Awake Hippocampal–Cortical Co-reactivation Is Associated with Forgetting

Abstract

Systems consolidation theories posit that consolidation occurs primarily through a coordinated communication between hippocampus and neocortex [Moscovitch, M., & Gilboa, A. Systems consolidation, transformation and reorganization: Multiple trace theory, trace transformation theory and their competitors. PsyArXiv, 2021; Kumaran, D., Hassabis, D., & McClelland,J.L.Whatlearningsystemsdointelligentagents need? Complementary learning systems theory updated. Trends in Cognitive Sciences, 20, 512–534, 2016; McClelland, J. L., & O’Reilly, R. C. Why there are complementary learning systems in the hippocampus and neocortex: Insights from the successes and failures of connectionist models of learning and memory. Psychological Review, 102, 419–457, 1995]. Recent sleep studies in rodents have shown that hippocam-pus and visual cortex replay the same information at temporal proximity (“co-replay”; Lansink,C.S.,Goltstein,P.M., Lankelma, J. V., McNaughton, B. L., & Pennartz, C. M. A. Hip-pocampus leads ventral striatum in replay of place-reward information. PLoS Biology, 7, e1000173, 2009; Peyrache, A., Khamassi,M.,Benchenane,K.,Wiener,S.I.,&Battaglia,F. P. Replay of rule-learning related neural patterns in the pre-frontal cortex during sleep. Nature Neuroscience, 12, 919– 926,2009;Wierzynski,C.M.,Lubenov,E.V.,Gu,M.,&Siapas, A. G. State-dependent spike-timing relationships between hippocampal and prefrontal circuits during sleep. Neuron, 61, 587–596, 2009; Ji, D., & Wilson, M. A. Coordinated memory replay in the visual cortex and hippocampus during sleep. Nature Neuroscience, 10, 100–107, 2007). We developed a novel repetition time (TR)-based co-reactivation analysis method to study hippocampal–cortical co-replays in humans using fMRI. Thirty-six young adults completed an image (face or scene) and location paired associate encoding task in the scanner, which were preceded and followed by resting state scans. We identified post-encoding rest TRs (± 1) that showed neural reactivation of each image–location trials in both hippo-campus (HPC) and category-selective cortex (fusiform face area [FFA]). This allowed us to characterize temporally proxi-mal coordinated reactivations (“co-reactivations”) between HPC and FFA. Moreover, we found that increased HPC–FFA co-reactivations were associated with incorrectly recognized trials after a 1-week delay (p =.004). Finally, we found that these HPC–FFA co-reactivations were also associated with trials that were initially correctly recognized immediately after encoding but were later forgotten in 1-day (p =.043) and 1-week delay period (p =.031). We discuss these results from a trace transformation perspective [Sekeres, M. J., Winocur, G., & Moscovitch, M. The hippocampus and related neocortical structures in memory transformation. Neuroscience Letters, 680, 39–53, 2018; Winocur, G., & Moscovitch, M. Memory transformation and systems consolidation. Journal of the International Neuropsychological Society, 17, 766–780, 2011] and speculate that HPC–FFA co-reactivations may be integrating related events, at the expense of disrupting event-specific details, hence leading to forgetting.