On the Influence of Reward on Action-Effect Binding

Ideomotor theory states that the formation of anticipatory representations about the perceptual consequences of an action [i.e., action-effect (A-E) binding] provides the functional basis of voluntary action control. A host of studies have demonstrated that A-E binding occurs fast and effortlessly, yet little is known about cognitive and affective factors that influence this learning process. In the present study, we sought to test whether the motivational value of an action modulates the acquisition of A-E associations. To this end, we linked specific actions with monetary incentives during the acquisition of novel A-E mappings. In a subsequent test phase, the degree of binding was assessed by presenting the former effect stimuli as task-irrelevant response primes in a forced-choice response task, absent reward. Binding, as indexed by response priming through the former action-effects, was only found for reward-related A-E mappings. Moreover, the degree to which reward associations modulated the binding strength was predicted by individuals’ trait sensitivity to reward. These observations indicate that the association of actions and their immediate outcomes depends on the motivational value of the action during learning, as well as on the motivational disposition of the individual. On a larger scale, these findings also highlight the link between ideomotor theories and reinforcement-learning theories, providing an interesting perspective for future research on anticipatory regulation of behavior

Goal-seeking compresses neural codes for space in the human hippocampus and orbitofrontal cortex

Humans can navigate flexibly to meet their goals. Here, we asked how the neural representation of allocentric space is distorted by goal-directed behavior. Participants navigated an agent to two successive goal locations in a grid world environment comprising four interlinked rooms, with a contextual cue indicating the conditional dependence of one goal location on another. Examining the neural geometry by which room and context were encoded in fMRI signals, we found that map-like representations of the environment emerged in both hippocampus and neocortex. Cognitive maps in hippocampus and orbitofrontal cortices were compressed so that locations cued as goals were coded together in neural state space, and these distortions predicted successful learning. This effect was captured by a computational model in which current and prospective locations are jointly encoded in a place code, providing a theory of how goals warp the neural representation of space in macroscopic neural signals

Management of swallowing disorders in ICU patients - A multinational expert opinion.

BACKGROUND Dysphagia is common in intensive care unit (ICU) patients, yet it remains underrecognized and often unmanaged despite being associated with life-threatening complications, prolonged ICU stays and hospitalization. PURPOSE To propose an expert opinion for the diagnosis and management of dysphagia developed from evidence-based clinical recommendations and practitioner insights. METHODS A multinational group of dysphagia and critical care experts conducted a literature review using a modified ACCORD methodology. Based on a fusion of the available evidence and the panel's clinical experience, an expert opinion on best practice management was developed. RESULTS The panel recommends adopting clinical algorithms intended to promote standardized, high-quality care that triggers timely systematic dysphagia screening, assessment, and treatment of extubated and tracheostomized patients in the ICU. CONCLUSIONS Given the lack of robust scientific evidence, two clinical management algorithms are proposed for use by multidisciplinary teams to improve early systematic detection and effective management of dysphagia in ICU patients. Additionally, emerging therapeutic options such as neurostimulation have the potential to improve the quality of ICU dysphagia care

Clinical determinants and neural correlates of presbyphagia in community-dwelling older adults

Background“Presbyphagia” refers to characteristic age-related changes in the complex neuromuscular swallowing mechanism. It has been hypothesized that cumulative impairments in multiple domains affect functional reserve of swallowing with age, but the multifactorial etiology and postulated compensatory strategies of the brain are incompletely understood. This study investigates presbyphagia and its neural correlates, focusing on the clinical determinants associated with adaptive neuroplasticity.Materials and methods64 subjects over 70 years of age free of typical diseases explaining dysphagia received comprehensive workup including flexible endoscopic evaluation of swallowing (FEES), magnetoencephalography (MEG) during swallowing and pharyngeal stimulation, volumetry of swallowing muscles, laboratory analyzes, and assessment of hand-grip-strength, nutritional status, frailty, olfaction, cognition and mental health. Neural MEG activation was compared between participants with and without presbyphagia in FEES, and associated clinical influencing factors were analyzed. Presbyphagia was defined as the presence of oropharyngeal swallowing alterations e.g., penetration, aspiration, pharyngeal residue pooling or premature bolus spillage into the piriform sinus and/or laryngeal vestibule.Results32 of 64 participants showed swallowing alterations, mainly characterized by pharyngeal residue, whereas the airway was rarely compromised. In the MEG analysis, participants with presbyphagia activated an increased cortical sensorimotor network during swallowing. As major clinical determinant, participants with swallowing alterations exhibited reduced pharyngeal sensation. Presbyphagia was an independent predictor of a reduced nutritional status in a linear regression model.ConclusionsSwallowing alterations frequently occur in otherwise healthy older adults and are associated with decreased nutritional status. Increased sensorimotor cortical activation may constitute a compensation attempt to uphold swallowing function due to sensory decline. Further studies are needed to clarify whether the swallowing alterations observed can be considered physiological per se or whether the concept of presbyphagia may need to be extended to a theory with a continuous transition between presbyphagia and dysphagia

