Appetitive Pavlovian conditioning is a learning mechanism of fundamental biological and pathophysiological significance. Nonetheless, its exploration in humans remains sparse, which is partly ...attributed to the lack of an established psychophysiological parameter that aptly represents conditioned responding. This study evaluated pupil diameter and other ocular response measures (gaze dwelling time, blink duration and count) as indices of conditioning. Additionally, a learning model was used to infer participants’ learning progress on the basis of their pupil dilation. Twenty‐nine healthy volunteers completed an appetitive differential delay conditioning paradigm with a primary reward, while the ocular response measures along with other psychophysiological (heart rate, electrodermal activity, postauricular and eyeblink reflex) and behavioral (ratings, contingency awareness) parameters were obtained to examine the relation among different measures. A significantly stronger increase in pupil diameter, longer gaze duration and shorter eyeblink duration was observed in response to the reward‐predicting cue compared to the control cue. The Pearce‐Hall attention model best predicted the trial‐by‐trial pupil diameter. This conditioned response was corroborated by a pronounced heart rate deceleration to the reward‐predicting cue, while no conditioning effect was observed in the electrodermal activity or startle responses. There was no discernible correlation between the psychophysiological response measures. These results highlight the potential value of ocular response measures as sensitive indices for representing appetitive conditioning.
Despite its central biological and pathophysiological significance, exploration of human appetitive Pavlovian conditioning remains sparse. This is commonly ascribed to the lack of a suitable measure that aptly reflects conditioned learning. In this study, we show that pupil diameter not only constitutes a sensitive and robust index for representing appetitive learning, but also precisely predicts individual trial‐by‐trial learning mechanisms in a Pearce‐Hall attention‐weighted learning model. Successful conditioning was confirmed by additional psychophysiological measures. These findings highlight the potential value of pupil diameter when exploring human appetitive conditioning and may help expedite research of this fundamental learning mechanism.
The research provides empirical evidence differentiating between market success and funding success in reward-based crowdfunding campaigns of video games and hypothesizes that the actual contribution ...of crowdfunding is more stemming from community support and feedback rather than funding amount. The paper uses publicly available data by combining three different sources. Project data from Kickstarter, a large crowdfunding website, in the video game category are extracted and matched with market success variables of ratings and revenues from two other public sources namely Metacritic and Steamspy. Regression results indicate that once the project is successfully funded, the funding amount does not have a significant effect on market success variables. On the other hand, the number of backers as a community support variable is a significant determinant of market success in terms of higher revenues and ratings for a project. Whether the project was successfully funded or not moderates some of the relationships. Prior literature is predominantly focused on crowdfunding success in terms of financing. Yet, this study empirically demonstrates that funding does not necessarily indicate that projects will be successful in the market and further shows the actual contribution of crowdfunding to the market success of video game projects is the community engagement, not the funding amount. This study contributes to the rapidly emerging crowdfunding literature by extending its boundaries from the crowdfunding platforms themselves to the differentiated effects of crowdfunding on market success, which has not been studied thoroughly. This paper provides a new avenue of research by suggesting not solely focusing on funding outcomes but understanding, defining and explaining the dynamics of the community aspect in crowdfunding platforms with their repercussions on market success. Future work can also highlight potential differences in these effects between product groups, as well as more holistically assess market success and capture interactions within the community on crowdfunding platforms.
To investigate the neural correlates of lucid dreaming.
Parallel EEG/fMRI recordings of night sleep.
Sleep laboratory and fMRI facilities.
Four experienced lucid dreamers.
N/A.
Out of 4 participants, ...one subject had 2 episodes of verified lucid REM sleep of sufficient length to be analyzed by fMRI. During lucid dreaming the bilateral precuneus, cuneus, parietal lobules, and prefrontal and occipito-temporal cortices activated strongly as compared with non-lucid REM sleep.
In line with recent EEG data, lucid dreaming was associated with a reactivation of areas which are normally deactivated during REM sleep. This pattern of activity can explain the recovery of reflective cognitive capabilities that are the hallmark of lucid dreaming.
