Lisa Genzel

The interaction between sleep quality and academic performance

Sleep quality has significant effects on cognitive performance and is influenced by multiple factors such as stress. Contrary to the ideal, medical students and residents suffer from sleep deprivation and stress at times when they should achieve the greatest amount of learning. In order to examine the relationship between sleep quality and academic performance, 144 medical students undertaking the pre-clinical board exam answered a survey regarding their subjective sleep quality (Pittsburgh sleep quality index, PSQI), grades and subjective stress for three different time points: semester, pre- and post-exam. Academic performance correlated with stress and sleep quality pre-exam (r = 0.276, p < 0.001 and r = 0.158, p < 0.03, note that low performance meant low sleep quality and high stress), however not with the stress or sleep quality during the semester and post-exam. 59% of all participants exhibited clinically relevant sleep disturbances (PSQI > 5) during exam preparation compared to 29% during the semester and 8% post-exam. This study shows that in medical students it is not the generally poor sleepers, who perform worse in the medical board exams. Instead students who will perform worse on their exams seem to be more stressed and suffer from poor sleep quality. However, poor sleep quality may negatively impact test performance as well, creating a vicious circle. Furthermore, the rate of sleep disturbances in medical students should be cause for intervention.

Sex and modulatory menstrual cycle effects on sleep related memory consolidation

The benefit of sleep in general for memory consolidation is well known. The relevance of sleep characteristics and the influence of hormones are not well studied. We explored the effects of a nap on memory consolidation of motor (finger-tapping-task) and verbal (associated-word-pairs) tasks in following settings: A: young, healthy males and females during early-follicular phase (n=40) and B: females during mid-luteal and early-follicular phase in the menstrual cycle (n=15). We found a sex and in women a menstrual cycle effect on memory performance following a nap. Men performed significantly better after a nap and women did so only in the mid-luteal phase of their menstrual cycle. Only the men and the women in their mid-luteal phase experienced a significant increase in spindle activity after learning. Furthermore, in women estrogen correlated significantly with the offline change in declarative learning and progesterone with motor learning. The ratio of the 2nd and 4th digit, which has been associated to fetal sex hormones and cognitive sex differences, significantly predicted the average performance of the female subjects in the learning tasks. Our results demonstrate that sleep-related memory consolidation has a higher complexity and more influencing factors than previously assumed. There is a sex and menstrual cycle effect, which seems to be mediated by female hormones and sleep spindles. Further, contrary to previous reports, consolidation of a simple motor task can be induced by a 45 min NREM sleep nap, thus not dependent on REM sleep.

The role of rapid eye movement sleep for amygdala-related memory processing

Over the years, rapid eye movement (REM) sleep has been associated with general memory consolidation, specific consolidation of perceptual, procedural, emotional and fear memories, brain maturation and preparation of waking consciousness. More recently, some of these associations (e.g., general and procedural memory consolidation) have been shown to be unlikely, while others (e.g., brain maturation and consciousness) remain inconclusive. In this review, we argue that both behavioral and neurophysiological evidence supports a role of REM sleep for amygdala-related memory processing: the amygdala-hippocampus-medial prefrontal cortex network involved in emotional processing, fear memory and valence consolidation shows strongest activity during REM sleep, in contrast to the hippocampus-medial prefrontal cortex only network which is more active during non-REM sleep. However, more research is needed to fully understand the mechanisms.

Medial Prefrontal-Hippocampal Connectivity and Motor Memory Consolidation in Depression and Schizophrenia

BACKGROUND Overnight memory consolidation is disturbed in both depression and schizophrenia, creating an ideal situation to investigate the mechanisms underlying sleep-related consolidation and to distinguish disease-specific processes from common elements in their pathophysiology. METHODS We investigated patients with depression and schizophrenia, as well as healthy control subjects (each n = 16), under a motor memory consolidation protocol with functional magnetic resonance imaging and polysomnography. RESULTS In a sequential finger-tapping task associated with the degree of hippocampal-prefrontal cortex functional connectivity during the task, significantly less overnight improvement was identified as a common deficit in both patient groups. A task-related overnight decrease in activation of the basal ganglia was observed in control subjects and schizophrenia patients; in contrast, patients with depression showed an increase. During the task, schizophrenia patients, in comparison with control subjects, additionally recruited adjacent cortical areas, which showed a decrease in functional magnetic resonance imaging activation overnight and were related to disease severity. Effective connectivity analyses revealed that the hippocampus was functionally connected to the motor task network, and the cerebellum decoupled from this network overnight. CONCLUSIONS While both patient groups showed similar deficits in consolidation associated with hippocampal-prefrontal cortex connectivity, other activity patterns more specific for disease pathology differed.

