Sleep Spindles Promote the Restructuring of Memory Representations in Ventromedial Prefrontal Cortex through Enhanced Hippocampal–Cortical Functional Connectivity

Abstract

Memory consolidation is hypothesized to involve the distribution and restructuring of memory representations across hippocampal and cortical regions. Theories suggest that, through extended hippocampal-cortical interactions, cortical ensembles come to represent more integrated, or overlapping, memory traces that prioritize commonalities across related memories. Sleep processes, particularly fast sleep spindles, are thought to support consolidation, but evidence for this relationship has been mostly limited to memory retention benefits. Whether fast spindles provide a mechanism for neural changes hypothesized to support consolidation, including the strengthening of hippocampal-cortical networks and integration across memory representations, remains unclear, as does the specificity of regions involved. Using functionalconnectivityanalysesofhumanfMRIdata(bothsexes),weshowthatfastspindledensityduringovernightsleepisrelatedtoenhanced hippocampal-cortical functional connectivity the next day, when restudying information learned before sleep. Spindle density modulated connectivity in distinct hippocampal-cortical networks depending on the category of the consolidated stimuli. Specifically, spindle density correlated with functional connectivity between anterior hippocampus and ventromedial prefrontal cortex (vmPFC) for object-word pairs, and posterior hippocampus and posteromedial cortex for scene-word pairs. Using multivariate pattern analyses, we also show that fast spindle density during postlearning sleep is associated with greater pattern similarity, or representational overlap, across individual object-word memories in vmPFC the next day. Further, the relationship between fast spindle density and representational overlap in vmPFC was mediated by the degree of anterior hippocampal-vmPFC functional connectivity. Together, these results suggest that fast spindles support the network distribution of memory traces, potentially restructuring memory representations in vmPFC.

Sleep leads to system-wide neural changes independent of allo- and egocentric spatial training in humans and rats

“…It is noticeable that brain areas that showed an increase due to sleep belong to the executive control network, which has previously been shown to be related to goal directed behavior [25] and spatial memory [26]. In contrast, the brain areas that showed a decrease belong to the default mode network, which has also been previously associated to spatial memory [27-31].…”

“…In regards to the changes seen in areas of the default mode network, ample amount of evidence has pointed to the importance of hippocampus and medial temporal lobe structures including the prefrontal cortex and precuneus (also known as retrosplenial cortex [54]) in spatial navigation in both human and rodent models [26, 55-57]. Furthermore, the default mode network is functionally modulated by sleep with persistent connectivity during light sleep and especially sleep spindles and gradually decoupling with deep sleep [34, 58-61] and thus could potentially play a role in offline consolidation processes coordinating the systems-wide consolidation process during sleep [8, 29-31, 62]. Recent evidence in rodents show the co-occurrence of cortical high-frequency oscillations in default mode network areas as well as posterior parietal cortex with hippocampal ripples during NonREM sleep [51], which may be the mechanisms how memories could be consolidated from the initial hippocampal storage to downstream areas such as the posterior parietal cortex via the cortical default mode network areas [8].…”

Reward biases spontaneous neural reactivation during sleep

“…These findings in humans are in line with the observation in rodents that neural oscillations during slow-wave sleep coordinate the replay of recently encoded memories in the hippocampus 24 , and across reward 25 and neocortical regions 26 . Post-learning increases in oscillatory activity during sleep (hippocampal sharp-wave ripples, 11-15 Hz sleep spindles,~1 Hz SWA) are known to enhance memory retention in both humans 1,5,[27][28][29][30][31] and animals 32,33 . Importantly, neuroimaging studies also suggested that overnight memory consolidation resulted in functional changes in brain regions specialized for the processing of task-relevant features, for example the hippocampus after a spatial navigation task 3 , or the primary visual cortex after a perceptual learning task 34,35 .…”

Isoflurane anesthesia disrupts the cortical metabolome

“…Among the most daunting unanswered questions in neuroscience are those that concern the mechanisms by which states of consciousness are generated. The role of the prefrontal cortex (PFC) as a modulator of states of consciousness is undergoing active investigation from an electrophysiology and connectivity perspective ( Carlén 2017 ; Cowan et al 2020 ; Joglekar et al 2018 ; Krone et al 2020 ; Pal et al 2018 ; van Vugt et al 2018 ). Although the PFC has long been known to modulate states of consciousness ( Muzur et al 2002 ), we are aware of only one study in mice that compared the PFC metabolome during wakefulness and sleep ( Bourdon et al 2018 ).…”