In the intestine, a single layer of epithelial cells effectively separates potentially harmful luminal content from the underlying tissue. The importance of an intact mucosal layer is highlighted by ...pathological disorders of the gut such as inflammatory bowel disease, in which disruption of the epithelial barrier leads to severe inflammation of the submucosal tissue compartments. Epithelial barrier function is provided by tightly regulated intercellular junctions, which consist of a plethora of membrane‐associated and transmembrane proteins organized in discreet, spatially restricted complexes. Classically, these complexes are known to be dynamic seals for fluids and small molecules, as well as to provide mechanical strength by anchoring cell‐cell contacts to the cytoskeleton. Rather than just acting as simple gates and adapters, however, junctional complexes themselves can relay extracellular stimuli to the epithelium and initiate cellular responses such as differentiation and apoptosis. In this review, we will highlight recent studies by our group and others which discuss how junctional proteins can promote outside‐to‐inside signaling and modulate epithelial cell fate. Unraveling the complex crosstalk between epithelial cells and their intercellular junctions is essential to understanding how epithelial barrier function is maintained in vivo and might provide new strategies for the treatment of inflammatory disorders of the intestine.
The influence of unit Reynolds number (
R
e
1
=
17.5
×
10
6
–
80
×
10
6
m
-
1
), Mach number (
M
=
0.35
–0.77) and incompressible shape factor (
H
12
=
2.50
–2.66) on laminar–turbulent boundary layer ...transition was systematically investigated in the Cryogenic Ludwieg-Tube Göttingen (DNW-KRG). For this investigation the existing two-dimensional wind tunnel model,
PaLASTra
, which offers a quasi-uniform streamwise pressure gradient, was modified to reduce the size of the flow separation region at its trailing edge. The streamwise temperature distribution and the location of laminar–turbulent transition were measured by means of temperature-sensitive paint (TSP) with a higher accuracy than attained in earlier measurements. It was found that for the modified
PaLASTra
model the transition Reynolds number (
R
e
tr
) exhibits a linear dependence on the pressure gradient, characterized by
H
12
. Due to this linear relation it was possible to quantify the so-called ‘unit Reynolds number effect’, which is an increase of
R
e
tr
with
R
e
1
. By a systematic variation of
M
,
R
e
1
and
H
12
in combination with a spectral analysis of freestream disturbances, a stabilizing effect of compressibility on boundary layer transition, as predicted by linear stability theory, was detected (‘Mach number effect’). Furthermore, two expressions were derived which can be used to calculate the transition Reynolds number as a function of the amplitude of total pressure fluctuations,
R
e
1
and
H
12
. To determine critical
N
-factors, the measured transition locations were correlated with amplification rates, calculated by incompressible and compressible linear stability theory. By taking into account the spectral level of total pressure fluctuations at the frequency of the most amplified Tollmien–Schlichting wave at transition location, the scatter in the determined critical
N
-factors was reduced. Furthermore, the receptivity coefficients dependence on incidence angle of acoustic waves was used to correct the determined critical
N
-factors. Thereby, a found dependency of the determined critical
N
-factors on
H
12
decreased, leading to an average critical
N
-factor of about 9.5 with a standard deviation of
σ
≈
0.8
.
Lesion volume measurements with magnetic resonance imaging are widely used to assess outcome in rodent models of stroke. In this study, we improved a mathematical framework to correct lesion size for ...edema which is based on manual delineation of the lesion and hemispheres. Furthermore, a novel MATLAB toolbox to register mouse brain MR images to the Allen brain atlas is presented. Its capability to calculate edema-corrected lesion size was compared to the manual approach. Automated image registration performed equally well in in a mouse middle cerebral artery occlusion model (Pearson r = 0.976, p = 2.265e-11). Information encapsulated in the registration was used to generate maps of edema induced tissue volume changes. These showed discrepancies to simplified tissue models underlying the manual approach. The presented techniques provide biologically more meaningful, voxel-wise biomarkers of vasogenic edema after stroke.
Fetal growth restriction (FGR) is the most common pregnancy complication in developed countries. Pregnancies affected by FGR, frequently concur with complications and high risk of neonatal morbidity ...and mortality. To date, no approved treatment is available for pregnant women affected with FGR. The objective of this study was to investigate the contribution of galectin-3 (gal-3), a β-galactoside binding protein involved in pregnancy, placental function and fetal growth. We demonstrated that lack of gal-3 during mouse pregnancy leads to placental dysfunction and drives FGR in the absence of a maternal preeclampsia syndrome. Analysis of gal-3 deficient dams revealed placental inflammation and malperfusion, as well as uterine natural killer cell infiltration with aberrant activation. Our results also show that FGR is associated with a failure to increase maternal circulating gal-3 levels during the second and third trimester in human pregnancies. Placentas from human pregnancies affected by FGR displayed lower gal-3 expression, which correlated with placental dysfunction. These data highlight the importance of gal-3 in the promotion of proper placental function, as its absence leads to placental disease and subsequent FGR.
