Memory consolidation in human sleep depends on inhibition of glucocorticoid release.

Early sleep dominated by slow-wave sleep has been found to be particularly relevant for declarative memory formation via hippocampo-neocortical networks. Concurrently, early nocturnal sleep is characterized by an inhibition of glucocorticoid release from the adrenals. Here, we show in healthy humans that this inhibition serves to support declarative memory consolidation during sleep. Elevating plasma glucocorticoid concentration during early sleep by administration of cortisol impaired consolidation of paired associate words, but not of non-declarative memory of visuomotor skills. Since glucocorticoid concentration was enhanced only during retention sleep, but not during acquisition or retrieval, a specific effect on the consolidation process is indicated. Blocking mineralocorticoid receptors by canrenoate did not affect memory, suggesting inactivation of glucocorticoid receptors to be the essential prerequisite for memory consolidation during early sleep.     

Declarative and procedural memory consolidation during sleep in patients with borderline personality disorder

Borderline personality disorder (BPD) is characterized by changes in subjective and objective measures of sleep quality. As recent findings point to the importance of sleep in memory consolidation, sleep-related memory consolidation was investigated in 15 female BPD patients (mean age 26.1+/-6.1 years) and 15 female healthy controls (mean age 25.6+/-6.8 years). Before and after the study night, declarative and procedural memory performance was tested by a paired associate list and a mirror tracing task. Subjective sleep quality was assessed by a sleep questionnaire, objective sleep quality was measured by a portable sleep recording device. During the study night the restorative value of sleep was significantly reduced in BPD patients (p<0.001), while objective sleep quality showed a trend for longer REM sleep duration (p=0.054). No significant differences were found regarding overnight performance improvement in the declarative and procedural memory tasks. Present findings suggest that declarative and procedural memory consolidation during sleep is intact in BPD patients.     

Effects of daytime naps on procedural and declarative memory in patients with schizophrenia

Sleep has been identified as a state that optimizes the consolidation of newly acquired information in memory. Straight memory deficits and sleep disturbances are well-known in patients with schizophrenia. This study tested the hypothesis that patients with schizophrenia have a deficit in procedural and declarative memory consolidation after a short midday nap when compared to healthy controls and patients with remitted to moderate major depression.Following a normal night’s sleep, 22 healthy subjects, 20 patients with major depression and 21 patients with schizophrenia were studied in a napping and wake condition in a random-order cross-over design, early in the afternoon. To test declarative memory, the Rey-Osterrieth Complex Figure Test respectively the Taylor Complex Figure Test and, for procedural learning, a mirror tracing task were performed.The present study is the first to demonstrate significant differences between individuals with schizophrenia, depression and healthy matched controls with regard to measures of sleep and memory performance after a short period of daytime sleep (napping). In particular we found that a daytime nap of only about 40 min led to improvement of declarative memory performance in all investigated groups, whereas no beneficial effect was seen on procedural performance in the group of medicated patients with schizophrenia in contrast to healthy controls and patients with remitted to moderate major depression.     

M1 muscarinic acetylcholine receptor agonism alters sleep without affecting memory consolidation

Preclinical studies have implicated cholinergic neurotransmission, specifically M1 muscarinic acetylcholine receptor (mAChR) activation, in sleep-associated memory consolidation. In the present study, we investigated the effects of administering the direct M1 mAChR agonist RS-86 on pre-post sleep memory consolidation. Twenty healthy human participants were tested in a declarative word-list task and a procedural mirror-tracing task. RS-86 significantly reduced rapid eye movement (REM) sleep latency and slow wave sleep (SWS) duration in comparison with placebo. Presleep acquisition and postsleep recall rates were within the expected ranges. However, recall rates in both tasks were almost identical for the RS-86 and placebo conditions. These results indicate that selective M1 mAChR activation in healthy humans has no clinically relevant effect on pre-post sleep consolidation of declarative or procedural memories at a dose that reduces REM sleep latency and SWS duration.     

