How do the sleep features that characterise depression impact memory?

Depression is associated with general sleep disturbance and abnormalities in sleep physiology. For example, compared with control subjects, depressed patients exhibit lower sleep efficiency, longer rapid eye movement (REM) sleep duration, and diminished slow-wave activity during non-REM sleep. A separate literature indicates that depression is also associated with many distinguishing memory characteristics, including emotional memory bias, overgeneral autobiographical memory, and impaired memory suppression. The sleep and memory features that hallmark depression may both contribute to the onset and maintenance of the disorder. Despite our rapidly growing understanding of the intimate relationship between sleep and memory, our comprehension of how sleep and memory interact in the aetiology of depression remains poor. In this narrative review, we consider how the sleep signatures of depression could contribute to the accompanying memory characteristics.

Targeted memory reactivation during sleep can induce forgetting of overlapping memories.

Memory reactivation during sleep can shape new memories into a long-term form. Reactivation of memories can be induced via the delivery of auditory cues during sleep. Although this targeted memory reactivation (TMR) approach can strengthen newly acquired memories, research has tended to focus on single associative memories. It is less clear how TMR affects retention for overlapping associative memories. This is critical, given that repeated retrieval of overlapping associations during wake can lead to forgetting, a phenomenon known as retrieval-induced forgetting (RIF). We asked whether a similar pattern of forgetting occurs when TMR is used to cue reactivation of overlapping pairwise associations during sleep. Participants learned overlapping pairs-learned separately, interleaved with other unrelated pairs. During sleep, we cued a subset of overlapping pairs using TMR. While TMR increased retention for the first encoded pairs, memory decreased for the second encoded pairs. This pattern of retention was only present for pairs not tested prior to sleep. The results suggest that TMR can lead to forgetting, an effect similar to RIF during wake. However, this effect did not extend to memories that had been strengthened via retrieval prior to sleep. We therefore provide evidence for a reactivation-induced forgetting effect during sleep.

Sounding It Out: Auditory Stimulation and Overnight Memory Processing.

PURPOSE OF REVIEW: Auditory stimulation is a technique that can enhance neural oscillations linked to overnight memory consolidation. In this review, we evaluate the impacts of auditory stimulation on the neural oscillations of sleep and associated memory processes in a variety of populations. RECENT FINDINGS: Cortical EEG recordings of slow-wave sleep (SWS) are characterised by two cardinal oscillations: slow oscillations (SOs) and sleep spindles. Auditory stimulation delivered in SWS enhances SOs and phase-coupled spindle activity in healthy children and adults, children with ADHD, adults with mild cognitive impairment and patients with major depression. Under certain conditions, auditory stimulation bolsters the benefits of SWS for memory consolidation, although further work is required to fully understand the factors affecting stimulation-related memory gains. Recent work has turned to rapid eye movement (REM) sleep, demonstrating that auditory stimulation can be used to manipulate REM sleep theta oscillations. SUMMARY: Auditory stimulation enhances oscillations linked to overnight memory processing and shows promise as a technique for enhancing the memory benefits of sleep.

No benefit of auditory closed-loop stimulation on memory for semantically-incongruent associations.

Auditory closed-loop stimulation has gained traction in recent years as a means of enhancing slow oscillatory activity and, consequently, sleep-associated memory consolidation. Previous studies on this topic have primarily focused on the consolidation of semantically-congruent associations. In this study, we investigated the effect of auditory closed-loop stimulation on the overnight retention of semantically-incongruent associations. Twelve healthy males (age: M = 20.06, SD = 2.02 years) participated in two experimental conditions (simulation and sham). In the stimulation condition, clicks were delivered in phase with slow oscillation up-states, whereas in the sham condition no auditory stimuli were applied. Corroborating earlier work, stimulation (vs. sham) enhanced the slow oscillation rhythm, phase-coupled spindle activity and slow oscillation power. However, there was no benefit of stimulation on overnight memory retention. These findings suggest that closed-loop stimulation does not benefit semantically-incongruent associations.

Sleep Loss Gives Rise to Intrusive Thoughts.

We propose a framework in which top-down inhibitory control networks are impaired by sleep deprivation, giving rise to intrusive thoughts and, consequently, emotion dysregulation. This process leads to a vicious cycle of sleeplessness, persistent unwanted thoughts, and heightened anxiety, ultimately increasing the risk of mental illness.

Losing Control: Sleep Deprivation Impairs the Suppression of Unwanted Thoughts.

