Biomedical subjects

Steffen Gais

Publications and source records attributed to Steffen Gais.

15 recordsLinked to original sources

PubMed2006

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.

Adult↗

PubMed2006

Combined blockade of cholinergic receptors shifts the brain from stimulus encoding to memory consolidation.

High central nervous system levels of acetylcholine (ACh) are commonly regarded as crucial for learning and memory, and a decline in cholinergic neurotransmission is associated with Alzheimer's dementia. However, recent findings revealed exceptions to this rule: The low ACh tone characterizing slow wave sleep (SWS) has proven necessary for consolidation of hippocampus-dependent declarative memories during this sleep stage. Such observations, together with recent models of a hippocampal-neocortical dialogue underlying systems memory consolidation, suggest that high levels of ACh support memory encoding, whereas low levels facilitate consolidation. We tested this hypothesis in human subjects by blocking cholinergic neurotransmission during wakefulness, starting 30 min after learning. Subjects received the muscarinic antagonist scopolamine (4 microg/kg bodyweight intravenously) and the nicotinic antagonist mecamylamine (5 mg orally). Compared to placebo, combined muscarinic and nicotinic receptor blockade significantly improved consolidation of declarative memories tested 10 hr later, but simultaneously impaired acquisition of similar material. Consolidation of procedural memories, which are not dependent on hippocampal functioning, was unaffected. Neither scopolamine nor mecamylamine alone enhanced declarative memory consolidation. Our findings support the notion that ACh acts as a switch between modes of acquisition and consolidation. We propose that the natural shift in central nervous system cholinergic tone from high levels during wakefulness to minimal levels during SWS optimizes declarative memory consolidation during a period with no need for new memory encoding.

Adult↗

PubMed2006

Sleep to remember.

Recently, compelling evidence has accumulated that links sleep to learning and memory. Sleep has been identified as a state that optimizes the consolidation of newly acquired information in memory. Consolidation is an active process that is presumed to rely on the covert reactivation and reorganization of newly encoded representations. Hippocampus-dependent memories benefit primarily from slow-wave sleep (SWS), whereas memories not depending on the hippocampus show greater gains over periods containing high amounts of rapid eye movement sleep. One way sleep does this is by establishing different patterns of neurotransmitters and neurohormone secretion between sleep stages. Another central role for consolidating memories is played by the slow oscillation, that is, the oscillating field potential change dominating SWS. The emergence of slow oscillations in neocortical networks depends on the prior use of these networks for encoding of information. Via efferent pathways, they synchronize the occurrence of sharp wave ripples accompanying memory reactivations in the hippocampus with thalamocortical spindle activity. Thus, hippocampal memories are fed back into neocortical networks at a time when these networks are depolarized and, because of concurrent spindle activity, can most sensitively react to these inputs with plastic changes underlying the formation of long-term memory representations.

Animals↗

PubMed2005

Processing of food stimuli is selectively enhanced during insulin-induced hypoglycemia in healthy men.

Recently it has been reported that during insulin-induced hypoglycemia selective attention is directed to food stimuli suggesting an adaptive cognitive strategy to escape from this potentially dangerous metabolic state. Here, we tested this hypothesis using a short-term memory task. We also aimed to define a hypoglycemic threshold level at which such an adaptive cognitive strategy first occurs. Fifteen healthy men underwent stepwise hypoglycemic (plasma glucose: 4.1-3.6-3.1-2.6 mmol/l) and euglycemic clamp experiments. Clamps were performed in a single blind fashion within a cross-over design with the order balanced across subjects. During the clamps cognitive function tests (short-term recall of food-related and non-food-related words; Stroop task) were applied at baseline and each hypoglycemic plateau, and at the corresponding time intervals of the euglycemic clamp. Performance on all cognitive function tests applied deteriorated during the hypoglycemic as compared to the euglcemic clamp (all P<0.02). Separate analyses at each hypoglycemic plateau revealed that food and non-food related short-term memory was similar during baseline and mild hypoglycemia. However, at the hypoglycemic target level of 2.6 mmol/l recall of food related words was higher than non-food related words when compared to the euglycemic control clamp condition (p=0.024). Performance on the word-color conflict Stroop task became significantly impaired first at the lowest hypoglycemic plateau (2.6 mmol/l), while performance on the Stroop subtests 'color naming' and 'word reading' were already impaired at higher plasma glucose levels (3.6 and 3.1 mmol/l; respectively). Collectively, data of the Stroop task indicate that the control of attention via executive mechanisms is less sensitive to insulin-induced hypoglycemia than pre-attentive automated stimulus processing (reading, naming). If executive control of attention becomes affected by hypoglycemia, cognitive resources appear to be preferentially allocated to the processing of food stimuli.

