Biomedical subjects

Jan Born

Publications and source records attributed to Jan Born.

At least 37 records · Page 2Linked to original sources

PubMed2005

Acute hypoxia decreases plasma VEGF concentration in healthy humans.

Vascular endothelial growth factor (VEGF) is known to be upregulated by hypoxia in vitro. However, in vivo data about VEGF regulation in chronic hypoxic diseases are conflicting. We investigated the effects of hypoxia on plasma VEGF concentration in healthy subjects. To control known confounders, such as insulin, glucose concentrations, or exercise, hypoxic effects on VEGF were studied during experimentally clamping glucose concentrations at rest. In a double-blind crossover study design, we induced hypoxia for 30 min by decreasing oxygen saturation to 75% (vs. normoxic control) in 14 healthy men. Plasma VEGF concentration was determined at baseline, immediately after hypoxia had ended, and after a further 150 min. Levels of its soluble (s)Flt-1 receptor were assessed at baseline and at the end of the clamp. In parallel, catecholamine and cortisol levels were monitored. To investigate potential effects of glucose administration on the release of VEGF, we performed a third session, reducing glucose infusion for 30 min while serum insulin was held stable thereby inducing hypoglycemia. Hypoxia decreased VEGF levels compared with the normoxic control (P<0.05). VEGF concentrations increased during hypoglycemia (P<0.02) but were comparable to the normoglycemic control at the end of the clamp (P>0.80). sFlt-1 receptor concentration remained unchanged during hypoxia and hypoglycemia compared with control (both P>0.4). Epinephrine concentration (P<0.01) increased upon hypoxia, whereas norepinephrine and cortisol did not change. Contrary to in vitro studies, in healthy humans hypoxia decreases plasma VEGF concentration, suggesting that systemic VEGF concentration may be differently regulated than the expression on cellular basis.

Adult↗

PubMed2005

Sleep-like concentrations of growth hormone and cortisol modulate type1 and type2 in-vitro cytokine production in human T cells.

Slow wave sleep (SWS) is characterized by maximum release of growth hormone (GH) and minimum release of cortisol. We hypothesized that this hormonal pattern during SWS leads, in addition to generally increased T cell cytokine production, to a shift towards type1 cytokines. To test this hypothesis, blood was sampled from 8 humans during SWS, and whole blood cultures were activated in-vitro with ionomycin and phorbol-myrestate-acetate (PMA) in the absence and presence of GH neutralizing antibody (Ab) or physiological concentrations of cortisol. Production of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-4, and tumor necrosis factor-alpha (TNF-alpha) was measured using multiparametric flow cytometry. GH Ab decreased IFN-gamma+CD4+ cells but had no effect on other cytokines. Cortisol alone and in combination with GH Ab decreased CD4+ and CD8+ cells producing IFN-gamma, TNF-alpha and IL-2. Simultaneously, these two reactants reduced IL-4+CD4+ cells, so that the ratio of IFN-gamma/IL4 producing CD4+ cells indicated an unexpected shift towards type1 dominance. Results support the view that release of GH by increasing particularly production of IFN-gamma can contribute to the shift in type1/type2 balance towards type1 activity characterizing SWS. Suppression of cortisol during this sleep period enhances both type1 and type2 activity. Yet, our finding of predominant type1 activity after cortisol administration, rules out any relevance of this suppression for the shift towards type1 activity during SWS.

Adult↗

PubMed2005

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.

Adrenocorticotropic Hormone↗

PubMed2005

Bifrontal transcranial direct current stimulation slows reaction time in a working memory task.