Impaired off-line memory consolidation in depression

Sleep is critically involved in the consolidation of procedural memory. In major depression (MD) and during antidepressant pharmacotherapy, changes in sleep EEG are well documented. Here, we test if off-line motor memory consolidation is impaired in MD. 50 medicated patients with an acute episode of MD, 50 normal controls and 12 patients with a remitted episode of MD were assessed using a sequential finger tapping task before and after a night of sleep. Although depressed patients and control subjects did not differ in practice-dependent learning, healthy subjects showed markedly overnight improvements in tapping performance of 18% while patients failed to show any improvement. This pattern became even more striking when the subjects were divided by an age threshold of 30years: In the 30+yrs group the healthy subjects showed 16% overnight increase in motor performance, whereas the patients showed -10% overnight decrease. In contrast, patients and controls in the </=30yrs group showed virtually the same motor performance, as well as remitted patients and controls in the 30+yrs group. In addition, the younger controls showed stronger overnight improvements than the older controls. This pattern might be interpreted as a synergistic interaction between age and depression: Off-line motor memory consolidation is not affected in young patients, but severely impaired in older patients with an acute episode of MD. This impairment seems to recover after remission from depression.

Ghrelin increases slow wave sleep and stage 2 sleep and decreases stage 1 sleep and REM sleep in elderly men but does not affect sleep in elderly women

Ghrelin increases non-REM sleep and decreases REM sleep in young men but does not affect sleep in young women. In both sexes, ghrelin stimulates the activity of the somatotropic and the hypothalamic-pituitary-adrenal (HPA) axis, as indicated by increased growth hormone (GH) and cortisol plasma levels. These two endocrine axes are crucially involved in sleep regulation. As various endocrine effects are age-dependent, aim was to study ghrelins effect on sleep and secretion of GH and cortisol in elderly humans. Sleep-EEGs (2300-0700 h) and secretion profiles of GH and cortisol (2000-0700 h) were determined in 10 elderly men (64.0+/-2.2 years) and 10 elderly, postmenopausal women (63.0+/-2.9 years) twice, receiving 50 microg ghrelin or placebo at 2200, 2300, 0000, and 0100 h, in this single-blind, randomized, cross-over study. In men, ghrelin compared to placebo was associated with significantly more stage 2 sleep (placebo: 183.3+/-6.1; ghrelin: 221.0+/-12.2 min), slow wave sleep (placebo: 33.4+/-5.1; ghrelin: 44.3+/-7.7 min) and non-REM sleep (placebo: 272.6+/-12.8; ghrelin: 318.2+/-11.0 min). Stage 1 sleep (placebo: 56.9+/-8.7; ghrelin: 50.9+/-7.6 min) and REM sleep (placebo: 71.9+/-9.1; ghrelin: 52.5+/-5.9 min) were significantly reduced. Furthermore, delta power in men was significantly higher and alpha power and beta power were significantly lower after ghrelin than after placebo injection during the first half of night. In women, no effects on sleep were observed. In both sexes, ghrelin caused comparable increases and secretion patterns of GH and cortisol. In conclusion, ghrelin affects sleep in elderly men but not women resembling findings in young subjects.

Sleep Spindles and Intelligence: Evidence for a Sexual Dimorphism

Sleep spindles are thalamocortical oscillations in nonrapid eye movement sleep, which play an important role in sleep-related neuroplasticity and offline information processing. Sleep spindle features are stable within and vary between individuals, with, for example, females having a higher number of spindles and higher spindle density than males. Sleep spindles have been associated with learning potential and intelligence; however, the details of this relationship have not been fully clarified yet. In a sample of 160 adult human subjects with a broad IQ range, we investigated the relationship between sleep spindle parameters and intelligence. In females, we found a positive age-corrected association between intelligence and fast sleep spindle amplitude in central and frontal derivations and a positive association between intelligence and slow sleep spindle duration in all except one derivation. In males, a negative association between intelligence and fast spindle density in posterior regions was found. Effects were continuous over the entire IQ range. Our results demonstrate that, although there is an association between sleep spindle parameters and intellectual performance, these effects are more modest than previously reported and mainly present in females. This supports the view that intelligence does not rely on a single neural framework, and stronger neural connectivity manifesting in increased thalamocortical oscillations in sleep is one particular mechanism typical for females but not males.

