Enhanced motor network engagement during reward gain anticipation in fibromyalgia.

Reward motivation is essential in shaping human behavior and cognition. Both reward motivation and reward brain circuits are altered in chronic pain conditions, including fibromyalgia. In this study of fibromyalgia patients, we used a data-driven independent component analysis (ICA) approach to investigate how brain networks contribute to altered reward processing. From females with fibromyalgia (N = 24) and female healthy controls (N = 24), we acquired fMRI data while participants performed a monetary incentive delay (MID) reward task. After analyzing the task-based fMRI data using ICA to identify networks, we analyzed 3 networks of interest: motor network (left), value-driven attention network, and basal ganglia network. Then, we evaluated correlation coefficients between each network timecourse versus a task-based timecourse which modeled gain anticipation. Compared to controls, the fibromyalgia cohort demonstrated significantly stronger correlation between the left motor network timecourse and the gain anticipation timecourse, indicating the left motor network was more engaged with gain anticipation in fibromyalgia. In an exploratory analysis, we compared motor network engagement during early versus late phases of gain anticipation. Across cohorts, greater motor network engagement (i.e., stronger correlation between network and gain anticipation) occurred during the late timepoint, which reflected enhanced motor preparation immediately prior to response. Consistent with the main results, patients exhibited greater engagement of the motor network during both early and late phases compared with healthy controls. Visual-attention and basal ganglia networks revealed similar engagement in the task across groups. As indicated by post-hoc analyses, motor network engagement was positively related to anxiety and negatively related to reward responsiveness. In summary, we identified enhanced reward-task related engagement of the motor network in fibromyalgia using a novel data-driven ICA approach. Enhanced motor network engagement in fibromyalgia may relate to impaired reward motivation, heightened anxiety, and possibly to altered motor processing, such as restricted movement or dysregulated motor planning.

Striatal hypoactivation during monetary loss anticipation in individuals with substance use disorders in a heterogenous urban American Indian sample.

Research suggests that disproportionate exposure to risk factors places American Indian (AI) peoples at higher risk for substance use disorders (SUD). Although SUD is linked to striatal prioritization of drug rewards over other appetitive stimuli, there are gaps in the literature related to the investigation of aversive valuation processing, and inclusion of AI samples. To address these gaps, this study compared striatal anticipatory gain and loss processing between AI-identified with SUD (SUD+; n = 52) and without SUD (SUD-; n = 35) groups from the Tulsa 1000 study who completed a monetary incentive delay (MID) task during functional magnetic resonance imaging. Results indicated that striatal activations in the nucleus accumbens (NAcc), caudate, and putamen were greatest for anticipating gains (ps < 0.001) but showed no group differences. In contrast to gains, the SUD+ exhibited lower NAcc (p = .01, d =0.53) and putamen (p = .04, d =0.40) activation to anticipating large losses than the comparison group. Within SUD+ , lower striatal responses during loss anticipations were associated with slower MID reaction times (NAcc: r = -0.43; putamen: r = -0.35) during loss trials. This is among the first imaging studies to examine underlying neural mechanisms associated with SUD within AIs. Attenuated loss processing provides initial evidence of a potential mechanism wherein blunted prediction of aversive consequences may be a defining feature of SUD that can inform future prevention and intervention targets.

Neural patterns during anticipation predict emotion regulation success for reappraisal.

The ability to exert control over emotions, termed emotion regulation (ER), is vital for everyday functioning. ER success may be influenced by processes relating to the anticipation (prior to active regulation) and implementation (during active regulation) of ER strategy use. We investigated whether brain activity patterns recorded using electroencephalography (EEG) during the first second of anticipation and implementation of two ER strategies-distraction and reappraisal-were related to regulation success. Participants viewed negative images that evoked disgust and sadness. Before each image was presented, participants were cued to either passively view the image or decrease their emotional responses. ER success scores were calculated from subsequent self-reported disgust and sadness ratings. Using multivariate support vector regression, ER success scores were predicted from spatiotemporal patterns of event-related potentials during the first second of anticipation and implementation phases of each ER strategy. For both sadness and disgust, reappraisal success could be predicted during anticipation, while distraction success could be predicted during implementation. These findings suggest that early anticipatory cognitive processes are a key determinant of reappraisal success, but may not be similarly important for distraction. This may be because reappraisal is more cognitively demanding than distraction, requiring enhanced preparation of mental resources.

