Under pressure: Response urgency modulates striatal and insula activity during decision-making under risk

When deciding whether to bet in situations that involve potential monetary loss or gain (mixed gambles), a subjective sense of pressure can influence the evaluation of the expected utility associated with each choice option. Here, we explored how gambling decisions, their psychophysiological and neural counterparts are modulated by an induced sense of urgency to respond. Urgency influenced decision times and evoked heart rate responses, interacting with the expected value of each gamble. Using functional MRI, we observed that this interaction was associated with changes in the activity of the striatum, a critical region for both reward and choice selection, and within the insula, a region implicated as the substrate of affective feelings arising from interoceptive signals which influence motivational behavior. Our findings bridge current psychophysiological and neurobiological models of value representation and action-programming, identifying the striatum and insular cortex as the key substrates of decision-making under risk and urgency

Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders

Background Cerebral palsy (CP) is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. Methods Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67), involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Results A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. Conclusions This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts

Expression of GAD67 and Novel GAD67 Splice Variants During Human Fetal Pancreas Development: GAD67 Expression in the Fetal Pancreas

Glutamic acid decarboxylase (GAD) is a major inhibitory neurotransmitter in the brain, which catalyses the reaction of l-glutamate to γ-aminobutyric acid. There are two isoforms of GAD, a 65-kDa form and a 67-kDa form, which are encoded by two different genes. As previous studies suggested a role for GAD67 splice variants during fetal pancreas development, we have investigated the mRNA expression of GAD67 and GAD67 splice variants in a series of 14 human fetal pancreases between 14 weeks gestation and term and in adult control pancreases by RT-PCR. In this study, we demonstrate mRNA expression of GAD67 and four GAD67 splice variants, including GAD25, in human fetal and adult specimens. Some of the splice variants, including various proportions of exon 7 or a new exon between exons 6 and 7, have not been described before in the human pancreas. We speculate that the expression of these GAD67 splice variants might be related to human fetal pancreas development

Human Perception of Fear in Dogs Varies According to Experience with Dogs

To investigate the role of experience in humans’ perception of emotion using canine visual signals, we asked adults with various levels of dog experience to interpret the emotions of dogs displayed in videos. The video stimuli had been pre-categorized by an expert panel of dog behavior professionals as showing examples of happy or fearful dog behavior. In a sample of 2,163 participants, the level of dog experience strongly predicted identification of fearful, but not of happy, emotional examples. The probability of selecting the “fearful” category to describe fearful examples increased with experience and ranged from.30 among those who had never lived with a dog to greater than.70 among dog professionals. In contrast, the probability of selecting the “happy” category to describe happy emotional examples varied little by experience, ranging from.90 to.93. In addition, the number of physical features of the dog that participants reported using for emotional interpretations increased with experience, and in particular, more-experienced respondents were more likely to attend to the ears. Lastly, more-experienced respondents provided lower difficulty and higher accuracy self-ratings than less-experienced respondents when interpreting both happy and fearful emotional examples. The human perception of emotion in other humans has previously been shown to be sensitive to individual differences in social experience, and the results of the current study extend the notion of experience-dependent processes from the intraspecific to the interspecific domain

Behaviour of motor unit action potential rate, estimated from surface EMG, as a measure of muscle activation level

BACKGROUND: Surface electromyography (EMG) parameters such as root-mean-square value (RMS) are commonly used to assess the muscle activation level that is imposed by the central nervous system (CNS). However, RMS is influenced not only by motor control aspects, but also by peripheral properties of the muscle and recording setup. To assess motor control separately, the number of motor unit action potentials (MUAPs) per second, or MUAP Rate (MR) is a potentially useful measure. MR is the sum of the firing rates of the contributing MUs and as such reflects the two parameters that the CNS uses for motor control: number of MUs and firing rate. MR can be estimated from multi-channel surface EMG recordings. The objective of this study was to explore the behaviour of estimated MR (eMR) in relation to number of active MUs and firing rate. Furthermore, the influence of parameters related to peripheral muscle properties and recording setup (number of fibers per MU, fiber diameter, thickness of the subcutaneous layer, signal-to-noise-ratio) on eMR was compared with their influence on RMS. METHODS: Physiological parameters were varied in a simulation model that generated multi-channel EMG signals. The behaviour of eMR in simulated conditions was compared with its behaviour in experimental conditions. Experimental data was obtained from the upper trapezius muscle during a shoulder elevation task (20–100 N). RESULTS: The simulations showed strong, monotonously increasing relations between eMR and number of active MUs and firing rate (r(2 )> 0.95). Because of unrecognized superimpositions of MUAPs, eMR was substantially lower than the actual MUAP Rate (aMR). The percentage of detected MUAPs decreased with aMR, but the relation between eMR and aMR was rather stable in all simulated conditions. In contrast to RMS, eMR was not affected by number of fibers per MU, fiber diameter and thickness of the subcutaneous layer. Experimental data showed a strong relation between eMR and force (individual second order polynomial regression: 0.96 < r(2 )< 0.99). CONCLUSION: Although the actual number of MUAPs in the signal cannot be accurately extracted with the present method, the stability of the relation between eMR and aMR and its independence of muscle properties make eMR a suitable parameter to assess the input from the CNS to the muscle at low contraction levels non-invasively

