139 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were used to document their structural brain networks. The 139 participants consist of 45 normal controls (NCs), 37 with early mild cognitive impairment (EMCI), 27 with late mild cognitive impairment (LMCI), and 30 AD patients. All subjects were further divided into three subgroups based on their age (56–65, 66–75, and 71–85 years). After the structural connectivity networks were built using anatomically-constrained deterministic tractography, their global and nodal topological properties were estimated, including network efficiency, characteristic path length, transitivity, modularity coefficient, clustering coefficient, and betweenness. Statistical analyses were then performed on these metrics using linear regression, and one- and two-way ANOVA testing to examine group differences and interactions between aging and AD propagation. No significant interactions were found between aging and AD propagation in the global topological metrics (network efficiency, characteristic path length, transitivity, and modularity coefficient). However, nodal metrics (clustering coefficient and betweenness centrality) of some cortical parcels exhibited significant interactions between aging and AD propagation, with affected parcels including left superior temporal, right pars triangularis, and right precentral. The results collectively confirm the age-related deterioration of structural networks in MCI and AD patients, providing novel insight into the cross effects of aging and AD disorder on brain structural networks. Some early symptoms of AD may also be due to age-associated anatomic vulnerability interacting with early anatomic changes associated with AD.
Metabolic signatures are frequently observed in cancer and are starting to be recognized as important regulators for tumor progression and therapy. Because metabolism genes are involved in tumor initiation and progression, little is known about the metabolic genomic profiles in low-grade glioma (LGG). Here, we applied bioinformatics analysis to determine the metabolic characteristics of patients with LGG from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). We also performed the ConsensusClusterPlus, the CIBERSORT algorithm, the Estimate software, the R package "GSVA," and TIDE to comprehensively describe and compare the characteristic difference between three metabolic subtypes. The R package WGCNA helped us to identify co-expression modules with associated metabolic subtypes. We found that LGG patients were classified into three subtypes based on 113 metabolic characteristics. MC1 patients had poor prognoses and MC3 patients obtained longer survival times. The different metabolic subtypes had different metabolic and immune characteristics, and may have different response patterns to immunotherapy. Based on the metabolic subtype, different patterns were exhibited that reflected the characteristics of each subtype. We also identified eight potential genetic markers associated with the characteristic index of metabolic subtypes. In conclusion, a comprehensive understanding of metabolism associated characteristics and classifications may improve clinical outcomes for LGG.
Subarachnoid hemorrhage (SAH) has a high mortality rate and causes long-term disability in many patients, often associated with cognitive impairment. However, the pathogenesis of delayed brain dysfunction after SAH is not fully understood. A growing body of evidence suggests that neuroinflammation and oxidative stress play a negative role in neurofunctional deficits. Red blood cells and hemoglobin, immune cells, proinflammatory cytokines, and peroxidases are directly or indirectly involved in the regulation of neuroinflammation and oxidative stress in the central nervous system after SAH. This review explores the role of various cellular and acellular components in secondary inflammation and oxidative stress after SAH, and aims to provide new ideas for clinical treatment to improve the prognosis of SAH.
Spike sorting is used to classify the spikes (action potentials acquired by physiological electrodes), aiming to identify their respective firing units. Now it has been developed to classify the spikes recorded by multi-electrode arrays (MEAs), with the improvement of micro-electrode technology. However, how to improve classification accuracy and maintain low time complexity simultaneously becomes a difficulty. A fast and accurate spike sorting approach named HTsort is proposed for high-density multi-electrode arrays in this paper. Several improvements have been introduced to the traditional pipeline that is composed of threshold detection and clustering method. First, the divide-and-conquer method is employed to utilize electrode spatial information to achieve pre-clustering. Second, the clustering method HDBSCAN (hierarchical density-based spatial clustering of applications with noise) is used to classify spikes and detect overlapping events (multiple spikes firing simultaneously). Third, the template merging method is used to merge redundant exported templates according to the template similarity and the spatial distribution of electrodes. Finally, the template matching method is used to resolve overlapping events. Our approach is validated on simulation data constructed by ourselves and publicly available data and compared to other state-of-the-art spike sorters. We found that the proposed HTsort has a more favorable trade-off between accuracy and time consumption. Compared with MountainSort and SpykingCircus, the time consumption is reduced by at least 40% when the number of electrodes is 64 and below. Compared with HerdingSpikes, the classification accuracy can typically improve by more than 10%. Meanwhile, HTsort exhibits stronger robustness against background noise than other sorters. Our more sophisticated spike sorter would facilitate neurophysiologists to complete spike sorting more quickly and accurately.
Accurate detection of the regions of Alzheimer's disease (AD) lesions is critical for early intervention to effectively slow down the progression of the disease. Although gray matter volumetric abnormalities are commonly detected in patients with mild cognition impairment (MCI) and patients with AD, the gray matter surface-based deterioration pattern associated with the progression of the disease from MCI to AD stages is largely unknown. To identify group differences in gray matter surface morphometry, including cortical thickness, the gyrification index (GI), and the sulcus depth, 80 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were split into healthy controls (HCs; N = 20), early MCIs (EMCI; N = 20), late MCIs (LMCI; N = 20), and ADs ( N = 20). Regions-of-interest (ROI)-based surface morphometry was subsequently studied and compared across the four stage groups to characterize the gray matter deterioration during AD progression. Co-alteration patterns (Spearman's correlation coefficient) across the whole brain were also examined. Results showed that patients with MCI and AD exhibited a significant reduction in cortical thickness ( p < 0.001) mainly in the cingulate region (four subregions) and in the temporal (thirteen subregions), parietal (five subregions), and frontal (six subregions) lobes compared to HCs. The sulcus depth of the eight temporal, four frontal, four occipital, and eight parietal subregions were also significantly affected ( p < 0.001) by the progression of AD. The GI was shown to be insensitive to AD progression (only three subregions were detected with a significant difference, p < 0.001). Moreover, Spearman's correlation analysis confirmed that the co-alteration pattern of the cortical thickness and sulcus depth indices is predominant during AD progression. The findings highlight the relevance between gray matter surface morphometry and the stages of AD, laying the foundation for in vivo tracking of AD progression. The co-alteration pattern of surface-based morphometry would improve the researchers' knowledge of the underlying pathologic mechanisms in AD.
