Genome-wide high-resolution mapping of DNA methylation reveals epigenetic variation in the offspring of sexual and asexual propagation in Robinia pseudoacacia.

KEY MESSAGE: We detected the genome-wide pattern of DNA methylation and its association with gene expression in sexual and asexual progenies of mature Robinia pseudoacacia trees. DNA methylation plays an important role in plant reproduction and development. Although some studies on sexual reproduction have been carried out in model plants, little is known about the dynamic changes in DNA methylation and their effect on gene expression in sexual and asexual progeny of woody plants. Here, through whole-genome bisulfite sequencing, we revealed DNA methylation patterns in the sexual and asexual progenies of mature Robinia pseudoacacia to understand the regulation of gene expression by DNA methylation in juvenile seedlings. An average of 53% CG, 34% CHG and 5% CHH contexts was methylated in the leaves of mature and juvenile individuals. The CHH methylation level of asexually propagated seedlings was significantly lower than that of seed-derived seedlings and mature trees. The intergenic regions had the highest methylation level. Analysis of differentially methylated regions (DMRs) showed that most of them were hypermethylated and located in the gene upstream and introns. A total of 24, 108 and 162 differentially expressed genes containing DMRs were identified in root sprouts (RSs), root cuttings (RCs) and seed-derived seedlings (SSs), respectively, and a large proportion of them showed hypermethylation. In addition, DMRs were enriched within GO subcategories including catalytic activity, metabolic process and cellular process. The results reveal widespread DNA methylation changes between mature plants and their progenies through sexual/asexual reproduction, which provides novel insights into DNA methylation reprogramming and the regulation of gene expression in woody plants.

Individual Variability of Human Cortical Spontaneous Activity by 3T/7T fMRI.

Mapping variability in cortical spontaneous activity (CSA) is an essential goal of understanding various sources of dark brain energy in human neuroscience. CSA was traditionally characterized using resting-state functional MRI (rfMRI) at 1.5T or 3T magnets while recently with 7T-rfMRI. However, the utility and interpretability of 7T-rfMRI must first be established for its variability. By leveraging rfMRI data from the Human Connectome Project (HCP), we derived CSA metrics with 3T-rfMRI and 7T-rfMRI for the same 84 healthy participants (52 females). The 7T-rfMRI produces different CSA metrics at multiple spatial-scales and their variability from the 3T-rfMRI. These differences were spatially dependent and varied according to specific cortical organization. For the amplitude metric, 7T-rfMRI enhanced its spatial contrasts in the anterior cortex but weakened it in the posterior cortex. An opposite pattern was observed for the connectivity metrics. The reliability changes of these metrics were scale dependent, indicating enhanced reliability for connectivity but weakened reliability for amplitude by 7T-rfMRI. These effects were primarily located in the high-order associate cortex, parsing the corresponding changes in individual differences with respect to 7T-rfMRI: (1) higher connectivity variability between participants and the lower connectivity variability within individual participants, and (2) lower amplitude variability between participants and higher amplitude variability within participants. Our work, for the first time, demonstrated the variability of the human CSA across space, rfMRI settings/platforms, and individuals. We discussed the statistical implications of our findings on CSA-based experimental designs and reproducible neuroscience as well as their translational value for personalized applications.

Optimizing network neuroscience computation of individual differences in human spontaneous brain activity for test-retest reliability.

A rapidly emerging application of network neuroscience in neuroimaging studies has provided useful tools to understand individual differences in intrinsic brain function by mapping spontaneous brain activity, namely intrinsic functional network neuroscience (ifNN). However, the variability of methodologies applied across the ifNN studies-with respect to node definition, edge construction, and graph measurements-makes it difficult to directly compare findings and also challenging for end users to select the optimal strategies for mapping individual differences in brain networks. Here, we aim to provide a benchmark for best ifNN practices by systematically comparing the measurement reliability of individual differences under different ifNN analytical strategies using the test-retest design of the Human Connectome Project. The results uncovered four essential principles to guide ifNN studies: (1) use a whole brain parcellation to define network nodes, including subcortical and cerebellar regions; (2) construct functional networks using spontaneous brain activity in multiple slow bands; and (3) optimize topological economy of networks at individual level; and (4) characterize information flow with specific metrics of integration and segregation. We built an interactive online resource of reliability assessments for future ifNN (https://ibraindata.com/research/ifNN).

Globally Aging Cortical Spontaneous Activity Revealed by Multiple Metrics and Frequency Bands Using Resting-State Functional MRI.

Most existing aging studies using functional MRI (fMRI) are based on cross-sectional data but misinterpreted their findings (i.e., age-related differences) as longitudinal outcomes (i.e., aging-related changes). To delineate aging-related changes the of human cerebral cortex, we employed the resting-state fMRI (rsfMRI) data from 24 healthy elders in the PREVENT-AD cohort, obtaining five longitudinal scans per subject. Cortical spontaneous activity is measured globally with three rsfMRI metrics including its amplitude, homogeneity, and homotopy at three different frequency bands (slow-5: 0.02-0.03 Hz, slow-4: 0.03-0.08 Hz, and slow-3 band: 0.08-0.22 Hz). General additive mixed models revealed a universal pattern of the aging-related changes for the global cortical spontaneous activity, indicating increases of these rsfMRI metrics during aging. This aging pattern follows specific frequency and spatial profiles where higher slow bands show more non-linear curves and the amplitude exhibits more extensive and significant aging-related changes than the connectivity. These findings provide strong evidence that cortical spontaneous activity is aging globally, inspiring its clinical utility as neuroimaging markers for neruodegeneration disorders.

