Acute normovolemic hemodilution in cardiac surgery: Rationale and design of a multicenter randomized trial.

BACKGROUND: Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. METHODS: This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 mL as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. RESULTS: The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. CONCLUSION: The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.

The influence of single-session reward-based attentional bias modification on attentional biases towards threat as measured by the N2pc component.

Attentional biases toward threatening faces have repeatedly been studied in the context of social anxiety, with etiological theories suggesting exacerbated biases as a possible cause for the latter. To counteract these postulated effects, research has focused on the concept of attentional bias manipulation (ABM), in which spatial contingencies between succeeding stimuli are traditionally employed in training paradigms designed to deliberately shift automatic attention processes away from threat-related stimuli. The ABM research field has been faced with various methodological challenges, such as inconsistent results, low reliabilities of dependent variables and a high susceptibility to moderating factors. We aimed to combine several recent approaches to address these issues. Drawing upon theories of value-driven attention, we explored reward-based contingencies in a Dot Probe task to improve the training's efficacy, combined with neurophysiological measures for greater reliability compared to reaction times, while evaluating the moderating effect of explicitness in the instruction. In a healthy sample (N = 60) and within a single session, we found a general attentional bias toward angry faces present across all conditions as indicated by the N2pc, which was, however, marked by large intrinsic lateralization effects, with submeasures exhibiting opposing polarities. This prompted us to explore an alternative, intrahemispheric calculation method. The new N2pc variant showed the attentional bias to have disappeared at the end of the training session within the explicit instruction group. Reliabilities of the main dependent variables were varied from excellent to questionable, which, together with the exploratory nature of the analysis, leaves this result as preliminary.

The reality of virtual reality.

Virtual reality (VR) has become a popular tool for investigating human behavior and brain functions. Nevertheless, it is unclear whether VR constitutes an actual form of reality or is more like an advanced simulation. Determining the nature of VR has been mostly achieved by self-reported presence measurements, defined as the feeling of being submerged in the experience. However, subjective measurements might be prone to bias and, most importantly, do not allow for a comparison with real-life experiences. Here, we show that real-life and VR height exposures using 3D-360° videos are mostly indistinguishable on a psychophysiological level (EEG and HRV), while both differ from a conventional 2D laboratory setting. Using a fire truck, three groups of participants experienced a real-life (N = 25), a virtual (N = 24), or a 2D laboratory (N = 25) height exposure. Behavioral and psychophysiological results suggest that identical exogenous and endogenous cognitive as well as emotional mechanisms are deployed to process the real-life and virtual experience. Specifically, alpha- and theta-band oscillations in line with heart rate variability, indexing vigilance, and anxiety were barely indistinguishable between those two conditions, while they differed significantly from the laboratory setup. Sensory processing, as reflected by beta-band oscillations, exhibits a different pattern for all conditions, indicating further room for improving VR on a haptic level. In conclusion, the study shows that contemporary photorealistic VR setups are technologically capable of mimicking reality, thus paving the way for the investigation of real-world cognitive and emotional processes under controlled laboratory conditions. For a video summary, see https://youtu.be/fPIrIajpfiA.

Midfrontal Theta Activity Is Sensitive to Approach-Avoidance Conflict.

Midfrontal theta (FMθ) in the human EEG is commonly viewed as a generic and homogeneous mechanism of cognitive control in general and conflict processing in particular. However, the role of FMθ in approach-avoidance conflicts and its cross-task relationship to simpler stimulus-response conflicts remain to be examined more closely. Therefore, we recorded EEG data while 59 healthy participants (49 female, 10 male) completed both an approach-avoidance task and a flanker task. Participants showed significant increases in FMθ power in response to conflicts in both tasks. To our knowledge, this is the first study to show a direct relationship between FMθ and approach-avoidance conflicts. Crucially, FMθ activity was task dependent and showed no cross-task correlation. To assess the possibility of multiple FMθ sources, we applied source separation [generalized eigendecomposition (GED)] to distinguish independent FMθ generators. The activity of the components showed a similar pattern and was again task specific. However, our results did not yield a clear differentiation between task-specific FMθ sources for each of the participants. Overall, our results show FMθ increases in approach-avoidance conflicts, as has been established only for more simple response conflict paradigms so far. The independence of task-specific FMθ increases suggests differential sensitivity of FMθ to different forms of behavioral conflict.SIGNIFICANCE STATEMENT FMθ is well established as an indicator for cognitive conflict in tasks involving simple stimulus-response conflicts. However, we do not yet know about its role in more complex forms of goal ambivalence, such as approach-avoidance conflicts. Thus, we implemented an approach-avoidance task and a flanker task to investigate FMθ in response to simple as well as more complex response conflicts. To our knowledge, this is the first study to show a direct relationship between FMθ and approach-avoidance conflicts. Although the transient FMθ increase is similar to that induced in a simple response conflict task, individual FMθ responsiveness to these two forms of conflict were independent of each other, suggesting intraindividual differences in the sensitivity of FMθ to different forms of behavioral conflict.

