Memory Consolidation In Humans Research Articles

Effects of Daytime Food Intake on Memory Consolidation during Sleep or Sleep Deprivation

Sleep enhances memory consolidation. Bearing in mind that food intake produces many metabolic signals that can influence memory processing in humans (e.g., insulin), the present study addressed the question as to whether the enhancing effect of sleep on memory consolidation is affected by the amount of energy consumed during the preceding daytime. Compared to sleep, nocturnal wakefulness has been shown to impair memory consolidation in humans. Thus, a second question was to examine whether the impaired memory consolidation associated with sleep deprivation (SD) could be compensated by increased daytime energy consumption. To these aims, 14 healthy normal-weight men learned a finger tapping sequence (procedural memory) and a list of semantically associated word pairs (declarative memory). After the learning period, standardized meals were administered, equaling either ∼50% or ∼150% of the estimated daily energy expenditure. In the morning, after sleep or wakefulness, memory consolidation was tested. Plasma glucose was measured both before learning and retrieval. Polysomnographic sleep recordings were performed by electroencephalography (EEG). Independent of energy intake, subjects recalled significantly more word pairs after sleep than they did after SD. When subjects stayed awake and received an energy oversupply, the number of correctly recalled finger sequences was equal to those seen after sleep. Plasma glucose did not differ among conditions, and sleep time in the sleep conditions was not influenced by the energy intake interventions. These data indicate that the daytime energy intake level affects neither sleep’s capacity to boost the consolidation of declarative and procedural memories, nor sleep’s quality. However, high energy intake was followed by an improved procedural but not declarative memory consolidation under conditions of SD. This suggests that the formation of procedural memory is not only triggered by sleep but is also sensitive to the fluctuations in the energy state of the body.

Hippocampal Sleep Features: Relations to Human Memory Function

The recent spread of intracranial electroencephalographic (EEG) recording techniques for presurgical evaluation of drug-resistant epileptic patients is providing new information on the activity of different brain structures during both wakefulness and sleep. The interest has been mainly focused on the medial temporal lobe, and in particular the hippocampal formation, whose peculiar local sleep features have been recently described, providing support to the idea that sleep is not a spatially global phenomenon. The study of the hippocampal sleep electrophysiology is particularly interesting because of its central role in the declarative memory formation. Recent data indicate that sleep contributes to memory formation. Therefore, it is relevant to understand whether specific patterns of activity taking place during sleep are related to memory consolidation processes. Fascinating similarities between different states of consciousness (wakefulness, REM sleep, non-REM sleep) in some electrophysiological mechanisms underlying cognitive processes have been reported. For instance, large-scale synchrony in gamma activity is important for waking memory and perception processes, and its changes during sleep may be the neurophysiological substrate of sleep-related deficits of declarative memory. Hippocampal activity seems to specifically support memory consolidation during sleep, through specific coordinated neurophysiological events (slow waves, spindles, ripples) that would facilitate the integration of new information into the pre-existing cortical networks. A few studies indeed provided direct evidence that rhinal ripples as well as slow hippocampal oscillations are correlated with memory consolidation in humans. More detailed electrophysiological investigations assessing the specific relations between different types of memory consolidation and hippocampal EEG features are in order. These studies will add an important piece of knowledge to the elucidation of the ultimate sleep function.

New Insights in Human Memory Interference and Consolidation

Learning new facts and skills in succession can be frustrating because no sooner has new knowledge been acquired than its retention is being jeopardized by learning another set of skills or facts. Interference between memories has recently provided important new insights into the neural and psychological systems responsible for memory processing. For example, interference not only occurs between the same types of memories, but can also occur between different types of memories, which has important implications for our understanding of memory organization. Converging evidence has begun to reveal that the brain produces interference independently from other aspects of memory processing, which suggests that interference may have an important but previously overlooked function. A memory's initial susceptibility to interference and subsequent resistance to interference after its acquisition has revealed that memories continue to be processed 'off-line' during consolidation. Recent work has demonstrated that off-line processing is not limited to just the stabilization of a memory, which was once the defining characteristic of consolidation; instead, off-line processing can have a rich diversity of effects, from enhancing performance to making hidden rules explicit. Off-line processing also occurs after memory retrieval when memories are destabilized and then subsequently restabalized during reconsolidation. Studies are beginning to reveal the function of reconsolidation, its mechanistic relationship to consolidation and its potential as a therapeutic target for the modification of memories.

