The common truncation variant in pancreatic lipase related protein 2 (PNLIPRP2) is expressed poorly and does not alter risk for chronic pancreatitis

A nonsense variant (p.W358X) of human pancreatic lipase related protein 2 (PNLIPRP2) is present in different ethnic populations with a high allele frequency. In cell culture experiments, the truncated protein mainly accumulates inside the cells and causes endoplasmic reticulum stress. Here, we tested the hypothesis that variant p.W358X might increase risk for chronic pancreatitis through acinar cell stress. We sequenced exon 11 of PNLIPRP2 in a cohort of 256 subjects with chronic pancreatitis (152 alcoholic and 104 non-alcoholic) and 200 controls of Hungarian origin. We observed no significant difference in the distribution of the truncation variant between patients and controls. We analyzed mRNA expression in human pancreatic cDNA samples and found the variant allele markedly reduced. We conclude that the p.W358X truncation variant of PNLIPRP2 is expressed poorly and has no significant effect on the risk of chronic pancreatitis

Tracking the implicit acquisition of nonadjacent transitional probabilities by ERPs

The implicit acquisition of complex probabilistic regularities has been found to be crucial in numerous automatized cognitive abilities, including language processing and associative learning. However, the neurocognitive processes supporting the implicit extraction of 2nd order non-adjacent transitional probabilities have not been completely elucidated. Therefore, this study investigated the sensitivity of event-related brain potentials (ERPs) to these probabilistic regularities embedded in a sequence of visual stimuli without providing explicit information on the structure of the stimulus stream. Healthy young adults (N = 32) performed a perceptual-motor RT task that included an alternating sequential regularity between non-adjacent trials while RTs and ERPs were measured time-locked to the onset of the stimulus. RT effects indicated the rapid acquisition of transitional probabilities. The acquisition process was also tracked by the P3 component. Modulations of the P3 amplitude indicated that the more probable short-range relations could be integrated in the internal representations formed on the experienced stimulus environment. Meanwhile, the less probable short-range relations delivered possibly surprising information over the course of the task, by which the internal representations could have been updated. These results suggest that representations on the probabilistic regularities of the ongoing stimulus context are implicitly formed and constantly revised. Overall, this study (1) highlights the role of predictive processes during implicit memory formation, and (2) delineates a potential to gain further insight into the dynamics of implicit acquisition processes

Effects of plasma transfusion on hepcidin production in human congenital hypotransferrinemia

Hepcidin is the key regulator of systemic iron homeostasis. We describe the modulation of hepcidin production induced by plasma transfusions in a patient with congenital hypotransferrinemia that offers a unique model in which to study the mechanism of hepcidin regulation by iron and erythropoiesis. Urinary hepcidin increased from zero at baseline, when hemoglobin and serum transferrin was low, to a maximum of 98 ng/mg creatinine on day 60, and subsequently decreased. Time-course of urinary hepcidin and serum transferrin concentration suggests that hepcidin production is regulated by the combination of marrow iron requirements and iron supply by transferrin

Error processing during the online retrieval of probabilistic sequence knowledge

Adaptive behavior involves rapid error processing and action evaluation. However, it has not been clarified how errors contribute to automatic behaviors that can be retrieved to successfully adapt to our complex environment. Automatic behaviors strongly rely on the process of probabilistic sequence learning and memory. Therefore, the present study investigated error processing during the online retrieval of probabilistic sequence knowledge. Twenty-four healthy young adults acquired and continuously retrieved a repeating stimulus sequence reflected by reaction time (RT) changes on a rapid forced-choice RT task. Performance was compared with a baseline that denoted the processing of random stimuli embedded in the probabilistic sequence. At the neurophysiological level, event-related brain potentials synchronized to responses were measured. Error processing was tracked by the error negativity (Ne) and the error positivity (Pe). The mean amplitude of the Ne gradually decreased as the task progressed, similarly for the sequence retrieval and the embedded baseline process. The mean amplitude of the Pe increased over time, likewise, irrespective of the type of the stimuli. Accordingly, we propose that automatic error detection (Ne) and conscious error evaluation (Pe) are not sensitive to sequence learning and retrieval. Overall, the present study provides insight into how error processing takes place for the retrieval of sequence knowledge in a probabilistic environment

