Deep Brain Stimulation of Nucleus Accumbens Region in Alcoholism Affects Reward Processing

The influence of bilateral deep brain stimulation (DBS) of the nucleus nucleus (NAcc) on the processing of reward in a gambling paradigm was investigated using H2[15O]-PET (positron emission tomography) in a 38-year-old man treated for severe alcohol addiction. Behavioral data analysis revealed a less risky, more careful choice behavior under active DBS compared to DBS switched off. PET showed win- and loss-related activations in the paracingulate cortex, temporal poles, precuneus and hippocampus under active DBS, brain areas that have been implicated in action monitoring and behavioral control. Except for the temporal pole these activations were not seen when DBS was deactivated. These findings suggest that DBS of the NAcc may act partially by improving behavioral control

Single neuron computations of cognition in the human brain

Understanding how information is encoded, processed, and decoded to produce behavior is a fundamental goal of neuroscience. In this dissertation, we aim to expand our understanding of our human decision-making processes at the single-neuronal level. We describe three studies exploring the neural substrate of decision-making in three separate brain regions. First, we describe a method for recording the activity of individual neurons in human subjects. The unique combination of behavioral and neurophysiological data will allow us to better understand the neural substrate of cognitive functions in humans. Second, we explored how decisions are represented in the brain. We recorded single neuronal responses in the human nucleus accumbens while subjects engaged in a financial decision-making task. We found that neurons in the nucleus accumbens predicted upcoming decisions well before the behavior was manifested. In addition, these neurons encoded a positive and negative prediction error signal, signaling the difference between expected and realized outcome. Third, we explored how the brain represents decision conflict and how it adapts to prime future decisions allowing tradeoff between speed and accuracy. We found that individual neurons in the human dorsal anterior cingulate cortex encode the level of decision conflict in a dose-dependent manner. In addition, these neurons encode historical conflict information, priming the neural circuit to future trials of the same or varying conflict levels. Following selective ablation of the dorsal anterior cingulate cortex, we found this signal was selectively abolished. Lastly, we explored how the brain represents decisions under conflict and if these decisions are malleable to external intervention. We found that neurons in the human subthalamic nucleus are selectively activated and encode the upcoming decision during situations of high decision conflict. Based on the physiological findings, we then applied intermittent stimulation through the implanted deep brain stimulation electrode during the same task, to demonstrate a causal interaction between the physiology and behavior. In conclusion, we describe a set of experiments that systematically explore human decision-making processes at the single-neuronal level

Neuroentrepreneurship : Recommendations for organizational innovation to enhance entrepreneurial activity

Entrepreneurship research faces a crossroads and a new approach is needed to better understand entrepreneurial behavior. Incorporating neuroscience to comprehend the entrepreneurial mindset seems promising. Nevertheless, the potential of neuroscience for entrepreneurship research is only slowly being realized. Based on an extensive literature review, this thesis examines the emerging role of neuroscience with respect to entrepreneurship. Referring to the model of the entrepreneurial process, this thesis investigates how entrepreneurs discover, exploit, and finally capture opportunities. In this context, explanations regarding trait, expertise, adaptation, and mindset of the entrepreneur are relevant for further examination. Moreover, decision-making in uncertain situations is analyzed. In this context, the dynamic interplay between the reflective and reflexive system is considered. Ultimately, this thesis provides recommendations for organizational innovation to enhance entrepreneurial activity

Medial Frontal Theta Negativities (MFTN) as Predictors of Anxiety Sensitivity Treatment Response

