Regulating craving by anticipating positive and negative outcomes : a multivariate pattern analysis and network connectivity approach

During self-control, we may resist short-term temptations in order to reach a favorable future (e.g., resisting cake to stay healthy). The neural basis of self-control is typically attributed to “cold,” unemotional cognitive control mechanisms which inhibit affect-related regions via the prefrontal cortex (PFC). Here, we investigate the neural underpinnings of regulating cravings by mentally evoking the positive consequences of resisting a temptation (e.g., being healthy) as opposed to evoking the negative consequences of giving in to a temptation (e.g., becoming overweight). It is conceivable that when using these types of strategies, regions associated with emotional processing [e.g., striatum, ventromedial prefrontal cortex (vmPFC)] are involved in addition to control-related prefrontal and parietal regions. Thirty-one participants saw pictures of unhealthy snacks in the fMRI scanner and, depending on the trial, regulated their craving by thinking of the positive consequences of resisting, or the negative consequences of not resisting. In a control condition, they anticipated the pleasure of eating and thus, allowed the craving to occur (now-condition). In line with previous studies, we found activation of a cognitive control network during self-regulation. In the negative future thinking condition, the insula was more active than in the positive condition, while there were no activations that were stronger in the positive (> negative) future thinking condition. However, additionally, multivariate pattern analysis showed that during craving regulation, information about the valence of anticipated emotions was present in the vmPFC, the posterior cingulate cortex (PCC) and the insula. Moreover, a network including vmPFC and PCC showed higher connectivity during the positive (> negative) future thinking condition. Since these regions are often associated with affective processing, these findings suggest that “hot,” affective processes may, at least in certain circumstances, play a role in self-control

A fast and intuitive method for calculating dynamic network reconfiguration and node flexibility

Dynamic interactions between brain regions, either during rest or performance of cognitive tasks, have been studied extensively using a wide variance of methods. Although some of these methods allow elegant mathematical interpretations of the data, they can easily become computationally expensive or difficult to interpret and compare between subjects or groups. Here, we propose an intuitive and computationally efficient method to measure dynamic reconfiguration of brain regions, also termed flexibility. Our flexibility measure is defined in relation to an a-priori set of biologically plausible brain modules (or networks) and does not rely on a stochastic data-driven module estimation, which, in turn, minimizes computational burden. The change of affiliation of brain regions over time with respect to these a-priori template modules is used as an indicator of brain network flexibility. We demonstrate that our proposed method yields highly similar patterns of whole-brain network reconfiguration (i.e., flexibility) during a working memory task as compared to a previous study that uses a data-driven, but computationally more expensive method. This result illustrates that the use of a fixed modular framework allows for valid, yet more efficient estimation of whole-brain flexibility, while the method additionally supports more fine-grained (e.g. node and group of nodes scale) flexibility analyses restricted to biologically plausible brain networks

Regulating Craving by Anticipating Positive and Negative Outcomes: A Multivariate Pattern Analysis and Network Connectivity Approach

During self-control, we may resist short-term temptations in order to reach a favorable future (e.g., resisting cake to stay healthy). The neural basis of self-control is typically attributed to “cold,” unemotional cognitive control mechanisms which inhibit affect-related regions via the prefrontal cortex (PFC). Here, we investigate the neural underpinnings of regulating cravings by mentally evoking the positive consequences of resisting a temptation (e.g., being healthy) as opposed to evoking the negative consequences of giving in to a temptation (e.g., becoming overweight). It is conceivable that when using these types of strategies, regions associated with emotional processing [e.g., striatum, ventromedial prefrontal cortex (vmPFC)] are involved in addition to control-related prefrontal and parietal regions. Thirty-one participants saw pictures of unhealthy snacks in the fMRI scanner and, depending on the trial, regulated their craving by thinking of the positive consequences of resisting, or the negative consequences of not resisting. In a control condition, they anticipated the pleasure of eating and thus, allowed the craving to occur (now-condition). In line with previous studies, we found activation of a cognitive control network during self-regulation. In the negative future thinking condition, the insula was more active than in the positive condition, while there were no activations that were stronger in the positive (> negative) future thinking condition. However, additionally, multivariate pattern analysis showed that during craving regulation, information about the valence of anticipated emotions was present in the vmPFC, the posterior cingulate cortex (PCC) and the insula. Moreover, a network including vmPFC and PCC showed higher connectivity during the positive (> negative) future thinking condition. Since these regions are often associated with affective processing, these findings suggest that “hot,” affective processes may, at least in certain circumstances, play a role in self-control