The relationship between REM sleep and memory consolidation in old age and effects of cholinergic medication.

BACKGROUND: Recent findings in young adults suggest that rapid eye movement (REM) sleep plays a role in procedural memory consolidation. The significance of REM sleep for memory consolidation in old age has not yet been investigated. METHODS: Effects of REM sleep manipulation on declarative and procedural memory consolidation were investigated in 107 healthy older adults, ages 60-82 years. Rapid eye movement sleep deprivation was achieved by REM sleep awakenings and compared with non-REM sleep awakenings. Rapid eye movement sleep augmentation was realized physiologically by REM sleep rebound and pharmacologically by administering an acetylcholinesterase inhibitor in a double-blind, placebo-controlled design. Memory performance was tested by a paired associate list and a mirror tracing task at 9:30 pm and 7:30 am with sleep intervening between 11:00 pm and 7:00 am. RESULTS: Although REM sleep deprivation led to a significant reduction in total and phasic REM sleep, memory consolidation remained unaffected. Both REM sleep augmentation groups showed a significant increase in phasic REM sleep, whereas only pharmacological cholinergic REM sleep manipulation exerted a significant positive effect on procedural memory consolidation. CONCLUSIONS: Because only after cholinergic stimulation of phasic REM sleep procedural memory consolidation is improved, cholinergic activation seems to be a crucial component of REM sleep-related memory consolidation in old age.     

Sleep-dependent surges in growth hormone do not contribute to sleep-dependent memory consolidation

In the search for the mechanisms that mediate the effects of sleep on the consolidation of memories, growth hormone (GH) recently became of interest, because in humans it is released mainly during slow-wave sleep (SWS), a period of enhanced declarative memory consolidation. In addition, recent studies showed that GH is involved in proper memory function in GH deficient and elderly humans and this effect has been linked to regulatory influences of GH on hippocampal NMDA receptors. Here, we blocked GH secretion by intravenous infusion of somatostatin in healthy young subjects during the first 3 h of sleep, which contain mainly SWS. Declarative and procedural memory consolidation was tested across this period, using a word pair association task and a mirror tracing task, respectively. Although GH was effectively suppressed, memory performance as well as sleep were entirely unaffected by this suppression. Whereas GH may in the long run generally support brain systems required for maintaining proper memory function, our data exclude a necessary contribution of the nocturnal surge in pituitary GH secretion to the acute processing and formation of specific memories during sleep.     

Effects of cortisol suppression on sleep-associated consolidation of neutral and emotional memory.

BACKGROUND: Previous research indicates that hippocampus-dependent declarative memory benefits from early nocturnal sleep, when slow-wave sleep (SWS) prevails and cortisol release is minimal, whereas amygdala-dependent emotional memory is enhanced through late sleep, when rapid eye movement (REM) sleep predominates. The role of the strong cortisol rise accompanying late sleep for emotional memory consolidation has not yet been investigated. METHODS: Effects of the cortisol synthesis inhibitor metyrapone on sleep-associated consolidation of memory for neutral and emotional texts were investigated in a randomized, double-blind, placebo-controlled study in 14 healthy men. Learning took place immediately before treatment, which was followed by 8 hours of sleep. Retrieval was tested at 11 am the next morning. RESULTS: Metyrapone suppressed cortisol during sleep and blocked particularly the late-night rise in cortisol. It reduced SWS and concomitantly impaired the consolidation of neutral texts. Emotional texts were spared from this impairing influence, however. Metyrapone even amplified emotional enhancement in text recall indicating amygdala-dependent memory. CONCLUSIONS: Cortisol blockade during sleep impairs hippocampus-dependent declarative memory formation but enhances amygdala-dependent emotional memory formation. The natural cortisol rise during late sleep may thus protect from overshooting emotional memory formation, a mechanism possibly pertinent to the development of posttraumatic stress disorder.     

