Depending on feedback timing, the neural structures involved in learning differ, with the dopamine system including the dorsal striatum and anterior cingulate cortex (ACC) being more important for ...learning from immediate than delayed feedback. As stress has been shown to promote striatum‐dependent learning, the current study aimed to explore if stress differentially affects learning from and processing of immediate and delayed feedback. One group of male participants was stressed using the socially evaluated cold pressor test, and another group underwent a control condition. Subsequently, participants performed a reward learning task with immediate (500 ms) and delayed (6,500 ms) feedback while brain activity was assessed with electroencephalography (EEG). While stress enhanced the accuracy for delayed relative to immediate feedback, it reduced the feedback‐related negativity (FRN) valence effect, which is the amplitude difference between negative and positive feedback. For the P300, a reduced valence effect was found in the stress group only for delayed feedback. Frontal theta power was most pronounced for immediate negative feedback and was generally reduced under stress. Moreover, stress reduced associations of FRN and theta power with trial‐by‐trial accuracy. Associations between stress‐induced cortisol increases and EEG components were examined using linear mixed effects analyses, which showed that the described stress effects were accompanied by associations between the stress‐induced cortisol increases and feedback processing. The results indicate that stress and cortisol affect different aspects of feedback processing. Instead of an increased recruitment of the dopamine system and the ACC, the results may suggest enhanced salience processing and reduced cognitive control under stress.
Stress influences the processing of and learning from feedback. Here, we demonstrate that stress‐induced reductions of frontal theta power, feedback‐related negativity (FRN), and P300 depend on feedback timing. Moreover, we reveal stress‐induced reductions of associations between theta and FRN with accuracy on the single‐trial level and show that stress effects on feedback processing are associated with cortisol increases. Our findings provide novel insights into stress effects on neural feedback processing and their dependency on feedback timing.
In the present study we introduce a sensitive video-based test for the evaluation of subtle mindreading difficulties: the Movie for the Assessment of Social Cognition (MASC). This new mindreading ...tool involves watching a short film and answering questions referring to the actors' mental states. A group of adults with Asperger syndrome (n = 19) and well-matched control subjects (n = 20) were administered the MASC and three other mindreading tools as part of a broader neuropsychological testing session. Compared to control subjects, Asperger individuals exhibited marked and selective difficulties in social cognition. A Receiver Operating Characteristic (ROC) analysis for the mindreading tests identified the MASC as discriminating the diagnostic groups most accurately. Issues pertaining to the multidimensionality of the social cognition construct are discussed.
Transcending human‐defined political and administrative boundaries, the world’s transboundary freshwater resources pose particularly challenging management problems. Water resource users at all ...scales frequently find themselves in direct competition for this economic and life‐sustaining resource, in turn creating tensions, and indeed conflict, over water supply, allocation, and quality. At the international scale, where the potential for conflict is of particular concern, significant efforts are underway to promote greater cooperation in the world’s international river basins, with notable achievements in the past decade following the Dublin and Rio conferences. Over the past ten years, the international community has adopted conventions, declarations, and legal statements concerning the management of international waters, while basin communities have established numerous new basin institutions. Despite these developments, significant vulnerabilities remain. Many international basins still lack any type of joint management structure, and certain fundamental management components are noticeably absent from those that do. An understanding of these weaknesses, however, offers an opportunity for both the international and basin communities to better respond to the specific institution‐building needs of basin communities and thereby foster broader cooperation over the world’s international water resources.
Induction chemotherapy and concurrent chemoradiation for responders or immediate surgery for non-responders is an effective treatment strategy head and neck squamous cell carcinoma (HNSCC) of the ...larynx and oropharynx. Biomarkers that predict outcome would be valuable in selecting patients for therapy. In this study, the presence and titer of high risk human papilloma virus (HPV) and expression of epidermal growth factor receptor (EGFR) in pre-treatment biopsies, as well as smoking and gender were examined in oropharynx cancer patients enrolled in an organ sparing trial. HPV16 copy number was positively associated with response to therapy and with overall and disease specific survival, whereas EGFR expression, current or former smoking behavior, and female gender (in this cohort) were associated with poor response and poor survival in multivariate analysis. Smoking cessation and strategies to target EGFR may be useful adjuncts for therapy to improve outcome in the cases with the poorest biomarker profile.
Extinction learning, which creates new safety associations, is thought to be the mechanism underlying exposure therapy, commonly used for the treatment of anxiety disorders and posttraumatic stress ...disorder. The relative strength and availability for retrieval of both the fear and safety memories determine the response in a given situation. While the fear memory is often context-independent and may easily generalize, extinction memory is highly context-specific. “Renewal” of the extinguished fear memory might thus occur following a shift in context. The aim of the current work was to create an enhanced and generalized extinction memory to a discrete stimulus using stress exposure before extinction learning, thereby preventing renewal. In our contextual fear conditioning paradigm, 40 healthy men acquired (Day 1), retrieved and extinguished (Day 2) the fear memories, with no differences between the stress and the control group. A significant difference between the groups emerged in the renewal test (Day 3). A renewal effect was seen in the control group (N = 20), confirming the context-dependency of the extinction memory. In contrast, the stress group (N = 20) showed no renewal effect. Fear reduction was generalized to the acquisition context as well, suggesting that stress rendered the extinction memory more context-independent. These results are in line with previous studies that showed contextualization disruption as a result of pre-learning stress, mediated by the rapid effects of glucocorticoids on the hippocampus. Our findings support research investigating the use of glucocorticoids or stress induction in exposure therapy and suggest the right timing of administration in order to optimize their effects.
