Age-related differences in brain activations during spatial memory formation in a well-learned virtual Morris water maze (vMWM) task.

The current study applied a rodent-based virtual Morris water maze (vMWM) protocol to an investigation of differences in search performance and brain activations between young and older male human adults. All participants completed in-lab practice and testing before performing the task in the fMRI scanner. Behavioral performance during fMRI scanning - measured in terms of corrected cumulative proximity (CCProx) to the goal - showed that a subgroup of older good performers attained comparable levels of search accuracy to the young while another subgroup of older poor performers exhibited consistently lower levels of search accuracy than both older good performers and the young. With regard to brain activations, young adults exhibited greater activations in the cerebellum and cuneus than all older adults, as well as older poor performers. Older good performers exhibited higher activation than older poor performers in the orbitofrontal cortex (BA 10/11), as well as in the cuneus and cerebellum. Brain-behavior correlations further showed that activations in regions involved in visuomotor control (cerebellum, lingual gyrus) and egocentric spatial processing (premotor cortex, precuneus) correlated positively with search accuracy (i.e., closer proximity to goal) in all participants. Notably, activations in the anterior hippocampus correlated positively with search accuracy (CCProx inversed) in the young but not in the old. Taken together, these findings implicated the orbitofrontal cortex and the cerebellum as playing crucial roles in executive and visuospatial processing in older adults, supporting the proposal of an age-related compensatory shift in spatial memory functions away from the hippocampus toward the prefrontal cortex.