Akinwale, O. | Search bioRxiv

bioRxiv2026

Non-invasive MRI mapping of tissue-CSF water exchange reveals glymphatic fluid movement in live human cortex

Efficient metabolic waste clearance, via the postulated glymphatic system, is essential for neural homeostasis. However, direct visualization of tissue-cerebrospinal fluid (CSF) exchange remains limited, leading to ongoing debate in the neuroscientific field. The present work revealed evidence of tissue-CSF water exchange in the live human cortex, by employing a novel MRI technique demonstrating the flux of water molecules across the perivascular interface. We observed robust water exchange inside the cortical ribbon, which was more prominent than white matter and deep brain tissue. We validated that the signal originates from CSF and is independent of cerebral perfusion. Water exchange between tissue and CSF declined with age. Furthermore, we demonstrated for the first time that tissue-CSF exchange was impaired in Alzheimers disease (AD), in particular in regions where the perivascular space is clogged by anti-amyloid immunotherapy.

bioengineering↗

bioRxiv2026

Granule cells reorient cortical manifolds to separate contexts but preserve their geometry

To learn effectively, animals must generalize across yet distinguish between related contexts. Generalization relies on low-dimensional neural manifolds found throughout the neocortex1,2, which accelerate learning by constraining neural activity to task-relevant axes3. Conversely, context separation is attributed to neural expansion layers that can project information into high-dimensional feature spaces4,5, most famously cerebellar granule cells (GrCs)6-8. To investigate the generalization-separation tradeoff, we simultaneously imaged key nodes in the universal cortico-cerebellar pathway9--premotor layer 5 pyramidal tract (L5PT) and GrCs--during parallel learning of two distinct skills with shared temporal structure. Rather than expanding the cortical representations, GrCs retained their low-rank encoding of each task. Across contexts, despite stable cortico-cerebellar coupling, L5PT activity patterns generalized while GrC patterns temporally remapped. But rather than independently scrambling, GrC populations remapped coherently: their low-dimensional trajectories "rotated" apart between tasks, separating the contexts while preserving the cortical geometry of each. Moreover, GrC trajectories diverged most strongly in expert animals. This suggests a fundamental architectural division of labor: the cortex provides invariant dynamic primitives for smooth generalization, while cerebellar activity reconfigures them to drive context-specific output.

neuroscience↗