Susanne Huber

Functional ADA Polymorphism Increases Sleep Depth and Reduces Vigilant Attention in Humans

Homeostatically regulated slow-wave oscillations in non-rapid eye movement (REM) sleep may reflect synaptic changes across the sleep-wake continuum and the restorative function of sleep. The nonsynonymous c.22G>A polymorphism (rs73598374) of adenosine deaminase (ADA) reduces the conversion of adenosine to inosine and predicts baseline differences in sleep slow-wave oscillations. We hypothesized that this polymorphism affects cognitive functions, and investigated whether it modulates electroencephalogram (EEG), behavioral, subjective, and biochemical responses to sleep deprivation. Attention, learning, memory, and executive functioning were quantified in healthy adults. Right-handed carriers of the variant allele (G/A genotype, n = 29) performed worse on the d2 attention task than G/G homozygotes (n = 191). To test whether this difference reflects elevated homeostatic sleep pressure, sleep and sleep EEG before and after sleep deprivation were studied in 2 prospectively matched groups of G/A and G/G genotype subjects. Deep sleep and EEG 0.75- to 1.5-Hz oscillations in non-REM sleep were significantly higher in G/A than in G/G genotype. Moreover, attention and vigor were reduced, whereas waking EEG alpha activity (8.5-12 Hz), sleepiness, fatigue, and α-amylase in saliva were enhanced. These convergent data demonstrate that genetic reduction of ADA activity elevates sleep pressure and plays a key role in sleep and waking quality in humans.

Judgment and action knowledge in speed adjustment tasks: experiments in a virtual environment

Two experiments were conducted to investigate childrens and adults’ knowledge of time and speed in action and judgment tasks. Participants had to set the speed of a moving car to a new speed so that it would reach a target line at the same time as a reference car moving at a higher speed and disappearing in a tunnel at the midway point. In Experiment 1 (24 10-year-olds, 24 adults), childrens and adults’ speed adjustments followed the normative pattern when responses had to be graded linearly as a function of the cars initial speed. In a non-linear condition, only adults’ action responses corresponded with the normative function. Simplifying the task by shortening the tunnel systematically in Experiment 2 (24 10-year-olds, 24 adults) enabled children to grade the speeds adequately in the action conditions only. Adults now produced normative response patterns in both judgment and action. Whether people show linearization biases was thus shown to depend on the interaction of age, task demands and response mode.

Task-Specific Knowledge of the Law of Pendulum Motion in Children and Adults

The present experiment investigated children and adults’ knowledge of the pendulum law under different task conditions. The question asked was whether adults and fourth-graders knew that the period of a pendulum is a function of pendulum length but is independent of its mass. The task was to judge the period on a rating scale (judgment task), to imagine the swinging pendulum and indicate the corresponding time interval (imagery task), or to adjust the period of a dynamically presented pendulum (perception task). Normative consideration of pendulum length as the only relevant factor was primarily found in the perception task and, for adults, in the imagery task, whereas in the judgment task, children and adults frequently considered the irrelevant dimension of mass. Most children showed poor imagery performance. Preceding adjustment (perception task) and rating (judgment task) had no differential influence on subsequent imagery performance.

Controlling reaching movements with predictable and unpredictable target motion in 10-year-old children and adults.

We investigated interception behavior in adults and 10-year-old children. Participants had to intercept virtual targets moving on either a predictable (linear) or unpredictable (non-linear) path (with random direction changes). Targets moved at two different velocities, which varied randomly from trial to trial. Participants reached for the targets via a force-feedback device. Reaching movements for linearly moving targets in a block of linearly moving targets were compared with reaching movements for linearly moving targets in the context of non-linearly moving targets. Movement direction and maximum speed of the first sub-movement were analyzed as well as frequency of target hits and number of sub-movements. Unpredictable target motion caused faster movement speeds than predictable target motion for both children and adults. Additionally, unpredictable target motion caused children and adults to gear their initial movement direction further towards the current position of the target, while with predictable target motion, they geared their initial movement direction further ahead of the target towards an anticipated interception position. Together, these results suggest differential processing of predictable and unpredictable object behavior in an interception task, and that this differential processing is already in place in 10-year-olds.

Dark chocolate intake buffers stress reactivity in humans.