Rhythms of sleep: orchestrating memory consolidation (Commentary on Clemens et al.)

During sleep, consolidation of declarative memory is thought to be mediated by a ‘dialogue’ between hippocampal and neocortical networks, promoting the reorganization of recent memory traces (Buzsaki, 1996; Clemens et al., 2005). Consistent with this hypothesis, several rodent studies have established a temporal relationship between 12 and 15 Hz cortical sleep spindle oscillations and high-frequency ripple bursts originating in the hippocampus (Clemens et al., 2006, 2007, 2011). Both spindles and ripples are thought to facilitate synaptic plasticity and the consolidation of memory. An accumulating body of evidence indicates that network-level ‘reactivation’ of recent experience occurs during ripple bursts in rodents (Ji & Wilson, 2007; Marshall & Born, 2007), while human studies demonstrate that spindle activity during post-learning sleep predicts enhanced retention of recently learned material (Siapas & Wilson, 1998; Sirota et al., 2003; Schabus et al., 2004; O’Neill et al., 2010). Nevertheless, the dynamics underlying a potential role for spindle–ripple interactions in cortical plasticity remain largely unknown. In their new study, Clemens et al. (2011); (this issue) report the first human data examining millisecond-timescale temporal interactions between hippocampal ripples and cortical sleep spindles. Intracranial EEG data were acquired in epilepsy patients from implanted parahippocampal foramen ovale electrodes, which the authors have previously established as sensitive for detecting 80–140 Hz ripple bursts similar to those described in the hippocampus proper (Sirota & Buzsaki, 2005). Clemens et al. (2011) demonstrate a correlation between spindles and hippocampal ripples on two distinct timescales. First, in line with the findings of prior studies (Sirota & Buzsaki, 2005; Clemens et al., 2006, 2007, 2011), ripple activity was increased during the ± 1 s window surrounding spindles. More significantly, however, Clemens and colleagues also found that ripple bursts were tightly phase-locked to the ‘troughs’ of the individual oscillations comprising a spindle (at which time neuronal excitation presumably reaches a maximum), with ripple activity reaching a peak just a few milliseconds prior to each trough. This phase-locking of ripples to spindle troughs on a millisecond timescale has been reported in only one prior study [in rodents (Clemens et al., 2007)], and is relevant to elucidating mechanisms of sleep-dependent plasticity for several reasons. Firstly, coordinated activity on this timescale cannot be explained via a generic influence of the < 1 Hz cortical slow oscillation, known to group sleep rhythms on the multi-second timescale (Steriade, 2003; Tamminen et al., 2010), suggesting there may be a particular functional significance for these more precisely timed interactions between ripples and spindles. Secondly, this observation supports the longstanding suggestion that hippocampal output during ripple bursts induces plasticity in cortical targets: as ripples are associated with the ‘reactivation’ of specific recent memory traces, timing their expression to maximally excitatory phases of a spindle could optimally facilitate hippocampus-mediated cortical plasticity. Interestingly, Clemens et al. (2011) found that ripple activity consistently peaks just prior to spindle troughs. In contrast, Sirota et al. (2003) reported that both ripples and CA1 unit activity peaked approximately 50 ms after spindle troughs in rodents, speculating that neocortical activity exerted a modulating influence on hippocampal networks, triggering the expression of ripples. The present findings may prompt some renewed discussion about the causal direction of this particular hippocampal–cortical interaction, as some models of sleep-dependent memory consolidation favor the notion that hippocampal memory reactivation during ripple bursts should exert a driving influence on mechanisms of plasticity in the cortex rather than vice versa. Regardless of such remaining questions, these observations by Clemens and colleagues add an important level of nuance to our understanding of oscillatory brain dynamics underlying sleep-dependent memory consolidation in humans, providing further evidence that the functional significance of sleep spindles lies in their facilitation of hippocampus-mediated cortical plasticity during sleep.

Ghrelin and memory consolidation

Introduction: Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor, has recently been proposed to play a role in cognitive processes. However, effects of ghrelin on memory consolidation in humans have not been studied yet.

