Dopamine-related deficit in reward learning after catecholamine depletion in unmedicated, remitted subjects with bulimia nervosa

Disturbances in reward processing have been implicated in bulimia nervosa (BN). Abnormalities in processing reward-related stimuli might be linked to dysfunctions of the catecholaminergic neurotransmitter system, but findings have been inconclusive. A powerful way to investigate the relationship between catecholaminergic function and behavior is to examine behavioral changes in response to experimental catecholamine depletion (CD). The purpose of this study was to uncover putative catecholaminergic dysfunction in remitted subjects with BN who performed a reinforcement-learning task after CD. CD was achieved by oral alpha-methyl-para-tyrosine (AMPT) in 19 unmedicated female subjects with remitted BN (rBN) and 28 demographically matched healthy female controls (HC). Sham depletion administered identical capsules containing diphenhydramine. The study design consisted of a randomized, double-blind, placebo-controlled crossover, single-site experimental trial. The main outcome measures were reward learning in a probabilistic reward task analyzed using signal-detection theory. Secondary outcome measures included self-report assessments, including the Eating Disorder Examination-Questionnaire. Relative to healthy controls, rBN subjects were characterized by blunted reward learning in the AMPT-but not in placebo-condition. Highlighting the specificity of these findings, groups did not differ in their ability to perceptually distinguish between stimuli. Increased CD-induced anhedonic (but not eating disorder) symptoms were associated with a reduced response bias toward a more frequently rewarded stimulus. In conclusion, under CD, rBN subjects showed reduced reward learning compared with healthy control subjects. These deficits uncover disturbance of the central reward processing systems in rBN related to altered brain catecholamine levels, which might reflect a trait-like deficit increasing vulnerability to BN.

Two new rapid SNP-typing methods for classifying Mycobacterium tuberculosis complex into the main phylogenetic lineages

There is increasing evidence that strain variation in Mycobacterium tuberculosis complex (MTBC) might influence the outcome of tuberculosis infection and disease. To assess genotype-phenotype associations, phylogenetically robust molecular markers and appropriate genotyping tools are required. Most current genotyping methods for MTBC are based on mobile or repetitive DNA elements. Because these elements are prone to convergent evolution, the corresponding genotyping techniques are suboptimal for phylogenetic studies and strain classification. By contrast, single nucleotide polymorphisms (SNP) are ideal markers for classifying MTBC into phylogenetic lineages, as they exhibit very low degrees of homoplasy. In this study, we developed two complementary SNP-based genotyping methods to classify strains into the six main human-associated lineages of MTBC, the "Beijing" sublineage, and the clade comprising Mycobacterium bovis and Mycobacterium caprae. Phylogenetically informative SNPs were obtained from 22 MTBC whole-genome sequences. The first assay, referred to as MOL-PCR, is a ligation-dependent PCR with signal detection by fluorescent microspheres and a Luminex flow cytometer, which simultaneously interrogates eight SNPs. The second assay is based on six individual TaqMan real-time PCR assays for singleplex SNP-typing. We compared MOL-PCR and TaqMan results in two panels of clinical MTBC isolates. Both methods agreed fully when assigning 36 well-characterized strains into the main phylogenetic lineages. The sensitivity in allele-calling was 98.6% and 98.8% for MOL-PCR and TaqMan, respectively. Typing of an additional panel of 78 unknown clinical isolates revealed 99.2% and 100% sensitivity in allele-calling, respectively, and 100% agreement in lineage assignment between both methods. While MOL-PCR and TaqMan are both highly sensitive and specific, MOL-PCR is ideal for classification of isolates with no previous information, whereas TaqMan is faster for confirmation. Furthermore, both methods are rapid, flexible and comparably inexpensive.