Unwanted memories often enter conscious awareness when individuals confront reminders. People vary widely in their talents at suppressing such memory intrusions; however, the factors that govern suppression ability are poorly understood. We tested the hypothesis that successful memory control requires sleep. Following overnight sleep or total sleep deprivation, participants attempted to suppress intrusions of emotionally negative and neutral scenes when confronted with reminders. The sleep-deprived group experienced significantly more intrusions (unsuccessful suppressions) than the sleep group. Deficient control over intrusive thoughts had consequences: Whereas in rested participants suppression reduced behavioral and psychophysiological indices of negative affect for aversive memories, it had no such salutary effect for sleep-deprived participants. Our findings raise the possibility that sleep deprivation disrupts prefrontal control over medial temporal lobe structures that support memory and emotion. These data point to an important role of sleep disturbance in maintaining and exacerbating psychiatric conditions characterized by persistent, unwanted thoughts.

Phase-locked auditory stimulation of theta oscillations during rapid eye movement sleep.

Auditory closed-loop stimulation is a non-invasive technique that has been widely used to augment slow oscillations during non-rapid eye movement sleep. Based on the principles of closed-loop stimulation, we developed a novel protocol for manipulating theta activity (3-7 Hz) in rapid eye movement (REM) sleep. Sixteen healthy young adults were studied in two overnight conditions: Stimulation and Sham. In the Stimulation condition, 1 s of 5 Hz amplitude-modulated white noise was delivered upon detection of two supra-threshold theta cycles throughout REM sleep. In the Sham condition, corresponding time points were marked but no stimulation was delivered. Auditory stimulation entrained EEG activity to 5 Hz and evoked a brief (~0.5 s) increase in theta power. Interestingly, this initial theta surge was immediately followed by a prolonged (~3 s) period of theta suppression. Stimulation also induced a prolonged (~2 s) increase in beta power. Our results provide the first demonstration that the REM sleep theta rhythm can be manipulated in a targeted manner via auditory stimulation. Accordingly, auditory stimulation might offer a fruitful avenue for investigating REM sleep electrophysiology and its relationship to behavior.

Sleep deprivation induces fragmented memory loss.

Sleep deprivation increases rates of forgetting in episodic memory. Yet, whether an extended lack of sleep alters the qualitative nature of forgetting is unknown. We compared forgetting of episodic memories across intervals of overnight sleep, daytime wakefulness, and overnight sleep deprivation. Item-level forgetting was amplified across daytime wakefulness and overnight sleep deprivation, as compared to sleep. Importantly, however, overnight sleep deprivation led to a further deficit in associative memory that was not observed after daytime wakefulness. These findings suggest that sleep deprivation induces fragmentation among item memories and their associations, altering the qualitative nature of episodic forgetting.

Sleep Preserves Physiological Arousal in Emotional Memory.

Traumatic experiences are associated with increased emotional arousal. Overnight consolidation strengthens the episodic content of emotional memories, but it is still unclear how sleep influences the associated arousal response. To investigate this question, we compared the effects of sleep and wake on psychophysiological and subjective reactivity during emotional memory retrieval. Participants provided affective ratings for negative and neutral images while heart rate deceleration (HRD) and skin conductance responses (SCRs) were monitored. Following a 12-hour delay of sleep or wakefulness, participants completed an image recognition task where HRD, SCRs and affective ratings were recorded again. HRD responses to previously-encoded ("old") negative images were preserved after sleep but diminished after wakefulness. No between-group difference in HRD was observed for novel negative images at recognition, indicating that the effects of sleep for old images were not driven by a generalised overnight increase in visceral activity, or circadian factors. No significant effects of sleep were observed for SCRs or subjective ratings. Our data suggest that cardiac arousal experienced at the time of encoding is sensitive to plasticity-promoting processes during sleep in a similar manner to episodic aspects of emotional memory.

Overnight retention of emotional memories is influenced by BDNF Val66Met but not 5-HTTLPR.

Emotional memory may be modulated by BDNF Val66Met and 5-HTTLPR polymorphisms. However, the influence of these genetic variants on the overnight retention of emotional memories has not been investigated in humans. Thirty-six healthy female students were selected to participate in this study based on 5-HTTLPR genotype status (L'/L', L'/S', S'/S'). Participants were also genotyped for BDNF Val66Met (Val/Val, Met carriers). We measured recognition performance for positive, neutral and negative images before and after overnight sleep. We found a significant interaction between BDNF Val66Met genotype group and image valence on post-sleep recognition performance. This interaction was driven by greater memory for negative and positive images, relative to neutral images, in Met carriers. We also found that longer Rapid Eye Movement (REM) sleep duration predicted greater post-sleep recognition performance for negative images in Met carriers, but not in Val homozygotes. We observed no influence of 5-HTTLPR polymorphisms on post- sleep recognition performance for positive, neutral or negative images. Our findings support a modulatory role for BDNF Val66Met in overnight emotional memory retention in females. We discuss the implications of this finding for understanding the influence of BDNF Val66Met on depression vulnerability.

