Comparing stroke prevention therapy of direct oral anticoagulants and vitamin K antagonists in patients with atrial fibrillation: a nationwide retrospective observational study.

BACKGROUND: Direct oral anticoagulants (DOACs) are not only increasingly being used for the initial stroke prevention therapy but progressively also substitute vitamin K antagonist (VKA) treatment in patients with non-valvular atrial fibrillation (AF). DOACs have been compared regarding therapeutic efficacy and adverse outcomes to warfarin in several pivotal studies and showed non-inferiority in terms of stroke prevention and superiority in terms of bleeding complications. However, comprehensive comparative studies are lacking for phenprocoumon, a VKA prescribed frequently outside the USA and the UK and accounting for 99% of all VKA prescriptions in Germany. Patients treated with phenprocoumon seem to meet more often international normalized ratio values in the therapeutic range, which may have implications concerning their efficacy and safety. This study aims at comparing the risk of stroke and bleeding in phenprocoumon- and DOAC-treated patients with AF in an adequately powered observational study population. METHODS: Retrospective analysis of stroke and bleeding incidence of 837,430 patients (1.27 million patient years) treated with DOAC or phenprocoumon for stroke prevention in German ambulatory care between 2010 and 2017. Relative risks of stroke and bleeding were estimated by calculating cox regression-derived hazard ratios (HR) and 95% confidence intervals (CI) of propensity score-matched cohorts. RESULTS: Patients treated with DOAC had an overall higher risk for stroke (HR 1.32; CI 1.29-1.35) and a lower risk for bleeding (0.89; 0.88-0.90) compared to phenprocoumon. When analyzed separately, the risk for stroke was higher for dabigatran (1.93; 1.82-2.03), apixaban (1.52; 1.46-1.58), and rivaroxaban (1.13; 1.10-1.17) but not for edoxaban (0.88; 0.74-1.05). The risk for bleeding was lower for dabigatran (0.85; 0.83-0.88), apixaban (0.71; 0.70-0.73), and edoxaban (0.29; 0.17-0.51) but not for rivaroxaban (1.03; 1.01-1.04). CONCLUSIONS: This study provides a comprehensive view of the stroke and bleeding risks associated with phenprocoumon and DOAC use in Germany. Phenprocoumon may be preferable to DOAC treatment for the prevention of strokes in AF in a real-world population cared for in ambulatory care.

Motivational effects on the processing of delayed intentions in the anterior prefrontal cortex.

Delaying intentions bears the risk of interference from distracting activities during the delay interval. Motivation can increase intention retrieval success but little is known about the underlying brain mechanisms. Here, we investigated whether motivational incentives (monetary reward) modulate the processing of delayed intentions in the anterior prefrontal cortex (aPFC), known to be crucial for intention processing. Using a mixed blocked and event-related functional Magnetic Resonance Imaging design, we specifically tested whether reward affects intention processing in the aPFC in a transient or in a sustained manner and whether this is related to individual differences in retrieval success. We found a generalized effect of reward on both correct intention retrieval and ongoing task performance. Fronto-parietal regions including bilateral lateral aPFC showed sustained activity increases in rewarded compared to non-rewarded blocks as well as transient reward-related activity during the storage phase. Additionally, individual differences in reward-related performance benefits were related to the degree of transient signal increases in right lateral aPFC, specifically during intention encoding. This suggests that the ability to integrate motivational relevance into the encoding of future intentions is crucial for successful intention retrieval in addition to general increases in processing effort. Bilateral aPFC is central to these motivation-cognition interactions.

Motivation by potential gains and losses affects control processes via different mechanisms in the attentional network.

Attentional control in demanding cognitive tasks can be improved by manipulating the motivational state. Motivation to obtain gains and motivation to avoid losses both usually result in faster reaction times and stronger activation in relevant brain areas such as the prefrontal cortex, but little is known about differences in the underlying neurocognitive mechanisms of these types of motivation in an attentional control context. In the present functional magnetic resonance imaging (fMRI) study, we tested whether potential gain and loss as motivating incentives lead to overlapping or distinct neural effects in the attentional network, and whether one of these conditions is more effective than the other. A Flanker task with word stimuli as targets and distracters was performed by 115 healthy participants. Using a mixed blocked and event-related design allowed us to investigate transient and sustained motivation-related effects. Participants could either gain money (potential gain) or avoid losing money (potential loss) in different task blocks. Participants showed a congruency effect with increased reaction times for incongruent compared to congruent trials. Potential gain led to generally faster responses compared to the neutral condition and to stronger improvements than potential loss. Potential loss also led to shorter response times compared to the neutral condition, but participants improved mainly during incongruent and not during congruent trials. The event-related fMRI data revealed a main effect of congruency with increased activity in the left inferior frontal gyrus (IFG) and inferior frontal junction area (IFJ), the pre-supplementary motor area (pre-SMA), bilateral insula, intraparietal sulcus (IPS) and visual word form area (VWFA). While potential gain led to increased activity in a cluster of the IFJ and the VWFA only during incongruent trials, potential loss was linked to activity increases in these regions during incongruent and congruent trials. The block analysis revealed greater activity in gain and loss blocks compared to the neutral condition in most of these regions but no differences in the direct comparison of gain and loss blocks. These findings show that potential monetary gain and loss rely on different mechanisms: Gain was more effective in reducing the reaction time compared to potential loss. Brain data indicate that in the gain context attentional control is executed specifically in incongruent trials, whereas the loss context induces an unspecific increase of attentional control. These findings extend previous studies by providing evidence for diverging neural mechanisms for the effects of different types of motivation on attentional control, specifying the underlying activity patterns in task- and stimulus-related regions.