Training in hypoxia and its effects on skeletal muscle tissue

It is well established that local muscle tissue hypoxia is an important consequence and possibly a relevant adaptive signal of endurance exercise training in humans. It has been reasoned that it might be advantageous to increase this exercise stimulus by working in hypoxia. However, as long-term exposure to severe hypoxia has been shown to be detrimental to muscle tissue, experimental protocols were developed that expose subjects to hypoxia only for the duration of the exercise session and allow recovery in normoxia (live low-train high or hypoxic training). This overview reports data from 27 controlled studies using some implementation of hypoxic training paradigms. Hypoxia exposure varied between 2300 and 5700 m and training duration ranged from 10 days to 8 weeks. A similar number of studies was carried out on untrained and on trained subjects. Muscle structural, biochemical and molecular findings point to a specific role of hypoxia in endurance training. However, based on the available data on global estimates of performance capacity such as maximal oxygen uptake (VO2max) and maximal power output (Pmax), hypoxia as a supplement to training is not consistently found to be of advantage for performance at sea level. There is some evidence mainly from studies on untrained subjects for an advantage of hypoxic training for performance at altitude. Live low-train high may be considered when altitude acclimatization is not an option.

Associative processing and paranormal belief

In the present study we introduce a novel task for the quantitative assessment of both originality and speed of individual associations. This 'BAG' (Bridge-the-Associative-Gap) task was used to investigate the relationships between creativity and paranormal belief. Twelve strong 'believers' and 12 strong 'skeptics' in paranormal phenomena were selected from a large student population (n > 350). Subjects were asked to produce single-word associations to word pairs. In 40 trials the two stimulus words were semantically indirectly related and in 40 other trials the words were semantically unrelated. Separately for these two stimulus types, response commonalities and association latencies were calculated. The main finding was that for unrelated stimuli, believers produced associations that were more original (had a lower frequency of occurrence in the group as a whole) than those of the skeptics. For the interpretation of the result we propose a model of association behavior that captures both 'positive' psychological aspects (i.e., verbal creativity) and 'negative' aspects (susceptibility to unfounded inferences), and outline its relevance for psychiatry. This model suggests that believers adopt a looser response criterion than skeptics when confronted with 'semantic noise'. Such a signal detection view of the presence/absence of judgments for loose semantic relations may help to elucidate the commonalities between creative thinking, paranormal belief and delusional ideation.

School-age children show a bias toward fantasy classifications after playing a platform game

We investigated the influence of playing a video game on children’s ability to distinguish between fantasy and reality. School-age children played a platform game for 15 min and then performed a fantasy/reality distinction task in which they were to judge whether images (from the platform game and from other games) were fantasy images or reality images. Unlike those in the control group (who played a memory game), the children in the experimental group showed a response bias toward mistakenly classifying reality images from the video game as fantasy images (as determined by means of an analysis based on signal detection theory). We conclude that playing the video game exerted a short-term influence on children’s ability to distinguish between fantasy and reality.

Using an adaptive autoregressive model for the early detection of action potential duration alternans

Cardiostim 2012, Nice, France

Rapid parallel adaptive radiations from a single hybridogenic ancestral population

The Alpine lake whitefish (Coregonus lavaretus) species complex is a classic example of a recent radiation, associated with colonization of the Alpine lakes following the glacial retreat (less than 15 kyr BP). They have formed a unique array of endemic lake flocks, each with one to six described sympatric species differing in morphology, diet and reproductive ecology. Here, we present a genomic investigation of the relationships between and within the lake flocks. Comparing the signal between over 1000 AFLP loci and mitochondrial control region sequence data, we use phylogenetic tree-based and population genetic methods to reconstruct the phylogenetic history of the group and to delineate the principal centres of genetic diversity within the radiation. We find significant cytonuclear discordance showing that the genomically monophyletic Alpine whitefish clade arose from a hybrid swarm of at least two glacial refugial lineages. Within this radiation, we find seven extant genetic clusters centred on seven lake systems. Most interestingly, we find evidence of sympatric speciation within and parallel evolution of equivalent phenotypes among these lake systems. However, we also find the genetic signature of human-mediated gene flow and diversity loss within many lakes, highlighting the fragility of recent radiations.