DREAM : A Toolbox to Decode Rhythms of the Brain System.

Rhythms of the brain are generated by neural oscillations across multiple frequencies. These oscillations can be decomposed into distinct frequency intervals associated with specific physiological processes. In practice, the number and ranges of decodable frequency intervals are determined by sampling parameters, often ignored by researchers. To improve the situation, we report on an open toolbox with a graphical user interface for decoding rhythms of the brain system (DREAM). We provide worked examples of DREAM to investigate frequency-specific performance of both neural (spontaneous brain activity) and neurobehavioral (in-scanner head motion) oscillations. DREAM decoded the head motion oscillations and uncovered that younger children moved their heads more than older children across all five frequency intervals whereas boys moved more than girls in the age of 7 to 9 years. It is interesting that the higher frequency bands contain more head movements, and showed stronger age-motion associations but weaker sex-motion interactions. Using data from the Human Connectome Project, DREAM mapped the amplitude of these neural oscillations into multiple frequency bands and evaluated their test-retest reliability. The resting-state brain ranks its spontaneous oscillation's amplitudes spatially from high in ventral-temporal areas to low in ventral-occipital areas when the frequency band increased from low to high, while those in part of parietal and ventral frontal regions are reversed. The higher frequency bands exhibited more reliable amplitude measurements, implying more inter-individual variability of the amplitudes for the higher frequency bands. In summary, DREAM adds a reliable and valid tool to mapping human brain function from a multiple-frequency window into brain waves.

Test-retest reliabilities of resting-state FMRI measurements in human brain functional connectomics: a systems neuroscience perspective.

Resting-state functional magnetic resonance imaging (RFMRI) enables researchers to monitor fluctuations in the spontaneous brain activities of thousands of regions in the human brain simultaneously, representing a popular tool for macro-scale functional connectomics to characterize normal brain function, mind-brain associations, and the various disorders. However, the test-retest reliability of RFMRI remains largely unknown. We review previously published papers on the test-retest reliability of voxel-wise metrics and conduct a meta-summary reliability analysis of seven common brain networks. This analysis revealed that the heteromodal associative (default, control, and attention) networks were mostly reliable across the seven networks. Regarding examined metrics, independent component analysis with dual regression, local functional homogeneity and functional homotopic connectivity were the three mostly reliable RFMRI metrics. These observations can guide the use of reliable metrics and further improvement of test-retest reliability for other metics in functional connectomics. We discuss the main issues with low reliability related to sub-optimal design and the choice of data processing options. Future research should use large-sample test-retest data to rectify both the within-subject and between-subject variability of RFMRI measurements and accelerate the application of functional connectomics.

Effects of non-local diffusion on structural MRI preprocessing and default network mapping: statistical comparisons with isotropic/anisotropic diffusion.

Neuroimaging community usually employs spatial smoothing to denoise magnetic resonance imaging (MRI) data, e.g., Gaussian smoothing kernels. Such an isotropic diffusion (ISD) based smoothing is widely adopted for denoising purpose due to its easy implementation and efficient computation. Beyond these advantages, Gaussian smoothing kernels tend to blur the edges, curvature and texture of images. Researchers have proposed anisotropic diffusion (ASD) and non-local diffusion (NLD) kernels. We recently demonstrated the effect of these new filtering paradigms on preprocessing real degraded MRI images from three individual subjects. Here, to further systematically investigate the effects at a group level, we collected both structural and functional MRI data from 23 participants. We first evaluated the three smoothing strategies' impact on brain extraction, segmentation and registration. Finally, we investigated how they affect subsequent mapping of default network based on resting-state functional MRI (R-fMRI) data. Our findings suggest that NLD-based spatial smoothing maybe more effective and reliable at improving the quality of both MRI data preprocessing and default network mapping. We thus recommend NLD may become a promising method of smoothing structural MRI images of R-fMRI pipeline.

PDE-based spatial smoothing: a practical demonstration of impacts on MRI brain extraction, tissue segmentation and registration.

Spatial smoothing is typically used to denoise magnetic resonance imaging (MRI) data. Gaussian smoothing kernels, associated with heat equations or isotropic diffusion (ISD), are widely adopted for this purpose because of their easy implementation and efficient computation, but despite these advantages, Gaussian smoothing kernels blur the edges, curvature and texture of images. To overcome these issues, researchers have proposed anisotropic diffusion (ASD) and non-local means [i.e., diffusion (NLD)] kernels. However, these new filtering paradigms are rarely applied to MRI analyses. In the current study, using real degraded MRI data, we demonstrated the effect of denoising using ISD, ASD and NLD kernels. Furthermore, we evaluated their impact on three common preprocessing steps of MRI data analysis: brain extraction, segmentation and registration. Results suggest that NLD-based spatial smoothing is most effective at improving the quality of MRI data preprocessing and thus should become the new standard method of smoothing in MRI data processing.