BACKGROUND: Weak transcortical direct current stimulation (tDCS) applied to the cortex can shift the membrane potential of superficial neurons thereby modulating cortical excitability and activity. Here we test the possibility of modifying ongoing activity associated with working memory by tDCS. The concept of working memory applies to a system that is capable of transiently storing and manipulating information, as an integral part of the human memory system. We applied anodal and cathodal transcranial direct current (tDCS) stimulation (260 microA) bilaterally at fronto-cortical electrode sites on the scalp over 15 min repeatedly (15 sec-on/15 sec-off) as well as sham-tDCS while subjects performed a modified Sternberg task. RESULTS: Reaction time linearly increased with increasing set size. The slope of this increase was closely comparable for real and sham stimulation indicating that our real stimulation did not effect time required for memory scanning. However, reaction time was slowed during both anodal and cathodal stimulation as compared to placebo (p < 0.05) indicating that real stimulation hampered neuronal processing related to response selection and preparation. CONCLUSION: Intermittent tDCS over lateral prefrontal cortex during a working memory task impairs central nervous processing related to response selection and preparation. We conclude that this decrease in performance by our protocol of intermittent stimulation results from an interference mainly with the temporal dynamics of cortical processing as indexed by event-related sustained and oscillatory EEG activity such as theta.

Adult↗

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

Changes in blood pressure and plasma catecholamine levels during prolonged hyperinsulinemia.

Hyperinsulinemia has been shown to induce activation of the sympathetic nervous system and vasodilatation. Whether these effects result in changes in blood pressure (BP) is discussed controversially. We measured BP and plasma catecholamine levels in 30 healthy men during a 60-minute baseline phase and 360-minute period of insulin infusion. In a double-blind, between-subject comparison, insulin was infused at a low rate (1.5 mU insulin/kg per minute) in one half of the subjects and at a high rate (15 mU/kg per minute) in the other half. Throughout the experiments, blood glucose levels were held constantly within the normal range by a simultaneous infusion of glucose. Serum insulin levels increased to a plateau of 543 +/- 34 pmol/L during low rate and to 24,029 +/- 1,595 pmol/L during high rate of insulin infusion. Compared with baseline, insulin infusion of either rate significantly increased systolic BP, BP amplitude, and heart rate (all P < .05). In comparison with the low rate of insulin infusion, the high rate provoked a more pronounced increase in heart rate (P < .02) and systolic BP (P < .05) but tended to decrease diastolic BP (P < .08) summing up to a distinctly more increased BP amplitude (P < .05). Plasma norepinephrine as well as epinephrine levels did not significantly change during the low-rate insulin infusion but significantly increased during high-rate insulin infusion (both P < .05). By showing a dose-dependent increasing influence of insulin on systolic BP and circulating catecholamine levels, the present study provides experimental evidence for the notion that hyperinsulinemia contributes to the development of hypertension.

Adult↗

PubMed2005

Immediate but not long-term intranasal administration of insulin raises blood pressure in human beings.

Intranasal administration of insulin has been shown to influence neuroendocrine functions via an effect on central nervous mechanisms. Because insulin, in particular when infused into cerebral arteries, induces blood pressure (BP) elevation by an unknown mechanism, we investigated whether insulin exerts similar effects on BP after intranasal administration. To evaluate the immediate effects of insulin on BP, 20 IU of human insulin was intranasally administered every 10 minutes over a 2-hour period. Blood pressure, heart rate, and muscular sympathetic nervous activity (MSNA) were continuously monitored. For evaluating the effects of subchronic administration of insulin, changes during and after 8 weeks of treatment with 160 IU insulin/d on BP were monitored. Compared with placebo, the immediate nasal administration of insulin raised diastolic BP (12.21% +/- 5.10%; P < .05), mean arterial BP (10.81% +/- 4.32%; P < .04), and systolic BP (9.53% +/- 4.66%; P < .08), whereas MSNA and heart rate were unaffected. In contrast, prolonged intranasal insulin administration did not affect BP (P > .62 for all comparisons). The immediate increase in BP in the face of an unsuppressed MSNA after insulin suggests that intranasal insulin transiently changes the baroreflex set point. Thus, data suggest that intranasal insulin administration affects BP regulatory centers in the brain. However, the effect is not observed with prolonged administration of the hormone, suggesting the emergence of counterregulatory processes.