Procedural learning in Tourette syndrome, ADHD, and comorbid Tourette-ADHD: Evidence from a probabilistic sequence learning task

Procedural memory, which is rooted in the basal ganglia, plays an important role in the implicit learning of motor and cognitive skills. Few studies have examined procedural learning in either Tourette syndrome (TS) or Attention Deficit Hyperactivity Disorder (ADHD), despite basal ganglia abnormalities in both of these neurodevelopmental disorders. We aimed to assess procedural learning in children with TS (n = 13), ADHD (n = 22), and comorbid TS-ADHD (n = 20), as well as in typically developing children (n = 21). Procedural learning was measured with a well-studied implicit probabilistic sequence learning task, the alternating serial reaction time task. All four groups showed evidence of sequence learning, and moreover did not differ from each other in sequence learning. This result, from the first study to examine procedural memory across TS, ADHD and comorbid TS-ADHD, is consistent with previous findings of intact procedural learning of sequences in both TS and ADHD. In contrast, some studies have found impaired procedural learning of non-sequential probabilistic categories in TS. This suggests that sequence learning may be spared in TS and ADHD, while at least some other forms of learning in procedural memory are impaired, at least in TS. Our findings indicate that disorders associated with basal ganglia abnormalities do not necessarily show procedural learning deficits, and provide a possible path for more effective diagnostic tools, and educational and training programs

Preparing for College and Graduate School

We know of no single programs that prepare students both for success in college and entry to graduate school. Here we will describe a 5- week summer program that attempts to do that.This 5- week summer program helps students with Math, Writing and gives them access to information on graduate schools and research as a career. We recruit primarily underrepresented or economically disadvantaged (Pell eligible) entering freshmen science students (likely science majors) using a rigorous application form that includes high school transcripts, letter of recommendation and an essay. For success in improving academic skills, motivation is key. That’s why we carefully and rigorously evaluate all candidates for this program. And that’s why we can claim some success.For science majors, Math is critical. So let’s begin with describing our Math program, which runs 3 days a week, for 5 weeks, all day, usually Mon, Tues and Fri

ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA): a multi-centre prospective cohort study protocol

Attention deficit hyperactivity disorder; Digital phenotyping; Remote monitoringTrastorno por déficit de atención con hiperactividad; Fenotipado digital; Monitoreo remotoTranstorn per dèficit d'atenció amb hiperactivitat; Fenotipat digital; Monitorització remotaBackground Emerging evidence points at substantial comorbidity between adult attention deficit hyperactivity disorder (ADHD) and cardiometabolic diseases, but our understanding of the comorbidity and how to manage cardiometabolic disease in adults with ADHD is limited. The ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA) project uses remote measurement technology to obtain real-world data from daily life to assess the extent to which ADHD medication treatment and physical activity, individually and jointly, may influence cardiometabolic risks in adults with ADHD. Our second main aim is to obtain valuable real-world data on adherence to pharmacological treatment and its predictors and correlates during daily life from adults with ADHD. Methods ART-CARMA is a multi-site prospective cohort study within the EU-funded collaboration ‘TIMESPAN’ (Management of chronic cardiometabolic disease and treatment discontinuity in adult ADHD patients) that will recruit 300 adults from adult ADHD waiting lists. The participants will be monitored remotely over a period of 12 months that starts from pre-treatment initiation. Passive monitoring, which involves the participants wearing a wrist-worn device (EmbracePlus) and downloading the RADAR-base Passive App and the Empatica Care App on their smartphone, provides ongoing data collection on a wide range of variables, such as physical activity, sleep, pulse rate (PR) and pulse rate variability (PRV), systolic peaks, electrodermal activity (EDA), oxygen saturation (SpO2), peripheral temperature, smartphone usage including social connectivity, and the environment (e.g. ambient noise, light levels, relative location). By combining data across these variables measured, processes such as physical activity, sleep, autonomic arousal, and indicators of cardiovascular health can be captured. Active remote monitoring involves the participant completing tasks using a smartphone app (such as completing clinical questionnaires or speech tasks), measuring their blood pressure and weight, or using a PC/laptop (cognitive tasks). The ART system is built on the RADAR-base mobile-health platform. Discussion The long-term goal is to use these data to improve the management of cardiometabolic disease in adults with ADHD, and to improve ADHD medication treatment adherence and the personalisation of treatment.The ART-CARMA study has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 965381. This communication reflects the views of the authors, and the European Commission is not responsible for any use that may be made of the information it contains. HD is supported by the UK Medical Research Council (MR/N013700/1) and King’s College London member of the MRC Doctoral Training Partnership in Biomedical Sciences