Substance P Saliva Reduction Predicts Pharyngeal Dysphagia in Parkinson's Disease

Introduction: Although patients with Parkinson's disease (PD) often suffer from oropharyngeal dysphagia, knowledge about the underlying pathophysiological mechanisms is limited. Substance P (SP) is a localization-independent neurotransmitter of the entire nervous system. Reduced levels of SP were found in saliva of patients with impaired cough reflex and in advanced stages of PD. The aim of the study was to investigate SP in PD patients in order to gain further insights into the underlying pathophysiology of PD-related dysphagia and to evaluate the potential of SP as a biomarker for early dysphagia.Methods: Flexible endoscopic evaluation of swallowing (FEES) was used to objectively assess pharyngeal swallowing function. From a cohort of 105 consecutive PD patients 20 subjects were recruited: in 10 of them pharyngeal dysphagia was excluded by FEES, the other 10 subjects showed signs of early pharyngeal dysphagia defined as hypopharyngeal sensory deficit with mild to moderate vallecular residues after swallowing solid consistencies. Analysis of the Substance P level in saliva of the 20 included PD patients was performed in the clinical on state condition by ELISA-type immunoassay. Significant differences were calculated by using the Mann-Whitney test.Results: Twenty PD patients with a mean age of 69.5 ± 12.5 years (8 female) were included in the study. No significant differences were found regarding gender, age, UPDRS III, Hoehn and Yahr stage, disease duration, and Levodopa equivalent dose between the non-dysphagic and dysphagic subjects. Dysphagia was mainly characterized by unrecognized residues in the valleculae without any aspiration risk for all of the tested consistencies in FEES and was thereby scored as mild in all cases. Saliva SP concentrations were significantly lower in PD patients with pharyngeal dysphagia compared to those with a normal pharyngeal swallowing function (9,644 vs. 17,591 pg/mL; p = 0.001).Conclusion: Reduced saliva SP concentrations may predict early pharyngeal swallowing dysfunction in PD patients. This finding supports the hypothesis that an impaired SP mediated neurotransmission has a significant impact for the development of dysphagia in PD patients. Larger studies are needed to confirm SP as a clinical useful biomarker for early detection of PD-related dysphagia

Experiences with array-based sequence capture; toward clinical applications

Although sequencing of a human genome gradually becomes an option, zooming in on the region of interest remains attractive and cost saving. We performed array-based sequence capture using 385K Roche NimbleGen, Inc. arrays to zoom in on the protein-coding and immediate intron-flanking sequences of 112 genes, potentially involved in mental retardation and congenital malformation. Captured material was sequenced using Illumina technology. A data analysis pipeline was built that detects sequence variants, positions them in relation to the gene, checks for presence in databases (eg, db single-nucleotide polymorphism (SNP)) and predicts the potential consequences at the level of RNA splicing and protein translation. In the samples analyzed, all known variants were reliably detected, including pathogenic variants from control cases and SNPs derived from array experiments. Although overall coverage varied considerably, it was reproducible per region and facilitated the detection of large deletions and duplications (copy number variations), including a partial deletion in the B3GALTL gene from a patient sample. For ultimate diagnostic application, overall results need to be improved. Future arrays should contain probes from both DNA strands, and to obtain a more even coverage, one could add fewer probes from densely and more probes from sparsely covered regions

Projections of hydrofluorocarbon (HFC) emissions and the resulting global warming based on recent trends in observed abundances and current policies