Administration, Intranasal↗

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↗

PubMed2005

Preserved inhibitory effect of recurrent hypoglycaemia on the male gonadotrophic axis.

OBJECTIVE: Hypoglycaemia-induced decreases in male LH and testosterone concentrations are possibly mediated by activation of the hypothalamus-pituitary-adrenal (HPA) axis or by an increase in PRL. As counterregulatory stress hormone release is attenuated during recurrent hypoglycaemia, we questioned whether the gonadotrophic axis and PRL adapt similarly. DESIGN: We performed two consecutive hypoglycaemic clamps on day 1 and one clamp on the following day in 15 healthy men. Blood concentrations of gonadotrophins, PRL, testosterone, ACTH and cortisol were measured during the first and the third clamp, taking place at the same time of day. RESULTS: During hypoglycaemia, serum concentrations of LH and testosterone decreased (P < 0.003 for both), PRL, ACTH and cortisol increased (P < 0.001), and FSH remained unchanged (P = 0.90). The hypoglycaemia-induced decreases in LH and testosterone concentrations were similar during the first and the last clamp (P > 0.28 for both) whereas the increase in PRL, ACTH and cortisol was markedly attenuated during the third clamp (P < 0.001). CONCLUSIONS: LH and testosterone responses do not adapt to recurrent hypoglycaemia, whereas the increase in PRL is attenuated, indicating adaptation. Considering the marked decrease in the responses of PRL and the HPA axis after antecedent hypoglycaemia, the data suggest that the hypoglycaemia-induced decreases in LH and testosterone concentrations, not adapting to recurrent hypoglycaemia, are mediated independently, probably by blood glucose itself.

Adaptation, Physiological↗

PubMed2005

Modulation of food intake by glucose in patients with type 2 diabetes.

OBJECTIVE: A gain in body weight is a common adverse effect of glucose-lowering therapies in patients with type 2 diabetes, the mechanisms of which are not completely understood. Blood glucose is considered to play a crucial role in the regulation of food intake. On this background, we hypothesized that a short-term reduction of blood glucose concentration to normal values acutely increases food intake in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: To test this hypothesis, 12 patients with type 2 diabetes were examined twice, once during a euglycemic (5.0 mmol/l) clamp experiment and another time during a hyperglycemic (10.5 mmol/l) clamp. The experiments were performed in a single-blind fashion with the order of conditions balanced across patients. On both clamp conditions, insulin was infused at a constant rate of 2.5 mU/kg per min for 125 min. Simultaneously, a glucose solution was infused at a variable rate to achieve target glycemic levels. During the final 30 min of the clamps, the patients were allowed to eat as much as they liked from a standard breakfast buffet. RESULTS: Compared with the hyperglycemic condition, the patients ingested on average 25 +/- 10% more energy during euglycemia (645 +/- 75 vs. 483 +/- 37 kcal; P = 0.029). The increased energy intake during euglycemia was equally distributed across macronutrient components, i.e., during euglycemia the patients ate more carbohydrates (+27.1 +/- 11.4%; P = 0.037), fat (+22.5 +/- 10.0%; P = 0.046), and proteins (+25.2 +/- 11.2%; P = 0.046) than during hyperglycemia. Circulating levels of insulin, amylin, leptin, ghrelin, and glucagon-like peptide-1 did not differ between the euglycemic and hyperglycemia clamp, excluding a major contribution of these hormones to the difference in food intake. Summing up the glucose administered intravenously and the food ingested yielded a remarkably similar total energy influx in both conditions (794 +/- 64 vs. 790 +/- 53 kcal; P = 0.961). CONCLUSIONS: Together our data suggest that total energy supply to the organism is tightly regulated on a short-term basis independent of the route of influx. Alternatively, it can be hypothesized that euglycemia stimulated or that hyperglycemia suppressed food intake at the subsequent buffet meal in our type 2 diabetic patients. Regardless of these different interpretations, our data indicate an important regulatory role of glucose for food intake in type 2 diabetic patients that is of considerable clinical relevance.