Effects of dexamethasone on declarative memory function in posttraumatic stress disorder

Alterations in the hypothalamic-pituitary-adrenal (HPA) axis and hippocampal-based memory have been associated with posttraumatic stress disorder (PTSD), and the administration of exogenous glucocorticoids has been shown to result in a transient verbal declarative memory impairment in healthy human subjects. The purpose of this study was to assess the effects of the glucocorticoid dexamethasone on verbal declarative memory function in patients with PTSD. Forty-two men and women with (n=14) and without (n=28) PTSD received placebo or dexamethasone (1 and 2 mg on two successive days) in a double-blind, randomized fashion. Declarative memory was assessed with paragraph recall at baseline (day 1) and day 3. There was a significant interaction between diagnosis and drug (dexamethasone vs. placebo) on paragraph recall related to a relative detrimental effect of dexamethasone on memory function in healthy subjects, but not those with PTSD. These findings are consistent with an altered sensitivity of declarative memory function in PTSD to regulation by glucocorticoids, possibly explainable by alterations in glucocorticoid receptors in the hippocampus or other brain regions mediating declarative memory.     

Sleep in major depression: relation to memory performance and outcome after interpersonal psychotherapy

BACKGROUND: Earlier findings suggest both a link between sleep and memory consolidation and a relationship between abnormal sleep at baseline and poor treatment outcome in major depression after interpersonal psychotherapy (IPT). METHODS: Pre-treatment polysomnography was examined in 32 patients with a major depressive episode (mean age = 39.5 years, 20 women). Declarative memory was tested by the Rey-Osterrieth Complex Figure Test and a paired associative word list and procedural learning was assessed by a mirror tracing skill. All patients were treated with IPT according to the manual and did not receive any antidepressant medication. Twenty-three patients took part in a minimum of 12 sessions of IPT. Remission was defined as 2 consecutive weeks with a score <8 on the Hamilton Rating Scale of Depression. RESULTS: Declarative visual memory performance was associated with total sleep time and total amount of rapid eye movement sleep. In IPT remitters (n = 14), there was a trend towards a decrease in rapid eye movement density (first period) and a significant decrease in delta power in pre-treatment sleep in comparison to non-remitters (n = 9). Treatment outcome after IPT was also associated with declarative memory performance at baseline (as a trend). CONCLUSIONS: Further indications of a role of sleep in memory processes and of the importance of specific sleep parameters as markers for a positive treatment response to psychotherapy were found.     

Comparing the benefits of caffeine, naps and placebo on verbal, motor and perceptual memory

Caffeine, the world's most common psychoactive substance, is used by approximately 90% of North Americans everyday. Little is known, however, about its benefits for memory. Napping has been shown to increase alertness and promote learning on some memory tasks. We directly compared caffeine (200mg) with napping (60-90min) and placebo on three distinct memory processes: declarative verbal memory, procedural motor skills, and perceptual learning. In the verbal task, recall and recognition for unassociated words were tested after a 7h retention period (with a between-session nap or drug intervention). A second, different, word list was administered post-intervention and memory was tested after a 20min retention period. The non-declarative tasks (finger tapping task (FTT) and texture discrimination task (TDT)) were trained before the intervention and then retested afterwards. Naps enhanced recall of words after a 7h and 20min retention interval relative to both caffeine and placebo. Caffeine significantly impaired motor learning compared to placebo and naps. Napping produced robust perceptual learning compared with placebo; however, naps and caffeine were not significantly different. These findings provide evidence of the limited benefits of caffeine for memory improvement compared with napping. We hypothesize that impairment from caffeine may be restricted to tasks that contain explicit information; whereas strictly implicit learning is less compromised.     