Dreaming of a Learning Task Is Associated with Enhanced Sleep-Dependent Memory Consolidation

It is now well established that postlearning sleep is beneficial for human memory performance. Meanwhile, human and animal studies have demonstrated that learning-related neural activity is re-expressed during posttraining nonrapid eye movement (NREM) sleep. NREM sleep processes appear to be particularly beneficial for hippocampus-dependent forms of memory. These observations suggest that learning triggers the reactivation and reorganization of memory traces during sleep, a systems-level process that in turn enhances behavioral performance. Here, we hypothesized that dreaming about a learning experience during NREM sleep would be associated with improved performance on a hippocampus-dependent spatial memory task. Subjects were trained on a virtual navigation task and then retested on the same task 5 hr after initial training. Improved performance at retest was strongly associated with task-related dream imagery during an intervening afternoon nap. Task-related thoughts during wakefulness, in contrast, did not predict improved performance. These observations suggest that sleep-dependent memory consolidation in humans is facilitated by the offline reactivation of recently formed memories, and furthermore that dream experiences reflect this memory processing. That similar effects were not observed during wakefulness suggests that these mnemonic processes are specific to the sleep state.

Sleep Deprivation Specifically Impairs Short-term Olfactory Memory in Drosophila

Sleep is crucial to memory consolidation in humans and other animals; however, the effect of insufficient sleep on subsequent learning and memory remains largely elusive. Learning and memory after 1-day sleep deprivation (slpD) was evaluated using Pavlovian olfactory conditioning in Drosophila, and locomotor activity was measured using the Drosophila Activity Monitoring System in a 12:12 light-dark cycle. We found that slpD specifically impaired 1-h memory in wild type Canton-S flies, and this effect could persist for at least 2 h. However, alternative stresses (heat stress, oxidative stress, starvation, and rotation stress) did not result in a similar effect and left the flies' memory intact. Mechanistic studies demonstrated that flies with either silenced transmission of the mushroom body (MB) during slpD or down-regulated cAMP levels in the MB demonstrated no slpD-induced 1-h memory impairment. We found that slpD specifically impaired 1-h memory in Drosophila, and either silencing of MB transmission during slpD or down-regulation of the cAMP level in the MB protected the flies from slpD-induced impairment.

Sleep and rest facilitate implicit memory in a visual search task

Several forms of learning have been demonstrated to show improvements with sleep. Based on rodent models, it has been suggested that replay of waking events in the hippocampus during sleep may underlie memory consolidation in humans. However, behavioral data for the role of sleep in human hippocampal-related memory have been inconsistent. To further investigate the role of sleep in hippocampal-mediated learning, we tested subjects in two sessions of a contextual cueing paradigm, a form of hippocampus-dependent implicit learning, separated by intervals of sleep, active wake, or carefully controlled quiet rest. Participants completed a visual search task, and unbeknownst to them, some search displays were occasionally repeated in the experiment. Contextual cueing was revealed by faster search speed on repeated trials ( Old) than unrepeated ones ( New), even though subjects were unaware of the trial repetition. Notably, performance in a second testing session was equivalent for participants who underwent quiet resting, daytime sleep, or nocturnal sleep between the two sessions. These four groups showed equivalent transfer of learning from Session 1. Notably, learning of New configurations in Session 2 was absent in the active wake group, but was equally strong among the other three groups. These results indicate that this form of hippocampal learning is independent of sleep, and vulnerable to proactive interference during active wake. They prompt a reevaluation of the hippocampal replay hypothesis as a general model of sleep-dependent learning.

Post-learning psychosocial stress enhances consolidation of neutral stimuli

Post-learning stress has been reported to enhance memory consolidation in humans. This effect was observed in studies using physical stressors or an anticipatory speech task. In the present study 58 participants (28 females and 30 males) were exposed to a psychosocial stressor (Trier Social Stress Test) or a control condition following the presentation of neutral and emotionally arousing positive and negative pictures, which were accompanied by a brief narrative. The stressor induced a significant neuroendocrine stress response in men and women. In a 24 h delayed free recall test the stress group showed an enhanced memory for neutral but not for emotionally arousing positive and negative items. Additionally, a significant correlation between the cortisol stress response and memory for neutral items was evident. Thus, in contrast to previous studies, post-learning stress primarily enhanced consolidation of neutral material. Several theoretical and methodological explanations for the observed effects are discussed.

