Functional Imaging of Hippocampal Layers Using VASO and BOLD on the Next Generation (NexGen) 7T Scanner

Spatial accuracy and venous biases are a central concern in mesoscale fMRI, with subcortical brain regions facing additional challenges due to lower sensitivity, high physiological noise, and complicated vasculature. Here, we optimized CBV VASO on the NexGen 7T scanner for layer-specific investigations of the human hippocampus. Both VASO and BOLD (from the same acquisition) detected significant hippocampal activation during an established autobiographical memory task. At the macroscale, activation patterns converged, showing pronounced memory task activation in the anterior hippocampus and consistent engagement across the frontoparietal neocortex. At the laminar scale, however, differences in depth-dependent profiles emerged within the subiculum: BOLD exhibited a pronounced bias toward the inner layers, consistent with the known venous drainage pattern in the subfield. Finally, the optimized effective TR of 3.2 s allowed exploratory study of retrieval stages and neocortical functional connectivity, which both supported hippocampal anterior-posterior dissociation using either VASO or BOLD. Thus, hippocampal fMRI allows mapping layer function with high accuracy and can provide deeper insights into a number of neuropsychological phenomena and disorders.