Neuro-Behavioral Dynamic Prediction of Interpersonal Cooperation and Aggression.

How to quickly predict an individual's behavioral choices is an important issue in the field of human behavior research. Using noninvasive electroencephalography, we aimed to identify neural markers in the prior outcome-evaluation stage and the current option-assessment stage of the chicken game that predict an individual's behavioral choices in the subsequent decision-output stage. Hierarchical linear modeling-based brain-behavior association analyses revealed that midfrontal theta oscillation in the prior outcome-evaluation stage positively predicted subsequent aggressive choices; also, beta oscillation in the current option-assessment stage positively predicted subsequent cooperative choices. These findings provide electrophysiological evidence for the three-stage theory of decision-making and strengthen the feasibility of predicting an individual's behavioral choices using neural oscillations.

Volatile and Intravenous Anesthetics for Brain Protection in Cardiac Surgery: Does the Choice of Anesthesia Matter?

Postoperative neurologic complications have a significant effect on morbidity, mortality, and long-term disability in patients undergoing cardiac surgery. The etiology of brain injury in patients undergoing cardiac surgery is multifactorial and remains unclear. There are several perioperative causative factors for neurologic complications, including microembolization, hypoperfusion, and systemic inflammatory response syndrome. Despite technologic advances and the development of new anesthetic drugs, there remains a high rate of postoperative neurologic complications. Moreover, despite the strong evidence that volatile anesthesia exerts cardioprotective effects in patients undergoing cardiac surgery, the neuroprotective effects of volatile agents remain unclear. Several studies have reported an association of using volatile anesthetics with improvement of biochemical markers of brain injury and postoperative neurocognitive function. However, there is a need for additional studies to define the optimal anesthetic drug for protecting the brain in patients undergoing cardiac surgery.

Do food images as action outcomes evoke a reward positivity?

Favourable compared to unfavourable action outcomes typically evoke a positive-going amplitude shift at frontomedial electrodes in the scalp-recorded electroencephalogram. Since prior studies on this Reward Positivity (RewP) have heavily relied on monetary outcomes, it is still debated whether the RewP is also elicited by other kinds of reward. We addressed this issue by focussing on food as another major category of daily reward. Twenty-eight healthy participants completed a decision task, in which they received images of personally liked, neutral or disliked food as outcome stimuli. Importantly, single trial outcomes were of relevance for a prolonged task goal (i.e., obtaining the liked foods and avoiding the disliked foods). The observed amplitude pattern did not correspond to the typical RewP effect observed for monetary outcomes. In particular, disliked foods evoked a similar positive-going amplitude shift as liked foods when compared to neutral foods. Exploratory analyses indicated that this pattern may result from a spatiotemporal overlap between a potential RewP response and other, emotion-related ERP components (i.e., the Early Posterior Negativity and the Late Positive Potential). We discuss our findings with regard to theoretical and methodological implications for the usage of the RewP in the study of reward processing.

The reward positivity reflects the integrated value of temporally threefold-layered decision outcomes.

In reinforcement learning, adaptive behavior depends on the ability to predict future outcomes based on previous decisions. The Reward Positivity (RewP) is thought to encode reward prediction errors in the anterior midcingulate cortex (aMCC) whenever these predictions are violated. Although the RewP has been extensively studied in the context of simple binary (win vs. loss) reward processing, recent studies suggest that the RewP scales complex feedback in a fine graded fashion. The aim of this study was to replicate and extend previous findings that the RewP reflects the integrated sum of instantaneous and delayed consequences of a singular outcome by increasing the feedback information content by a third temporal dimension. We used a complex reinforcement-learning task where each option was associated with an immediate, intermediate and delayed monetary outcome and analyzed the RewP in the time domain as well as fronto-medial theta power in the time-frequency domain. To test if the RewP sensitivity to the three outcome dimensions reflect stable trait-like individual differences in reward processing, a retesting session took place 3 months later. The results confirm that the RewP reflects the integrated value of complex temporally extended consequences in a stable manner, albeit there was no relation to behavioral choice. Our findings indicate that the medial frontal cortex receives fine graded information about complex action outcomes that, however, may not necessarily translate to cognitive or behavioral control processes.