Ripples in the medial temporal lobe are relevant for human memory consolidation

High-frequency oscillations (ripples) have been described in the hippocampus and rhinal cortex of both animals and human subjects and have been linked to replay and consolidation of previously acquired information. More specifically, studies in rodents suggested that ripples are generated in the hippocampus and are then transferred into the rhinal cortex, and that they occur predominantly during negative half waves of neocortical slow oscillations. Recordings in human epilepsy patients used either microelectrodes or foramen ovale electrodes; it is thus unclear whether macroelectrodes, which are routinely used for pre-surgical investigations, allow the recording of ripples as well. Furthermore, no direct link between ripples and behavioural performance has yet been established. Here, we recorded intracranial electroencephalogram with macroelectrodes from the hippocampus and rhinal cortex contralateral to the seizure onset zone in 11 epilepsy patients during a memory consolidation task while they were having an afternoon 'nap', i.e. a sleep period of approximately 1 h duration. We found that ripples could reliably be detected both in the hippocampus and in the rhinal cortex and had a similar frequency composition to events recorded previously with microelectrodes in humans. Results from cross-correlation analysis revealed that hippocampal events were closely locked to rhinal events and were consistent with findings on transmission of ripples from the hippocampus into the rhinal cortex. Furthermore, hippocampal ripples were significantly locked to the phase of hippocampal delta band activity, which might provide a mechanism for the reported phase-locking to neocortical slow oscillations. Ripples occurred with the highest incidence during periods when subjects lay awake during the nap time. Finally, we found that the number of rhinal, but not hippocampal, ripples was correlated with the number of successfully recalled items (post-nap) learned prior to sleep. These data confirm previous recordings in animals and humans, but move beyond them in several respects: they are the first recordings of ripples in humans during a cognitive task and suggest that ripples are indeed related to behavioural performance; furthermore, they propose a mechanism for phase-locking of ripples to neocortical slow waves via phase coupling to hippocampal delta activity; finally, they show that ripples can be recorded reliably with standard macroelectrodes in the human brain.

The NMDA agonist D-cycloserine facilitates fear memory consolidation in humans.

Animal research suggests that the consolidation of fear and extinction memories depends on N-methyl D-aspartate (NMDA)-type glutamate receptors. Using a fear conditioning and extinction paradigm in healthy normal volunteers, we show that postlearning administration of the NMDA partial agonist D-cycloserine (DCS) facilitates fear memory consolidation, evidenced behaviorally by enhanced skin conductance responses, relative to placebo, for presentations of a conditioned stimulus (CS) at a memory test performed 72 h later. DCS also enhanced CS-evoked neural responses in a posterior hippocampus/collateral sulcus region and in the medial prefrontal cortex at test. Our data suggest a role for NMDA receptors in regulating fear memory consolidation in humans.

Daytime sleep condenses the time course of motor memory consolidation

Two behavioral phenomena characterize human motor memory consolidation: diminishing susceptibility to interference by a subsequent experience and the emergence of delayed, offline gains in performance. A recent model proposes that the sleep-independent reduction in interference is followed by the sleep-dependent expression of offline gains. Here, using the finger-opposition sequence-learning task, we show that an interference experienced at 2 h, but not 8 h, following the initial training prevented the expression of delayed gains at 24 h post-training. However, a 90-min nap, immediately post-training, markedly reduced the susceptibility to interference, with robust delayed gains expressed overnight, despite interference at 2 h post-training. With no interference, a nap resulted in much earlier expression of delayed gains, within 8 h post-training. These results suggest that the evolution of robustness to interference and the evolution of delayed gains can coincide immediately post-training and that both effects reflect sleep-sensitive processes.

Sleep and sleep disturbances: biological basis and clinical implications

Sleep is a neurochemical process involving sleep promoting and arousal centers in the brain. Sleep performs an essential restorative function and facilitates memory consolidation in humans. The remarkably standardized bouts of consolidated sleep at night and daytime wakefulness reflect an interaction between the homeostatic sleep need that is manifested by increase in sleep propensity after sleep deprivation and decrease during sleep and the circadian pacemaker. Melatonin, the hormone produced nocturnally by the pineal gland, serves as a time cue and sleep-anticipating signal. A close interaction exists between the sleep-wake, melatonin, core temperature, blood pressure, immune and hormonal rhythms leading to optimization of the internal temporal order. With age the robustness of the circadian system decreases and the prevalence of sleep disorders, particularly insomnia, increases. Deviant sleep patterns are associated with increased risks of morbidity, poor quality of life and mortality. Current sleep pharmacotherapies treat insufficient sleep quantity, but fail to improve daytime functioning. New treatment modalities for sleep disorders that will also improve daytime functioning remain a scientific and medical challenge.

