title: Evidence for a virtual human analog of a rodent relational memory task: a study of aging and fMRI in young adults.
abstract: A radial maze concurrent spatial discrimination learning paradigm consisting of two stages was previously designed to assess the flexibility property of relational memory in mice, as a model of human declarative memory. Aged mice and young adult mice with damage to the hippocampus, learned accurately Stage 1 of the task which required them to learn a constant reward location in a specific set of arms (i.e., learning phase). In contrast, they were impaired relative to healthy young adult mice in a second stage when faced with rearrangements of the same arms (i.e., flexibility probes). This mnemonic inflexibility in Stage 2 is thought to derive from insufficient relational processing by the hippocampus during initial learning (Stage 1) which favors stimulus-response learning, a form of procedural learning. This was proposed as a model of the selective declarative and relational memory decline classically described in elderly people. As a first step to examine the validity of this model, we adapted this protocol to humans using a virtual radial-maze. (1) We showed that performance in the flexibility probes in young and older adults positively correlated with performance in a wayfinding task, suggesting that our paradigm assesses relational memory. (2) We demonstrated that older healthy participants displayed a deficit in the performance of the flexibility probes (Stage 2), similar to the one previously seen in aged mice. This was associated with a decline in the wayfinding task. (3) Our fMRI data in young adults confirmed that hippocampal activation during early discrimination learning in Stage 1 correlated with memory flexibility in Stage 2, whereas caudate nucleus activation in Stage 1 negatively correlated with subsequent flexibility. By enabling relational memory assessment in mice and humans, our radial-maze paradigm provides a valuable tool for translational research.
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Verdun, Quebec, Canada H4H 1R3. nicole.etchamendy@u-bordeaux1.fr
authors.forename: Nicole
authors.initials: N
authors.lastname: Etchamendy
authors.forename: Kyoko
authors.initials: K
authors.lastname: Konishi
authors.forename: G Bruce
authors.initials: GB
authors.lastname: Pike
authors.forename: Aline
authors.initials: A
authors.lastname: Marighetto
authors.forename: Véronique D
authors.initials: VD
authors.lastname: Bohbot
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology* / Q000523:psychology*; D000818:Animals; D004193:Discrimination Learning / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000293:injuries / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D008875:Middle Aged; D023421:Models, Animal; D011597:Psychomotor Performance / Q000502:physiology; D013028:Space Perception / Q000502:physiology; D013647:Task Performance and Analysis; D057170:Translational Research, Biomedical; D014584:User-Computer Interface; D055815:Young Adult