Aiming at ecological validity-Midfrontal theta oscillations in a toy gun shooting task.

Laboratory electroencephalography (EEG) studies have already provided important insights into the neuronal mechanisms of performance monitoring. However, to our knowledge no study so far has examined neuronal correlates of performance monitoring using an ecologically valid task outside a typical laboratory setting. Therefore, we examined midfrontal theta and the feedback-related negativity (FRN) using mobile EEG in a physical shooting task within an ecologically valid environment with highly dynamical visual feedback. Participants shot a target using a toy gun while moving and looking around freely. Shots that missed the target evoked stronger midfrontal theta activity than hits and this response was rather phase-unlocked. There was no difference between misses and hits in the FRN. The results raise the question whether the absence of certain ERP components like the FRN could be due to methodological reasons or to the fact that partially different neuronal processes may be activated in the laboratory as compared to more ecologically valid tasks. Overall, our results indicate that crucial neurocognitive processes of performance monitoring can be assessed in highly dynamic and ecologically valid settings by mobile EEG.

Causal underpinnings of working memory and Stroop interference control: Testing the effects of anodal and cathodal tDCS over the left DLPFC.

By means of transcranial direct current stimulation applied to the left dorsolateral prefrontal cortex, we investigated the causal role of increased or decreased excitability of this brain region for two facets of executive functions: working memory and Stroop interference control. We tested 1) whether anodal tDCS of the left DLPFC enhances working memory 15 minutes after termination of stimulation and in the absence of direct task practice under stimulation; 2) whether anodal tDCS of the left DLPFC enhances interference control, as evidenced by Stroop performance and Stroop sequence effects; and 3) whether cathodal tDCS leads to compromised executive functioning compared to anodal stimulation. In a between-subject design with 88 healthy psychology students, we compared the impact of anodal and cathodal stimulation against a sham condition, on performance on a Stroop task (during active stimulation) and on an n-back task (completed 15 minutes after active stimulation ended). We found significantly enhanced accuracy in the n-back task after anodal stimulation compared with sham, as well as speeded reactions in the Stroop tasks independent of trial type. By contrast, we found no modulation of Stroop interference effects or Stroop sequence effects. No inhibitory effects of cathodal stimulation were observed. These results support the causal role of the left DLPFC in working memory but lend no support to its involvement in Stroop interference control.

Attentional bias modification in social anxiety: Effects on the N2pc component.

Several meta-analyses to date have confirmed the efficacy of attentional bias modification (ABM) in shifting reaction times away from threatening stimuli, reducing anxiety symptoms, and buffering against stressor vulnerability. The reliability of reaction time differences, however, has been found to show unacceptable psychometric properties. In this study, we tested the impact of an extensive Dot-Probe ABM procedure, consisting of close to 7000 trials, concurrently with behavioral and electrophysiological measures within a large sample of over 100 highly socially anxious participants. Results indicated that the N2pc component demonstrates superior internal consistency and more statistical power in detecting attentional biases and their modification than reaction time (RT) differences. RTs were neither indicative of an attentional bias before ABM nor of a modification over time. In contrast, the N2pc indexed both an initial attentional preference for threatening stimuli and an alteration of this relationship after training. Outcomes were not specific for attentional training away from threat but also occurred in the no-contingency control procedure, casting doubt on the theoretic underpinnings of ABM. Electrophysiological measures are an important complement to the ABM literature and should be further utilized to assess attentional biases with excellent reliability.

When two become one: Electrocortical correlates of the integration of multiple action consequences.

In a recent study we have demonstrated that the feedback-related negativity (FRN) reflects the integrated value of instantaneous and delayed decision consequences (Osinsky et al. 2017). In the present work, we extend this research by using a novel choice task in which instant and delayed consequence values of a single decision outcome can be manipulated independently of each other in a trial-wise manner. Fifty-nine healthy participants completed this task while EEG was recorded. Twenty-two of them returned one week later for a retesting, allowing for investigating temporal stability of individual FRN indices. Our results show that the FRN mainly reflects the additively integrated value of instant and delayed outcome consequences. Individual differences in the FRN sensitivity to the two consequence dimensions were specifically predictive for consequence-driven adjustments in choice behavior and moderately stable over time. Altogether, our findings are inconsistent with the idea that the FRN reflects a simple binary distinction between favorable and unfavorable action outcomes. Rather, the FRN appears to mirror a fine-grained scaling of action outcomes, which results from stable personal reward preferences and which is used for adjusting choice behavior. Given that the FRN is generated in the anterior midcingulate cortex, our study adds to recent literature according to which this structure uses multiple information to learn complex action-outcome values.