Brain structural network changes provide key information about the aging process of the brain. Unfortunately, there has yet to be a detailed characterization of these structural networks across different age groups. Efforts to classify these networks have also been hampered by their reliance on technically limited traditional methods, which are unable to track multiple fiber orientations within a voxel and consequently are prone to false detection and artifacts. In this study, a newly developed Ensemble Average Propagator (EAP) based probabilistic tractography method was applied to construct a structural network, with the strength of the link between any two brain functional regions estimated according to the alignment of the EAP along connecting pathways. Age-related changes in the topological organization of human brain structural networks were thereby characterized across a broad age range (ages 8-75 years). The data from 48 healthy participants were divided into four age groups (Group 1 aged 8-15 years; Group 2 aged 25-35 years; Group 3 aged 45-55 years; and, Group 4 aged 65-75 years; N = 12 per group). We found that the brain structural network continues to strengthen during later adolescence and adulthood, through the first 20-30 years of life. Older adults, aged 65-75, had a significantly less optimized topological organization in their structural network, with decreased global efficiency and increased path lengths versus subjects in other groups. This study suggests that probabilistic tractography based on EAP provides a reliable method to construct macroscale structural connectivity networks to capture the age-associated changes of brain structures.
An important task for neuroscience is to accurately construct structural connectivity network of human brain. Tractography constructed based on high angular resolution diffusion imaging (HARDI) provides valuable information of human brain structural connections. Existing algorithms, mainly categorized as deterministic or probabilistic, come with inherent limitations (e.g., fiber direction uncertainty induced by noise, or anatomically unreasonable connections and heavy computational cost). In this study, a novel integrated algorithm was proposed to construct brain structural connectivity network by incorporating the deterministic path planning and probabilistic connection strength estimation, based on ensemble average propagator (EAP). We first estimated EAPs from multi-shell samples using the spherical polar Fourier imaging (SPFI), and then extracted diffusion orientations coinciding with neural fiber tracts. Only under angular constraints, the deterministic path planning algorithm was subsequently used to find all reasonable pathways between pairwise white matter (WM) voxels in different regions of interest (ROIs). Consequently, a train of consecutive WM voxels along each of the identified pathways was determined, and the connection strength of these pathways was computed by integrating their EAP alignment over a solid angle. The connection strength of a pair of WM voxels was assigned as the connection strength with the largest connection possibility. Finally, the connection strength between two ROIs was calculated as the sum of all the connection probabilities of each pair of WM voxels in the ROIs. A comparison against voxel-graph based probabilistic tractography method was performed on Fibercup phantom dataset, and the results demonstrated that the proposed method can produce better structural connection and is more computationally economical. Lastly, three datasets from Human Connectome Project (HCP) S1200 group were tested and their structural connectivity networks were constructed for topological analysis. The results showed great consistency in network metrics with previous WM network studies in healthy adults.
Alzheimer's disease (AD) causes the progressive deterioration of neural connections, disrupting structural connectivity (SC) networks within the brain. Graph-based analyses of SC networks have shown that topological properties can reveal the course of AD propagation. Different whole-brain parcellation schemes have been developed to define the nodes of these SC networks, although it remains unclear which scheme can best describe the AD-related deterioration of SC networks. In this study, four whole-brain parcellation schemes with different numbers of parcels were used to define SC network nodes. SC networks were constructed based on high angular resolution diffusion imaging (HARDI) tractography for a mixed cohort that includes 20 normal controls (NC), 20 early mild cognitive impairment (EMCI), 20 late mild cognitive impairment (LMCI), and 20 AD patients, from the Alzheimer's Disease Neuroimaging Initiative. Parcellation schemes investigated in this study include the OASIS-TRT-20 (62 regions), AAL (116 regions), HCP-MMP (180 regions), and Gordon-rsfMRI (333 regions), which have all been widely used for the construction of brain structural or functional connectivity networks. Topological characteristics of the SC networks, including the network strength, global efficiency, clustering coefficient, rich-club, characteristic path length, k-core, rich-club coefficient, and modularity, were fully investigated at the network level. Statistical analyses were performed on these metrics using Kruskal-Wallis tests to examine the group differences that were apparent at different stages of AD progression. Results suggest that the HCP-MMP scheme is the most robust and sensitive to AD progression, while the OASIS-TRT-20 scheme is sensitive to group differences in network strength, global efficiency, k-core, and rich-club coefficient at k-levels from 18 and 39. With the exception of the rich-club and modularity coefficients, AAL could not significantly identify group differences on other topological metrics. Further, the Gordon-rsfMRI atlas only significantly differentiates the groups on network strength, characteristic path length, k-core, and rich-club coefficient. Results show that the topological examination of SC networks with different parcellation schemes can provide important complementary AD-related information and thus contribute to a more accurate and earlier diagnosis of AD.
Aiming at real-time temperature detection and data upload of mining equipment, a distributed remote data monitoring system based on CAN bus is designed. Using the microcontroller STM32, CAN transceiver TJA1050, K-type thermocouple as the intelligent node for on-site temperature acquisition, the data of multiple intelligent nodes is centralized to the control board through the CAN bus network The control board displays the data on the LCD and transmits it to the database remotely via Ethernet or GPRS.