Investigation of the human neural correlates of memory for sequences of events and their changes in typical aging
Memory for sequences of events, an ability present in humans, nonhuman primates, and rodents, is a critical component of episodic memory and is known to decline in typical aging (Allen and Fortin, 2013; Allen et al., 2015; Fabiani and Friedman, 1997; Pinto-Hamuy and Linck, 1965; Roberts et al., 2014; Tolentino et al., 2012; Tulving, 1984). The use of a cross-species task allows for complementary approaches in the rat and human in order to provide a greater understanding of the neural mechanisms underlying sequence memory ability. Using a non-spatial sequence memory paradigm in combination with blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI), we present evidence that memory for sequences of events activates the hippocampus and medial prefrontal cortex in humans, paralleling recording studies and temporary inactivations in rats performing the cross-species task. In addition, these areas show functional connectivity over the course of the task to a greater degree than other regions, supporting the hypothesis that sequence memory in the human is subserved by the hippocampus and medial prefrontal cortex and their functional interactions. After demonstrating homology for the neural substrates of sequence memory in the rat and human, we sought to investigate the behavioral and neural changes associated with typical aging. We found that typically aging older adults showed behavioral impairments on the sequence memory task. Equating performance between young and older adults, using BOLD fMRI we found evidence for similar neural substrates, but decreased activity in older adults. In addition, we found that functional connectivity between hippocampus and medial prefrontal cortex decreased with age, as did connectivity between other regions that in young adults showed high connectivity. Future studies using variants of the cross-species task in both rats and humans, combined with additional imaging modalities, will further elucidate the underlying neurobiological changes in typical aging.