Influence of pain anticipation on brain activity and pain perception in Gulf War Veterans with chronic musculoskeletal pain.

Anticipation of a painful experience can influence brain activity and increase sensitivity to experimental somatosensory stimuli in healthy adults, but this response is poorly understood among individuals with chronic musculoskeletal pain (CMP). Studies of brain and perceptual responses to somatosensory stimuli are used to make inferences about central nervous system dysfunction as a potential mechanism of symptoms. As such, we sought to (a) determine the influence of pain anticipation on pain-relevant brain regions and pain perception, and (b) characterize potential differences in these responses between Gulf War Veterans with CMP and matched healthy control (CO) Veterans. CMP (N = 30) and CO Veterans (N = 31) were randomized to conditions designed to generate expectations that either painful (pain) or nonpainful (no pain) stimuli would be administered. Brain responses to five nonpainful thermal stimuli were measured during fMRI, and each stimulus was rated for pain intensity and unpleasantness. In the pain condition, an incremental linear decrease in activity across stimuli was observed in the posterior cingulate cortex, cingulate cortex, and middle temporal gyrus. Further, in the pain condition, differential responses were observed between CMP and CO Veterans in the middle temporal gyrus. These findings indicate that brain responses to nonpainful thermal stimuli in Veterans with CMP are sensitive to pain anticipation, and we recommend accounting for the influence of pain anticipation in future investigations of central nervous system dysfunction in CMP.

Bupropion increases activation in nucleus accumbens during anticipation of monetary reward.

RATIONALE: Bupropion is used for major depressive disorder, smoking cessation aid, and obesity. It blocks reuptake of dopamine and noradrenaline and antagonizes nicotinic acetylcholine receptor. Animal studies showed that bupropion enhanced rewarding effects. In addition, bupropion has the potential to treat patients with reward processing dysfunction. However, neural substrates underlying the bupropion effects on reward function in human subjects are not fully understood. OBJECTIVES: We investigated single-dose administration of bupropion on neural response of reward anticipation in healthy subjects using a monetary incentive delay (MID) task by functional magnetic resonance imaging (fMRI), especially focusing on nucleus accumbens (NAc) activity to non-drug reward stimuli under bupropion treatment. METHODS: We used a randomized placebo-controlled within-subject crossover design. Fifteen healthy adults participated in two series of an fMRI study, taking either placebo or bupropion. The participants performed the MID task during the fMRI scanning. The effects of bupropion on behavioral performance and blood oxygenation level-dependent (BOLD) signal in NAc during anticipation of monetary gain were analyzed. RESULTS: We found that bupropion significantly increased BOLD responses in NAc during monetary reward anticipation. The increased BOLD responses in NAc were observed with both low and high reward incentive cues. There was no significant difference between placebo and bupropion in behavioral performance. CONCLUSIONS: Our findings provide support for the notion that bupropion enhances non-drug rewarding effects, suggesting a possible mechanism underlying therapeutic effects for patients with motivational deficit.

Apparent Effects of Opioid Use on Neural Responses to Reward in Chronic Pain.

Neural responses to incentives are altered in chronic pain and by opioid use. To understand how opioid use modulates the neural response to reward/value in chronic pain, we compared brain functional magnetic resonance imaging (fMRI) responses to a monetary incentive delay (MID) task in patients with fibromyalgia taking opioids (N = 17), patients with fibromyalgia not taking opioids (N = 17), and healthy controls (N = 15). Both groups of patients with fibromyalgia taking and not taking opioids had similar levels of pain, psychological measures, and clinical symptoms. Neural responses in the nucleus accumbens to anticipated reward and non-loss outcomes did not differ from healthy controls in either fibromyalgia group. However, neural responses in the medial prefrontal cortex differed, such that patients with fibromyalgia not taking opioids demonstrated significantly altered responses to anticipated rewards and non-loss outcomes compared to healthy controls, but patients with fibromyalgia taking opioids did not. Despite limitations including the use of additional non-opioid medications by fibromyalgia patients taking opioids, these preliminary findings suggest relatively "normalized" neural responses to monetary incentives in chronic pain patients who take opioids versus those who do not.

ß1-Integrins in the Developing Orbitofrontal Cortex Are Necessary for Expectancy Updating in Mice.