Impairment of visuospatial memory is associated with decreased slow wave sleep in schizophrenia

Cognitive impairments such as memory deficits and sleep disturbances are common clinical features of schizophrenia. Since sleep plays an important role in consolidation of memory, we hypothesize, that there is an interrelationship between distinct alterations in sleep and memory performance in schizophrenia. We studied 17 patients with schizophrenia on stable antipsychotic medication with amisulpride (age range 22–44 years; 7 women) and 17 healthy controls (matched for age, gender and educational level). Sleep was recorded and scored according to the standard criteria by Rechtschaffen and Kales. Immediately before polysomnography and the morning after we performed neuropsychological tasks including Rey–Osterrieth Complex Figure Test and a test for recall of spatial location for testing aspects of declarative memory and a mirror tracing skill for procedural memory. In comparison to healthy controls, the patients showed a significant increase in sleep onset latency and a significant decrease in sleep efficiency and amount of slow wave sleep (SWS). Furthermore, the patients' performance in recall of the Rey-figure and of spatial location the next morning was significantly impaired. These impairments in the tests for visuospatial memory were positively correlated with reduction in the amount of SWS and in sleep efficiency. These results point to a functional interrelationship between regulation of SWS and performance in visuospatial memory in schizophrenia. If these results of our pilot study hold true, they will allow the development of innovative treatment strategies for neuropsychological deficits in patients with schizophrenia.     

Daytime naps improve procedural motor memory

BACKGROUND AND PURPOSE: To investigate the impact of a short daytime nap on procedural and declarative memory consolidation. PATIENTS AND METHODS: Following a normal night's sleep, 34 young healthy subjects were randomly assigned to a nap or wake condition of about 45min in the early afternoon after learning procedural and declarative memory tasks. Subjects were controlled for alertness and cortisol secretion. RESULTS: The afternoon naps were dominated by sleep stage 2 but contained some slow wave sleep (SWS) and rapid eye movement (REM) sleep as well. Naps significantly improved procedural, but not declarative, memory. Females showed more improvement than males in the declarative memory tasks irrespective of nap or wake. There was no difference between groups with respect to cortisol secretion or alertness. CONCLUSIONS: A short nap is favorable for consolidation of procedural memory. The possibly confounding effect of gender should always be considered in research on sleep and memory.     

Napping to renew learning capacity: enhanced encoding after stimulation of sleep slow oscillations

As well as consolidating memory, sleep has been proposed to serve a second important function for memory, i.e. to free capacities for the learning of new information during succeeding wakefulness. The slow wave activity (SWA) that is a hallmark of slow wave sleep could be involved in both functions. Here, we aimed to demonstrate a causative role for SWA in enhancing the capacity for encoding of information during subsequent wakefulness, using transcranial slow oscillation stimulation (tSOS) oscillating at 0.75 Hz to induce SWA in healthy humans during an afternoon nap. Encoding following the nap was tested for hippocampus‐dependent declarative materials (pictures, word pairs, and word lists) and procedural skills (finger sequence tapping). As compared with a sham stimulation control condition, tSOS during the nap enhanced SWA and significantly improved subsequent encoding on all three declarative tasks (picture recognition, cued recall of word pairs, and free recall of word lists), whereas procedural finger sequence tapping skill was not affected. Our results indicate that sleep SWA enhances the capacity for encoding of declarative materials, possibly by down‐scaling hippocampal synaptic networks that were potentiated towards saturation during the preceding period of wakefulness.     

Effects of glucocorticoids on declarative memory function in major depression.

BACKGROUND: Major depression has been associated with hypercortisolemia in a subset of patients with depression. Administration of exogenous cortisol and other glucocorticoids to healthy human subjects has been observed to result in a transient impairment in verbal declarative memory function. The purpose of this study was to assess the effects of the glucocorticoid, dexamethasone, on verbal declarative memory function in patients with untreated unipolar major depressive disorder (MDD). METHODS: Fifty two men and women with (n = 28) and without (n = 24) MDD received placebo or dexamethasone (1 mg and 2 mg on 2 successive days) in a double-blind, randomized fashion. Declarative memory was assessed with paragraph recall at baseline (day 1) and day 3. RESULTS: There was a significant interaction between diagnosis and drug (dexamethasone vs. placebo) on paragraph recall. In the healthy subjects, memory improved from baseline to day 3 with placebo and was unchanged with dexamethasone, whereas in MDD patients memory function showed a pattern of decreasing with placebo and improving with dexamethasone from baseline to day 3. CONCLUSIONS: These findings are consistent with an altered sensitivity of declarative memory function in MDD to regulation by glucocorticoids. Possible explanations of the findings include alterations in glucocorticoid receptors in the hippocampus or other brain regions mediating declarative memory, or differential sensitivity to dexamethasone-induced reductions in cortisol, in patients with MDD.     