A deficit in the ability to form new human memories without sleep

Evidence indicates that sleep after learning is critical for the subsequent consolidation of human memory. Whether sleep before learning is equally essential for the initial formation of new memories, however, remains an open question. We report that a single night of sleep deprivation produces a significant deficit in hippocampal activity during episodic memory encoding, resulting in worse subsequent retention. Furthermore, these hippocampal impairments instantiate a different pattern of functional connectivity in basic alertness networks of the brainstem and thalamus. We also find that unique prefrontal regions predict the success of encoding for sleep-deprived individuals relative to those who have slept normally. These results demonstrate that an absence of prior sleep substantially compromises the neural and behavioral capacity for committing new experiences to memory. It therefore appears that sleep before learning is critical in preparing the human brain for next-day memory formation-a worrying finding considering society's increasing erosion of sleep time.

Refinements and confinements in a two-stage model of memory consolidation

Matthew Walker's model overcomes the unrefined classical concept of consolidation as a unitary process. Presently still confined in its scope to selective data mainly referring to procedural motor learning, the model nonetheless provides a valuable starting point for further refinements, which would be required for a more comprehensive account of different types and aspects of human memory consolidation.

The relationships between memory systems and sleep stages

Sleep function remains elusive despite our rapidly increasing comprehension of the processes generating and maintaining the different sleep stages. Several lines of evidence support the hypothesis that sleep is involved in the off-line reprocessing of recently-acquired memories. In this review, we summarize the main results obtained in the field of sleep and memory consolidation in both animals and humans, and try to connect sleep stages with the different memory systems. To this end, we have collated data obtained using several methodological approaches, including electrophysiological recordings of neuronal ensembles, post-training modifications of sleep architecture, sleep deprivation and functional neuroimaging studies. Broadly speaking, all the various studies emphasize the fact that the four long-term memory systems (procedural memory, perceptual representation system, semantic and episodic memory, according to Tulving's SPI model; Tulving, 1995) benefit either from non-rapid eye movement (NREM) (not just SWS) or rapid eye movement (REM) sleep, or from both sleep stages. Tulving's classification of memory systems appears more pertinent than the declarative/non-declarative dichotomy when it comes to understanding the role of sleep in memory. Indeed, this model allows us to resolve several contradictions, notably the fact that episodic and semantic memory (the two memory systems encompassed in declarative memory) appear to rely on different sleep stages. Likewise, this model provides an explanation for why the acquisition of various types of skills (perceptual-motor, sensory-perceptual and cognitive skills) and priming effects, subserved by different brain structures but all designated by the generic term of implicit or non-declarative memory, may not benefit from the same sleep stages.

Effect of amantadine on motor memory consolidation in humans

Motor skills, once learned, need to be consolidated over time in order to become resistant to disruption or interference. In some instances, the consolidation phase can also include spontaneous gains in performance even in the absence of further rehearsal on a motor task. Clinical and behavioral evidence suggest that N-methyl-D-aspartate (NMDA)-receptor activity is required for motor learning acquisition and behavioral synaptic plasticity. However, the involvement of NMDA receptors in motor consolidation, leading to stabilization of the recently formed motor memory, has not yet been assessed in humans. To address this issue, we used post-training administration of amantadine, a low-affinity NMDA-receptor channel blocker. In a double-blind design, 200 mg of amantadine or a matching placebo was given orally to two different groups of 11 healthy young volunteers each. The subjects were tested twice 24 h apart, using a motor adaptation paradigm consisting of an eight-target-pointing task. Comparison of the mean performance levels on this task revealed that subjects in both groups improved their performance levels significantly on Day 2 compared to Day 1, regardless of the treatment administered. Our data indicate that amantadine failed to block motor learning consolidation in subjects that had already learned the motor adaptation task. Thus, although required in some stages (e.g. acquisition) of motor memory processes, the present results suggest that NMDA-receptor activation may not be essential for consolidation of motor adaptation in humans.

