Hemispheric asymmetry of endogenous neural oscillations in young children: implications for hearing speech in noise

Speech signals contain information in hierarchical time scales, ranging from short-duration (e.g., phonemes) to long-duration cues (e.g., syllables, prosody). A theoretical framework to understand how the brain processes this hierarchy suggests that hemispheric lateralization enables specialized tracking of acoustic cues at different time scales, with the left and right hemispheres sampling at short (25 ms; 40 Hz) and long (200 ms; 5 Hz) periods, respectively. In adults, both speech-evoked and endogenous cortical rhythms are asymmetrical: low-frequency rhythms predominate in right auditory cortex, and high-frequency rhythms in left auditory cortex. It is unknown, however, whether endogenous resting state oscillations are similarly lateralized in children. We investigated cortical oscillations in children (3–5 years; N = 65) at rest and tested our hypotheses that this temporal asymmetry is evident early in life and facilitates recognition of speech in noise. We found a systematic pattern of increasing leftward asymmetry for higher frequency oscillations; this pattern was more pronounced in children who better perceived words in noise. The observed connection between left-biased cortical oscillations in phoneme-relevant frequencies and speech-in-noise perception suggests hemispheric specialization of endogenous oscillatory activity may support speech processing in challenging listening environments, and that this infrastructure is present during early childhood

Search for lepton-flavour-violating decays of Higgs-like bosons.

A search is presented for a Higgs-like boson with mass in the range 45 to 195 GeV/c2 decaying into a muon and a tau lepton. The dataset consists of proton-proton interactions at a centre-of-mass energy of 8 TeV , collected by the LHCb experiment, corresponding to an integrated luminosity of 2 fb-1 . The tau leptons are reconstructed in both leptonic and hadronic decay channels. An upper limit on the production cross-section multiplied by the branching fraction at 95% confidence level is set and ranges from 22 pb for a boson mass of 45 GeV/c2 to 4 pb for a mass of 195 GeV/c2

Reward-Related Dorsal Striatal Activity Differences between Former and Current Cocaine Dependent Individuals during an Interactive Competitive Game

Cocaine addiction is characterized by impulsivity, impaired social relationships, and abnormal mesocorticolimbic reward processing, but their interrelationships relative to stages of cocaine addiction are unclear. We assessed blood-oxygenation-level dependent (BOLD) signal in ventral and dorsal striatum during functional magnetic resonance imaging (fMRI) in current (CCD; n = 30) and former (FCD; n = 28) cocaine dependent subjects as well as healthy control (HC; n = 31) subjects while playing an interactive competitive Domino game involving risk-taking and reward/punishment processing. Out-of-scanner impulsivity-related measures were also collected. Although both FCD and CCD subjects scored significantly higher on impulsivity-related measures than did HC subjects, only FCD subjects had differences in striatal activation, specifically showing hypoactivation during their response to gains versus losses in right dorsal caudate, a brain region linked to habituation, cocaine craving and addiction maintenance. Right caudate activity in FCD subjects also correlated negatively with impulsivity-related measures of self-reported compulsivity and sensitivity to reward. These findings suggest that remitted cocaine dependence is associated with striatal dysfunction during social reward processing in a manner linked to compulsivity and reward sensitivity measures. Future research should investigate the extent to which such differences might reflect underlying vulnerabilities linked to cocaine-using propensities (e.g., relapses)

Understanding within-session loss-chasing: an experimental investigation of the impact of stake size on cognitive control

Loss-chasing is a central feature of problematic gambling, yet it remains a poorly conceived and understood concept. Loss-chasing is believed to stem from an ero- sion of cognitive control when gambling. The opportunity to gamble at significantly dis- parate stake sizes on a gambling activity is considered to be a risk factor for loss-chasing. This study investigated the impact of gambling at disparate stake sizes on executive processes integral to maintaining cognitive control when gambling, namely response inhibition and reflection impulsivity. Frequent adult non-problem gamblers (n = 32) participated in a repeated measures experiment; and gambled at three disparate stake sizes (£20, £2 and no stake per bet) on a simulated gambling task. Participants’ response inhibition performance and reflection impulsivity levels after gambling at various stake sizes were compared via a go/no-go task and information sampling task, respectively. Quality of decision-making i.e. the evaluation of available information to make probability judgements was impaired after gambling at higher stakes in comparison to lower stakes, indicating an increase in reflection impulsivity. No effect on response inhibition was observed. Although exploratory, this suggests that the opportunity for participants to substantially increase stake size on a gambling activity may be a risk factor for impaired cognitive performance when gambling, and perhaps create vulnerability for within-session loss-chasing in some players. Keywords Problem gambling - Cognitive control - Loss-chasing - Response inhibition - Reflection impulsivit

Alternative Splicing and Nonsense-Mediated RNA Decay Contribute to the Regulation of SHOX Expression

