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Statistical effects of cortical metrics derived from standard T1‐ and T2‐weighted magnetic resonance imaging (MRI) images, such as gray–white matter contrast (GWC), boundary sharpness coefficient (BSC), T1‐weighted/T2‐weighted ratio (T1w/T2w), and cortical thickness (CT), are often interpreted as representing or being influenced by intracortical myelin content with little empirical evidence to justify these interpretations. We first examined spatial correspondence with more biologically specific microstructural measures, and second compared between‐marker age‐related trends with the underlying hypothesis that different measures primarily driven by similar changes in myelo‐ and microstructural underpinnings should be highly related. Cortical MRI markers were derived from MRI images of 127 healthy subjects, aged 18–81, using cortical surfaces that were generated with the CIVET 2.1.0 pipeline. Their gross spatial distributions were compared with gene expression‐derived cell‐type densities, histology‐derived cytoarchitecture, and quantitative R1 maps acquired on a subset of participants. We then compared between‐marker age‐related trends in their shape, direction, and spatial distribution of the linear age effect. The gross anatomical distributions of cortical MRI markers were, in general, more related to myelin and glial cells than neuronal indicators. Comparing MRI markers, our results revealed generally high overlap in spatial distribution (i.e., group means), but mostly divergent age trajectories in the shape, direction, and spatial distribution of the linear age effect. We conclude that the microstructural properties at the source of spatial distributions of MRI cortical markers can be different from microstructural changes that affect these markers in aging. [ABSTRACT FROM AUTHOR]

While numerous studies have used magnetic resonance imaging (MRI) to elucidate normative age‐related trajectories in subcortical structures across the human lifespan, there exists substantial heterogeneity among different studies. Here, we investigated the normative relationships between age and morphology (i.e., volume and shape), and microstructure (using the T1‐weighted/T2‐weighted [T1w/T2w] signal ratio as a putative index of myelin and microstructure) of the striatum, globus pallidus, and thalamus across the adult lifespan using a dataset carefully quality controlled, yielding a final sample of 178 for the morphological analyses, and 162 for the T1w/T2w analyses from an initial dataset of 253 healthy subjects, aged 18–83. In accordance with previous cross‐sectional studies of adults, we observed age‐related volume decrease that followed a quadratic relationship between age and bilateral striatal and thalamic volumes, and a linear relationship in the globus pallidus. Our shape indices consistently demonstrated age‐related posterior and medial areal contraction bilaterally across all three structures. Beyond morphology, we observed a quadratic inverted U‐shaped relationship between T1w/T2w signal ratio and age, with a peak value occurring in middle age (at around 50 years old). After permutation testing, the Akaike information criterion determined age relationships remained significant for the bilateral globus pallidus and thalamus, for both the volumetric and T1w/T2w analyses. Our findings serve to strengthen and expand upon previous volumetric analyses by providing a normative baseline of morphology and microstructure of these structures to which future studies investigating patients with various disorders can be compared. [ABSTRACT FROM AUTHOR]

Background: Although several volumetric studies have attempted to examine the relationship between hippocampal subfields and age, their findings are heterogenous. Here, in addition to typical volumetric measures, we investigated age‐related alterations of hippocampal subfield shape and microstructure. Method: The present work included 161 healthy participants (ages 18‐81) recruited as part of two local datasets. Standard T1‐weighted (T1w; MPRAGE sequence, 1 mm3 voxels) and high‐resolution T2‐weighted (T2w, 0.64 mm3 voxels) magnetic resonance images were acquired. The minc‐bpipe‐library pipeline (https://github.com/CobraLab/minc‐bpipe‐library) was used to preprocess images. The MAGeT‐Brain algorithm (Pipitone et al., 2014) was utilized for segmentation of the hippocampal subfields (Amaral et al., 2016). The volume and shape (i.e. surface area [SA] and displacement) of the grey matter (GM) subfields (i.e. Cornus Ammonis [CA]1, CA2CA3, CA4 and dentate gyrus [CA4DG], stratum radiatum/lacunosum/moleculare and subiculum) and the volume of associated white matter (WM) regions (i.e. fimbria, fornix, alveus and mammillary bodies [MB]) were estimated using T1w images. Mean T1w/T2w signal intensity ratio (Glasser & Van Essen, 2011) of each subfield was calculated to examine microstructural alterations sensitive to myelin. Linear‐mixed effects models and Akaike information criterion were used to select the most appropriate age relationships from multiple fits (i.e. linear, quadratic, and cubic) for each structure of interest. Sex and ipsilateral hippocampal GM or WM volume were included as covariates. Statistical analyses were performed in R 3.5.0; comparisons surviving p<0.05 (Bonferroni‐corrected) were reported. Result: Right CA1 and alveus volumes were positively cubically related to age and bilateral CA4DG volumes were negatively linearly related to age. T1w/T2w intensity linearly decreased with age for all subregions except for bilateral fornix and MB, which expressed quadratic evolution with age (Figures 1‐2). Age was also inversely related to bilateral SA reduction in the head and medial‐posterior hippocampus, and lateral outward and medial inward displacement (Figure 3). Conclusion: The current work suggests that certain subfields of the hippocampus are more (e.g. CA1) or less (e.g. CA4DG) preserved in healthy aging. These differences do not appear to be explained by microstructural variation. [ABSTRACT FROM AUTHOR]

Retrograde signaling is essential for neuronal growth, function and survival; however, we know little about how signaling endosomes might be directed from synaptic terminals onto retrograde axonal pathways. We have identified Khc-73, a plus-end directed microtubule motor protein, as a regulator of sorting of endosomes in Drosophila larval motor neurons. The number of synaptic boutons and the amount of neurotransmitter release at the Khc-73 mutant larval neuromuscular junction (NMJ) are normal, but we find a significant decrease in the number of presynaptic release sites. This defect in Khc-73 mutant larvae can be genetically enhanced by a partial genetic loss of Bone Morphogenic Protein (BMP) signaling or suppressed by activation of BMP signaling in motoneurons. Consistently, activation of BMP signaling that normally enhances the accumulation of phosphorylated form of BMP transcription factor Mad in the nuclei, can be suppressed by genetic removal of Khc-73. Using a number of assays including live imaging in larval motor neurons, we show that loss of Khc-73 curbs the ability of retrograde-bound endosomes to leave the synaptic area and join the retrograde axonal pathway. Our findings identify Khc-73 as a regulator of endosomal traffic at the synapse and modulator of retrograde BMP signaling in motoneurons. [ABSTRACT FROM AUTHOR]