Navigating a changing environment requires associating stimuli and actions with their likely outcomes and modifying these associations when they change. These processes involve the orbitofrontal cortex (OFC). Although some molecular mediators have been identified, developmental factors are virtually unknown. We hypothesized that the cell adhesion factor ß1-integrin is essential to OFC function, anticipating developmental windows during which ß1-integrins might be more influential than others. We discovered that OFC-selective ß1-integrin silencing before adolescence, but not later, impaired the ability of mice to extinguish conditioned fear and select actions based on their likely outcomes. Early-life knock-down also reduced the densities of dendritic spines, the primary sites of excitatory plasticity in the brain, and weakened sensitivity to cortical inputs. Notwithstanding these defects in male mice, females were resilient to OFC (but not hippocampal) ß1-integrin loss. Existing literature suggests that resilience may be explained by estradiol-mediated transactivation of ß1-integrins and tropomyosin receptor kinase B (trkB). Accordingly, we discovered that a trkB agonist administered during adolescence corrected reward-related decision making in ß1-integrin-deficient males. In sum, developmental ß1-integrins are indispensable for OFC function later in life.SIGNIFICANCE STATEMENT The orbitofrontal cortex (OFC) is a subregion of the frontal cortex that allows organisms to link behaviors and stimuli with anticipated outcomes, and to make predictions about the consequences of one's behavior. Aspects of OFC development are particularly prolonged, extending well into adolescence, likely optimizing organisms' abilities to prospectively calculate the consequences of their actions and select behaviors appropriately; these decision making strategies improve as young individuals mature into adulthood. Molecular factors are not, however, well understood. Our experiments reveal that a cell adhesion protein termed "ß1-integrin" is necessary for OFC neuronal maturation and function. Importantly, ß1-integrins operate during a critical period equivalent to early adolescence in humans to optimize the ability of organisms to update expectancies later in life.

Reward-Related Expectations Trigger Dendritic Spine Plasticity in the Mouse Ventrolateral Orbitofrontal Cortex.

An essential aspect of goal-directed decision-making is selecting actions based on anticipated consequences, a process that involves the orbitofrontal cortex (OFC) and potentially, the plasticity of dendritic spines in this region. To investigate this possibility, we trained male and female mice to nose poke for food reinforcers, or we delivered the same number of food reinforcers non-contingently to separate mice. We then decreased the likelihood of reinforcement for trained mice, requiring them to modify action-outcome expectations. In a separate experiment, we blocked action-outcome updating via chemogenetic inactivation of the OFC. In both cases, successfully selecting actions based on their likely consequences was associated with fewer immature, thin-shaped dendritic spines and a greater proportion of mature, mushroom-shaped spines in the ventrolateral OFC. This pattern was distinct from spine loss associated with aging, and we identified no effects on hippocampal CA1 neurons. Given that the OFC is involved in prospective calculations of likely outcomes, even when they are not observable, constraining spinogenesis while preserving mature spines may be important for solidifying durable expectations. To investigate causal relationships, we inhibited the RNA-binding protein fragile X mental retardation protein (encoded by Fmr1), which constrains dendritic spine turnover. Ventrolateral OFC-selective Fmr1 knockdown recapitulated the behavioral effects of inducible OFC inactivation (and lesions; also shown here), impairing action-outcome conditioning, and caused dendritic spine excess. Our findings suggest that a proper balance of dendritic spine plasticity within the OFC is necessary for one's ability to select actions based on anticipated consequences.SIGNIFICANCE STATEMENT Navigating a changing environment requires associating actions with their likely outcomes and updating these associations when they change. Dendritic spine plasticity is likely involved, yet relationships are unconfirmed. Using behavioral, chemogenetic, and viral-mediated gene silencing strategies and high-resolution microscopy, we find that modifying action-outcome expectations is associated with fewer immature spines and a greater proportion of mature spines in the ventrolateral orbitofrontal cortex (OFC). Given that the OFC is involved in prospectively calculating the likely outcomes of one's behavior, even when they are not observable, constraining spinogenesis while preserving mature spines may be important for maintaining durable expectations.

Activation of the rat hypothalamic supramammillary nucleus by food anticipation, food restriction or ghrelin administration.