Chronic inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are a major health burden worldwide. Numerous conserved signaling pathways control tissue injury and repair ...during colitis, but owing to the complexity of the inflammatory process, their individual contribution remains poorly understood. A key regulatory pathway in the intestinal mucosa is Wnt/β-catenin signaling, which acts as the central organizer of epithelial stem cell identity and maintenance. Apart from this core function, there is mounting evidence that the Wnt pathway is highly interconnected with numerous other signaling cascades, and that combinatorial signaling events shape epithelial homeostasis and tissue regeneration. Here we provide an updated view of how Wnt signaling intersects with major inflammatory pathways, with a particular focus on intestinal inflammation. Elucidating the reciprocal actions of Wnt ligands and cytokines has the potential to reveal new treatment options for chronic colitis and other inflammatory disorders.
Multiple sclerosis (MS) is a chronic neuroinflammatory disease that involves both white and gray matter. Although gray matter damage is a major contributor to disability in MS patients, conventional ...clinical magnetic resonance imaging (MRI) fails to accurately detect gray matter pathology and establish a clear correlation with clinical symptoms. Using magnetic resonance elastography (MRE), we previously reported global brain softening in MS and experimental autoimmune encephalomyelitis (EAE). However, it needs to be established if changes of the spatiotemporal patterns of brain tissue mechanics constitute a marker of neuroinflammation. Here, we use advanced multifrequency MRE with tomoelastography postprocessing to investigate longitudinal and regional inflammation-induced tissue changes in EAE and in a small group of MS patients. Surprisingly, we found reversible softening in synchrony with the EAE disease course predominantly in the cortex of the mouse brain. This cortical softening was associated neither with a shift of tissue water compartments as quantified by T2-mapping and diffusion-weighted MRI, nor with leukocyte infiltration as seen by histopathology. Instead, cortical softening correlated with transient structural remodeling of perineuronal nets (PNNs), which involved abnormal chondroitin sulfate expression and microgliosis. These mechanisms also appear to be critical in humans with MS, where tomoelastography for the first time demonstrated marked cortical softening. Taken together, our study shows that neuroinflammation (i) critically affects the integrity of PNNs in cortical brain tissue, in a reversible process that correlates with disease disability in EAE, (ii) reduces the mechanical integrity of brain tissue rather than leading to water accumulation, and (iii) shows similar spatial patterns in humans and mice. These results raise the prospect of leveraging MRE and quantitative MRI for MS staging and monitoring treatment in affected patients.
Topographic non-invasive near infrared spectroscopy (NIRS) has become a well-established tool for functional brain imaging. Applying up to 100 optodes over the head of a subject, allows achieving a ...spatial resolution in the centimeter range. This resolution is poor compared to other functional imaging tools.
However, recently it was shown that diffuse optical tomography (DOT) as an extension of NIRS based on high-density (HD) probe arrays and supplemented by an advanced image reconstruction procedure allows describing activation patterns with a spatial resolution in the millimeter range. Building on these findings, we hypothesize that HD-DOT may render very focal activations accessible which would be missed by the traditionally used sparse arrays.
We examined activation patterns in the primary somatosensory cortex, since its somatotopic organization is very fine-grained. We performed a vibrotactile stimulation study of the first and fifth finger in eight human subjects, using a 900-channel continuous-wave DOT imaging system for achieving a higher resolution than conventional topographic NIRS. To compare the results to a well-established high-resolution imaging technique, the same paradigm was investigated in the same subjects by means of functional magnetic resonance imaging (fMRI).
In this work, we tested the advantage of ultrahigh-density probe arrays and show that highly focal activations would be missed by classical next-nearest neighbor NIRS approach, but also by DOT, when using a sparse probe array. Distinct activation patterns for both fingers correlated well with the expected neuroanatomy in five of eight subjects. Additionally we show that activation for different fingers is projected to different tissue depths in the DOT image. Comparison to the fMRI data yielded similar activation foci in seven out of ten finger representations in these five subjects when comparing the lateral localization of DOT and fMRI results.
► Ultrahigh-density DOT can resolve cortical activation in the millimeter range. ► Highly focal activations can be missed by classical NIRS and conventional DOT. ► Ultrahigh-density DOT and fMRI have comparable acces to cortical activation.
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