Evidence of neutral and adaptive genetic divergence between European trout populations sampled along altitudinal gradients

Species with a wide geographical distribution are often composed of distinct subgroups which may be adapted to their local environment. European trout (Salmo trutta species complex) provide an example of such a complex consisting of several genetically and ecologically distinct forms. However, trout populations are strongly influenced by human activities, and it is unclear to what extent neutral and adaptive genetic differences have persisted. We sampled 30 Swiss trout populations from heterogeneous environments along replicated altitudinal gradients in three major European drainages. More than 850 individuals were genotyped at 18 microsatellite loci which included loci diagnostic for evolutionary lineages and candidate markers associated with temperature tolerance, reproductive timing and immune defence. We find that the phylogeographic structure of Swiss trout populations has not been completely erased by stocking. Distinct genetic clusters corresponding to the different drainages could be identified, although nonindigenous alleles were clearly present, especially in the two Mediterranean drainages. We also still detected neutral genetic differentiation within rivers which was often associated with the geographical distance between populations. Five loci showed evidence of divergent selection between populations with several drainage-specific patterns. Lineage-diagnostic markers, a marker linked to a quantitative trait locus for upper temperature tolerance in other salmonids and a marker linked to the major histocompatibility class I gene were implicated in local adaptation and some patterns were associated with altitude. In contrast, tentative evidence suggests a signal of balancing selection at a second immune relevant gene (TAP2). Our results confirm the persistence of both neutral and potentially adaptive genetic differences between trout populations in the face of massive human-mediated dispersal.

Head to head comparison of optical coherence tomography, intravascular ultrasound echogenicity and virtual histology for the detection of changes in polymeric struts over time: insights from the ABSORB trial

To analyse and to compare the changes in the various optical coherence tomography (OCT), echogenicity and intravascular ultrasound virtual histology (VH) of the everolimus-eluting bioresorbable scaffold (ABSORB) degradation parameters during the first 12 months after ABSORB implantation. In the ABSORB study, changes in the appearance of the ABSORB scaffold were monitored over time using various intracoronary imaging modalities. The scaffold struts exhibited a progressive change in their black core area by OCT, in their ultrasound derived grey level intensity quantified by echogenicity, and in their backscattering ultrasound signal, identified as "pseudo dense-calcium" (DC) by VH.

Influence of the condition of the adjacent tooth surface on fluorescence measurements for the detection of approximal caries

The aim of this study was to test whether the status of the adjacent tooth surface has an influence on the signal of a new laser fluorescence (LF) device for the detection of approximal caries. Seventy-eight teeth were selected from a pool of extracted permanent human molars, frozen at -20 degrees C until use. Before being measured the teeth were defrosted, cleaned, and any calculus removed. As a control, a defined approximal surface of each tooth was measured with the LF device holding the tip with the detecting- and the reverse-side on it, but without a neighboring tooth contacting the surface. The proximal site under examination was then placed adjacent to a tooth, which had deep dentinal caries, a composite restoration, a provisional ZnO-Eugenol restoration, or a ceramic restoration. The adjacent tooth with the ZnO-Eugenol restoration, the composite restoration, and the dentinal caries all demonstrated a statistically significant increase of LF readings on sound tooth surfaces. Teeth with enamel or dentinal caries were only slightly (and not statistically significantly) influenced by the different types of neighboring surfaces compared with the control LF readings. It can be concluded that caries detection of approximal tooth surfaces with the new LF system might be influenced by the condition of the adjacent tooth surface.

Dissociated lateralization of transient and sustained blood oxygen level-dependent signal components in human primary auditory cortex

Among other auditory operations, the analysis of different sound levels received at both ears is fundamental for the localization of a sound source. These so-called interaural level differences, in animals, are coded by excitatory-inhibitory neurons yielding asymmetric hemispheric activity patterns with acoustic stimuli having maximal interaural level differences. In human auditory cortex, the temporal blood oxygen level-dependent (BOLD) response to auditory inputs, as measured by functional magnetic resonance imaging (fMRI), consists of at least two independent components: an initial transient and a subsequent sustained signal, which, on a different time scale, are consistent with electrophysiological human and animal response patterns. However, their specific functional role remains unclear. Animal studies suggest these temporal components being based on different neural networks and having specific roles in representing the external acoustic environment. Here we hypothesized that the transient and sustained response constituents are differentially involved in coding interaural level differences and therefore play different roles in spatial information processing. Healthy subjects underwent monaural and binaural acoustic stimulation and BOLD responses were measured using high signal-to-noise-ratio fMRI. In the anatomically segmented Heschl's gyrus the transient response was bilaterally balanced, independent of the side of stimulation, while in opposite the sustained response was contralateralized. This dissociation suggests a differential role at these two independent temporal response components, with an initial bilateral transient signal subserving rapid sound detection and a subsequent lateralized sustained signal subserving detailed sound characterization.

