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Powell, K.

Publications and source records attributed to Powell, K..

3 recordsLinked to original sources

Implementation of a pre- and in-scan system to minimize head motion in pediatric participants undergoing fMRI scans

BackgroundPerforming fMRI scans of children can be a difficult task, as participants tend to move while being scanned. Head motion represents a significant confound in functional magnetic resonance imaging (fMRI) connectivity analyses, and methods to limit the impact of movement on data quality are needed. One approach has been to use shorter MRI protocols, though this potentially reduces the reliability of the results. ObjectiveHere we describe steps we have taken to limit head motion in an ongoing fMRI study of children undergoing a 60 minute MRI scan protocol. Specifically, we have used a mock scan protocol that trains participants to lie still while being scanned. We provide a detailed protocol and describe other in-scanner measures we have implemented, including an incentive system and the use of a weighted blanket. Materials and methodsParticipants who received a formal mock scan (n = 12) were compared to participants who had an informal mock scan (n = 7). A replication group of participants (n = 16), including five with autism spectrum disorder, who received a formal mock scan were also compared to the informal mock scan group. The primary measure of interest was the mean frame-to-frame displacement across eight functional runs during the fMRI protocol. ResultsParticipants in the formal mock scan and replication group tended to exhibit more low-motion functional scans than the informal mock scan group (P < 0.05). Across different functional scan conditions (i.e. while watching movie clips, performing an attention task, and during resting-state scans), effect sizes tended to be large (Hedges g > 0.8). ConclusionResults indicate that with appropriate measures, it is possible to achieve low-motion fMRI data in younger participants undergoing a long scan protocol.

neuroscience

Targeting lateral inhibition to improve vision following macular degeneration

Macular degeneration is the leading cause of blindness in the developed world. Whilst most patients lose sight owing to atrophic changes, no treatments currently exist that improve the vision deficit due to atrophy. Here, we identify loss of lateral inhibition as a specific mechanism by which photoreceptor degeneration reduces visual function beyond the atrophic area. We find that this inhibition is adaptive, and that if modulated can improve visual function, making inhibitory circuits an unexpected therapeutic target for age related macular degeneration and related disorders.

neuroscience

Human intestinal tissue-resident memory CD8+ T cells comprise transcriptionally and functionally distinct subsets

Tissue-resident memory T (TRM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However transcriptional heterogeneity of human intestinal TRM cells remains undefined, and definitive markers of CD103-TRM cells are lacking. Here, we investigated transcriptional and functional heterogeneity of human TRM cells through the study of donor-derived intestinal TRM cells from intestinal transplant recipients. Single-cell transcriptional profiling identified four conventional TRM populations, with two distinct transcriptional states of CD8+ TRM cells, delineated by ITGAE and ITGB2 expression. We defined a transcriptional signature discriminating the two CD8+ populations, including differential expression of key residency-associated genes and cytotoxic molecules. Flow cytometry of recipient-derived cells infiltrating the graft and intestinal lymphocytes from healthy gut confirmed the two CD8+ TRM phenotypes, with {beta}2-integrin acting as a CD103-CD8+ TRM marker. CD103+ CD8+ TRM cells produced IL-2, and demonstrated greater polyfunctional cytokine production, while {beta}2-integrin+ CD69+ CD103-TRM cells had higher granzyme expression. Phenotypic and functional analysis of intestinal CD4+ T cells identified many parallels, including a distinct {beta}2-integrin+ population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal TRM cells, and suggest a role for {beta}2-integrin in TRM development. SummaryHeterogeneity within human tissue-resident memory T (TRM) cells is poorly understood. We show that transcriptionally, phenotypically, and functionally distinct CD4+ and CD8+ TRM subsets exist in the human intestine, and that {beta}2-integrin expression identifies a distinct population of CD8+ TRM cells.

immunology