Dataset Information

Activation-based association profiles differentiate network roles across cognitive loads.

ABSTRACT: Working memory (WM) is a complex and pivotal cognitive system underlying the performance of many cognitive behaviors. Although individual differences in WM performance have previously been linked to the blood oxygenation level-dependent (BOLD) response across several large-scale brain networks, the unique and shared contributions of each large-scale brain network to efficient WM processes across different cognitive loads remain elusive. Using a WM paradigm and functional magnetic resonance imaging (fMRI) from the Human Connectome Project, we proposed a framework to assess the association and shared-association strength between imaging biomarkers and behavioral scales. Association strength is the capability of individual brain regions to modulate WM performance and shared-association strength measures how different regions share the capability of modulating performance. Under higher cognitive load (2-back), the frontoparietal executive control network (FPN), dorsal attention network (DAN), and salience network showed significant positive activation and positive associations, whereas the default mode network (DMN) showed the opposite pattern, namely, significant deactivation and negative associations. Comparing the different cognitive loads, the DMN and FPN showed predominant associations and globally shared-associations. When investigating the differences in association from lower to higher cognitive loads, the DAN demonstrated enhanced association strength and globally shared-associations, which were significantly greater than those of the other networks. This study characterized how brain regions individually and collaboratively support different cognitive loads.

SUBMITTER: Zuo N

PROVIDER: S-EPMC6865538 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Activation-based association profiles differentiate network roles across cognitive loads.

Zuo Nianming N Salami Alireza A Yang Yihong Y Yang Zhengyi Z Sui Jing J Jiang Tianzi T

Human brain mapping 20190310 9

Working memory (WM) is a complex and pivotal cognitive system underlying the performance of many cognitive behaviors. Although individual differences in WM performance have previously been linked to the blood oxygenation level-dependent (BOLD) response across several large-scale brain networks, the unique and shared contributions of each large-scale brain network to efficient WM processes across different cognitive loads remain elusive. Using a WM paradigm and functional magnetic resonance imagi ...[more]

PMID: 30854745

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Project description:BackgroundDrug repositioning offers the possibility of faster development times and reduced risks in drug discovery. With the rapid development of high-throughput technologies and ever-increasing accumulation of whole genome-level datasets, an increasing number of diseases and drugs can be comprehensively characterized by the changes they induce in gene expression, protein, metabolites and phenotypes.Methodology/principal findingsWe performed a systematic, large-scale analysis of genomic expression profiles of human diseases and drugs to create a disease-drug network. A network of 170,027 significant interactions was extracted from the approximately 24.5 million comparisons between approximately 7,000 publicly available transcriptomic profiles. The network includes 645 disease-disease, 5,008 disease-drug, and 164,374 drug-drug relationships. At least 60% of the disease-disease pairs were in the same disease area as determined by the Medical Subject Headings (MeSH) disease classification tree. The remaining can drive a molecular level nosology by discovering relationships between seemingly unrelated diseases, such as a connection between bipolar disorder and hereditary spastic paraplegia, and a connection between actinic keratosis and cancer. Among the 5,008 disease-drug links, connections with negative scores suggest new indications for existing drugs, such as the use of some antimalaria drugs for Crohn's disease, and a variety of existing drugs for Huntington's disease; while the positive scoring connections can aid in drug side effect identification, such as tamoxifen's undesired carcinogenic property. From the approximately 37K drug-drug relationships, we discover relationships that aid in target and pathway deconvolution, such as 1) KCNMA1 as a potential molecular target of lobeline, and 2) both apoptotic DNA fragmentation and G2/M DNA damage checkpoint regulation as potential pathway targets of daunorubicin.Conclusions/significanceWe have automatically generated thousands of disease and drug expression profiles using GEO datasets, and constructed a large scale disease-drug network for effective and efficient drug repositioning as well as drug target/pathway identification.

Dataset Information

Activation-based association profiles differentiate network roles across cognitive loads.

Publications

Activation-based association profiles differentiate network roles across cognitive loads.

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