Adult↗

PubMed2005

Differential effects of sleep deprivation on saccadic eye movements.

STUDY OBJECTIVES: This study was designed to show the influence of sleep deprivation on different types of saccadic eye movements. DESIGN: Performance of saccadic eye movements was compared after normal sleep and sleep deprivation in a randomized, within-subjects paradigm. Parameters of voluntary and reflexive saccades were measured before and after experimental nights and after a night of recovery sleep. Additionally, subjects spent 1 adaptation night in the laboratory before the experiments. SETTING: Experiments took place under controlled laboratory conditions. PARTICIPANTS: Fifteen healthy male volunteers (aged 19-30 years). INTERVENTIONS: Each subject participated in 1 night of sleep deprivation followed by a night of recovery sleep and, on another occasion, in 2 successive nights of undisturbed sleep. MEASUREMENTS AND RESULTS: Horizontal prosaccades, antisaccades, and memory-guided saccades were recorded by means of electrooculography. They were analysed semiautomatically with respect to accuracy, peak velocity, and latency. Peak velocity was significantly reduced in all saccade tasks after 1 night of sleep deprivation but recovered after another night of sleep. Latency was prolonged after sleep deprivation only for memory-guided saccades; accuracy showed a decrease after 1 night without sleep only for prosaccades. CONCLUSIONS: Sleep deprivation has a general impairing effect on the peak velocity of saccades, reflecting possible dysfunction at the level of the brainstem reticular formation. Deficits of accuracy and latency point to dysfunction of specific brain sites such as the supplementary eye field and cerebellum, whereas the cardinal functions of the frontal and parietal eye fields were not affected. These results suggest the possibility of measuring fatigue by means of saccadic parameters, especially saccadic peak velocity.

Adult↗

PubMed2004

Learning increases human electroencephalographic coherence during subsequent slow sleep oscillations.

Learning is assumed to induce specific changes in neuronal activity during sleep that serve the consolidation of newly acquired memories. To specify such changes, we measured electroencephalographic (EEG) coherence during performance on a declarative learning task (word pair associations) and subsequent sleep. Compared with a nonlearning control condition, learning performance was accompanied with a strong increase in coherence in several EEG frequency bands. During subsequent non-rapid eye movement sleep, coherence only marginally increased in a global analysis of EEG recordings. However, a striking and robust increase in learning-dependent coherence was found when analyses were performed time-locked to the occurrence of slow oscillations (<1 Hz). Specifically, the surface-positive half-waves of the slow oscillation resulting from widespread cortical depolarization were associated with distinctly enhanced coherence after learning in the slow-oscillatory, delta, slow-spindle, and gamma bands. The findings identify the depolarizing phase of the slow oscillations in humans as a time period particularly relevant for a reprocessing of memories in sleep.

Adult↗

PubMed2004

Low acetylcholine during slow-wave sleep is critical for declarative memory consolidation.

The neurotransmitter acetylcholine is considered essential for proper functioning of the hippocampus-dependent declarative memory system, and it represents a major neuropharmacological target for the treatment of memory deficits, such as those in Alzheimer's disease. During slow-wave sleep (SWS), however, declarative memory consolidation is particularly strong, while acetylcholine levels in the hippocampus drop to a minimum. Observations in rats led to the hypothesis that the low cholinergic tone during SWS is necessary for the replay of new memories in the hippocampus and their long-term storage in neocortical networks. However, this low tone should not affect nondeclarative memory systems. In this study, increasing central nervous cholinergic activation during SWS-rich sleep by posttrial infusion of 0.75 mg of the cholinesterase inhibitor physostigmine completely blocked SWS-related consolidation of declarative memories for word pairs in human subjects. The treatment did not interfere with consolidation of a nondeclarative mirror tracing task. Also, physostigmine did not alter memory consolidation during waking, when the endogenous central nervous cholinergic tone is maximal. These findings are in line with predictions that a low cholinergic tone during SWS is essential for declarative memory consolidation.

Acetylcholine↗

PubMed2004

Sleep inspires insight.