The circulating orexigenic hormone ghrelin targets many brain areas involved in feeding control and signals via a dedicated receptor, the growth hormone secretagogue receptor 1A. One unexplored target area for ghrelin is the supramammillary nucleus (SuM), a hypothalamic area involved in motivation and reinforcement and also recently linked to metabolic control. Given that ghrelin binds to the SuM, we explored whether SuM cells respond to ghrelin and/or are activated when endogenous ghrelin levels are elevated. We found that peripheral ghrelin injection activates SuM cells in rats, reflected by an increase in the number of cells expressing c-Fos protein in this area, as welll as by the predominantly excitatory response of single SuM cells recorded in in vivo electrophysiological studies. Further c-Fos mapping studies reveal that this area is also activated in rats in situations when circulating ghrelin levels are known to be elevated: in food-restricted rats anticipating the consumption of food and in fed rats anticipating the consumption of an energy-dense food. We also show that intra-SuM injection of ghrelin induces a feeding response in rats suggesting that, if peripheral ghrelin is able to access the SuM, it may have direct effects on this brain region. Collectively, our data demonstrate that the SuM is activated when peripheral ghrelin levels are high, further supporting the emerging role for this brain area in metabolic and feeding control.

Effects of speech rate, preview time of visual context, and participant instructions reveal strong limits on prediction in language processing.

There is a consensus among language researchers that people can predict upcoming language. But do people always predict when comprehending language? Notions that "brains … are essentially prediction machines" certainly suggest so. In three eye-tracking experiments we tested this view. Participants listened to simple Dutch sentences ('Look at the displayed bicycle') while viewing four objects (a target, e.g. a bicycle, and three unrelated distractors). We used the identical visual stimuli and the same spoken sentences but varied speech rates, preview time, and participant instructions. Target nouns were preceded by definite gender-marked determiners, which allowed participants to predict the target object because only the targets but not the distractors agreed in gender with the determiner. In Experiment 1, participants had four seconds preview and sentences were presented either in a slow or a normal speech rate. Participants predicted the targets as soon as they heard the determiner in both conditions. Experiment 2 was identical except that participants were given only a one second preview. Participants predicted the targets only in the slow speech condition. Experiment 3 was identical to Experiment 2 except that participants were explicitly told to predict. This led only to a small prediction effect in the normal speech condition. Thus, a normal speech rate only afforded prediction if participants had an extensive preview. Even the explicit instruction to predict the target resulted in only a small anticipation effect with a normal speech rate and a short preview. These findings are problematic for theoretical proposals that assume that prediction pervades cognition.

A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response.

The TTC12-ANKK1-DRD2 gene-cluster has been implicated in adult smoking. Here, we investigated the contribution of individual genes in the TTC12-ANKK1-DRD2 cluster in smoking and their association with smoking-associated reward processing in adolescence. A meta-analysis of TTC12-ANKK1-DRD2 variants and self-reported smoking behaviours was performed in four European adolescent cohorts (N = 14,084). The minor G-allele of rs2236709, mapping TTC12, was associated with self-reported smoking (p = 5.0 × 10-4) and higher plasma cotinine levels (p = 7.0 × 10-5). This risk allele was linked to an increased ventral-striatal blood-oxygen level-dependent (BOLD) response during reward anticipation (n = 1,263) and with higher DRD2 gene expression in the striatum (p = 0.013), but not with TTC12 or ANKK gene expression. These data suggest a role for the TTC12-ANKK1-DRD2 gene-cluster in adolescent smoking behaviours, provide evidence for the involvement of DRD2 in the early stages of addiction and support the notion that genetically-driven inter-individual differences in dopaminergic transmission mediate reward sensitivity and risk to smoking.

Altered prefrontal correlates of monetary anticipation and outcome in chronic pain.

