Human cortical–hippocampal dialogue in wake and slow-wave sleep

Abstract

Declarative memory consolidation is hypothesized to require a twostage, reciprocal cortical-hippocampal dialogue. According to this model, higher frequency signals convey information from the cortex to hippocampus during wakefulness, but in the reverse direction during slow-wave sleep (SWS). Conversely, lower-frequency activity propagates from the information "receiver" to the "sender" to coordinate the timing of information transfer. Reversal of sender/ receiver roles across wake and SWS implies that higher-and lower-frequency signaling should reverse direction between the cortex and hippocampus. However, direct evidence of such a reversal has been lacking in humans. Here, we use human resting-state fMRI and electrocorticography to demonstrate that δ-band activity and infraslow activity propagate in opposite directions between the hippocampus and cerebral cortex. Moreover, both δ activity and infraslow activity reverse propagation directions between the hippocampus and cerebral cortex across wake and SWS. These findings provide direct evidence for state-dependent reversals in human cortical-hippocampal communication.D eclarative memories are initially hippocampus-dependent and gradually become hippocampus-independent over time, that is, consolidated (1, 2). It is theorized that a two-stage reciprocal dialogue between the hippocampus and the cerebral cortex underlies memory consolidation (3-5). According to this model, active behavior generates experiential codes in the cortex that are transmitted to the hippocampus, which houses a labile information store. Later, during slow-wave sleep (SWS), recently acquired hippocampal information is reactivated and transmitted to the cerebral cortex, where it is integrated into a more permanent memory store (5, 6). Thus, the hippocampus and cerebral cortex are proposed to exchange roles in sending and receiving information across wake and SWS (5, 6). Importantly, this model does not imply that all signals travel from the "sender" to the "receiver." Instead, the theory proposes that high-frequency activity carries information from the sender to receiver, that is, from the cortex to hippocampus or the hippocampus to cortex, depending on the stage of memory consolidation (wake or SWS, respectively) (4). Conversely, low-frequency activity propagates from the receiver back to the sender to coordinate the transfer of high-frequency information through modulation of the sender's excitability (4, 7-9). Hence, the two-stage reciprocal dialogue model predicts that lower and higher frequency activity between the hippocampus and cortex should propagate in opposite directions across wake and SWS, as illustrated in the schematic in Fig. 1. However, such reversal has not been directly observed in humans.We have recently analyzed temporal lags (delays) in neural signals to study the net propagation of spontaneous activity. In particular, we investigated resting-state fMRI (rs-fMRI) blood oxygen level-dependent (BOLD) signals and demonstrated directed propagation of infraslow activity (<0.1...

Low-frequency hippocampal–cortical activity drives brain-wide resting-state functional MRI connectivity

“…Hippocampal-cortical activity is state dependent, so the light anesthesia used here may alter their characteristics (34,66,67,79). Nevertheless, prior work revealed synchronized interhemispheric delta oscillations as a major contributor to infraslow rsfMRI connectivity in anesthetized rodents (16,17).…”

“…Note that a recent human rsfMRI study of low-frequency hippocampal-cortical propagation also showed characteristics of activity propagation between the hippocampus and visual cortex (34). Interestingly, the robust detection of BOLD responses in bilateral visual cortices observed in the present study suggests that low-frequency activity initiated in dDG may drive slow oscillatory activity to coordinate visual memory replay in the visual cortex and hippocampus (C) Quantification of the interhemispheric rsfMRI connectivity (Left; n = 12; paired t test followed by Bonferroni's post hoc test; *P < 0.05, **P < 0.01, and ***P < 0.001; error bars indicate ±SEM).…”

“…Nevertheless, prior work revealed synchronized interhemispheric delta oscillations as a major contributor to infraslow rsfMRI connectivity in anesthetized rodents (16,17). A recent human rsfMRI study demonstrated that low-frequency oscillations, such as delta, propagate from the hippocampus toward cortex and slowly in the opposite direction during sleep (34). An EEG study in humans reported EEG differences under anesthesia and sleep/wake conditions, but the authors observed sleep oscillations (i.e., slow and delta dominant) under anesthesia (80).…”

“…We used a lower statistical threshold (t > 2.5, corresponding to P < 0.01) for 0. also identified the hippocampus as a densely connected region that may coordinate brain functional connectivity (32)(33)(34). Furthermore, a recent study demonstrated the propagation of lowfrequency activity from the hippocampus to the cortex in humans (34). Thus, directly examining hippocampal activity with respect to brain-wide propagation and connectivity is essential to uncover the fundamental neural basis of rsfMRI.…”

Resting-state Functional Magnetic Resonance Imaging in Presurgical Functional Mapping

“…Resting state fMRI measures something very different; since there is no imposed task, RS-fMRI reveals resting state networks, that is, the topography of temporally synchronous spontaneous neural activity. Although the physiological functions of intrinsic brain activity remain uncertain (for discussion see 44,45 ), RSNs are of practical interest as they topographically resemble fMRI responses to a wide range of cognitive, sensory, and motor tasks. Here, we compare T-fMRI responses to a finger-tapping task, which recruits the hand area of sensori-motor cortex, versus the full sensorimotor network as revealed by RS-fMRI, which is more extensive and includes Brodmann areas 1–4 as well as supplementary motor cortex.…”