The effect of sleep deprivation on emotional memory consolidation in participants reporting depressive symptoms.

Sleep has been shown to play a crucial role in the consolidation of emotionally salient memories. However, the influence of sleep, and Sleep Deprivation (SD), on emotional memory consolidation in depressive individuals remains elusive. For this experiment we recruited two groups of healthy students, one reporting mild-to-severe depressive symptoms, and another reporting minimal/no depressive symptoms (assessed using the Beck Depression Inventory; BDI-II). We measured recognition performance for positive, neutral and negative images before and after a 12 h overnight retention interval, during which participants either remained awake in the laboratory or returned home to sleep normally. We found a significant depressive symptomatology group × sleep condition × image valence interaction on memory consolidation across the 12 h retention interval [F(2, 98) = 3.12, p = .049, ηp2 = 0.060]. We also found that depressive participants who slept normally consolidated significantly more negative and neutral images across the 12 h retention interval than depressive participants who were sleep deprived [t(24) = 2.35, p = .028, t(24) = 2.79, p = .010, respectively]. Our preliminary results indicate that SD may impair the consolidation of negative and neutral memories in depressive participants, but not in participants reporting minimal/no depressive symptoms.

The influence of REM sleep and SWS on emotional memory consolidation in participants reporting depressive symptoms.

Negative emotional memory bias is thought to play a causal role in the onset and maintenance of major depressive disorder. Rapid Eye Movement (REM) sleep has been shown to selectively consolidate negative emotional memories in healthy participants, and is greater in quantity and density in depressed patients. Slow-Wave Sleep (SWS) is typically associated with the consolidation of non-emotional memories. However, the effects of REM sleep and SWS on emotional memory consolidation have not been investigated in participants reporting depressive symptoms. In this study, we recruited two groups of healthy participants; one reporting mild-to-moderate depressive symptoms, and another reporting minimal depressive symptoms (assessed using the Beck Depression Inventory; BDI-II). Using a within-subjects split-night design, we measured consolidation of positive, neutral and negative images across a 3 h retention interval rich in either REM sleep or SWS. We found a significant sleep condition x image valence interaction in participants reporting depressive symptoms [F (2, 20) = 4.73, p = .021], but not participants reporting minimal depressive symptoms [F (2, 22) = .17, p = .845]. Participants reporting depressive symptoms consolidated significantly more neutral memories during SWS, and marginally more negative memories during REM sleep, than those reporting minimal depressive symptoms [t (21) = 2.44, p = .023; t (21) = 1.96, p = .064, respectively]. Our preliminary results demonstrate that REM sleep and SWS have differential effects on the consolidation of emotional and neutral images in participants reporting depressive symptoms. Further studies including larger sample sizes are required to investigate whether REM sleep alterations promote the development of negative memory bias in major depressive disorder.

The 'affect tagging and consolidation' (ATaC) model of depression vulnerability.

Since the 1960's polysomnographic sleep research has demonstrated that depressive episodes are associated with REM sleep alterations. Some of these alterations, such as increased REM sleep density, have also been observed in first-degree relatives of patients and remitted patients, suggesting that they may be vulnerability markers of major depressive disorder (MDD), rather than mere epiphenomena of the disorder. Neuroimaging studies have revealed that depression is also associated with heightened amygdala reactivity to negative emotional stimuli, which may also be a vulnerability marker for MDD. Several models have been developed to explain the respective roles of REM sleep alterations and negatively-biased amygdala activity in the pathology of MDD, however the possible interaction between these two potential risk-factors remains uncharted. This paper reviews the roles of the amygdala and REM sleep in the encoding and consolidation of negative emotional memories, respectively. We present our 'affect tagging and consolidation' (ATaC) model, which argues that increased REM sleep density and negatively-biased amygdala activity are two separate, genetically influenced risk-factors for depression which interact to promote the development of negative memory bias - a well-known cognitive vulnerability marker for depression. Predictions of the ATaC model may motivate research aimed at improving our understanding of sleep dependent memory consolidation in depression aetiology.