Search bioRxiv⌕ Search

Biology subjects

Jia, T.

Publications and source records attributed to Jia, T..

24 records · Page 2Linked to original sources

A novel analytical decoder of BOLD signals for dissociating latent neurobehavioral processes

How to retrieve latent neurobehavioral processes from complex neurobiological signals is an important yet unresolved challenge. Here, we develop a novel approach, orthogonal-Decoding multi-Cognitive Processes (DeCoP), to reveal underlying latent neurobehavioral processing and show that its performance is superior to traditional non-orthogonal decoding in terms of both false inference and robustness. Processing value and salience information are two fundamental but mutually confounded pathways of reward reinforcement essential for decision making. During reward/punishment anticipation, we applied DeCoP to decode brain-wide responses into spatially overlapping, yet functionally independent, evaluation and readiness processes, which are modulated differentially by meso-limbic vs nigro-striatal dopamine systems. Using DeCoP, we further demonstrated that most brain regions only encoded abstract information but not the exact input, except for dACC and insula. Furthermore, our novel analytical principle could be applied generally to decode multiple latent neurobehavioral processes and thus advance both the design and hypothesis testing for cognitive tasks.

neuroscience↗

Assessing Study Reproducibility through MMRI: A Novel Approach for Large-scale High-throughput Association Studies

Magnetic Resonance Imaging (MRI) technology has been increasingly used in large-scale association studies. Reproducibility of statistically significant findings generated by MRI-based association studies, especially structural MRI (sMRI) and functional MRI (fMRI), has been recently heavily debated. However, there is still a lack of overall reproducibility assessment for MRI-based association studies. It is also crucial to elucidate the relationship between overall reproducibility and sample size in an experimental design. In this study, we proposed an overall reproducibility index for large-scale high-throughput MRI-based association studies. We performed the overall reproducibility assessments for several recent large sMRI/fMRI databases and observed satisfactory overall reproducibility. Furthermore, we performed the sample size evaluation for the purpose of achieving a desirable overall reproducibility. Additionally, we evaluated the overall reproducibility of GMV changes for UKB vs. PPMI and UKB vs. HCP. We demonstrated that both sample size and some experimental factors play important roles in the overall reproducibility for different experiments. In summary, a systematic assessment of overall reproducibility is fundamental and crucial in the current large-scale high-throughput MRI-based research.

neuroscience↗

Thousands of missing variants in the UK BioBankare recoverable by genome realignment

The UK Biobank is an unprecedented resource for human disease research. In March 2019, 49,997 exomes were made publicly available to investigators. Here we note that thousands of variant calls are unexpectedly absent from the current dataset, with 641 genes showing zero variation. We show that the reason for this was an erroneous read alignment to the GRCh38 reference. The missing variants can be recovered by modifying read alignment parameters to correctly handle the expanded set of contigs available in the human genome reference.

genetics↗

Neurobehavioural characterisation and stratification of reinforcement-related behaviour

AbstractReinforcement-related cognitive processes, such as reward processing, impulsiveness and emotional processing are critical components of externalising and internalising behaviours. It is unclear to what extent each of these processes contributes to individual behavioural symptoms, how their neural substrates give rise to distinct behavioural outcomes, and if neural profiles across different reinforcement-related processes might differentiate individual behaviours. We created a statistical framework that enabled us to directly compare functional brain activation during reward anticipation, motor inhibition and viewing of emotional faces in the European IMAGEN cohort of 2000 14-year-old adolescents. We observe significant correlations and modulation of reward anticipation and motor inhibition networks in hyperactivity, impulsivity, inattention and conduct symptoms, and describe neural signatures across neuroimaging tasks that differentiate these behaviours. We thus characterise shared and distinct functional brain activation patterns that underlie different externalising symptoms and identify neural stratification markers, while accounting for clinically observed co-morbidity.

neuroscience↗

Pluripotent Stem Cells Can Be Isolated from Human Peripheral Nerves after in vitro BMP-2 Stimulation

We have recently identified a population of cells within the peripheral nerves of adult mice that can respond to BMP-2 exposure or physical injury to rapidly proliferate. More importantly, these cells exhibited embryonic differentiation potentials that could be induced into osteoblastic and endothelial cells in vitro. The current study examined human nerve specimens to compare and characterize the cells after BMP-2 stimulation. Fresh pieces of human nerve tissue were minced and treated with either BMP-2 (750ng/ml) or vehicle for 12 hours at 37{degrees}C, before digested in 0.2% collagenase and 0.05% trypsin-EDTA. Isolated cells were cultured in restrictive stem cell medium. Significantly more cells were obtained from the nerve pieces with BMP-2 treatment in comparison with the non-treated controls. Cell colonies were starting to form at day 3. Expressions of the 4 transcription factors Klf4, c-Myc, Sox2 and Oct4 were confirmed at both transcriptional and translational levels. The cells can be maintained in the stem cell culture medium for at least 6 weeks without changing morphologies. When the cells were switched to fibroblast growth medium, dispersed spindle-shaped cells were noted and became fibroblast activated protein- (FAP) positive following immunocytochemistry staining. The data suggested that human peripheral nerve tissue also contain a population of cells that can respond to BMP-2 and express all four transcription factors KLF4, Sox2, cMyc, and Oct4. These cells are capable to differentiate into FAP-positive fibroblasts. It is proposed that these cells are possibly at the core of a previously unknown natural mechanism for healing injury.

cell biology↗

Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3,337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc) -three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. CpG sites associated with hippocampus volume were significantly enriched within cancer-related genes and within regulatory elements containing the transcriptionally repressive histone H3K27 tri-methylation mark that is vital for stem cell fate specification. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.

genomics↗