APOE and immunity: Research highlights

INTRODUCTION: At the Alzheimer's Association's APOE and Immunity virtual conference, held in October 2021, leading neuroscience experts shared recent research advances on and inspiring insights into the various roles that both the apolipoprotein E gene (APOE) and facets of immunity play in neurodegenerative diseases, including Alzheimer's disease and other dementias. METHODS: The meeting brought together more than 1200 registered attendees from 62 different countries, representing the realms of academia and industry. RESULTS: During the 4-day meeting, presenters illuminated aspects of the cross-talk between APOE and immunity, with a focus on the roles of microglia, triggering receptor expressed on myeloid cells 2 (TREM2), and components of inflammation (e.g., tumor necrosis factor α [TNFα]). DISCUSSION: This manuscript emphasizes the importance of diversity in current and future research and presents an integrated view of innate immune functions in Alzheimer's disease as well as related promising directions in drug development

Being there: a preliminary study examining the role of presence in Internet Gaming Disorder

Internet Gaming Disorder (IGD) has been introduced as an emerging mental health condition requiring further study. Associations between IGD and gaming presence (i.e., absorption in the virtual environment) have been implied. The aim of the present study was twofold: (a) to evaluate the extent to which presence contributes to IGD severity and, (b) to examine longitudinal differences in IGD according to the initial level of presence experienced. The participants comprising 125 emerging adults aged 18 to 29 years completed either: (i) three face-to-face assessments (one month apart, over three months) or (ii) a cross-sectional, online assessment. IGD was assessed with the nine-item IGD Scale Short Form and presence was assessed using the Presence Questionnaire. Regression and latent growth modelling analyses were conducted. Findings demonstrated that the level of gaming presence related to IGD severity but not to linear change in severity over a three-month period. The study shows that emergent adults who play internet games may be at a high risk of IGD given a more salient sense of being present within the gaming environment. Clinical implications considering prevention and intervention initiatives are discussed

Increased TIMP-3 expression alters the cellular secretome through dual inhibition of the metalloprotease ADAM10 and ligand-binding of the LRP-1 receptor

The tissue inhibitor of metalloproteinases-3 (TIMP-3) is a major regulator of extracellular matrix turnover and protein shedding by inhibiting different classes of metalloproteinases, including disintegrin metalloproteinases (ADAMs). Tissue bioavailability of TIMP-3 is regulated by the endocytic receptor low-density-lipoprotein receptor-related protein-1 (LRP-1). TIMP-3 plays protective roles in disease. Thus, different approaches have been developed aiming to increase TIMP-3 bioavailability, yet overall effects of increased TIMP-3 in vivo have not been investigated. Herein, by using unbiased mass-spectrometry we demonstrate that TIMP-3-overexpression in HEK293 cells has a dual effect on shedding of transmembrane proteins and turnover of soluble proteins. Several membrane proteins showing reduced shedding are known as ADAM10 substrates, suggesting that exogenous TIMP-3 preferentially inhibits ADAM10 in HEK293 cells. Additionally identified shed membrane proteins may be novel ADAM10 substrate candidates. TIMP-3-overexpression also increased extracellular levels of several soluble proteins, including TIMP-1, MIF and SPARC. Levels of these proteins similarly increased upon LRP-1 inactivation, suggesting that TIMP-3 increases soluble protein levels by competing for their binding to LRP-1 and their subsequent internalization. In conclusion, our study reveals that increased levels of TIMP-3 induce substantial modifications in the cellular secretome and that TIMP-3-based therapies may potentially provoke undesired, dysregulated functions of ADAM10 and LRP-1

Allosteric effects in cyclophilin mutants may be explained by changes in nano-microsecond time scale motions

The relationship between molecular motion and catalysis in enzymes is debated. Here, simulations of cyclophilin A and three catalytically-impaired mutants reveal a nanosecond-scale interconversion between active and inactive conformations, orders of magnitude faster than previously suggested

Bessel-Weighted Asymmetries in Semi Inclusive Deep Inelastic Scattering

The concept of weighted asymmetries is revisited for semi-inclusive deep inelastic scattering. We consider the cross section in Fourier space, conjugate to the outgoing hadron's transverse momentum, where convolutions of transverse momentum dependent parton distribution functions and fragmentation functions become simple products. Individual asymmetric terms in the cross section can be projected out by means of a generalized set of weights involving Bessel functions. Advantages of employing these Bessel weights are that they suppress (divergent) contributions from high transverse momentum and that soft factors cancel in (Bessel-) weighted asymmetries. Also, the resulting compact expressions immediately connect to previous work on evolution equations for transverse momentum dependent parton distribution and fragmentation functions and to quantities accessible in lattice QCD. Bessel weighted asymmetries are thus model independent observables that augment the description and our understanding of correlations of spin and momentum in nucleon structure.Comment: Matches published version, JHEP style, 36 pages and 2 figures, minor correction