The emissions of hydrofluorocarbons (HFCs) have increased significantly in the past 2 decades, primarily as a result of the phaseout of ozone-depleting substances under the Montreal Protocol and the use of HFCs as their replacements. In 2015, large increases were projected in HFC use and emissions in this century in the absence of regulations, contributing up to 0.5° C to global surface warming by 2100. In 2019, the Kigali Amendment to the Montreal Protocol came into force with the goal of limiting the use of HFCs globally, and currently, regulations to limit the use of HFCs are in effect in several countries. Here, we analyze trends in HFC emissions inferred from observations of atmospheric abundances and compare them with previous projections. Total CO2eq. inferred HFC emissions continue to increase through 2019 (to about 0.8 GtCO2eq.yr-1) but are about 20 % lower than previously projected for 2017-2019, mainly because of the lower global emissions of HFC-143a. This indicates that HFCs are used much less in industrial and commercial refrigeration (ICR) applications than previously projected. This is supported by data reported by the developed countries and the lower reported consumption of HFC-143a in China. Because this time period preceded the beginning of the Kigali provisions, this reduction cannot be linked directly to the provisions of the Kigali Amendment. However, it could indicate that companies transitioned away from the HFC-143a with its high global warming potential (GWP) for ICR applications in anticipation of national or global mandates. There are two new HFC scenarios developed based (1) on current trends in HFC use and Kigali-independent (K-I) control policies currently existing in several countries and (2) current HFC trends and compliance with the Kigali Amendment (KA-2022). These current policies reduce projected emissions in 2050 from the previously calculated 4.0-5.3 GtCO2eq.yr-1 to 1.9-3.6 GtCO2eq.yr-1. The added provisions of the Kigali Amendment are projected to reduce the emissions further to 0.9-1.0 GtCO2eq.yr-1 in 2050. Without any controls, projections suggest a HFC contribution of 0.28-0.44° C to global surface warming by 2100, compared to a temperature contribution of 0.14-0.31° C that is projected considering the national K-I policies current in place. Warming from HFCs is additionally limited by the Kigali Amendment controls to a contribution of about 0.04°C by 2100

<i>GRIN2A</i>-related disorders:genotype and functional consequence predict phenotype

Alterations of the N-methyl-d-aspartate receptor (NMDAR) subunit GluN2A, encoded by GRIN2A, have been associated with a spectrum of neurodevelopmental disorders with prominent speech-related features, and epilepsy. We performed a comprehensive assessment of phenotypes with a standardized questionnaire in 92 previously unreported individuals with GRIN2A-related disorders. Applying the criteria of the American College of Medical Genetics and Genomics to all published variants yielded 156 additional cases with pathogenic or likely pathogenic variants in GRIN2A, resulting in a total of 248 individuals. The phenotypic spectrum ranged from normal or near-normal development with mild epilepsy and speech delay/apraxia to severe developmental and epileptic encephalopathy, often within the epilepsy-aphasia spectrum. We found that pathogenic missense variants in transmembrane and linker domains (misTMD+Linker) were associated with severe developmental phenotypes, whereas missense variants within amino terminal or ligand-binding domains (misATD+LBD) and null variants led to less severe developmental phenotypes, which we confirmed in a discovery (P = 10-6) as well as validation cohort (P = 0.0003). Other phenotypes such as MRI abnormalities and epilepsy types were also significantly different between the two groups. Notably, this was paralleled by electrophysiology data, where misTMD+Linker predominantly led to NMDAR gain-of-function, while misATD+LBD exclusively caused NMDAR loss-of-function. With respect to null variants, we show that Grin2a+/- cortical rat neurons also had reduced NMDAR function and there was no evidence of previously postulated compensatory overexpression of GluN2B. We demonstrate that null variants and misATD+LBD of GRIN2A do not only share the same clinical spectrum (i.e. milder phenotypes), but also result in similar electrophysiological consequences (loss-of-function) opposing those of misTMD+Linker (severe phenotypes; predominantly gain-of-function). This new pathomechanistic model may ultimately help in predicting phenotype severity as well as eligibility for potential precision medicine approaches in GRIN2A-related disorders

Priming determinist beliefs diminishes implicit (but not explicit) components of self-agency

Weakening belief in the concept of free will yields pronounced effects upon social behavior, typically promoting selfish and aggressive over pro-social and helping tendencies. Belief manipulations have furthermore been shown to modulate basic and unconscious processes involved in motor control and self-regulation. Yet, to date, it remains unclear how high-level beliefs can impact such a wide range of behaviors. Here, we tested the hypothesis that priming disbelief in free will diminishes the sense of agency, i.e., the intrinsic sensation of being in control of one’s own actions. To this end, we measured participants’ implicit and explicit self-agency under both anti-free will and control conditions. Priming disbelief in free will reduced implicit but not explicit components of agency. These findings suggest that free will beliefs have a causal impact on the pre-reflective feeling of being in control of one’s actions, and solidify previous proposals that implicit and explicit agency components tap into distinct facets of action awareness