One month of human memory consolidation enhances retrieval-related hippocampal activity

We studied the role of the hippocampus in memory retrieval at 1 day and 1 month following associative learning of word pairs. Retrieval-related brain activity was recorded using functional magnetic resonance imaging in 20 healthy students, of which 12 were good learners and eight were poor learners. At the day lag, the poor learners exhibited enhanced neural recruitment in the hippocampus and neocortex to reach a retrieval performance comparable to that of the good learners. Over the 20 subjects, there was a positive correlation between retrieval-related hippocampal activity at the day lag and forgetting over the month retention interval (the greater the activity, the more forgetting). Although the poor learners' retrieval performance declined dramatically from the day to the month lag, the good learners maintained a high retrieval performance, which distinguishes them as good memory consolidators. Their retrieval-related hippocampal and neocortical activity increased from the day to the month lag. This increase was observed both when retrieval performance was matched between the day and the month lag and when the learning procedure for information retrieved at the day and the month lag was matched. This activity increase in the task-specialized neural network from the day lag to the month lag may reflect an increase in task demands or the proliferation of hippocampal-neocortical memory traces during memory consolidation as suggested by the multiple trace theory.

Medial temporal lobe activity for recognition of recent and remote famous names: an event-related fMRI study

Previous neuroimaging studies examining recognition of famous faces have identified activation of an extensive bilateral neural network [Gorno Tempini, M. L., Price, C. J., Josephs, O., Vandenberghe, R., Cappa, S. F., Kapur, N. et al. (1998). The neural systems sustaining face and proper-name processing. Brain, 121, 2103–2118], including the medial temporal lobe (MTL) and specifically the hippocampal complex [Haist, F., Bowden, G. J., & Mao, H. (2001). Consolidation of human memory over decades revealed by functional magnetic resonance imaging. Nature Neuroscience, 4, 1139–1145; Leveroni, C. L., Seidenberg, M., Mayer, A. R., Mead, L. A., Binder, J. R., & Rao, S. M. (2000). Neural systems underlying the recognition of familiar and newly learned faces. Journal of Neuroscience, 20, 878–886]. One model of hippocampal functioning in autobiographical, episodic memory retrieval argues that the hippocampal complex remains active in retrieval tasks regardless of time or age of memory (multiple trace theory, MTT), whereas another proposal posits that the hippocampal complex plays a time-limited role in retrieval of autobiographical memories. The current event-related fMRI study focused on the medial temporal lobe and its response to recognition judgments of famous names from two distinct time epochs (1990s and 1950s) in 15 right-handed healthy older adults (mean age = 70 years). A pilot study with an independent sample of young and older subjects ensured that the stimuli were representative of a recent and remote time period. Increased MR signal activity was observed on a bilateral basis for both the hippocampus and parahippocampal gyrus (PHG) during recognition of familiar names from both the recent and remote time periods when compared to non-famous names. However, the impulse response functions in the right hippocampus and right PHG demonstrated a differential response to stimuli from different time epochs, with the 1990s names showing the greatest MR signal intensity change, followed by the 1950s names, followed by foils. The finding that recognition of famous names produced significant bilateral MTL activation regardless of time epoch relative to foils provides support for the MTT model. However, the finding of a temporal gradient in the right MTL also provides support for the HC model, given the greater MTL response associated with recently famous names relative to remotely famous names.

Enhanced human memory consolidation with post-learning stress: interaction with the degree of arousal at encoding.

Abundant evidence indicates that endogenous stress hormones such as epinephrine and corticosterone modulate memory consolidation in animals. We recently provided the first demonstration that an endogenous stress hormone (epinephrine) can enhance human memory consolidation. However, these findings also suggested that post-learning stress hormone activation does not uniformly enhance memory for all recently acquired information; rather, that it interacts with the degree of arousal at initial encoding of material in modulating memory for the material. Here we tested this hypothesis by administering cold pressor stress (CPS) or a control procedure to subjects after they viewed slides of varying emotional content, and assessing memory for the slides 1 wk later. CPS, which significantly elevated salivary cortisol levels, enhanced memory for emotionally arousing slides compared with the controls, but did not affect memory for relatively neutral slides. These findings further support the view that post-learning stress hormone-related activity interacts with arousal at initial encoding to modulate memory consolidation.