Combination of Resting State fMRI, DTI, and sMRI Data to Discriminate Schizophrenia by N-way MCCA + jICA

Multimodal brain imaging data have shown increasing utility in answering both scientifically interesting and clinically relevant questions. Each brain imaging technique provides a different view of brain function or structure, while multimodal fusion capitalizes on the strength of each and may uncover hidden relationships that can merge findings from separate neuroimaging studies. However, most current approaches have focused on pair-wise fusion and there is still relatively little work on N-way data fusion and examination of the relationships among multiple data types. We recently developed an approach called “mCCA + jICA” as a novel multi-way fusion method which is able to investigate the disease risk factors that are either shared or distinct across multiple modalities as well as the full correspondence across modalities. In this paper, we applied this model to combine resting state fMRI (amplitude of low-frequency fluctuation, ALFF), gray matter (GM) density, and DTI (fractional anisotropy, FA) data, in order to elucidate the abnormalities underlying schizophrenia patients (SZs, n = 35) relative to healthy controls (HCs, n = 28). Both modality-common and modality-unique abnormal regions were identified in SZs, which were then used for successful classification for seven modality-combinations, showing the potential for a broad applicability of the mCCA + jICA model and its results. In addition, a pair of GM-DTI components showed significant correlation with the positive symptom subscale of Positive and Negative Syndrome Scale (PANSS), suggesting that GM density changes in default model network along with white-matter disruption in anterior thalamic radiation are associated with increased positive PANSS. Findings suggest the DTI anisotropy changes in frontal lobe may relate to the corresponding functional/structural changes in prefrontal cortex and superior temporal gyrus that are thought to play a role in the clinical expression of SZ

Interactions of Dnd Proteins involved in bacterial DNA phosphorothioate modification

DNA phosphorothioation (PT) is the first discovered physiological DNA backbone modification, in which a non-bridging oxygen atom of the phosphodiester bond is replaced with a sulfur atom in Rp (Rectus for plane) configuration. PT modification is governed by a highly conserved gene cluster dndA/IscS-dndBCDE that is widespread across bacterial and archaeal species. However little is known about how these proteins coordinately react with each other to perform oxygen–sulfur swap. We here demonstrated that IscS, DndC, DndD and DndE formed a protein complex of which the molecular ratio for four proteins in the complex is approximate 1:1:1:1. DndB here displayed little or weak affinity to the complex and the constructs harboring dndACDE can confer the host in vivo PT modification. Using co-purification and pull-down strategy, we demonstrated that the four proteins assembly into a pipeline in collinear to its gene organization, namely, IscS binding to DndC, DndC binding to DndD, and DndD binding to DndE. Moreover, weak interactions between DndE and IscS, DndE and DndC were also identified

Towards Developmental Connectomics of the Human Brain

Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and developmental dyslexia). Collectively, we showed that delineation of the brain network from a connectomics perspective offers a unique and refreshing view of both normal development and neuropsychiatric disorders

Differences of inter-tract correlations between neonates and children around puberty: A study based on microstructural measurements with DTI

The human brain development is a complicated yet well-organized process. Metrics derived from diffusion tensor imaging (DTI), including fractional anisotropy (FA), radial (RD), axial (AxD) and mean diffusivity (MD), have been used to noninvasively access the microstructural development of human brain white matter (WM). At birth, most of the major WM tracts are apparent but in a relatively disorganized pattern. Brain maturation is a process of establishing an organized pattern of these major WM tracts. However, how the linkage pattern of major WM tracts changes during development remains unclear. In this study, DTI data of 26 neonates and 28 children around puberty were acquired. 10 major WM tracts, representing four major tract groups involved in distinctive brain functions, were traced with DTI tractography for all 54 subjects. With the 10 by 10 correlation matrices constructed with Spearman’s pairwise inter-tract correlations and based on tract-level measurements of FA, RD, AxD and MD of both age groups, we assessed if the inter-tract correlations become stronger from birth to puberty. In addition, hierarchical clustering was performed based on the pairwise correlations of WM tracts to reveal the clustering pattern for each age group and pattern shift from birth to puberty. Stronger and enhanced microstructural inter-tract correlations were found during development from birth to puberty. The linkage patterns of two age groups differ due to brain development. These changes of microstructural correlations from birth to puberty suggest inhomogeneous but organized myelination processes which cause the reshuffled inter-tract correlation pattern and make homologous tracts tightly clustered. It opens a new window to study WM tract development and can be potentially used to investigate atypical brain development due to neurological or psychiatric disorders