Right hemisphere advantage in statistical learning: evidence from a probabilistic sequence learning task

Picking up statistical regularities of patterns from the environment is essential for predictive and adaptive behavior. One of the most important challenges is to understand how statistical learning occurs and how the acquired information consolidates and stabilizes in the brain. Evidence suggests that the prefrontal cortex (PFC) has a critical role in these processes; the division of labor between hemispheres, however, is less characterized. The aim of the present study was to directly investigate the causal role of the right and left PFC in statistical learning and its consolidation. Healthy, young adults were trained on a probabilistic sequence learning task. Anodal transcranial direct current stimulation (tDCS) over the right or left dorsolateral PFC (DLPFC) was applied during the training in order to modify learning-related cortical plasticity in the targeted brain regions by increasing neural excitability. Performance was tested during and immediately after the stimulation, 2-hour and 24-hour later. We found that the anodal tDCS over the right DLPFC led to enhanced learning performance both after the 2-hour and 24-hour retention periods, suggesting the causal role of this area in statistical learning. In contrast, we did not find any effect of left DLPFC stimulation on learning. These results highlight the role of the right fronto-striatal network in statistical learning and its consolidation

Statistical characteristics of finger-tapping data in Huntington’s disease

Measuring the rate of finger tapping is a technique commonly used as an indicator of impairment in degenerative neurological conditions, such as Huntington’s disease. The information it provides can be greatly enhanced by analysing not simply the overall tapping rate, but also the statistical characteristics of the individual times between each successive response. Recent technological improvements in the recording equipment allow the responses to be analysed extremely quickly, and permit modification of the task in the interest of greater clinical specificity. Here we illustrate its use with some pilot data from a group of manifest HD patients and age-matched controls. Even in this small cohort, differences in the responses are apparent that appear to relate to the severity of the disease as measured by conventional behavioural tests

Perceiving structure in unstructured stimuli: implicitly acquired prior knowledge impacts the processing of unpredictable transitional probabilities

It is unclear how implicit prior knowledge is involved and remains persistent in the extraction of the statistical structure underlying sensory input. Therefore, this study investigated whether the implicit knowledge of second-order transitional probabilities characterizing a stream of visual stimuli impacts the processing of unpredictable transitional probabilities embedded in a similar input stream. Young adults (N = 50) performed a four-choice reaction time (RT) task that consisted of structured and unstructured blocks. In the structured blocks, more probable and less probable short-range nonadjacent transitional probabilities were present. In the unstructured blocks, the unique combinations of the short-range transitional probabilities occurred with equal probability; therefore, they were unpredictable. All task blocks were visually identical at the surface level. While one-half of the participants completed the structured blocks first followed by the unstructured blocks, this was reversed in the other half of them. The change in the structure was not explicitly denoted, and no feedback was provided on the correctness of each response. Participants completing the structured blocks first showed faster RTs to more probable than to less probable short-range transitional probabilities in both the structured and unstructured blocks, indicating the persistent effect of prior knowledge. However, after extended exposure to the unstructured blocks, they updated this prior knowledge. Participants completing the unstructured blocks first showed the RT difference only in the structured blocks, which was not constrained by the preceding exposure to unpredictable stimuli. The results altogether suggest that implicitly acquired prior knowledge of predictable stimuli influences the processing of subsequent unpredictable stimuli. Updating this prior knowledge seems to require a longer stretch of time than its initial acquisition