Anxiety is one of the most prevalent mental health problems around the world. Despite a number of widely available interventions, it can take weeks or months to see effects, and nearly half of individuals may not respond. In an effort to better understand response rates, a large body of evidence indicates the most consistent predictor of treatment outcomes is activity in the anterior cingulate cortex (ACC). Although activity in ACC can be measured by medial frontal theta event related potentials (ERPs) at a finer temporal resolution, these neurophysiological components have not been evaluated as predictors of treatment response. There is also a lack of research on the functional networks associated with ACC treatment prediction, despite implications for prefrontal engagement of cognitive control processes. The present study aimed to examine these gaps in the literature by using task-based electroencephalography (EEG) and medial frontal theta negativities (MFTN) as predictors of anxiety sensitivity treatment response. Using amplitude as well as functional connectivity measures (i.e., inter-channel phase synchrony), baseline MFTN (i.e., Theta-FN, Theta-N2) were assessed as predictors of treatment response at mid-treatment, 1-week post treatment, and 6 months post treatment. Subjects underwent a baseline EEG before completing three sessions of a computerized cognitive behavioral intervention. Contrary to the hypothesis, findings revealed MFTN amplitude did not predict treatment response. However, medial to lateral prefrontal theta phase synchrony demonstrated significant prediction effects, such that lower phase synchrony was associated with greater symptom improvement at mid-treatment, 1-week post treatment, and 6 months post treatment. This effect was specific to certain task conditions (i.e., gain feedback and go stimuli), as well as to the combined anxiety and depression treatment group. Results demonstrated accuracy and consistency of treatment prediction, as well as incremental validity after controlling for self-report measures. Finally, results provide additional support for a convergent medial frontal theta process, and suggest that low engagement of regulatory and proactive control mechanisms may be predictive of better response to cognitive behavioral interventions. This work represents a novel finding that may contribute to the improvement in treatment efficacy by serving as a target for future interventions and individualized treatment selection

Different Types of Decision Making Impairments in Anorexia Nervosa

Research on neurocognitive aspects in Anorexia Nervosa (AN) has outlined a cognitive profile characterized by deficiency in the ability to set-shifting (cognitive flexibility) and weak central coherence. A smaller agreement emerges in relation to the compromission of decisional profiles frequently observed in patients with AN since both the complexity of the pathology and the executive function itself make it unclear the nature of these alterations and its relationships with specific or independent clinical and enviornmental variables. The aim of this study was: to investigate different types of decision-making (DM) ability, veridical and adaptive, in a sample of patients with AN using the Iowa Gambling Task and the Cognitive Bias Task; to analyze test performance using a specific cognitive model for the Iowa Gambling Task (Expectancy Valence Learning Model), and to study the relationship with clinical features, focusing on their relationship with neuropsychological profiles and clinical variables; to explore the neural correlations of the two tasks with functional connectivity; to observe the the impact of the genetic profile on different types of DM. Materials and Methods: The sample, consisting of 310 female subjects with AN lifetime and 301 female subjects without diagnosis of lifetime eating disorders, was tested in relation to DM abilities through the Iowa Gambling Task and cognitive Bias Task. All of the participants completed a baseline assessment including the Structured Clinical Interview (SCID) for the DSM-IV, section for eating disorders, and neuropsychological tests including the Wisconsin Card Sorting Test, and Trail Making Test for assessing abilities of abstraction and cognitive flexibility; 10 "and 30" interference memory test for evaluation of working memory, Stop Signal Task for evaluation of inibitory control. The Expectancy Valence Model (EVM) was used to analyze the results obtained in IGT. A genotyping was performed to evaluate the impact of the major polymorphisms implicated in decision-making (158 Val → Met) of the COMT gene and single nucleotide A / G polymorphism (SNP rs25531) of the serotonin carrier gene 5 - HTTLPR. In a smaller subgroup of 35 AN and 34 Healthy control seed based resting state Functional connectivity was explored. Compared to the group of healthy subjects, the decision-making profile of patients suffering from AN was worse in both Iowa Gambling Task (IGT), which evaluates veridical DM, and Cognitive Bias Task (Cbias), which evaluates adaptive DM, regardless of the diagnostic subtype (restrictive vs. binging/purging), psychopathology severity, scholarity, manual 3 dominance or outcome specific treatment. However in IGT the affective decision-making seems to be independent of IMC, conversely in Cbias the adaptive decisional profile was influenced by underweight. Both types of decision-making in patients were not affected by neurocognitive or clinical variables considered. The unfavorable geotype in AN resulted the homozygous for the met allele of the Comt gene and for the short variant of the serotonin transporter gene. The resting functional connectivity explored on the seeds of interest (executive network, orbitofrontal cortex, accumbens and amygdala) in a subgroup of patients and controls showed significantly different patterns of correlation with the scores of IGt and Cbias. In addition, different resting neural patterns appear to be involved in the two different tasks considered. Only in the AN group a positive correlation between the scores on IGT and the activity of the amygdala resulted. In AN group an higher coactivation within the executive, accumbens and orbitofrontal networks was linked to higher context-independency decisional style assessed with CBias, whereas for the executive network the opposite was true for healthy women. In summary our results confirm an impairment of different types of decision making in AN and highlitght the importance of assessing decisional processes with different specific tasks in clinical sample. In particular different maladaptative strategies are associated with ineffective decisional profiles in AN, consisting in a “myopia for the future” and “anxiety inhibition” in veridical situations and in a difficulty to update/review one’s own mindset according to new environmental stimuli (context indipendent reasoning strategies) in adaptive decisional framework. The severity of malnurishment seems to influence adaptive decisional style conferring a bias toward a context indipent reasoning, suggesting the need of metacognitive approach to help patients to be more aware of their tendency to automatically use selection bias in DM contexts. Genetic polimorphysms may in part account for the impaired decision making observed in AN patients, with a negative impact of met Comt allele and the short variant of 5HTTLPR polymorphism. Functional connectivity suggests the presence of different dysfunctional decision making networks in AN patients in the two decisional framework, confirming the importance of emotion and anxiety on decisional performance in AN. Since the cross sectional design of our study, further and longitudinal studies with recovered and at risk subjects are necessary to confirm our results