To the Editor: Dark chocolate consumption substantially lowers cardiovascular mortality due to the high content of polyphenolic flavonoids [(1)][1], but underlying mechanisms remain unclear. Psychosocial stress is a risk factor that supposedly promotes cardiovascular disease (CVD) by inducing

Effects of dark chocolate consumption on the prothrombotic response to acute psychosocial stress in healthy men

Flavanoid-rich dark chocolate consumption benefits cardiovascular health, but underlying mechanisms are elusive. We investigated the acute effect of dark chocolate on the reactivity of prothrombotic measures to psychosocial stress. Healthy men aged 20-50 years (mean ± SD: 35.7 ± 8.8) were assigned to a single serving of either 50 g of flavonoid-rich dark chocolate (n=31) or 50 g of optically identical flavonoid-free placebo chocolate (n=34). Two hours after chocolate consumption, both groups underwent an acute standardised psychosocial stress task combining public speaking and mental arithmetic. We determined plasma levels of four stress-responsive prothrombotic measures (i. e., fibrinogen, clotting factor VIII activity, von Willebrand Factor antigen, fibrin D-dimer) prior to chocolate consumption, immediately before and after stress, and at 10 minutes and 20 minutes after stress cessation. We also measured the flavonoid epicatechin, and the catecholamines epinephrine and norepinephrine in plasma. The dark chocolate group showed a significantly attenuated stress reactivity of the hypercoagulability marker D-dimer (F=3.87, p=0.017) relative to the placebo chocolate group. Moreover, the blunted D-dimer stress reactivity related to higher plasma levels of the flavonoid epicatechin assessed before stress (F=3.32, p = 0.031) but not to stress-induced changes in catecholamines (ps=0.35). There were no significant group differences in the other coagulation measures (ps≥0.87). Adjustments for covariates did not alter these findings. In conclusion, our findings indicate that a single consumption of flavonoid-rich dark chocolate blunted the acute prothrombotic response to psychosocial stress, thereby perhaps mitigating the risk of acute coronary syndromes triggered by emotional stress.

Whole Transcriptome Screening Reveals Myelination Deficits in Dysplastic Human Temporal Neocortex

Abstract Focal cortical dysplasias (FCDs) are local malformations of the human neocortex with strong epileptogenic potential. To investigate the underlying pathomechanisms, we performed a whole human transcriptome screening to compare the gene expression pattern of dysplastic versus nondysplastic temporal neocortex. Tissue obtained from FCD IIIa cases (mean age 20.5 years) who had undergone surgical treatment, due to intractable epilepsy, was compared with nondysplastic specimens (mean age 19.9 years) by means of Affymetrix arrays covering 28 869 genes. We found 211 differentially expressed genes (DEX) among which mainly genes important for oligodendrocyte differentiation and myelination were downregulated in FCD IIIa. These findings were confirmed as functionally important by Database for Annotation, Visualization, and Integrated Discovery (DAVID) analysis. The reduced expression of myelin‐associated transcripts was confirmed for FCD Ia, IIa, and IIIa by real‐time RT‐qPCR. In addition, we found that the density of myelin basic protein mRNA‐expressing oligodendrocytes and of 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase‐positive myelin fibers was significantly reduced in dysplastic cortex. Moreover, high‐resolution confocal imaging and 3D reconstruction revealed that the myelin fiber network was severely disorganized in dysplastic neocortex, indicating a disturbance of myelin sheath formation and maintenance in FCD.

Dark chocolate attenuates intracellular pro-inflammatory reactivity to acute psychosocial stress in men: A randomized controlled trial

Flavanol-rich dark chocolate consumption relates to lower risk of cardiovascular mortality, but underlying mechanisms are elusive. We investigated the effect of acute dark chocolate consumption on inflammatory measures before and after stress. Healthy men, aged 20-50years, were randomly assigned to a single intake of either 50g of flavanol-rich dark chocolate (n=31) or 50g of optically identical flavanol-free placebo-chocolate (n=34). Two hours after chocolate intake, both groups underwent the 15-min Trier Social Stress Test. We measured DNA-binding-activity of the pro-inflammatory transcription factor NF-κB (NF-κB-BA) in peripheral blood mononuclear cells, as well as plasma and whole blood mRNA levels of the pro-inflammatory cytokines IL-1β and IL-6, and the anti-inflammatory cytokine IL-10, prior to chocolate intake as well as before and several times after stress. We also repeatedly measured the flavanol epicatechin and the stress hormones epinephrine and cortisol in plasma and saliva, respectively. Compared to the placebo-chocolate-group, the dark-chocolate-group revealed a marginal increase in IL-10 mRNA prior to stress (p=0.065), and a significantly blunted stress reactivity of NF-κB-BA, IL-1β mRNA, and IL-6 mRNA (ps⩽0.036) with higher epicatechin levels relating to lower pro-inflammatory stress reactivity (ps⩽0.033). Stress hormone changes to stress were controlled. None of the other measures showed a significant chocolate effect (ps⩾0.19). Our findings indicate that acute flavanol-rich dark chocolate exerts anti-inflammatory effects both by increasing mRNA expression of the anti-inflammatory cytokine IL-10 and by attenuating the intracellular pro-inflammatory stress response. This mechanism may add to beneficial effects of dark chocolate on cardiovascular health.