Off-line memory consolidation impairments in multiple sclerosis patients receiving high-dose corticosteroid treatment mirror consolidation impairments in depression

BACKGROUND Sleep supports the consolidation of procedural memory, however patients with major depression show impaired motor memory performance after a night of sleep. It was hypothesized that this impairment is related to hypothalamic-pituitary-adrenal (HPA) axis dysfunction. We tested if high-dose administration of corticosteroids impairs off-line motor memory consolidation in patients with multiple sclerosis (MS). METHODS Nine patients with MS receiving high-dose corticosteroid therapy (methylprednisolone) and nine MS patients receiving alternative therapy (mitoxantrone) were assessed using a sequential finger tapping task before and after a night with polysomnography. In addition, nine patients with major depression (MD) receiving antidepressants and nine healthy controls were assessed. RESULTS Although the four groups did not differ in practice-dependent learning, healthy subjects and MS patients receiving mitoxantrone showed markedly overnight-improvements in tapping performance of 17% and 24% while MS patients receiving high-dose corticosteroid therapy and depressed patients showed -9% and -10% overnight decrease. MS patients with and without corticosteroid therapy did not differ in their amount of REM sleep, nor did MD patients and healthy controls. In addition, we did not find any correlation between REM sleep and memory consolidation. CONCLUSION Our results show that a strong intervention into the HPA system like in MS high-dose corticosteroid therapy impairs off-line motor memory consolidation comparable to the impairments seen in depressed patients. We propose therefore that depression-related changes in plasma corticosteroid levels rather than in sleep per se underlie off-line memory consolidation impairments in MD.

Initial Investigation of the Effects of an Experimentally Learned Schema on Spatial Associative Memory in Humans

Networks of interconnected neocortical representations of prior knowledge, “schemas,” facilitate memory for congruent information. This facilitation is thought to be mediated by augmented encoding and accelerated consolidation. However, it is less clear how schema affects retrieval. Rodent and human studies to date suggest that schema-related memories are differently retrieved. However, these studies differ substantially as most human studies implement pre-experimental world-knowledge as schemas and tested item or nonspatial associative memory, whereas animal studies have used intraexperimental schemas based on item-location associations within a complex spatial layout that, in humans, could engage more strategic retrieval processes. Here, we developed a paradigm conceptually linked to rodent studies to examine the effects of an experimentally learned spatial associative schema on learning and retrieval of new object-location associations and to investigate the neural mechanisms underlying schema-related retrieval. Extending previous findings, we show that retrieval of schema-defining associations is related to activity along anterior and posterior midline structures and angular gyrus. The existence of such spatial associative schema resulted in more accurate learning and retrieval of new, related associations, and increased time allocated to retrieve these associations. This retrieval was associated with right dorsolateral prefrontal and lateral parietal activity, as well as interactions between the right dorsolateral prefrontal cortex and medial and lateral parietal regions, and between the medial prefrontal cortex and posterior midline regions, supporting the hypothesis that retrieval of new, schema-related object-location associations in humans also involves augmented monitoring and systematic search processes.

Complex Motor Sequence Skills Profit from Sleep

Simple motor memory has been shown to benefit from sleep; however, more complex motor skills have rarely been investigated so far. We investigated complex motor learning using a dance mat and choreographies in 36 healthy, young male subjects. Subjects performed one song and two new songs in three sessions distributed over 24 h to test sequence-specific learning and skill transfer. Each song had a unique choreography. One group learned the main song in the evening and was retested 12 and 24 h later on the main song and each one new song (PM-AM-PM). The second group underwent the same procedure; however, the first session was in the morning (AM-PM-AM). Thus, one group slept before the first retest (PM-AM-PM) while the other group slept between the first and the second retest (AM-PM-AM). Regarding sequence-specific learning, sleep induced a significant difference between the groups, which disappeared after both groups had slept. A significant transfer effect occurred independent of sleep. During both new songs, no difference between the groups was seen; however, the second and third songs were learned significantly faster than the first song. This study could show that complex motor sequence learning benefits from sleep while skill transfer seems to occur independently of sleep.