Sleep restores daytime deficits in procedural memory in children with attention-deficit/hyperactivity disorder

Sleep supports the consolidation of declarative and procedural memory. While prefrontal cortex (PFC) activity supports the consolidation of declarative memory during sleep, opposite effects of PFC activity are reported with respect to the consolidation of procedural memory during sleep. Patients with attention-deficit/hyperactivity disorder (ADHD) are characterised by a prefrontal hypoactivity. Therefore, we hypothesised that children with ADHD benefit from sleep with respect to procedural memory more than healthy children. Sixteen children with ADHD and 16 healthy controls (aged 9-12) participated in this study. A modification of the serial-reaction-time task was conducted. In the sleep condition, learning took place in the evening and retrieval after a night of sleep, whereas in the wake condition learning took place in the morning and retrieval in the evening without sleep. Children with ADHD showed an improvement in motor skills after sleep compared to the wake condition. Sleep-associated gain in reaction times was positively correlated with the amount of sleep stage 4 and REM-density in ADHD. As expected, sleep did not benefit motor performance in the group of healthy children. These data suggest that sleep in ADHD normalizes deficits in procedural memory observed during daytime. It is discussed whether in patients with ADHD attenuated prefrontal control enables sleep-dependent gains in motor skills by reducing the competitive interference between explicit and implicit components within a motor task.     

The whats and whens of sleep-dependent memory consolidation

Sleep benefits memory consolidation. The reviewed studies indicate that this consolidating effect is not revealed under all circumstances but is linked to specific psychological conditions. Specifically, we discuss to what extent memory consolidation during sleep depends on the type of learning materials, type of learning and retrieval test, different features of sleep and the subject population. Post-learning sleep enhances consolidation of declarative, procedural and emotional memories. The enhancement is greater for weakly than strongly encoded associations and more consistent for explicitly than implicitly encoded memories. Memories associated with expected reward gain preferentially access to sleep-dependent consolidation. For declarative memories, sleep benefits are more consistently revealed with recall than recognition procedures at retrieval testing. Slow wave sleep (SWS) particularly enhances declarative memories whereas rapid eye movement (REM) sleep preferentially supports procedural and emotional memory aspects. Declarative memory profits already from rather short sleep periods (1–2 h). Procedural memory profits seem more dose-dependent on the amount of sleep following the day after learning. Children's sleep with high amounts of SWS distinctly enhances declarative memories whereas elderly and psychiatric patients with disturbed sleep show impaired sleep-associated consolidation often of declarative memories. Based on the constellation of psychological conditions identified we hypothesize that access to sleep-dependent consolidation requires memories to be encoded under control of prefrontal-hippocampal circuitry, with the same circuitry controlling subsequent consolidation during sleep.     

Procedural memory in Parkinson's disease: impaired motor but not visuoperceptual learning

A current model proposes that memory consists of two functionally separate systems that have different neurological substrates. Declarative memory appears to be dependent on the diencephalic medial temporal lobe system whereas some speculate that the basal ganglia may be a neurological substrate for procedural memory. This study tested the role of the basal ganglia in regulating different types of procedural skills by comparing performance on a motor and a visuoperceptual skill learning task. Twenty Parkinson's (PD) patients and 20 normal control subjects performed two procedural learning tasks (rotary pursuit and mirror reading) and one declarative learning task (paired associates) over 3 days. The results showed that PD patients were not impaired on mirror reading or paired associate learning. On rotary pursuit, performance levels on day 1 were similar between groups, but the PD group showed less improvement across days than controls. However, only patients with more advanced symptoms of PD showed impaired rotary pursuit learning, and this could not be attributed directly to deficits in primary motor or general cognitive function. These findings suggest that the underlying processes/procedures for procedural learning are specific to the task, and are supported by different neuroanatomical systems.     