Differential predictors for alcohol use in adolescents as a function of familial risk

Abstract: Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions

Differential predictors for alcohol use in adolescents as a function of familial risk

Abstract: Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions

Untersuchungen mittels resting-state funktioneller Magnetresonanztomographie

The human brain is a network of interconnected regions, both on an anatomical and functional level. Although the brain´s intrinsic functional architecture provides a crucial basis for our behavior, it is still incompletely characterized. Using a multi-methodological approach across three studies, the work presented in this thesis aimed to explore and characterize different aspects of the brain´s intrinsic functional architecture, as measured with resting-state functional magnetic resonance imaging (rs-fMRI). Specifically, study 1 investigated the relationship between amygdala resting-state functional connectivity (rs-FC) within the face processing circuit and the personality dimension of neuroticism, as well as how the 5-HTTLPR/rs25531 polymorphism impacts this relationship. Here, we provide first evidence that variants of the 5-HTTLPR/rs25531 genotype and different levels of neuroticism may be linked to rs-FC between amygdala and occipital face area, which, in turn, may partly account for altered processing of negative facial emotions. In the second study we explored the potential benefits of global signal regression (GSR) as a crucial preprocessing step in rs-fMRI analyses for unmasking ‘true’ inter-regional relationships in brain networks. Here we provide initial evidence for the potential of amygdala rs-FC to segregate face-sensitive areas within the fusiform gyrus when GSR is applied. This illustrates how GSR might be used in rs-fMRI data analysis as a method to segregate functionally distinct brain areas. Study 3 describes the development of “GraphVar”, a user-friendly toolbox for comprehensive large-scale graph theoretical analyses of brain networks, which facilitates future research on complex brain networks and their topology. This toolbox will make graph theoretical analysis methods readily available to a broad audience of brain researchers, and has already been downloaded over 2000 times since its first release.Das menschliche Gehirn besteht aus einem Netzwerk anatomisch und funktionell verknüpfter Regionen. Obwohl die funktionelle Architektur dieses Netzwerkes maßgebend unser Verhalten beeinflusst, ist sie noch zu großen Teilen unerforscht. Mit Hilfe funktioneller Magnetresonanztomographie und Messungen des Gehirns im Ruhezustand (rs-fMRI) versucht die vorliegende Arbeit durch multimethodale Ansätze in drei Studien zur weiteren Charakterisierung seiner funktionellen Architektur beizutragen. Studie 1 untersuchte zu diesem Zweck den Zusammenhang zwischen funktionellen Verbindungen der Amygdala im Gesichtserkennungsnetzwerk und der Persönlichkeitsdimension Neurotizismus sowie des assoziierten Polymorphismus 5-HTTLPR/rs25531. Die Studie zeigte, dass die Stärke der Verbindung von Amygdala zum okzipitalen Gesichtsfeld mit Ausprägungen des 5-HTTLPR/rs25531 Genotyps und zugleich auch mit Ausprägung der Persönlichkeitsdimension Neurotizismus variiert. Die Ergebnisse legen nahe, dass die Variation dieser Verbindungsstärke grundlegend für interindividuelle Unterschiede in der Verarbeitung von negativen Gesichtsausdrücken sein könnte. Studie 2 untersuchte die Möglichkeit, durch Herausfiltern des im Ruhezustand vorhandenen globalen Signals spontaner neuronaler Fluktuationen aus den rs-fMRI Daten (GSR) die im Gehirn verankerten „echten“ Netzwerkverbindungen regional zu spezifizieren. Die gewonnenen Ergebnisse zeigen, dass die funktionellen Verbindungen der Amygdala im Gesichtserkennungsnetzwerk durch das Herausfiltern dieses Signals direkt den Gesichtserkennungsregionen im Gyrus Fusiformis zugeordnet werden können. Diese Resultate deuten darauf hin, dass GSR in rs-fMRI Daten auch in anderen Teilen des Gehirns genutzt werden könnte, um Regionen unterschiedlicher Funktionalität voneinander abzugrenzen. Studie 3 diente der Entwicklung von „GraphVar“, einem benutzerfreundlichen Computerprogramm zur umfassenden Analyse von Gehirnnetzwerken und deren Topologie. Dieses Programm wurde mit der Hoffnung entwickelt, verschiedene Netzwerkanalysemethoden und deren Anwendung für eine große Zahl von Hirnforschern zugänglicher zu gestalten, und zählt seit seiner Veröffentlichung bereits über 2000 Downloads