Insight denotes a mental restructuring that leads to a sudden gain of explicit knowledge allowing qualitatively changed behaviour. Anecdotal reports on scientific discovery suggest that pivotal insights can be gained through sleep. Sleep consolidates recent memories and, concomitantly, could allow insight by changing their representational structure. Here we show a facilitating role of sleep in a process of insight. Subjects performed a cognitive task requiring the learning of stimulus-response sequences, in which they improved gradually by increasing response speed across task blocks. However, they could also improve abruptly after gaining insight into a hidden abstract rule underlying all sequences. Initial training establishing a task representation was followed by 8 h of nocturnal sleep, nocturnal wakefulness, or daytime wakefulness. At subsequent retesting, more than twice as many subjects gained insight into the hidden rule after sleep as after wakefulness, regardless of time of day. Sleep did not enhance insight in the absence of initial training. A characteristic antecedent of sleep-related insight was revealed in a slowing of reaction times across sleep. We conclude that sleep, by restructuring new memory representations, facilitates extraction of explicit knowledge and insightful behaviour.

Adolescent↗

PubMed2004

Differences between nighttime and daytime hypoglycemia counterregulation in healthy humans.

Disturbances in hormonal counterregulation may be the main reason why many type 1 diabetic patients are asymptomatic during nighttime hypoglycemia. While it is known that sleep attenuates counterregulatory responses to hypoglycemia, the influence of the time of day on hormonal counterregulation regulation remains obscure. We induced hypoglycemia at 2 different time intervals, ie, in the morning and in the early night, in healthy subjects staying awake throughout the experiments. As compared with the morning hypoglycemia, epinephrine response during early nighttime hypoglycemia was markedly enhanced (P < .001). Baseline corticotropin (ACTH) and cortisol levels were higher in the morning than during nighttime (P < .001 for both). However, the increase of both hormones was stronger at nighttime (P = .045 and P < .001, respectively), so that at the end of the hypoglycemic clamp, levels at nighttime were comparable to morning levels. In the morning, the increase in glucagon levels was more pronounced than during nighttime (P = .019), but given that baseline glucagon levels were distinctly higher at nighttime than in the morning (P = .003), at the end of the clamps, levels of this hormone remained still higher at nighttime than in the morning (P = .017). The increase in growth hormone during hypoglycemia did not differ between morning and nighttime (P = .728). Data shows that several components of hormonal counterregulation against hypoglycemia are influenced by the time of day. Especially, the markedly enhanced epinephrine response to early nighttime hypoglycemia could be clinically important, because this neuroendocrine response is known to play a crucial role in mediating the awareness of and metabolic defensive mechanism against hypoglycemia.

Adult↗

PubMed2003

Hypoglycemia counterregulation during sleep.

STUDY OBJECTIVES: In insulin-treated patients with diabetes, episodes of severe hypoglycemia often occur during sleep, which might reflect an altered counterregulation and reduced awareness. This study examined the influence of sleep on the counterregulatory response to hypoglycemia in healthy subjects. DESIGN: Subjects participated in two experimental conditions; statistical tests relied on within subject comparisons. SETTING: University hospital sleep laboratory. PARTICIPANTS: 15 healthy young men. INTERVENTIONS: Hypoglycemia (2.8 mmol/l) was induced for 45 min by insulin infusion once during sleep and once at the same time of night while being awake. MEASUREMENTS AND RESULTS: Counterregulatory hormone concentrations (epinephrine, norepinephrine, ACTH and cortisol) and sleep recordings were obtained. Differences in the hormonal responses to hypoglycemia between sleep and wake conditions remained non-significant, indicating that sleep does not exert a primary influence on the strength of counterregulation. However, the glycemic threshold for the onset of counterregulation was significantly changed during sleep: The average onset threshold for epinephrine and norepinephrine counterregulation was 3.3 +/- 0.1 mmol/l for the wake condition and 2.7 +/- 0.1 mmol/l for the sleep condition (P < 0.001). A decrease in sleep depth coincided with the onset of the counterregulatory response, with most subjects showing signs of awakening. CONCLUSIONS: During sleep, the organism is less sensitive to hypoglycemia. Hypoglycemia per se has an awakening effect.

Adolescent↗

PubMed2002

Grouping of spindle activity during slow oscillations in human non-rapid eye movement sleep.