BOLD correlates of edge detection in human auditory cortex

Edges are important cues defining coherent auditory objects. As a model of auditory edges, sound on- and offset are particularly suitable to study their neural underpinnings because they contrast a specific physical input against no physical input. Change from silence to sound, that is onset, has extensively been studied and elicits transient neural responses bilaterally in auditory cortex. However, neural activity associated with sound onset is not only related to edge detection but also to novel afferent inputs. Edges at the change from sound to silence, that is offset, are not confounded by novel physical input and thus allow to examine neural activity associated with sound edges per se. In the first experiment, we used silent acquisition functional magnetic resonance imaging and found that the offset of pulsed sound activates planum temporale, superior temporal sulcus and planum polare of the right hemisphere. In the planum temporale and the superior temporal sulcus, offset response amplitudes were related to the pulse repetition rate of the preceding stimulation. In the second experiment, we found that these offset-responsive regions were also activated by single sound pulses, onset of sound pulse sequences and single sound pulse omissions within sound pulse sequences. However, they were not active during sustained sound presentation. Thus, our data show that circumscribed areas in right temporal cortex are specifically involved in identifying auditory edges. This operation is crucial for translating acoustic signal time series into coherent auditory objects.

Platelet activation and signal transduction by convulxin, a C-type lectin from Crotalus durissus terrificus (tropical rattlesnake) venom via the p62/GPVI collagen receptor

Convulxin, a powerful platelet activator, was isolated from Crotalus durissus terrificus venom, and 20 amino acid N-terminal sequences of both subunits were determined. These indicated that convulxin belongs to the heterodimeric C-type lectin family. Neither antibodies against GPIb nor echicetin had any effect on convulxin-induced platelet aggregation showing that, in contrast to other venom C-type lectins acting on platelets, GPIb is not involved in convulxin-induced platelet activation. In addition, partially reduced/denatured convulxin only affects collagen-induced platelet aggregation. The mechanism of convulxin-induced platelet activation was examined by platelet aggregation, detection of time-dependent tyrosine phosphorylation of platelet proteins, and binding studies with 125I-convulxin. Convulxin induces signal transduction in part like collagen, involving the time-dependent tyrosine phosphorylation of Fc receptor gamma chain, phospholipase Cgamma2, p72(SYK), c-Cbl, and p36-38. However, unlike collagen, pp125(FAK) and some other bands are not tyrosine-phosphorylated. Convulxin binds to a glycosylated 62-kDa membrane component in platelet lysate and to p62/GPVI immunoprecipitated by human anti-p62/GPVI antibodies. Convulxin subunits inhibit both aggregation and tyrosine phosphorylation in response to collagen. Piceatannol, a tyrosine kinase inhibitor with some specificity for p72(SYK), showed differential effects on collagen and convulxin-stimulated signaling. These results suggest that convulxin uses the p62/GPVI but not the alpha2beta1 part of the collagen signaling pathways to activate platelets. Occupation and clustering of p62/GPVI may activate Src family kinases phosphorylating Fc receptor gamma chain and, by a mechanism previously described in T- and B-cells, activate p72(SYK) that is critical for downstream activation of platelets.

Automatic Reduction of Artifacts in EEG-Signals

Electroencephalograms (EEG) are often contaminated with high amplitude artifacts limiting the usability of data. Methods that reduce these artifacts are often restricted to certain types of artifacts, require manual interaction or large training data sets. Within this paper we introduce a novel method, which is able to eliminate many different types of artifacts without manual intervention. The algorithm first decomposes the signal into different sub-band signals in order to isolate different types of artifacts into specific frequency bands. After signal decomposition with principal component analysis (PCA) an adaptive threshold is applied to eliminate components with high variance corresponding to the dominant artifact activity. Our results show that the algorithm is able to significantly reduce artifacts while preserving the EEG activity. Parameters for the algorithm do not have to be identified for every patient individually making the method a good candidate for preprocessing in automatic seizure detection and prediction algorithms.