Chronic pain may alter both affect- and value-related behaviors, which represents a potentially treatable aspect of chronic pain experience. Current understanding of how chronic pain influences the function of brain reward systems, however, is limited. Using a monetary incentive delay task and functional magnetic resonance imaging (fMRI), we measured neural correlates of reward anticipation and outcomes in female participants with the chronic pain condition of fibromyalgia (N = 17) and age-matched, pain-free, female controls (N = 15). We hypothesized that patients would demonstrate lower positive arousal, as well as altered reward anticipation and outcome activity within corticostriatal circuits implicated in reward processing. Patients demonstrated lower arousal ratings as compared with controls, but no group differences were observed for valence, positive arousal, or negative arousal ratings. Group fMRI analyses were conducted to determine predetermined region of interest, nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC), responses to potential gains, potential losses, reward outcomes, and punishment outcomes. Compared with controls, patients demonstrated similar, although slightly reduced, NAcc activity during gain anticipation. Conversely, patients demonstrated dramatically reduced mPFC activity during gain anticipation-possibly related to lower estimated reward probabilities. Further, patients demonstrated normal mPFC activity to reward outcomes, but dramatically heightened mPFC activity to no-loss (nonpunishment) outcomes. In parallel to NAcc and mPFC responses, patients demonstrated slightly reduced activity during reward anticipation in other brain regions, which included the ventral tegmental area, anterior cingulate cortex, and anterior insular cortex. Together, these results implicate altered corticostriatal processing of monetary rewards in chronic pain.

Brain Activity during Methamphetamine Anticipation in a Non-Invasive Self-Administration Paradigm in Mice.

The ability to sense time and anticipate events is critical for survival. Learned responses that allow anticipation of the availability of food or water have been intensively studied. While anticipatory behaviors also occur prior to availability of regularly available rewards, there has been relatively little work on anticipation of drugs of abuse, specifically methamphetamine (MA). In the present study, we used a protocol that avoided possible CNS effects of stresses of handling or surgery by testing anticipation of MA availability in animals living in their home cages, with daily voluntary access to the drug at a fixed time of day. Anticipation was operationalized as the amount of wheel running prior to MA availability. Mice were divided into four groups given access to either nebulized MA or water, in early or late day. Animals with access to MA, but not water controls, showed anticipatory activity, with more anticipation in early compared to late day and significant interaction effects. Next, we explored the neural basis of the MA anticipation, using c-FOS expression, in animals euthanized at the usual time of nebulization access. In the dorsomedial hypothalamus (DMH) and orbitofrontal cortex (OFC), the pattern of c-FOS expression paralleled that of anticipatory behavior, with significant main and interaction effects of treatment and time of day. The results for the lateral septum (LS) were significant for main effects and marginally significant for interaction effects. These studies suggest that anticipation of MA is associated with activation of brain regions important in circadian timing, emotional regulation, and decision making.

Sex differences in circadian food anticipatory activity are not altered by individual manipulations of sex hormones or sex chromosome copy number in mice.

Recent studies in mice have demonstrated a sexual dimorphism in circadian entrainment to scheduled feeding. On a time restricted diet, males tend to develop food anticipatory activity (FAA) sooner than females and with a higher amplitude of activity. The underlying cause of this sex difference remains unknown. One study suggests that sex hormones, both androgens and estrogens, modulate food anticipatory activity in mice. Here we present results suggesting that the sex difference in FAA is unrelated to gonadal sex hormones. While a sex difference between males and females in FAA on a timed, calorie restricted diet was observed there were no differences between intact and gonadectomized mice in the onset or magnitude of FAA. To test other sources of the sex difference in circadian entrainment to scheduled feeding, we used sex chromosome copy number mutants, but there was no difference in FAA when comparing XX, XY-, XY-;Sry Tg, and XX;Sry Tg mice, demonstrating that gene dosage of sex chromosomes does not mediate the sex difference in FAA. Next, we masculinized female mice by treating them with 17-beta estradiol during the neonatal period; yet again, we saw no difference in FAA between control and masculinized females. Finally, we observed that there was no longer a sex difference in FAA for older mice, suggesting that the sex difference in FAA is age-dependent. Thus, our study demonstrates that singular manipulations of gonadal hormones, sex chromosomes, or developmental patterning are not able to explain the difference in FAA between young male and female mice.

Minimal Circuit Model of Reward Prediction Error Computations and Effects of Nicotinic Modulations.

