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Slater, N.

Publications and source records attributed to Slater, N..

3 recordsLinked to original sources

Source-space EEG functional connectivity and prediction of cognition in Parkinsons disease: No added benefit of individualized head models over standard templates

IntroductionCognitive decline is a major non-motor feature of Parkinsons disease (PD), but reliable and accessible biomarkers remain limited. Resting-state electroencephalography (EEG) is a promising candidate because it is low-cost, portable, and well suited to repeated assessment. Recent work has increasingly focused on source-space functional connectivity (FC) for the prediction of cognition. However, the influence of source modelling based on an individualized MRI-based head model relative to that based on standard template model is unknown. MethodsTo compare these two source-space EEG FC methods, we analysed EEG data from the New Zealand Parkinsons Progression Programme, including 136 people with PD and 51 age-similar controls. Source space resting-state EEG, parcellated with the HCP-MMP1 atlas, was used to derive amplitude envelope correlation (AEC) and debiased weighted phase lag index (dwPLI) across six canonical frequency bands. The resulting twenty-four FC modalities were evaluated using six machine-learning regression algorithms within a nested cross-validation framework. ResultsTheta-, alpha-, and beta-band FC showed the most consistent prediction of global cognition. The strongest performance was observed for theta- and alpha-band AEC and dwPLI features (max R{superscript 2} = 0.170, 95% CI = 0.067-0.262; max r = 0.439, 95% CI = 0.328-0.537). Standard and individualized head models showed comparable predictive performance across nearly all modalities. The feature-importance neuroanatomical patterns for Cole-Anticevic networks were also similar between the two head-model options. ConclusionsWe found that source-space resting-state EEG FC can predict cognitive performance in PD. The comparability of the two head models suggests that the more user-friendly and less resource-intensive standard template head model is sufficient for this purpose. This supports feasible, scalable, and clinically accessible EEG-based FC biomarkers of cognition in PD.

neuroscience↗

Super-Resolved Spatial Transcriptomics Reveals Early Changes in RNA Localization in the 5xFAD Hippocampus

Cell-type-specific changes in gene expression and RNA localization are hallmarks of Alzheimers disease (AD) and other neurodegenerative disorders, yet spatial dysregulation in early disease stages remains poorly defined. Here, we applied Expansion Sequencing (ExSeq) to map the spatial distribution of 101 genes at super-resolution in the hippocampus of 4-week-old 5xFAD and wild-type (WT) mice, prior to overt pathology. We uncovered early alterations in RNA spatial organization and gene expression, including 23 genes showing altered localization without changes in abundance in the 5xFAD hippocampus. Using spatial expression analysis and single-cell neighborhood analysis, we identified cell-type- and region-specific molecular programs associated with synaptic function, neuroinflammation, and metabolic stress that differed between 5xFAD and WT mice. Spatial RNA velocity further revealed state differences influenced by local cell to cell interactions. Together, these results suggest that RNA positioning and transcriptional programs are perturbed at early disease stages. Finally, we provide the full super-resolution ExSeq dataset as an open resource for spatial and cell-type-specific analyses in early Alzheimers disease research. HighlightsO_LISuper-resolved transcriptomic profiling of the hippocampus at early disease stages C_LIO_LIIdentification of 23 genes with altered spatial localization without changes in abundance C_LIO_LIEarly alterations in single-cell neighborhood organization in the 5xFAD hippocampus C_LIO_LISpatial RNA velocity reveals cell-type-specific cell state differences shaped by cell-cell proximity C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=187 SRC="FIGDIR/small/678295v2_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1b46cf2org.highwire.dtl.DTLVardef@5cc55eorg.highwire.dtl.DTLVardef@a1ade4org.highwire.dtl.DTLVardef@9f833e_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

Rational nanotoolbox with theranostic potential for medicated pro-regenerative corneal implants

Cornea diseases are a leading cause of blindness and the disease burden is exacerbated by the increasing shortage around the world for cadaveric donor corneas. Despite the advances in the field of regenerative medicine, successful transplantation of laboratory made artificial corneas has not been fully realised in clinical practice. The causes of failure of such artificial corneal implants are multifactorial and include latent infections from viruses and other micorbes, enzyme over-expression, implant degradation, extrusion or delayed epithelial regeneration. Therefore, there is an urgent unmet need for developing customized corneal implants to suit the host environment, counter the effects of inflammation or infection and that are able to track early signs of implant failure in situ. In the present work, we describe a nano toolbox comprising tools for drug release and in addition capable of being infection responsive, promoting regeneration including non-invasive monitoring of in situ corneal environment. These nano constructs can be incorporated within pro-regenerative biosynthetic implants, transforming them into theranostic devices able to respond to biological changes following implantation.

biochemistry↗