Based on findings primarily in cats, the grouping of spindle activity and fast brain oscillations by slow oscillations during slow-wave sleep (SWS) has been proposed to represent an essential feature in the processing of memories during sleep. We examined whether a comparable grouping of spindle and fast activity coinciding with slow oscillations can be found in human SWS. For negative and positive half-waves of slow oscillations (dominant frequency, 0.7-0.8 Hz) identified during SWS in humans (n = 13), wave-triggered averages of root mean square (rms) activity in the theta (4-8 Hz), alpha (8-12 Hz), spindle (12-15 Hz), and beta (15-25 Hz) range were formed. Slow positive half-waves were linked to a pronounced and microV (23.4%; p < 0.001, with reference to baseline) at the midline central electrode (Cz). In contrast, spindle activity was suppressed during slow negative half-waves, on average by -0.65 +/- 0.06 microV at Cz (-22%; p < 0.001). An increase in spindle activity 400-500 msec after negative half-waves was more than twofold the increase during slow positive half-waves (p < 0.001). A similar although less pronounced dynamic was observed for beta activity, but not for alpha and theta frequencies. Discrete spindles identified during stages 2 and 3 of non-rapid eye movement (REM) sleep coincided with a discrete slow positive half-wave-like potential preceded by a pronounced negative half-wave (p < 0.01). These results provide the first evidence in humans of grouping of spindle and beta activity during slow oscillations. They support the concept that phases of cortical depolarization during slow oscillations, reflected by surface-positive (depth-negative) field potentials, drive the thalamocortical spindle activity. The drive is particularly strong during cortical depolarization, expressed as surface-positive field potentials.

Adolescent↗

PubMed2002

Learning-dependent increases in sleep spindle density.

Declarative memory consolidation is enhanced by sleep. In the investigation of underlying mechanisms, mainly rapid eye movement (REM) sleep and slow-wave sleep have been considered. More recently, sleep stage 2 with sleep spindles as a most prominent feature has received increasing attention. Specifically, in rats hippocampal ripples were found to occur in temporal proximity to cortical sleep spindles, indicating an information transfer between the hippocampus and neocortex, which is supposed to underlie the consolidation of declarative memories during sleep. This study in humans looks at the changes in EEG activity during nocturnal sleep after extensive training on a declarative learning task, as compared with a nonlearning control task of equal visual stimulation and subjectively rated cognitive strain. Time spent in each sleep stage, spindle density, and EEG power spectra for 28 electrode locations were determined. During sleep after training, the density of sleep spindles was significantly higher after the learning task as compared with the nonlearning control task. This effect was largest during the first 90 min of sleep (p < 0.01). Additionally, spindle density was correlated to recall performance both before and after sleep (r = 0.56; p < 0.05). Power spectra and time spent in sleep stages did not differ between learning and nonlearning conditions. Results indicate that spindle activity during non-REM sleep is sensitive to previous learning experience.

Adolescent↗

PubMed2002

Post-trial administration of vasopressin in humans does not enhance memory formation (vasopressin and memory consolidation).

Many animal studies show an enhancing effect of vasopressin (VP) on memory, but not all human studies could confirm this finding. This study examined the influence of post-learning administration of VP (40 IU, intranasally) on the consolidation of declarative memories in healthy humans during different intervals of sleep and waking. We could not find any effect of VP on memory consolidation, but EEG activity indicated a significant arousing influence of VP. Results suggest that if VP affects memory function it might do so primarily at the stage of encoding of the materials to be learned but it leaves unaffected processes of consolidation.

Administration, Intranasal↗

PubMedDate not supplied

Sleep after learning aids memory recall.

In recent years, the effect of sleep on memory consolidation has received considerable attention. In humans, these studies concentrated mainly on procedural types of memory, which are considered to be hippocampus-independent. Here, we show that sleep also has a persisting effect on hippocampus-dependent declarative memory. In two experiments, we examined high school students' ability to remember vocabulary. We show that declarative memory is enhanced when sleep follows within a few hours of learning, independent of time of day, and with equal amounts of interference during retention intervals. Sleep deprivation has a detrimental effect on memory, which was significant after a night of recovery sleep. Thus, fatigue accumulating during wake intervals could be ruled out as a confound.

Adolescent↗

PubMedDate not supplied

Declarative memory consolidation: mechanisms acting during human sleep.

Of late, an increasing number of studies have shown a strong relationship between sleep and memory. Here we summarize a series of our own studies in humans supporting a beneficial influence of slow-wave sleep (SWS) on declarative memory formation, and try to identify some mechanisms that might underlie this influence. Specifically, these experiments show that declarative memory benefits mainly from sleep periods dominated by SWS, whereas there is no consistent benefit of this memory from periods rich in rapid eye movement (REM) sleep. A main mechanism of declarative memory formation is believed to be the reactivation of newly acquired memory representations in hippocampal networks that stimulates a transfer and integration of these representations into neocortical neuronal networks. Consistent with this model, spindle activity and slow oscillation-related EEG coherence increase during early sleep after intense declarative learning in humans, signs that together point toward a neocortical reprocessing of the learned material. In addition, sleep seems to provide an optimal milieu for declarative memory reprocessing and consolidation by reducing cholinergic activation and the cortisol feedback to the hippocampus during SWS.

Acetylcholine↗