Die Rolle antizipierter Emotionen und interozeptiver Vorhersagen in der Selbstkontrolle – Untersuchungen auf Verhaltens- und neuronaler Ebene mittels funktioneller Magnetresonanztomographie

Aufbauend auf Theorien der affektiven Vorhersage und Modellen der interozeptiven prädiktiven Inferenz wurde in der vorliegenden Habilitationsschrift auf Verhaltens- und neuronaler Ebene mittels funktioneller Magnetresonanztomographie (fMRT) in zwei Studiensätzen untersucht, ob antizipierte Emotionen (Studiensatz 1 mit Studien 1-2: Kruschwitz et al., 2018a; Kruschwitz et al., 2018b) und interozeptive Vorhersagen (Studiensatz 2 mit Studien 3-5: Kruschwitz et al., 2014; Kruschwitz et al., 2019; Walter et al., 2020) eine funktionelle Rolle bei der Ausübung von Selbstkontrolle spielen. Studie 1 (Kruschwitz et al., 2018a) konzentrierte sich auf die Existenz antizipierter Emotionen, ihre neuronalen Korrelate und ihre Formbarkeit mittels kognitiver Kontrolle. Neben der Beobachtung, dass Hirnregionen, die der Verarbeitung positiver und negativer affektiver Reize zugrunde liegen, koaktiviert werden können, wenn bivalente Stimuli antizipiert werden, konnte gezeigt werden, dass kognitive Kontrolle durch bewusstes Zukunftsdenken genutzt werden kann, um die Aktivierung antizipierter Emotionen während der Erwartung bivalenter Reize entweder auf die positiven oder die negativen Aspekte zu verlagern. Das untersuchte Szenario nähert sich alltäglichen Selbstkontrollstrategien an, in denen kurz- und langfristige Konsequenzen gegeneinander abgewogen werden müssen. Studie 2 (Kruschwitz et al., 2018b) untersuchte mithilfe einer nahrungsbezogenen Craving-Regulationsaufgabe, ob Hirnregionen, die mit der Verarbeitung von antizipierten Emotionen in Zusammenhang stehen, aktiviert werden, wenn in einer Selbstkontrollsituation über positive und negative langfristige Konsequenzen nachgedacht wird. Wie vorhergesagt konnte gezeigt werden, dass Selbstkontrolle nicht nur mit Aktivierung in kognitiven Kontrollregionen assoziiert war, sondern auch Regionen rekrutiert wurden, die in Kruschwitz et al., 2018a mit der Verarbeitung antizipierter Emotionen in Zusammenhang gebracht wurden. Der Befund der Koaktivierung von kognitivem Kontrollsystem und affektassoziierten Regionen stellt die Sicht des "dualen Systems" zur Selbstkontrolle in Frage, wonach ein rein kognitives Kontrollsystem impulsive emotionale Reaktionen auf unmittelbare Ergebnisse unterdrückt. In Studie 3 (Kruschwitz et al., 2014) wurde eine inspiratorische Atemlastaufgabe etabliert, um interindividuelle Unterschiede in der Wahrnehmung aversiver interozeptiver Störungen zu untersuchen. Indem gezeigt wurde, dass interozeptive Sensitivität durch die menschliche Persönlichkeit beeinflusst wird, lieferte diese Studie eine Voraussetzung für die Annahme, dass individuelle Unterschiede in der Selbstkontrolle auch mit Unterschieden in der interozeptiven Vorhersage zusammenhängen könnten. In Studie 4 (Kruschwitz et al., 2019) wurde dieser vermutete Zusammenhang direkt untersucht, indem die inspiratorische Atemlastaufgabe mit der Selbstkontrollaufgabe aus Studie 2 verknüpft wurde. In Übereinstimmung mit der aufgestellten Hypothese waren Personen, die die Aversität des zukünftigen interozeptiven Zustands genauer vorhersagten (oder sogar überschätzten), besser in der Lage, ihr Verlangen nach ungesunden Snacks durch Antizipation negativer Langzeitfolgen des Verzehrs herunterzuregulieren. Folglich konnte geschlussfolgert werden, dass Selbstkontrolle durch den Grad beeinflusst wird, in dem ein Individuum Vorhersagemodelle seiner eigenen zukünftigen interozeptiven Zustände generiert. In Studie 5 (Walter et al., 2020) wurden die gleichen experimentellen Protokolle wie in Studie 4 in einer fMRT-Umgebung mit einer neuen unabhängigen Stichprobe durchgeführt, um Einblick in den neuronalen Mechanismus zu gewinnen, der Grundlage für den demonstrierten Zusammenhang von Selbstkontrolle und interozeptiven Vorhersagen darstellt. Es konnte erneut festgestellt werden, dass Personen, die zukünftige interozeptive Zustände korrekt vorhersagten (oder sogar überschätzen), effektiver in der Lage waren, ihr Verlangen nach ungesunden Snacks herunterzuregulieren. Auf neuronaler Ebene konnte beobachtet werden, dass die anteriore Insula und das prä-supplementärmotorische Areal (prä-SMA), die in beiden Aufgaben rekrutiert wurden, teilweise zu diesen Effekten beitrugen, da Hirn-Verhaltens-Korrelationen mit diesen Arealen sowohl innerhalb als auch zwischen den beiden Aufgaben gefunden wurden. Zusammenfassend untermauern die hier vorgestellten Ergebnisse die anfangs aufgestellte Hypothese, dass es oft nicht ausreicht, kognitive Repräsentationen von Langzeitergebnissen zu aktivieren, um Versuchungen zu widerstehen, sondern dass Selbstkontrolle auch von affektiven und interozeptiven Repräsentationen abhängt, die durch Antizipationen zukünftiger Ergebnisse zum Zeitpunkt der Entscheidung hervorgerufen werden