Trends in antipsychotic use among children and adolescents in Germany: a study using 2011-2020 nationwide outpatient claims data.

Introduction: We aimed to provide an update on trends in antipsychotic (AP) use among children and adolescents in Germany. Materials and methods: Based on nationwide outpatient claims data from Germany, we conducted a cross-sectional study. For each year from 2011 to 2020, we determined the prevalence of AP use, defined as the proportion of children and adolescents with at least one AP dispensation. We evaluated trends in AP use by age, sex, and AP class (typical vs. atypical). Additionally, we assessed trends in the specialty of AP prescribers and the frequency of psychiatric diagnoses among AP users. Results: Overall, data from more than 12 million children and adolescents were included for each calendar year (2011: 12,488,827; 2020: 13,330,836). From 2011 to 2020, the overall prevalence of pediatric AP use increased from 3.16 to 3.65 per 1,000, due to an increase in use of both typical APs (from 1.16 to 1.35 per 1,000) and atypical APs (from 2.35 to 2.75 per 1,000). The largest increase in AP use was found among 15- to 19-year-old females, with an increase from 3.88 per 1,000 in 2011 to 7.86 per 1,000 in 2020 (+103%), mainly due to rising quetiapine use (from 1.17 to 3.46 per 1,000). Regarding prescribers' specialty, the proportion of APs prescribed by child and adolescent psychiatrists increased during the studied period (2011: 24.8%; 2020: 36.4%), whereas prescriptions by pediatricians (2011: 26.0%; 2020: 19.9%) and general practitioners (2011: 18.0%; 2020: 12.4%) decreased. Risperidone was the most commonly used AP in males, and quetiapine was the leading AP in females, each with the highest prevalence in 15- to 19-year-olds. In male risperidone users in this age group, the most frequent diagnosis was attention-deficit/hyperactivity disorder (50.4%), while in female quetiapine users it was depression (82.0%). Discussion: Use of APs among children and adolescents in Germany has continued to increase over the last decade. The sharp increase in AP use among 15- to 19-year-old females, which is largely due to an increased use of quetiapine, is remarkable. Potential reasons for this increase-e.g., limited access to psychosocial treatments-should be carefully analyzed. Also, the introduction of more restrictive prescribing guidelines might be considered.

Dynamic computation of value signals via a common neural network in multi-attribute decision-making.

Studies in decision neuroscience have identified robust neural representations for the value of choice options. However, overall values often depend on multiple attributes, and it is not well understood how the brain evaluates different attributes and integrates them to combined values. In particular, it is not clear whether attribute values are computed in distinct attribute-specific regions or within the general valuation network known to process overall values. Here, we used a functional magnetic resonance imaging choice task in which abstract stimuli had to be evaluated based on variations of the attributes color and motion. The behavioral data showed that participants responded faster when overall values were high and attribute value differences were low. On the neural level, we did not find that attribute values were systematically represented in areas V4 and V5, even though these regions are associated with attribute-specific processing of color and motion, respectively. Instead, attribute values were associated with activity in the posterior cingulate cortex, ventral striatum and posterior inferior temporal gyrus. Furthermore, overall values were represented in dorsolateral and ventromedial prefrontal cortex, and attribute value differences in dorsomedial prefrontal cortex, which suggests that these regions play a key role for the neural integration of attribute values.

Salience network dynamics underlying successful resistance of temptation.

