Age Sensitive Hippocampal Functional Connectivity: New Insights from 3D CNNs and Saliency Mapping

Grey matter loss in the hippocampus is a hallmark of neurobiological aging, yet understanding the corresponding changes in its functional connectivity remains limited. Seed-based functional connectivity (FC) analysis enables voxel-wise mapping of the hippocampus's synchronous activity with cortical regions, offering a window into functional reorganization during aging. In this study, we develop an interpretable deep learning framework to predict brain age from hippocampal FC using a three-dimensional convolutional neural network (3D CNN) combined with LayerCAM saliency mapping. This approach maps key hippocampal-cortical connections, particularly with the precuneus, cuneus, posterior cingulate cortex, parahippocampal cortex, left superior parietal lobule, and right superior temporal sulcus, that are highly sensitive to age. Critically, disaggregating anterior and posterior hippocampal FC reveals distinct mapping aligned with their known functional specializations. These findings provide new insights into the functional mechanisms of hippocampal aging and demonstrate the power of explainable deep learning to uncover biologically meaningful patterns in neuroimaging data.

Perivascular space Identification Nnunet for Generalised Usage (PINGU)

Perivascular spaces(PVSs) form a central component of the brain\'s waste clearance system, the glymphatic system. These structures are visible on MRI images, and their morphology is associated with aging and neurological disease. Manual quantification of PVS is time consuming and subjective. Numerous deep learning methods for PVS segmentation have been developed, however the majority have been developed and evaluated on homogenous datasets and high resolution scans, perhaps limiting their applicability for the wide range of image qualities acquired in clinic and research. In this work we train a nnUNet, a top-performing biomedical image segmentation algorithm, on a heterogenous training sample of manually segmented MRI images of a range of different qualities and resolutions from 6 different datasets. These are compared to publicly available deep learning methods for 3D segmentation of PVS. The resulting model, PINGU (Perivascular space Identification Nnunet for Generalised Usage), achieved voxel and cluster level dice scores of 0.50(SD=0.15), 0.63(0.17) in the white matter(WM), and 0.54(0.11), 0.66(0.17) in the basal ganglia(BG). Performance on data from unseen sites was substantially lower for both PINGU(0.20-0.38(WM, voxel), 0.29-0.58(WM, cluster), 0.22-0.36(BG, voxel), 0.46-0.60(BG, cluster)) and the publicly available algorithms(0.18-0.30(WM, voxel), 0.29-0.38(WM cluster), 0.10-0.20(BG, voxel), 0.15-0.37(BG, cluster)), but PINGU strongly outperformed the publicly available algorithms, particularly in the BG. Finally, training PINGU on manual segmentations from a single site with homogenous scan properties gave marginally lower performances on internal cross-validation, but in some cases gave higher performance on external validation. PINGU stands out as broad-use PVS segmentation tool, with particular strength in the BG, an area of PVS related to vascular disease and pathology.