Blood Glucose↗

PubMed2004

Gut protein uptake and mechanisms of meal-induced cortisol release.

The enhanced cortisol release after protein-rich meals might represent a neuroendocrine response to food allergens. We tested whether the antigenicity of proteins contributes to this effect. Twelve healthy men nasogastrically received casein, its less allergenic hydrolysate, and placebo. Contrary to expectations, secretion of cortisol (area under the curve, 742.70 +/- 73.48 vs. 542.95 +/- 70.31 micromol/liter.min, P < 0.03) and ACTH (2020.21 +/- 251.10 vs. 1649.82 +/- 241.23 micromol/liter.min, P < 0.05) was stronger on casein-hydrolysate than casein. Systemic immune activity remained unaffected as indicated by unchanged IL-6 plasma concentrations. This finding indicates that the grade of hydrolysis of a protein and the presence of particular amino acids, rather than its antigenicity, are crucial for the pituitary-adrenal response to nutrients. To further examine whether this response is triggered at the gastrointestinal mucosa or after the substance has reached the circulation, in a supplementary experiment, amino acids were given either nasogastrically or iv to healthy men (n = 4). Only the nasogastric infusion of amino acids induced a significant rise in cortisol concentrations. Serum concentrations of tryptophan, which is known to directly excite the hypothalamo-pituitary-adrenal axis, were comparable for both conditions. We conclude that the meal-related hypothalamo-pituitary-adrenal axis response to amino acids results from a signal that rather acts at the gastrointestinal mucosa than directly via the circulating blood.

Adrenocorticotropic Hormone↗

PubMed2004

Transcranial direct current stimulation during sleep improves declarative memory.

In humans, weak transcranial direct current stimulation (tDCS) modulates excitability in the motor, visual, and prefrontal cortex. Periods rich in slow-wave sleep (SWS) not only facilitate the consolidation of declarative memories, but in humans, SWS is also accompanied by a pronounced endogenous transcortical DC potential shift of negative polarity over frontocortical areas. To experimentally induce widespread extracellular negative DC potentials, we applied anodal tDCS (0.26 mA) [correction] repeatedly (over 30 min) bilaterally at frontocortical electrode sites during a retention period rich in SWS. Retention of declarative memories (word pairs) and also nondeclarative memories (mirror tracing skills) learned previously was tested after this period and compared with retention performance after placebo stimulation as well as after retention intervals of wakefulness. Compared with placebo stimulation, anodal tDCS during SWS-rich sleep distinctly increased the retention of word pairs (p < 0.005). When applied during the wake retention interval, tDCS did not affect declarative memory. Procedural memory was also not affected by tDCS. Mood was improved both after tDCS during sleep and during wake intervals. tDCS increased sleep depth toward the end of the stimulation period, whereas the average power in the faster frequency bands (,alpha, and beta) was reduced. Acutely, anodal tDCS increased slow oscillatory activity <3 Hz. We conclude that effects of tDCS involve enhanced generation of slow oscillatory EEG activity considered to facilitate processes of neuronal plasticity. Shifts in extracellular ionic concentration in frontocortical tissue (expressed as negative DC potentials during SWS) may facilitate sleep-dependent consolidation of declarative memories.

Adult↗

PubMed2004

Manipulating central nervous mechanisms of food intake and body weight regulation by intranasal administration of neuropeptides in man.