•Previous studies show that pre-learning stress disrupts memory contextualization•We tested whether this effect can reduce context-dependency of extinction memories•For this aim we investigated the effects of preextinction stress on fear renewal•In line with the hypothesis stress abolished fear renewal•Findings support the use of glucocorticoids or stress induction in exposure therapy
This paper introduces a new, unsupervised method for sorting and tracking the action potentials of individual neurons in multiunit extracellular recordings. Presuming the data are divided into short, ...sequential recording intervals, the core of our strategy relies upon an extension of a traditional mixture model approach that incorporates clustering results from the preceding interval in a Bayesian manner, while still allowing for signal nonstationarity and changing numbers of recorded neurons. As a natural byproduct of the sorting method, current and prior signal clusters can be matched over time in order to track persisting neurons. We also develop techniques to use prior data to appropriately seed the clustering algorithm and select the model class. We present results in a principal components space; however, the algorithm may be applied in any feature space where the distribution of a neuron's spikes may be modeled as Gaussian. Applications of this signal classification method to recordings from macaque parietal cortex show that it provides significantly more consistent clustering and tracking results than traditional methods based on expectation-maximization optimization of mixture models. This consistent tracking ability is crucial for intended applications of the method.
Autosomal dominant tubulointerstitial kidney disease (ADTKD) refers to a group of disorders with a bland urinary sediment, slowly progressive chronic kidney disease (CKD), and autosomal dominant ...inheritance. Due to advances in genetic diagnosis, ADTKD is becoming increasingly recognized as a cause of CKD in both children and adults. ADTKD-
REN
presents in childhood with mild hypotension, CKD, hyperkalemia, acidosis, and anemia. ADTKD-
UMOD
is associated with gout and CKD that may present in adolescence and slowly progresses to kidney failure.
HNF1β
mutations often present in childhood with anatomic abnormalities such as multicystic or dysplastic kidneys, as well as CKD and a number of other extra-kidney manifestations. ADTKD-
MUC1
is less common in childhood, and progressive CKD is its sole clinical manifestation, usually beginning in the late teenage years. This review describes the pathophysiology, genetics, clinical characteristics, diagnosis, and treatment of the different forms of ADTKD, with an emphasis on diagnosis. We also present data on kidney function in children with ADTKD from the Wake Forest Rare Inherited Kidney Disease Registry.
Diet is associated with cancer prognosis, including head and neck cancer (HNC), and has been hypothesized to influence epigenetic state by determining the availability of functional groups involved ...in the modification of DNA and histone proteins. The goal of this study was to describe the association between pretreatment diet and HNC tumor DNA methylation. Information on usual pretreatment food and nutrient intake was estimated via food frequency questionnaire (FFQ) on 49 HNC cases. Tumor DNA methylation patterns were assessed using the Illumina Goldengate Methylation Cancer Panel. First, a methylation score, the sum of individual hypermethylated tumor suppressor associated CpG sites, was calculated and associated with dietary intake of micronutrients involved in one-carbon metabolism and antioxidant activity, and food groups abundant in these nutrients. Second, gene specific analyses using linear modeling with empirical Bayesian variance estimation were conducted to identify if methylation at individual CpG sites was associated with diet. All models were controlled for age, sex, smoking, alcohol and HPV status. Individuals reporting in the highest quartile of folate, vitamin B12 and vitamin A intake, compared with those in the lowest quartile, showed significantly less tumor suppressor gene methylation, as did patients reporting the highest cruciferous vegetable intake. Gene specific analyses identified differential associations between DNA methylation and vitamin B12 and vitamin A intake when stratifying by HPV status. These preliminary results suggest that intake of folate, vitamin A and vitamin B12 may be associated with the tumor DNA methylation profile in HNC and enhance tumor suppression.
The Trier Social Stress Test (TSST) is a well-established laboratory stressor leading to a robust activation of the hypothalamus-pituitary-adrenal (HPA) axis. Existing control conditions are often ...not adequate to investigate participants' behavior during the situation as participants are often left alone in the room. This present study aimed to evaluate a friendly version of the TSST as control condition, the friendly-TSST (f-TSST). We expected that the f-TSST would not activate the HPA axis or increase the negative affect (NA). Forty-eight healthy male and female students (24 males) aged between 18 and 30 years were randomly exposed to either the TSST or the f-TSST. The latter features a similar structure and similar cognitive demands as in the TSST, and a social interaction with a committee. The main difference lies in the friendly and warm behavior of the committee opposed to the neutral and reserved behavior in the TSST, typically inducing social-evaluative threat. Salivary cortisol, salivary α-amylase (sAA), and affect were measured to evaluate the stress response to the respective procedure. As expected, the f-TSST neither activated the HPA axis nor increased the NA. The TSST by contrast led to an increase in both measures. A comparable and significant increase in the sAA-concentrations occurred in both conditions. The f-TSST could be useful as a standardized control condition for future stress studies. On a conceptual level our data indicate that mere social performance in the absence of social-evaluative threat and performance pressure does not activate the HPA axis.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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