Executive Dysfunction and Reward Dysregulation: Interactions in Drug Addiction

Cocaine addiction is a serious public health hazard, and contributes to disastrous outcomes for individuals who suffer from it. Addiction is accompanied by an inability to control one\u27s own behavior, and a preoccupation with cocaine at the expense of other rewarding pursuits. Previous research has suggested that difficulties with executive function and reward processing may underlie these problems, but the extent to which each contributes to addiction severity, or how these two factors may interact, remains to be elucidated. By using event related potential (ERP) measures in combination with information about self-reported anhedonia over three experiments, we set out to more clearly define the phenotype of cocaine addiction and to investigate the extent to which executive dysfunction and reward dysregulation are associated with addiction severity. A model was designed to examine these factors. In addition, in a fourth study we investigated the integrity of executive functioning in both neutral and emotional contexts in abstinent cocaine users. We found that cocaine users show much more anhedonia than controls, and this anhedonia is associated with addiction severity. In addition, anhedonia is associated with poorer ability to monitor behavior when working toward reward, with increased reward motivation in both controls and cocaine users, and also with reduced consummatory reward response in cocaine users. Intriguingly, however, anhedonia is not associated with executive function deficits that are found in cocaine users, and these same executive function deficits are not associated with addiction severity. Finally, we show these executive function deficits to be normalized in abstinent cocaine abusers, and show that abstinent cocaine abusers do not modulate inhibitory response in response to emotional stimuli. Combined, these findings suggest that addiction is a phenotype defined by the presence of both reward dysregulation and executive dysfunction, and that reward dysregulation especially is associated with increased severity of the syndrome. These findings are then discussed in terms of a possible mechanistic model