Sleep states and memory processes in humans: procedural versus declarative memory systems

The present paper focuses on human studies attempting to relate sleep states to memory processes. These studies typically present learning material to participants and then examine their ability to recall this material after intervening post-training sleep or sleep deprivation. Most experiments utilize either sleep recording or sleep deprivation following task acquisition to reach their conclusions, although cueing and position emission tomography (PET) scan studies have also been done. Results strongly suggest that REM sleep is involved with the efficient memory processing of cognitive procedural material but not declarative material. Although there are some data to suggest that stage 3/4 or NREM sleep is necessary for declarative memory consolidation, NREM may in fact simply be occurring at the same time as another factor that is actually involved in the memory processing. Preliminary results suggest that the length of the NREM–REM sleep cycle may be important for declarative memory. Preliminary data also suggest that stage 2 sleep may be involved with the memory for motor procedural but not cognitive procedural tasks. Sleep researchers would do well to capitalize on the latest advancements in memory research by choosing tasks that represent special memory systems and examining their relationships to sleep states.     

Procedural memory in Parkinson's disease: Impaired motor but not visuoperceptual learning

Abstract

A current model proposes that memory consists of two functionally separate systems that have different neurological substrates. Declarative memory appears to be dependent on the diencephalic medial temporal lobe system whereas some speculate that the basal ganglia may be a neurological substrate for procedural memory. This study tested the role of the basal ganglia in regulating different types of procedural skills by comparing performance on a motor and a visuoperceptual skill learning task. Twenty Parkinson's (PD) patients and 20 normal control subjects performed two procedural learning tasks (rotary pursuit and mirror reading) and one declarative learning task (paired associates) over 3 days. The results showed that PD patients were not impaired on mirror reading or paired associate learning. On rotary pursuit, performance levels on day 1 were similar between groups, but the PD group showed less improvement across days than controls. However, only patients with more advanced symptoms of PD showed impaired rotary pursuit learning, and this could not be attributed directly to deficits in primary motor or general cognitive function. These findings suggest that the underlying processes/procedures for procedural learning are specific to the task, and are supported by different neuroanatomical systems.     

Opposite effects of cortisol on consolidation of temporal sequence memory during waking and sleep

Memory functions involve three stages: encoding, consolidation, and retrieval. Modulating effects of glucocorticoids (GCs) have been consistently observed for declarative memory with GCs enhancing encoding and impairing retrieval, but surprisingly, little is known on how GCs affect memory consolidation. Studies in rats suggest a beneficial effect of GCs that were administered during postlearning wake periods, whereas in humans, cortisol impaired memory consolidation when administered during postlearning sleep. These inconsistent results raise the question whether effects of GCs critically depend on the brain state during consolidation (sleep vs. wake). Here, we compare for the first time directly the effects of cortisol on memory consolidation during postlearning sleep and wakefulness in different measures of declarative memory. Cortisol (13 mg vs. placebo) was intravenously infused during a postlearning nap or a time-matched period of wakefulness after participants had encoded neutral and emotional text material. Memory for the texts was tested (a) by asking for the contents of the texts ("item" memory) and (b) for the temporal order of the contents within the texts ("relational" memory). Neither postlearning infusion of cortisol during sleep nor during wakefulness affected retention of content words of emotional or neutral texts. Critically, however, the retention of temporal order within the texts, known to rely most specifically on the hippocampus proper within the medial-temporal lobe memory system, was distinctly improved by cortisol infusion during the wake phase but impaired by cortisol during sleep. These results point toward fundamentally different mechanisms of hippocampal memory consolidation, depending on the brain state.