Dopamine (DA) neurons in the ventral tegmental area (VTA) are thought to encode reward prediction errors (RPE) by comparing actual and expected rewards. In recent years, much work has been done to identify how the brain uses and computes this signal. While several lines of evidence suggest the interplay of the DA and the inhibitory interneurons in the VTA implements the RPE computation, it still remains unclear how the DA neurons learn key quantities, for example the amplitude and the timing of primary rewards during conditioning tasks. Furthermore, endogenous acetylcholine and exogenous nicotine, also likely affect these computations by acting on both VTA DA and GABA (γ -aminobutyric acid) neurons via nicotinic-acetylcholine receptors (nAChRs). To explore the potential circuit-level mechanisms for RPE computations during classical-conditioning tasks, we developed a minimal computational model of the VTA circuitry. The model was designed to account for several reward-related properties of VTA afferents and recent findings on VTA GABA neuron dynamics during conditioning. With our minimal model, we showed that the RPE can be learned by a two-speed process computing reward timing and magnitude. By including models of nAChR-mediated currents in the VTA DA-GABA circuit, we showed that nicotine should reduce the acetylcholine action on the VTA GABA neurons by receptor desensitization and potentially boost DA responses to reward-related signals in a non-trivial manner. Together, our results delineate the mechanisms by which RPE are computed in the brain, and suggest a hypothesis on nicotine-mediated effects on reward-related perception and decision-making.

Nicotine Increases Activation to Anticipatory Valence Cues in Anterior Insula and Striatum.

Introduction: Smoking is associated with significant morbidity and mortality. Understanding the neurobiology of the rewarding effects of nicotine promises to aid treatment development for nicotine dependence. Through its actions on mesolimbic dopaminergic systems, nicotine engenders enhanced responses to drug-related cues signaling rewards, a mechanism hypothesized to underlie the development and maintenance of nicotine addiction. Methods: We evaluated the effects of acute nicotine on neural responses to anticipatory cues signaling (nondrug) monetary reward or loss among 11 nonsmokers who had no prior history of tobacco smoking. In a double-blind, crossover design, participants completed study procedures while wearing nicotine or placebo patches at least 1 week apart. In each drug condition, participants underwent functional magnetic resonance imaging while performing the monetary incentive delay task and performed a probabilistic monetary reward task, probing reward responsiveness as measured by response bias toward a more frequently rewarded stimulus. Results: Nicotine administration was associated with enhanced activation, compared with placebo, of right fronto-anterior insular cortex and striatal regions in response to cues predicting possible rewards or losses and to dorsal anterior cingulate for rewards. Response bias toward rewarded stimuli correlated positively with insular activation to anticipatory cues. Conclusion: Nicotinic enhancement of monetary reward-related brain activation in the insula and striatum in nonsmokers dissociated acute effects of nicotine from effects on reward processing due to chronic smoking. Reward responsiveness predicted a greater nicotinic effect on insular activation to salient stimuli. Implications: Previous research demonstrates that nicotine enhances anticipatory responses to rewards in regions targeted by midbrain dopaminergic systems. The current study provides evidence that nicotine also enhances responses to rewards and losses in the anterior insula. A previous study found enhanced insular activation to rewards and losses in smokers and ex-smokers, a finding that could be due to nicotine sensitization or factors related to current or past smoking. Our finding of enhanced anterior insula response after acute administration of nicotine in nonsmokers provides support for nicotine-induced sensitization of insular response to rewards and losses.

Positive Outcome Expectations and Tobacco Product Use Behaviors in Youth.

BACKGROUND: Outcome expectations are an important determinant of health behavior, according to Social Cognitive Theory; yet recent literature has not examined the relationship between outcome expectations and tobacco product use (e.g., use of cigarettes, cigars, hookah, e-cigarettes, or smokeless tobacco). OBJECTIVES: This study examines if outcome expectations at baseline, among an adolescent cohort of never users of tobacco products, predicts tobacco product use (i.e., cigarettes, hookah, e-cigarette, cigar, or smokeless tobacco) or susceptibility to use at 6-month follow-up. METHODS: Data are from the first two waves of a Texas cohort study of urban middle school and high school students, which were collected in 2014-2015. Logistic regression analyses were used; these adjusted for socio-demographic variables. Analyses were limited to never users of any tobacco product at baseline (n = 1999, N = 357,035). RESULTS: Outcome expectations related to stress relief predicted ever use of (AOR: 4.21, 95% CI 1.84-9.60) and susceptibility (AOR: 2.97, 95% CI 1.01-8.70) to tobacco products. Additional outcome expectations (e.g., relaxation, concentration, slimness, etc.) were not associated with ever use or susceptibility. Conclusions/Importance: This study extends the literature regarding outcome expectations among adolescents regarding tobacco products. It is important that interventions offer alternative solutions to stress relief that do not include tobacco products.

