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Godfrey, M.

Publications and source records attributed to Godfrey, M..

2 recordsLinked to original sources

Measuring robust functional connectivity from resting-state MEG using amplitude and entropy correlation across frequency-bands and temporal scales

Recent studies have shown how MEG can reveal spatial patterns of functional connectivity using frequency-specific oscillatory coupling measures and that these may be modified in disease. However, there is a need to understand both how repeatable these patterns are across participants and how these measures relate to the moment-to-moment variability (or irregularity) of neural activity seen in healthy brain function. In this study, we used Multi-scale Rank-Vector Entropy (MRVE) to calculate the dynamic timecourses of signal variability over a range of temporal scales. The correlation of MRVE timecourses was then used to detect functional connections in resting state MEG recordings that were robust over 183 participants and varied with temporal scale. We then compared these MRVE connectivity patterns to those derived using more standard amplitude-amplitude coupling measures, using methods designed to quantify the consistency of these patterns across participants. Using oscillatory amplitude envelope correlation (AEC), the most consistent connectivity patterns, across the cohort, were seen in the alpha and beta frequency bands. At fine temporal scales (corresponding to scale frequencies, fS = 30-150Hz), MRVE correlation detected mostly occipital and parietal connections and these showed high similarity with the networks identified by AEC in the alpha and beta frequency bands. The most consistent connectivity profiles between participants were given by MRVE correlation at fS = 75Hz and AEC in the beta band. It was also found that average mid-to fine scale variability within each region (fS [~] 10-150Hz) negatively correlated with the regions overall connectivity strength with other brain areas, as measured by fine scale MRVE correlation (fS [~] 30-150Hz) and by alpha and beta band AEC. These findings suggest that local activity at frequencies fS {gtrsim} 10Hz becomes more regular when a region exhibits high levels of resting state connectivity.

neuroscience↗

Dose-dependent functions of SWI/SNF BAF in permitting and inhibiting cell proliferation in vivo

SWI/SNF complexes regulate transcription through chromatin remodeling and opposing gene silencing by Polycomb-group (PcG) proteins. Genes that encode SWI/SNF subunits are frequently mutated in human cancer. The selective advantage, subunit bias, and common heterozygosity of such mutations remains poorly understood. Here, we characterized how functional loss of various SWI/SNF subunits and PcG EZH2 affect proliferation-differentiation decisions in vivo, making use of the reproducible development of the nematode C. elegans. We applied a lineage-specific genetics strategy to create partial or complete SWI/SNF subunit loss, as well as double gene knockout with PcG EZH2. Our data show that a high SWI/SNF BAF dosage is needed to oppose Polycomb-mediated transcriptional repression and to arrest cell division during differentiation. In contrast, even in the absence of the PcG EZH2-related methyltransferase, a low level of the SWI/SNF BAF complex is necessary and sufficient to sustain cell proliferation and hyperplasia. Our data provide experimental support for the theory that during carcinogenesis partial SWI/SNF BAF loss-of-function mutations are selected because they eliminate a tumor suppressor activity while maintaining an essential transcription regulatory function.

developmental biology↗