The human SHOX gene is composed of seven exons and encodes a paired-related homeodomain transcription factor. SHOX mutations or deletions have been associated with different short stature syndromes implying a role in growth and bone formation. During development, SHOX is expressed in a highly specific spatiotemporal expression pattern, the underlying regulatory mechanisms of which remain largely unknown. We have analysed SHOX expression in diverse embryonic, fetal and adult human tissues and detected expression in many tissues that were not known to express SHOX before, e.g. distinct brain regions. By using RT-PCR and comparing the results with RNA-Seq data, we have identified four novel exons (exon 2a, 7-1, 7-2 and 7-3) contributing to different SHOX isoforms, and also established an expression profile for the emerging new SHOX isoforms. Interestingly, we found the exon 7 variants to be exclusively expressed in fetal neural tissues, which could argue for a specific role of these variants during brain development. A bioinformatical analysis of the three novel 3′UTR exons yielded insights into the putative role of the different 3′UTRs as targets for miRNA binding. Functional analysis revealed that inclusion of exon 2a leads to nonsense-mediated RNA decay altering SHOX expression in a tissue and time specific manner. In conclusion, SHOX expression is regulated by different mechanisms and alternative splicing coupled with nonsense-mediated RNA decay constitutes a further component that can be used to fine tune the SHOX expression level

Reliance on habits at the expense of goal-directed control following dopamine precursor depletion

Rationale Dopamine is well known to play an important role in learning and motivation. Recent animal studies have implicated dopamine in the reinforcement of stimulus-response habits, as well as in flexible, goal-directed action. However, the role of dopamine in human action control is still not well understood. Objectives We present the first investigation of the effect of reducing dopamine function in healthy volunteers on the balance between habitual and goal-directed action control. Methods The dietary intervention of acute dietary phenylalanine and tyrosine depletion (APTD) was adopted to study the effects of reduced global dopamine function on action control. Participants were randomly assigned to either the APTD or placebo group (ns = 14) to allow for a between-subjects comparison of performance on a novel three-stage experimental paradigm. In the initial learning phase, participants learned to respond to different stimuli in order to gain rewarding outcomes. Subsequently, an outcome-devaluation test and a slips-of-action test were conducted to assess whether participants were able to flexibly adjust their behaviour to changes in the desirability of the outcomes. Results APTD did not prevent stimulus-response learning, nor did we find evidence for impaired response-outcome learning in the subsequent outcome-devaluation test. However, when goal-directed and habitual systems competed for control in the slips-of-action test, APTD tipped the balance towards habitual control. These findings were restricted to female volunteers. Conclusions We provide direct evidence that the balance between goal-directed and habitual control in humans is dopamine dependent. The results are discussed in light of gender differences in dopamine function and psychopathologies

Cocaine Is Low on the Value Ladder of Rats: Possible Evidence for Resilience to Addiction

International audienceBACKGROUND:Assessing the relative value of cocaine and how it changes with chronic drug use represents a long-standing goal in addiction research. Surprisingly, recent experiments in rats--by far the most frequently used animal model in this field--suggest that the value of cocaine is lower than previously thought.METHODOLOGY/PRINCIPAL FINDINGS:Here we report a series of choice experiments that better define the relative position of cocaine on the value ladder of rats (i.e., preference rank-ordering of different rewards). Rats were allowed to choose either taking cocaine or drinking water sweetened with saccharin--a nondrug alternative that is not biologically essential. By systematically varying the cost and concentration of sweet water, we found that cocaine is low on the value ladder of the large majority of rats, near the lowest concentrations of sweet water. In addition, a retrospective analysis of all experiments over the past 5 years revealed that no matter how heavy was past cocaine use most rats readily give up cocaine use in favor of the nondrug alternative. Only a minority, fewer than 15% at the heaviest level of past cocaine use, continued to take cocaine, even when hungry and offered a natural sugar that could relieve their need of calories.CONCLUSIONS/SIGNIFICANCE:This pattern of results (cocaine abstinence in most rats; cocaine preference in few rats) maps well onto the epidemiology of human cocaine addiction and suggests that only a minority of rats would be vulnerable to cocaine addiction while the large majority would be resilient despite extensive drug use. Resilience to drug addiction has long been suspected in humans but could not be firmly established, mostly because it is difficult to control retrospectively for differences in drug self-exposure and/or availability in human drug users. This conclusion has important implications for preclinical research on the neurobiology of cocaine addiction and for future medication development

Evidence for Habitual and Goal-Directed Behavior Following Devaluation of Cocaine: A Multifaceted Interpretation of Relapse