"What could have been, if only ...?" - life in counterfactuals

„Regret“ (wörtlich übersetzt: das Bedauern) ist eine kognitiv basierte Emotion, die mittels kontrafaktischem Denken das Ergebnis einer getroffenen Entscheidung mit einer attraktiver scheinenden Alternative vergleicht. Das Ziel der vorliegenden Studie war in einer EEG/EKP – Studie die Beziehung von „Regret“ und der “feedback – related negativity“ (FRN) in einem „Regret Gambling Task“ zu untersuchen. In weiterer Folge wurde sowohl die P3a, als auch die P3b untersucht. Unter Anwendung eines “Regret Gambling Task” wurde „Regret“ indu-ziert, indem dessen Hauptelement, der “Agency” – Effekt, durch eine freie und erzwungene Wahlbedingung operationalisiert wurde. „Regret“, als auch eine FRN, wurden in der freien Wahlbedingung durch Vorgabe unterschiedlicher Verlustergebnisse hervorgerufen. In der freien Wahlbedingung “Gewinn” wurde eine P3 erzeugt, sowohl eine P3a mit frontaler, als auch eine P3b mit parietaler Aktivierung. Die mittleren Amplituden der ereigniskorrelierten Potentiale (EKP) wurden hinsichtlich der gestellten Hypothesen statistisch analysiert. Die Verhaltensdaten wurden mit nicht – parametrischen Methoden ausgewertet. Diese zeigten keinen signifikanten “Agency” – Effekt. Es konnte ein signifikanter Effekt bezüglich der ver-schiedenen Verlust – Ergebnisvarianten festgestellt werden. Alle Verlustbedingungen zeigten signifikante Unterschiede zu der Gewinnbedingung. Die mittleren Amplituden der EKP – Da-ten zeigten einen signifikanten Haupteffekt bezüglich des „Agency“ – Effekts und der ver-schiedenen Ergebnisvarianten. Weiters einen signifikanten Interaktionseffekt (“Agency” x Ergebnis) für die FRN, die P3a und die P3b in den interessierenden Zeitfenstern. Es konnte keine signifikante graduelle Abstufung in der mittleren Amplitude der FRN zwischen den Ver-lustergebnissen in der freien Wahlbedingung festgestellt werden. Das weist darauf hin, dass die FRN nicht das elektrophysiologische Äquivalent zu „Regret“ darstellt. Vielmehr könnte die FRN die elektrophysiologische „Zündung“ für das Erleben der kognitiven Emotion von „Regret“ mittels kontrafaktischen Denkens darstellen. Die FRN, als auch „Regret“ dienen damit der Verhaltensregulatio. Die Interaktion einer “Bottom – Up” und “Top – Down” – Zwei – Stufen Verarbeitung von Belohnung von Coricelli et al. (2005), als auch das “Adaptive Cri-tic” Model von Holroyd und Coles (2002; Holroyd, et al., 2006) stellen zwei Bezugsrahmen dar, die diese Schlussfolgerung untermauern. Die P3, besonders die P3a, könnten das dia-metrisch entgegengesetzte elektrophysiologische Startsignal für die Emotion von „Relief“ (wörtlich übersetzt mit: Erleichterung) darstellen, das dem Erhalt von zielführendem Verhal-ten dient. Weitere Forschung dazu wäre wünschenswert.Regret is a cognitively based emotion using counterfactual thoughts to compare an outcome with a more desirable alternative. The aim of the present study was to conduct an EEG study to examine the relationship of the feedback – related negativity (FRN) and regret in a regret gambling task. Furthermore the P3a and the P3b were examined. The regret gambling task was used to elicit regret by operationalizing the core element of regret, the agency – effect through free – and forced – choice conditions and inducing regret in the free – choice condi-tions through distinct feedback types bearing losses, which also elicited a FRN. The free – choice “win” – condition elicited a large peaking P3, as well a P3a with frontal and a P3b with parietal activation. The collected EEG data was explored regarding the hypothesis. Behav-ioural data was explored using a non – parametric design. Behavioural results did not reveal a significant agency – effect. One significant effect could be found for the distinct loss feed-back – types and of course the different loss – feedback types were rated significantly differ-ent to the “win” condition. The EEG data showed a significant main effect of agency and feedback, as well as a significant interaction effect (agency x feedback) for the FRN, the P3a and the P3b in the timeframe of interest according to their peaks. Nevertheless no significant gradual distinction in the mean amplitude of the FRN could be found in the free – choice loss – feedback types. This indicates that the FRN does not resemble the electrophysiological equivalent to regret. It could be concluded that the FRN resembles the electrophysiological ignition giving rise to the experience of the cognitive emotion of regret using counterfactuals. It is stated that the FRN as well as regret are both serving for behaviour regulation. This in-terpretation is linked to the proposed interaction of a bottom – up and top – down two level reward processing by Coricelli et al. (2005) and the adaptive critic model by Holroyd and Coles (2002; Holroyd, et al., 2006). The interpretation was made that the P3, especially the P3a, electrophysiologically resembles the diametrical opposed starting signal for the emotion of relief to preserve goal – achieving behaviour. Further research will be needed to test this hypothesis

