Sleep transforms the cerebral trace of declarative memories

Abstract

After encoding, memory traces are initially fragile and have to be reinforced to become permanent. The initial steps of this process occur at a cellular level within minutes or hours. Besides this rapid synaptic consolidation, systems consolidation occurs within a time frame of days to years. For declarative memory, the latter is presumed to rely on an interaction between different brain regions, in particular the hippocampus and the medial prefrontal cortex (mPFC). Specifically, sleep has been proposed to provide a setting that supports such systems consolidation processes, leading to a transfer and perhaps transformation of memories. Using functional MRI, we show that postlearning sleep enhances hippocampal responses during recall of word pairs 48 h after learning, indicating intrahippocampal memory processing during sleep. At the same time, sleep induces a memory-related functional connectivity between the hippocampus and the mPFC. Six months after learning, memories activated the mPFC more strongly when they were encoded before sleep, showing that sleep leads to long-lasting changes in the representation of memories on a systems level.

Fig. 1.

Brain activity during learning and recall tasks, respectively, for words correctly recalled 2 days after learning as compared with the Korean control task. Activity during learning (A) and cued recall of word pairs (B) is centered mainly in the extrastriate visual system. Note that words represented concrete objects, and subjects were instructed to imagine a picture containing both items of a pair, which explains the strong implication of this pathway known to be crucial for object representation (21). No significant activity was found in area 17 of the visual cortex, perhaps reflecting the imaginary nature of the task. Maps displayed at P_FWE < 0.05.

Fig. 2.

Changes in hippocampal activity during correct word recall over sleep and sleep deprivation. (A) Between the immediate (PRE) and 2-day delayed (POST) recall sessions, the hippocampal involvement in correct word recall increases significantly, but only when subjects slept during the first night after learning (S-SD × POST-PRE). (B) Hippocampal activity ([26 −16 −22]) across the whole 6-month retention interval. In the sleep condition (open circles), activity increases from 30 min to 2 days (Z = 3.00, P_SVC = 0.04), whereas no significant changes can be found when subjects were sleep-deprived the night after learning (filled circles). S and SD conditions differ only at the 2-day interval (t₁₅ = 3.4, P = 0.003).

Fig. 3.

Areas functionally related to the hippocampus during correct word recall on day two after sleep or sleep deprivation. Two days after learning, if subjects were allowed to sleep, the hippocampus was functionally connected to the precuneus and the mPFC during correct word recall (blue). However, if subjects were sleep-deprived the night after learning, the prefrontal sites did not relate to hippocampal activation (red).

Fig. 4.

Differences in brain activity during the 6-month retest session for correctly recalled words learned before sleep vs. before sleep deprivation (S-SD). (A) Correct word recall after 6 months activates the mPFC and the occipital cortex more strongly for words from the sleep condition than for words from the sleep-deprivation condition. Note that at the 2-day interval, no activity per se was found, but only a strong functional relation to hippocampal activity. Now, at the 6-month interval, independent mPFC activity is found, but no more significant hippocampal activity. (B) The difference in brain activity in the mPFC developed mainly during the interval between the 2-day and 6-month recall sessions. It is supported by a steady increase in mPFC activity for words from the S condition over the 6-month period (open circles) and a marked drop in mPFC activity for words from the SD condition (filled circles) during the 6-month session ([−6 26 −10], Z = −3.87, P_SVC = 0.004).