BACKGROUND:Cocaine addiction is characterized as a chronically relapsing disorder. It is believed that cues present during self-administration become learned and increase the probability that relapse will occur when they are confronted during abstinence. However, the way in which relapse-inducing cues are interpreted by the user has remained elusive. Recent theories of addiction posit that relapse-inducing cues cause relapse habitually or automatically, bypassing processing information related to the consequences of relapse. Alternatively, other theories hypothesize that relapse-inducing cues produce an expectation of the drug's consequences, designated as goal-directed relapse. Discrete discriminative stimuli signaling the availability of cocaine produce robust cue-induced responding after thirty days of abstinence. However, it is not known whether cue-induced responding is a goal-directed action or habit. METHODOLOGY/PRINCIPAL FINDINGS:We tested whether cue-induced responding is a goal-directed action or habit by explicitly pairing or unpairing cocaine with LiCl-induced sickness (n = 7/group), thereby decreasing or not altering the value of cocaine, respectively. Following thirty days of abstinence, no difference in responding between groups was found when animals were reintroduced to the self-administration environment alone, indicating habitual behavior. However, upon discriminative stimulus presentations, cocaine-sickness paired animals exhibited decreased cue-induced responding relative to unpaired controls, indicating goal-directed behavior. In spite of the difference between groups revealed during abstinent testing, no differences were found between groups when animals were under the influence of cocaine. CONCLUSIONS/SIGNIFICANCE:Unexpectedly, both habitual and goal-directed responding occurred during abstinent testing. Furthermore, habitual or goal-directed responding may have been induced by cues that differed in their correlation with the cocaine infusion. Non-discriminative stimulus cues were weak correlates of the infusion, which failed to evoke a representation of the value of cocaine and led to habitual behavior. However, the discriminative stimulus-nearly perfectly correlated with the infusion-likely evoked a representation of the value of the infusion and led to goal-directed behavior. These data indicate that abstinent cue-induced responding is multifaceted, dynamically engendering habitual or goal-directed behavior. Moreover, since goal-directed behavior terminated habitual behavior during testing, therapeutic approaches aimed at reducing the perceived value of cocaine in addicted individuals may reduce the capacity of cues to induce relapse

Measurement of CP observables in the process B ⁰ → DK ^*0 with two- and four-body D decays

Measurements of $C\!P$ observables in $B^0 \to DK^{*0}$ decays are presented, where $D$ represents a superposition of $D^0$ and $\bar{D}^0$ states. The $D$ meson is reconstructed in the two-body final states $K^+\pi^-$, $\pi^+ K^-$, $K^+K^-$ and $\pi^+\pi^-$, and, for the first time, in the four-body final states $K^+\pi^-\pi^+\pi^-$, $\pi^+ K^-\pi^+\pi^-$ and $\pi^+\pi^-\pi^+\pi^-$. The analysis uses a sample of neutral $B$ mesons produced in proton-proton collisions, corresponding to an integrated luminosity of 1.0, 2.0 and 1.8 $\rm fb^{-1}$ collected with the LHCb detector at centre-of-mass energies of $\sqrt{s} =$ 7, 8 and 13 TeV, respectively. First observations of the decays $B^0 \to D(\pi^+ K^-)K^{*0}$ and $B^0 \to D(\pi^+\pi^-\pi^+\pi^-)K^{*0}$ are obtained. The measured observables are interpreted in terms of the $C\!P$-violating weak phase $\gamma$

Updated measurement of time-dependent CP -violating observables in Bs0→J/ψ^K+^K- decays

The decay-time-dependent $CP$ asymmetry in $B^{0}_{s}\to J/\psi K^{+} K^{-}$ decays is measured using proton-proton collision data, corresponding to an integrated luminosity of $1.9\,\mathrm{fb^{-1}}$, collected with the LHCb detector at a centre-of-mass energy of $13\,\mathrm{TeV}$ in 2015 and 2016. Using a sample of approximately 117\,000 signal decays with an invariant $K^{+} K^{-}$ mass in the vicinity of the $\phi(1020)$ resonance, the $CP$-violating phase $\phi_s$ is measured, along with the difference in decay widths of the light and heavy mass eigenstates of the $B^{0}_{s}$-$\bar{B}^{0}_{s}$ system, $\Delta\Gamma_s$. The difference of the average $B^{0}_{s}$ and $B^{0}$ meson decay widths, $\Gamma_s-\Gamma_d$, is determined using in addition a sample of $B^{0} \to J/\psi K^{+} \pi^{-}$ decays. The values obtained are $\phi_s = -0.083\pm0.041\pm0.006\,\mathrm{rad}$, $\Delta\Gamma_s = 0.077 \pm 0.008 \pm 0.003\, \mathrm{ps^{-1}}$ and $\Gamma_s-\Gamma_d = -0.0041 \pm 0.0024 \pm 0.0015\,\mathrm{ps^{-1}}$, where the first uncertainty is statistical and the second systematic. These are the most precise single measurements of these quantities to date and are consistent with expectations based on the Standard Model and with a previous LHCb analysis of this decay using data recorded at centre-of-mass energies 7 and 8 TeV. Finally, the results are combined with recent results from $B^{0}_{s}\to J/\psi \pi^{+} \pi^{-}$ decays obtained using the same dataset as this analysis, and with previous independent LHCb results