Brain responses to vestibular pain and its anticipation in women with Genito-Pelvic Pain/Penetration Disorder.

OBJECTIVE: In DSM-5, pain-related fear during anticipation of vaginal penetration is a diagnostic criterion of Genito-Pelvic Pain/Penetration Disorder (GPPPD). We aimed to investigate subjective and brain responses during anticipatory fear and subsequent induction of vestibular pain in women with GPPPD. METHODS: Women with GPPPD (n = 18) and age-matched healthy controls (HC) (n = 15) underwent fMRI scanning during vestibular pain induction at individually titrated pain threshold after a cued anticipation period. (Pain-related) fear and anxiety traits were measured with questionnaires prior to scanning, and anticipatory fear and pain intensity were rated during scanning using visual analog scales. RESULTS: Women with GPPPD reported significantly higher levels of anticipatory fear and pain intensity. During anticipation and pain induction they had stronger and more extensive brain responses in regions involved in cognitive and affective aspects of pain perception, but the group difference did not reach significance for the anticipation condition. Pain-related fear and anxiety traits as well as anticipatory fear ratings were positively associated with pain ratings in GPPPD, but not in HC. Further, in HC, a negative association was found between anticipatory fear ratings and brain responses in regions involved in cognitive and affective aspects of pain perception, but not in women with GPPPD. CONCLUSIONS: Women with GPPPD are characterized by increased subjective and brain responses to vestibular pain and, to a lesser extent, its anticipation, with fear and anxiety associated with responses to pain, supporting the introduction of anticipatory fear as a criterion of GPPPD in DSM-5.

Expert - Non-expert differences in visual behaviour during alpine slalom skiing.

The aim of this study was to investigate visual behaviour of expert and non-expert ski athletes during an alpine slalom. Fourteen non-experts and five expert slalom skiers completed an alpine slalom course in an indoor ski slope while wearing a head-mounted eye tracking device. Experts completed the slalom clearly faster than non-experts, but no significant difference was found in timing and position of the turn initiation. Although both groups already looked at future obstacles approximately 0,5s before passing the upcoming pole, the higher speed of experts implied that they shifted gaze spatially earlier in the bend than non-experts. Furthermore, experts focussed more on the second next pole while non-expert slalom skiers looked more to the snow surface immediately in front of their body. No difference was found in the fixation frequency, average fixation duration, and quiet eye duration between both groups. These results suggest that experts focus on the timing of their actions while non-experts still need to pay attention to the execution of these actions. These results also might suggest that ski trainers should instruct non-experts and experts to focus on the next pole and, shift their gaze to the second next pole shortly before reaching it. Based on the current study it seems unadvisable to instruct slalom skiers to look several poles ahead during the actual slalom. However, future research should test if these results still hold on a real outdoor slope, including multiple vertical gates.

Impairment in predictive processes during auditory mismatch negativity in ScZ: Evidence from event-related fields.

Patients with schizophrenia (ScZ) show pronounced dysfunctions in auditory perception but the underlying mechanisms as well as the localization of the deficit remain unclear. To examine these questions, the current study examined whether alterations in the neuromagnetic mismatch negativity (MMNm) in ScZ-patients could involve an impairment in sensory predictions in local sensory and higher auditory areas. Using a whole-head MEG-approach, we investigated the MMNm as well as P300m and N100m amplitudes during a hierarchical auditory novelty paradigm in 16 medicated ScZ-patients and 16 controls. In addition, responses to omitted sounds were investigated, allowing for a critical test of the predictive coding hypothesis. Source-localization was performed to identify the generators of the MMNm, omission responses as well as the P300m. Clinical symptoms were examined with the positive and negative syndrome scale. Event-related fields (ERFs) to standard sounds were intact in ScZ-patients. However, the ScZ-group showed a reduction in the amplitude of the MMNm during both local (within trials) and global (across trials) conditions as well as an absent P300m at the global level. Importantly, responses to sound omissions were reduced in ScZ-patients which overlapped both in latency and generators with the MMNm sources. Thus, our data suggest that auditory dysfunctions in ScZ involve impaired predictive processes that involve deficits in both automatic and conscious detection of auditory regularities. Hum Brain Mapp 38:5082-5093, 2017. © 2017 Wiley Periodicals, Inc.