The impact of motivational and affective context on error-induced learning

I THEORETISCHER HINTERGRUND 1 1. Einleitung 1 2. Literaturübersicht 3 Überblick 3 Theorien zum Verstärkungslernen 3 Begriffsbestimmung Verstärkungslernen 3 Zustände, Handlungen und Verstärkungen 4 Instrumentelle vs. Klassische Konditionierung 5 Motivationale Mechanismen des Instrumentellen Lernens 6 Mathematische Modelle des Verstärkungslernens 9 Zusammenfassung und Implikationen für die vorliegende Studie 14 Neuronale Grundlagen des Verstärkungslernens 14 Die "Dopamine Reward Prediction Error"-Hypothese 15 Unterschiedliche Funktionen dopaminerger Neurotransmission in den Basalganglien und im Präfrontalen Kortex 17 Die Integration von Kognition, Emotion und Handlung im Anterioren Cingulären Kortex 25 Zusammenfassung und Implikationen für die vorliegende Studie 30 Die Bedeutung des affektiven und motivationalen Handlungskontexts bei Lern- und Entscheidungsprozessen 31 Grundlegende Konzepte 31 Persönlichkeitseigenschaften, Motivation und Emotion 35 Unkontrollierbare Misserfolgserfahrungen und Lernen – Sonderfall eines Defizits in der Regulation von Motivation und Affekt? 39 Hirnmechanismen der Interaktion von Motivation, Emotion, und Kognition 42 Die neurophysiologischen Konsequenzen von Misserfolgserfahrungen 44 Zusammenfassung und Implikationen für die vorliegende Studie 45 Elektrophysiologische Korrelate des Verstärkungslernens 46 Die Fehlernegativierung (Error Negativity, Ne) 46 Die Feedback-Related Negativity (FRN) 49 Die Fehlerpositivierung (Error Positivity, Pe) 52 Motivationale und affektive Einflüsse auf Error Negativity, Feedback-Related Negativity und Error Positivity 54 Zusammenfassung und Implikationen für die vorliegende Studie 59 Integrative theoretische Ansätze zur Handlungsüberwachung 59 Die "Reinforcement Learning Theory" von Holroyd and Coles – Ein integrativer theoretischer Ansatz zu Fehlerverarbeitung und Lernen 60 Alternative Ansätze zur Error Negativity und ähnlichen EKP-Komponenten 64 Zusammenfassung und Implikationen für die vorliegende Studie 68 3. Fragestellung and Überblick über die Studien 70 II EMPIRISCHER TEIL 74 4. Studienziele: Experiment 1 und 2 74 5. Experiment 1 76 Studiendesign 76 Hypothesen 76 Lernbedingte Modulationen der Ne, FRN und Pe 77 Effekte von Misserfolg auf die Verhaltens- und EKP-Korrelate des Lernens 79 Die modulierende Rolle der Persönlichekit 82 Methoden 83 Versuchsteilnehmer 83 Überblick über den Versuchsablauf 84 Reizmaterial und Aufgaben 85 EEG-Aufnahme 88 Datenanalyse 88 Ergebnisse 91 Kontrollananlysen 91 Verhaltensdaten 92 EKP-Daten 96 Zusammenfassung Experiment 1 106 6. Experiment 2 108 Hypothesen 108 Methoden 110 Versuchsteilnehmer 110 Reizmaterial, Aufgaben und Ablauf 110 Ergebnisse 110 Kontrollananlysen 110 Verhaltensdaten 112 EKP-Daten 115 Zusammenfassung Experiment 2 124 7. Vorläufige Diskussion Experiment 1 and 2 125 Zusammenfassung der Hauptbefunde 125 Lernbedingte Veränderungen in den antwort- und feedback-bezogenen EKPs 127 Effekte von Misserfolg auf Fehlerverarbeitung und Lernen 132 8. Experiment 3 147 Fragestellung und Untersuchungsziele 147 Studiendesign 152 Hypothesen 152 Methoden 156 Versuchsteilnehmer 156 Reizmaterial und Aufgabe 156 Trialablauf 157 Versuchsablauf 158 EEG-Aufnahme 158 Datenanalyse 159 Ergebnisse 162 Verhaltensdaten 162 EKP-Daten 164 9. Vorläufige Diskussion Experiment 3 176 Zusammenfassung der Hauptbefunde 176 Lernbedingte Veränderungen in Ne, FRN, and Pe 177 Effecte appetitiver und aversiver Motivation auf Fehlerverarbeitung und Lernen 179 Der Beitrag cingulärer Subregionen zur Fehlerverarbeitung 187 10. Gesamtdiskussion 190 Lernbedingte Veränderungen in den EKP-Korrelaten der Fehler- und Feedback- verarbeitung 191 Affektive and motivationale Einflüsse auf Handlungsüberwachung und Lernen 195 Beschränkungen der vorliegenden Studie und Ausblick 205 Schlussfolgerungen 208The aim of this project was to examine the impact of affective-motivational context on the ability to use error signals for behavioural adaptation in feedback-based learning. Evidence