Work first then play: Prior task difficulty increases motivation-related brain responses in a risk game.

Task motivation depends on what we did before. A recent theory differentiates between tasks that we want to do and tasks that we have to do. After a have-to task, motivation shifts towards a want-to task. We measured this shift of motivation via brain responses to monetary feedback in a risk game that was used as want-to task in our study. We tested 20 healthy participants that were about 28 years old in a within-subjects design. Participants worked on a Stroop task (have-to task) or an easier version of the Stroop task as a control condition and played a risk game afterwards (want-to task). After the Stroop task, brain responses to monetary feedback in the risk game were larger compared to the easier control task, especially for feedback indicating higher monetary rewards. We conclude that higher amplitudes of feedback-related brain responses in the risk game reflect the shift of motivation after a have-to task towards a want-to task.

The Feedback-related Negativity Reflects the Combination of Instantaneous and Long-term Values of Decision Outcomes.

Hundreds of ERP studies have reported a midfrontal negative-going amplitude shift following negative compared with positive action outcomes. This feedback-related negativity (FRN) effect is typically thought to reflect an early and binary mechanism of action evaluation in the posterior midcingulate cortex. However, in prior research on the FRN effect, the instantaneous value and the long-term value of action outcomes have been perfectly confounded. That is, instantaneously positive outcomes were generally consistent with task goals, whereas instantaneously negative outcomes were inconsistent with task goals. In this study, we disentangled these two outcome aspects in two experiments. Our results reveal an interaction of instantaneous and long-term outcome values. More precisely, our findings strongly suggest that the FRN effect is mainly driven by a reward positivity, which is evoked only by outcomes that possess an instantaneously positive value and also help the organism to reach its long-term goals. These findings add to a recent literature according to which the posterior midcingulate cortex acts as a hierarchical reinforcement learning system and suggest that this system integrates instant and long-term action-outcome values. This, in turn, might be crucial for learning optimal behavioral strategies in a given setting.

The N2pc component reliably captures attentional bias in social anxiety.

We systematically compared different measures of attentional bias (i.e., reaction times, the N2pc component in the EEG, and explicit stimulus ratings) on their ability to reveal attentional engagement to threatening versus neutral facial stimuli in a Dot Probe Task and tested their relation to trait measures of general and social anxiety. We found that the N2pc component reflects a bias toward angry faces with excellent internal consistency. Similar results were obtained for explicit ratings. Reaction time (RT) differences, however, were not indicative of attentional biases and showed zero odd-even reliability. We further found that both higher (i.e., more negative) N2pc amplitudes and earlier peak latencies were associated with more severe symptoms of social anxiety even when controlling for general trait anxiety. The explicit rating biases were also specifically associated with social anxiety. Conversely, the RT bias was not related to social anxiety levels but to general trait anxiety. This highlights the importance of valid and reliable outcome measures for interventions such as attentional bias modification protocols. Mutual exclusivity of different bias operationalizations is discussed.

Ingroup/outgroup membership modulates fairness consideration: neural signatures from ERPs and EEG oscillations.

Previous studies have shown that ingroup/outgroup membership influences individual's fairness considerations. However, it is not clear yet how group membership influences brain activity when a recipient evaluates the fairness of asset distribution. In this study, subjects participated as recipients in an Ultimatum Game with alleged members of both an experimentally induced ingroup and outgroup. They either received extremely unequal, moderately unequal, or equal offers from proposers while electroencephalogram was recorded. Behavioral results showed that the acceptance rates for unequal offers were higher when interacting with ingroup partners than with outgroup partners. Analyses of event related potentials revealed that proposers' group membership modulated offer evaluation at earlier processing stages. Feedback-related negativity was more negative for extremely and moderately unequal offers compared to equal offers in the ingroup interaction whereas it did not show differential responses to different offers in the outgroup interaction. Analyses of event related oscillations revealed that the theta power (4-6 Hz) was larger for moderately unequal offers than equal offers in the ingroup interaction whereas it did not show differential responses to different offers in the outgroup interaction. Thus, early mechanisms of fairness evaluation are strongly modulated by the ingroup/outgroup membership of the interaction partner.

Dispositional Anxiety and Frontal-Midline Theta: On the Modulatory Influence of Sex and Situational Threat.