Self-control and the ability to resist temptation are critical for successful completion of long-term goals. Contemporary models in cognitive neuroscience emphasize the primary role of prefrontal cognitive control networks in aligning behavior with such goals. Here, we use gaze pattern analysis and dynamic functional connectivity fMRI data to explore how individual differences in the ability to resist temptation are related to intrinsic brain dynamics of the cognitive control and salience networks. Behaviorally, individuals exhibit greater gaze distance from target location (e.g. higher distractibility) during presentation of tempting erotic images compared with neutral images. Individuals whose intrinsic dynamic functional connectivity patterns gravitate toward configurations in which salience detection systems are less strongly coupled with visual systems resist tempting distractors more effectively. The ability to resist tempting distractors was not significantly related to intrinsic dynamics of the cognitive control network. These results suggest that susceptibility to temptation is governed in part by individual differences in salience network dynamics and provide novel evidence for involvement of brain systems outside canonical cognitive control networks in contributing to individual differences in self-control.

Decomposing Self-Control: Individual Differences in Goal Pursuit Despite Interfering Aversion, Temptation, and Distraction.

Self-control can be defined as the ability to exert control over ones impulses. Currently, most research in the area relies on self-report. Focusing on attentional control processes involved in self-control, we modified a spatial selective attentional cueing task to test three domains of self-control experimentally in one task using aversive, tempting, and neutral picture-distractors. The aims of the study were (1) to investigate individual differences in the susceptibility to aversive, tempting, and neutral distraction within one paradigm and (2) to test the association of these three self-control domains to conventional measures of self-control including self-report. The final sample consisted of 116 participants. The task required participants to identify target letters "E" or "F" presented at a cued target location while the distractors were presented. Behavioral and eyetracking data were obtained during the performance of the task. High task performance was encouraged via monetary incentives. In addition to the attentional self-control task, self-reported self-control was assessed and participants performed a color Stroop task, an unsolvable anagram task and a delay of gratification task using chocolate sweets. We found that aversion, temptation, and neutral distraction were associated with significantly increased error rates, reaction times and gaze pattern deviations. Overall task performance on our task correlated with self-reported self-control ability. Measures of aversion, temptation, and distraction showed moderate split-half reliability, but did not correlate with each other across participants. Additionally, participants who made a self-controlled decision in the delay of gratification task were less distracted by temptations in our task than participants who made an impulsive choice. Our individual differences analyses suggest that (1) the ability to endure aversion, resist temptations and ignore neutral distractions are independent of each other and (2) these three domains are related to other measures of self-control.

Individual differences in self-reported self-control predict successful emotion regulation.

Both self-control and emotion regulation enable individuals to adapt to external circumstances and social contexts, and both are assumed to rely on the overlapping neural resources. Here, we tested whether high self-reported self-control is related to successful emotion regulation on the behavioral and neural level. One hundred eight participants completed three self-control questionnaires and regulated their negative emotions during functional magnetic resonance imaging using reappraisal (distancing). Trait self-control correlated positively with successful emotion regulation both subjectively and neurally, as indicated by online ratings of negative emotions and functional connectivity strength between the amygdala and prefrontal areas, respectively. This stronger overall connectivity of the left amygdala was related to more successful subjective emotion regulation. Comparing amygdala activity over time showed that high self-controllers successfully maintained down-regulation of the left amygdala over time, while low self-controllers failed to down-regulate towards the end of the experiment. This indicates that high self-controllers are better at maintaining a motivated state supporting emotion regulation over time. Our results support assumptions concerning a close relation of self-control and emotion regulation as two domains of behavioral control. They further indicate that individual differences in functional connectivity between task-related brain areas directly relate to differences in trait self-control.

The suggestible brain: posthypnotic effects on value-based decision-making.

Hypnosis can affect perception, motor function and memory. However, so far no study using neuroimaging has investigated whether hypnosis can influence reward processing and decision-making. Here, we assessed whether posthypnotic suggestions can diminish the attractiveness of unhealthy food and whether this is more effective than diminishing attractiveness by one's own effort via autosuggestion. In total, 16 participants were hypnotized and 16 others were instructed to associate a color cue (blue or green) with disgust regarding specific snacks (sweet or salty). Afterwards, participants bid for snack items shown on an either blue or green background during functional magnetic resonance imaging measurement. Both hypnosis and autosuggestion successfully devalued snacks. This was indicated by participants' decision-making, their self-report and by decreased blood oxygen level-dependent signal in the ventromedial prefrontal cortex (vmPFC), a region known to represent value. Different vmPFC subregions coded for cue and snack type. The cue had significantly stronger effects on vmPFC after hypnosis than after autosuggestion, indicating that hypnosis was more effective in genuinely reducing value. Supporting previous findings, the precuneus was involved in the hypnotic effects by encoding whether a snack was sweet or salty during hypnotic cue presentation. Our results demonstrate that posthypnotic suggestions can influence valuation and decision-making.