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Dauby, S.

Publications and source records attributed to Dauby, S..

2 recordsLinked to original sources

Pooling quantitative MRI data: A multi-protocol study of healthy subcortical ageing

Quantitative MRI (qMRI) measures relaxation rates, exchange rates and proton densities that reflect biophysical properties of tissue and are ideally free from protocol- and scanner-dependence. In practice, qMRI has not yet achieved this level of independence from sequence and hardware choice, and quantitative estimates often differ across sites and acquisition schemes. At the same time pooling data across different sources can be beneficial to statistical power of longitudinal, cross-sectional or case-control studies. Here we investigate how protocol and hardware differences can affect pooling data from different sources in large ultra high field (UHF) qMRI studies in the context of healthy aging. We combine the openly available ageing UHF qMRI MP2RAGEME-based dataset with two different MPM-based sets of qMRI data. We evaluate how pooling affects age dependence of qMRI parameters and investigate protocol-related biases, with a particular focus on subcortical structures. We focus the analysis, first, on replication and expansion of the reference qMRI dataset on normative aging, second, the examination of the protocol influence on the estimated qMRI values, and third, on detecting the protocol effect on the age dependence inferred from the data. We find that the age-related changes for R1 measure around 4-17% of the lifespan mean in different structures. Similarly, age-related R2* variation in different structures constitutes around 6-30%. Subcortical structure volume change is on the order of 5-27%. We further observe larger relative difference between protocols for R1 and volume, while R2* remains more consistent for most regions. We show how pooling the UHF qMRI data from different sites and collected with different quantitative protocols can be both detrimental and beneficial for the analysis outcomes.

neuroscience↗

Cell Type Specific Enhancers for Dorsolateral Prefrontal Cortex.

The dorsolateral prefrontal cortex (DLPFC) is crucial to primate cognitive functions, but a paucity of cell type specific tools limits studies of DLPFC neurocomputational principles. Therefore, we set out to identify enhancers that fit inside Adeno-Associated Virus (AAV) vectors and that elicited functional, cell type specific gene expression in the non-human primate (NHP) DLPFC. We used single nucleus RNA-Seq and ATAC-Seq from rhesus macaque tissue samples to define DLPFC cell types and their associated open chromatin regions (OCRs). We trained machine learning (ML) models to recognize the unique regulatory grammar associated with each DLPFC neuron type, performed in silico screening of all OCRs, and identified candidate enhancers most likely to elicit cell type specific transgene expression in each neuron type. For layer 3 pyramidal neurons (L3PNs) and layer 5 extratelencephalic neurons (L5ETs), we cloned the top twelve identified candidates into AAVs and injected them into NHP DLPFC. In situ observation of enhancer-driven expression revealed the best performers, RMacL3-01 and RMacL5ET-01. We validated RMacL3-01 and RMacL5ET-01 using one-at-a-time injections in NHP DLPFC. RMacL3-01 restricted GFP expression to pyramidal neurons in layers 2 and 3, whereas RMacL5ET-01 restricted expression to POU3F1+ neurons in layer 5. RMacL3-01 elicited functional levels of channelrhodopsin expression that enabled optical activation of single- and multi-unit activity in NHP DLFPC. Together, these results and resources establish a solid foundation to study cell type specific principles of primate cognitive functions.

neuroscience↗