Maintaining a stable body weight set-point is assumed to rely on a homeostatic central nervous system (CNS) regulation of body fat with the particular involvement of hypothalamic pathways. The peripheral adiposity signals insulin and leptin convey information on the amount of energy stored as body fat to the arcuate nucleus of the hypothalamus, where anabolic/orexigenic and catabolic/anorexigenic pathways interact to regulate food intake and energy expenditure. One of the most prominent orexigenic messengers is neuropeptide Y (NPY), whereas melanocortins, including alpha-melanocyte-stimulating hormone (alpha-MSH), are essential for inducing anorexigenic effects. The melanocortin receptor 4 (MC4-R) plays the most important role in mediating catabolic effects of alpha-MSH. In this review, we present a series of own studies on NPY, insulin and MSH/ACTH4-10, an MC4-R agonist. The studies were all based on the intranasal route of administration which enables a direct access of the peptides to hypothalamic functions. NPY acutely attenuated electrocortical signs of meal-related satiety. Prolonged intranasal administration of insulin as well as of MSH induced weight loss in healthy human subjects. However, overweight subjects did not lose body fat after MSH administration. The results corroborate in humans the significance of all three messengers for the central nervous regulation of adiposity and might contribute to the future development of medical strategies against body-weight-related disorders.

Administration, Intranasal↗

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

Hypoxia causes glucose intolerance in humans.

Hypoxic respiratory diseases are frequently accompanied by glucose intolerance. We examined whether hypoxia is a cause of glucose intolerance in healthy subjects. In a double-blind within-subject crossover design, hypoxic versus normoxic conditions were induced in 14 healthy men for 30 minutes by decreasing oxygen saturation to 75% (versus 96% in control subjects) under the conditions of a euglycemic clamp. The rate of dextrose infusion needed to maintain stable blood glucose levels was monitored. Neurohormonal stress response was evaluated by measuring catecholamine and cortisol concentrations as well as cardiovascular parameters, and symptoms of anxiety. To differentiate between the effects of stress hormonal response, and hypoxia itself, on glucose intolerance, we performed hypoglycemic clamps as a nonspecific control. We found a significant decrease in dextrose infusion rate over a period of 150 minutes after the start of hypoxia (p < 0.01). Hypoxia also increased plasma epinephrine concentration (p < 0.01), heart rate (p < 0.01), and symptoms of anxiety (p < 0.05), whereas the other parameters remained unaffected. Glucose intolerance was closely comparable between hypoxic and hypoglycemic conditions (p < 0.9) despite clear differences in stress hormonal responses. Hypoxia acutely causes glucose intolerance. One of the factors mediating this effect could be an elevated release of epinephrine.

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

Sleep associated regulation of T helper 1/T helper 2 cytokine balance in humans.

Recent human studies suggested a supportive influence of regular nocturnal sleep on immune responses to experimental infection (vaccination). We hypothesized here that sleep could ease such responses by shifting the balance between T helper 1 (Th1) and T helper 2 (Th2) cytokine activity towards Th1 dominance thereby favoring cellular over humoral responses to infection. We compared the Th1/Th2 cytokine balance in 14 healthy men during regular nocturnal sleep (between 23:00 and 07:00 h) and while remaining awake during the same nocturnal interval, in a within-subject cross-over design. Blood was collected every 2 h. Production of T cell derived cytokines--interferon-gamma (IFN-gamma), interleukin-2 (IL-2), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-alpha)--was measured at the single cell level using multiparametric flow cytometry. Also, several immunoactive hormones--prolactin, growth hormone (GH), thyroid stimulating hormone (TSH), cortisol, and melatonin--were measured, the release of which is known to be regulated by sleep. Compared with wakefulness, early nocturnal sleep induced a shift in the Th1/Th2 cytokine balance towards increased Th1 activity, as indicated by an increased (p <.05) ratio of IFN-gamma/IL-4 producing T helper cells. However, the Th1 shift was only of moderate size and replaced by Th2 dominance during late sleep (p <.05). It could be mediated via release of prolactin and GH which both were distinctly increased during sleep (p <.001). Though unexpected, the most pronounced effect of sleep on T cell cytokine production was a robust decrease in TNF-alpha producing CD8+ cells probably reflecting increased extravasation of cytotoxic effector and memory T cells.

Adult↗