How specific is specific phobia? Different neural response patterns in two subtypes of specific phobia

Specific phobia of the animal subtype has been employed as a model disorder exploring the neurocircuitry of anxiety disorders, but evidence is lacking whether the detected neural response pattern accounts for all animal subtypes, nor across other phobia subtypes. The present study aimed at directly comparing two subtypes of specific phobia: snake phobia (SP) representing the animal, and dental phobia (DP) representing the blood-injection-injury subtype. Using functional magnetic resonance imaging (fMRI), brain activation and skin conductance was measured during phobogenic video stimulation in 12 DP, 12 SP, and 17 healthy controls. For SP, the previously described activation of fear circuitry structures encompassing the insula, anterior cingulate cortex and thalamus could be replicated and was furthermore associated with autonomic arousal. In contrast, DP showed circumscribed activation of the prefrontal and orbitofrontal cortex (PFC/OFC) when directly compared to SP, being dissociated from autonomic arousal. Results provide preliminary evidence for the idea that snake and dental phobia are characterized by distinct underlying neural systems during sustained emotional processing with evaluation processes in DP being controlled by orbitofrontal areas, whereas phobogenic reactions in SP are primarily guided by limbic and paralimbic structures. Findings support the current diagnostic classification conventions, separating distinct subtypes in DSM-IV-TR. They highlight that caution might be warranted though for generalizing findings derived from animal phobia to other phobic and anxiety disorders. If replicated, results could contribute to a better understanding of underlying neurobiological mechanisms of specific phobia and their respective classification