for a neural error-processing system has been inferred from the error negativity (Ne), a component in the event-related potential (ERP) elicited when participants commit errors on reaction time tasks. According to an influential theoretical account on error processing and learning, the Ne reflects the transmission of a negative reinforcement learning signal from the midbrain dopamine system to the anterior cingulate cortex (ACC) and indicates that the outcome of an action is “worse than expected”. Importantly, the Ne has been suggested to increase with learning, reflecting the development of an internal representation of the correct response. Moreover, it has been shown that the Ne predicts the extent to which individuals learn from their errors. At the same time, there is accumulating evidence indicating that the Ne varies as a function of motivational and affective variables. Consequently, it has been proposed that the Ne might index broader activity of the action-regulation circuitry in the limbic system, including the affective evaluation of an error. Given the critical role of error processing in learning, an important, but thus far neglected question concerns the influence of experimental manipulations of affective and motivational states on action monitoring processes in feedback-based learning. The empirical work includes two ERP studies. The main goal of the first study was to determine the extent to which self-relevant failure influences error monitoring – as reflected in the Ne – and behavioural adaptation during subsequent learning. Therefore, I conducted an experimental design with two phases (pre- and posttest) in which subjects performed a probabilistic learning task. Between pre- and posttest, participants were assigned to one of two groups receiving either failure feedback or no feedback during a visual search task described as diagnostic of intellectual abilities. To disentangle the effects of failure and motivational disengagement due to prolonged task performance, the posttest was linked to intelligence (Experiment 1) or described in neutral terms (Experiment 2). The aim of the second study (Experiment 3) was to examine whether gain and loss anticipation have dissociable effects on behavioural and ERP correlates of error processing in feedback-based learning. To this end, predictive cues indicating the incentive value (gain, loss, or neutral) of the upcoming target were incorporated in the learning task. The incentive value was manipulated on a trial-by-trial basis. Experiments 1 and 2 showed that failure induction resulted in an increase of the Ne from pre- to posttest. Amplitude enhancement was not accompanied by higher posttest accuracy and therefore cannot simply be explained by changes in task performance. Rather than affecting overall performance failure feedback resulted in higher post-error accuracy indicating a higher impact of error signals on behavioural adaptation on a trial-to-trial basis. This suggests a failure-related shift towards a reactive, error-driven mode of adaptive control rather than an overall increase in the recruitment of cognitive control processes. In Study 2, behavioural performance was improved on gain and loss trials compared to neutral trials, suggesting that participants used the incentive value information to optimize performance. Moreover, in the loss condition, participants were more likely to switch responses after errors than in the gain condition (better lose-shift performance). In support of the assumption that the Ne constitutes a teaching signal that reflects the affective-motivational context of maladaptive decisions, larger Ne amplitudes were observed on error trials in the loss condition compared to gain and neutral conditions. In line with a growing body of evidence indicating a close interaction between cognition, emotion, and motivation in executive control, these findings underscore the importance of factors related to affective and motivational state in elucidating the neural mechanisms of action monitoring and behavioural adaptation