In their adaptive control hypothesis, Cavanagh and Shackman (2015) recently claimed that dispositional anxiety is correlated with frontal-midline theta (FMθ) as a generic "need for control" signal of the anterior midcingulate cortex. Here, we tested this assumption, also considering potential modulatory influences of anticipatory threat and individuals' sex. In a nonclinical sample of 168 participants (84 women), electroencephalogram was recorded while individuals performed a simple two-choice task. Half of the participants were assigned to a threat anticipation condition (anticipation of public speaking), whereas the other half was assigned to a control condition. State anxiety was monitored across the experiment. Dispositional anxiety was assessed by self-report scales, which were completed before individuals came to the laboratory. Target stimuli in the two-choice task induced a transient increase in FMθ power that was subject to an interaction of dispositional anxiety, sex, and experimental group. Only in women who anticipated public speaking did we observe a substantial positive relation between dispositional anxiety and general FMθ power. Our results indicate that the link between dispositional anxiety and FMθ is not universal but rather depends on complex interactions of individuals' sex and situational threat.

Patterns of theta oscillation reflect the neural basis of individual differences in epistemic motivation.

Theta oscillations in the EEG have been shown to reflect ongoing cognitive processes related to mental effort. Here, we show that the pattern of theta oscillation in response to varying cognitive demands reflects stable individual differences in the personality trait epistemic motivation: Individuals with high levels of epistemic motivation recruit relatively more cognitive resources in response to situations possessing high, compared to low, cognitive demand; individuals with low levels do not show such a specific response. Our results provide direct evidence for the theory of the construct need for cognition and add to our understanding of the neural processes underlying theta oscillations. More generally, we provide an explanation how individual differences in personality traits might be represented on a neural level.

Specific Reaction Patterns to Distinct Positive Emotional Cues Related to Incentive Motivation in Dependence of the Taq1A-Polymorphism: Molecular Genetic Associations of Early and Late Event-Related Potentials.

BACKGROUND/AIMS: Early and late event-related potential (ERP) responses, representing early subconscious and late motivational processes, were recorded for positive emotional words related to 'wanting' and 'liking', in dependence of the dopamine-related Taq1A genotype (ANKK1/DRD2). Research suggests that 'wanting' as opposed to 'liking' is related to dopaminergic processes. Therefore, it was hypothesized that risk allele carriers of the Taq1A polymorphism exhibit late ERP changes in reaction to words representing incentive motivation, i.e. 'wanting' (word categories 'lust' and 'anticipation'), but not to words representing 'liking' ('closeness'). METHODS: Seventy-two male participants performed an emotional-word Stroop task during EEG recording and were genotyped according to the Taq1A polymorphism of ANKK1/DRD2. RESULTS: Positive emotional words related to anticipation and lust revealed blunted responses in the late positive potential (LPP) in carriers of the A1 allele, an effect absent in response to 'liking'-related words. These differences were not evident in the earlier posterior negativity (EPN). CONCLUSION: As no differences in dependence of the Taq1A genotype were observed in reaction to 'wanting'- and 'liking'-related words in the EPN, but merely in the LPP, it can be assumed that incentive-motivational stimuli only modify motivation-related ERP responses in carriers of the A1 allele of the Taq1A polymorphism, indicating the role of dopamine in late ERP components.

Influences of State and Trait Affect on Behavior, Feedback-Related Negativity, and P3b in the Ultimatum Game.

The present study investigates how different emotions can alter social bargaining behavior. An important paradigm to study social bargaining is the Ultimatum Game. There, a proposer gets a pot of money and has to offer part of it to a responder. If the responder accepts, both players get the money as proposed by the proposer. If he rejects, none of the players gets anything. Rational choice models would predict that responders accept all offers above 0. However, evidence shows that responders typically reject a large proportion of all unfair offers. We analyzed participants' behavior when they played the Ultimatum Game as responders and simultaneously collected electroencephalogram data in order to quantify the feedback-related negativity and P3b components. We induced state affect (momentarily emotions unrelated to the task) via short movie clips and measured trait affect (longer-lasting emotional dispositions) via questionnaires. State happiness led to increased acceptance rates of very unfair offers. Regarding neurophysiology, we found that unfair offers elicited larger feedback-related negativity amplitudes than fair offers. Additionally, an interaction of state and trait affect occurred: high trait negative affect (subsuming a variety of aversive mood states) led to increased feedback-related negativity amplitudes when participants were in an angry mood, but not if they currently experienced fear or happiness. We discuss that increased rumination might be responsible for this result, which might not occur, however, when people experience happiness or fear. Apart from that, we found that fair offers elicited larger P3b components than unfair offers, which might reflect increased pleasure in response to fair offers. Moreover, high trait negative affect was associated with decreased P3b amplitudes, potentially reflecting decreased motivation to engage in activities. We discuss implications of our results in the light of theories and research on depression and anxiety.