@phdthesis{Friedel2016,
  author    = {Friedel, Eva},
  title     = {Der Einfluss von Kognition und Stresserleben auf die Entscheidungsfindung und deren Rolle f{\"u}r Alkoholabh{\"a}ngigkeit},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-91609},
  school      = {Universit{\"a}t Potsdam},
  pages     = {41},
  year      = {2016},
  abstract  = {Ziel der vorliegenden Arbeit ist es, belohnungsabh{\"a}ngiges (instrumentelles) Lernen und Entscheidungsfindungsprozesse auf Verhaltens- und neuronaler Ebene in Abh{\"a}ngigkeit von chronischem Stresserleben (erfasst {\"u}ber den Lifetime Stress Inventory, Holmes und Rahe 1962) und kognitiven Variablen (eingeteilt in eine fluide und eine kristalline Intelligenzkomponente) an gesunden Probanden zu untersuchen. Dabei steht zu Beginn die Sicherung der Konstruktvalidit{\"a}t zwischen den bislang oft synonym verwendeten Begriffen modellfrei ~ habituell, bzw. modellbasiert ~ zielgerichtet im Fokus. Darauf aufbauend soll dann insbesondere der differentielle und interaktionelle Einfluss von chronischem Stresserleben und kognitiven Variablen auf Entscheidungsprozesse (instrumentelles Lernen) und deren neuronales Korrelat im VS untersucht und dargestellt werden. Abschließend wird die Relevanz der untersuchten belohnungsabh{\"a}ngigen Lernprozesse f{\"u}r die Entstehung und Aufrechterhaltung der Alkoholabh{\"a}ngigkeit zusammen mit weiteren Einflussvariablen in einem {\"U}bersichtspapier diskutiert.},
  language  = {de}
}
@misc{FriedelSchlagenhaufBecketal.2014,
  author    = {Friedel, Eva and Schlagenhauf, Florian and Beck, Anne and Dolan, Raymond J. and Huys, Quentin J. M. and Rapp, Michael A. and Heinz, Andreas},
  title     = {The effects of life stress and neural learning signals on fluid intelligence},
  series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe},
  number    = {621},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-43514},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-435140},
  pages     = {35 -- 43},
  year      = {2014},
  abstract  = {Fluid intelligence (fluid IQ), defined as the capacity for rapid problem solving and behavioral adaptation, is known to be modulated by learning and experience. Both stressful life events (SLES) and neural correlates of learning [specifically, a key mediator of adaptive learning in the brain, namely the ventral striatal representation of prediction errors (PE)] have been shown to be associated with individual differences in fluid IQ. Here, we examine the interaction between adaptive learning signals (using a well-characterized probabilistic reversal learning task in combination with fMRI) and SLES on fluid IQ measures. We find that the correlation between ventral striatal BOLD PE and fluid IQ, which we have previously reported, is quantitatively modulated by the amount of reported SLES. Thus, after experiencing adversity, basic neuronal learning signatures appear to align more closely with a general measure of flexible learning (fluid IQ), a finding complementing studies on the effects of acute stress on learning. The results suggest that an understanding of the neurobiological correlates of trait variables like fluid IQ needs to take socioemotional influences such as chronic stress into account.},
  language  = {en}
}
@article{FriedelSchlagenhaufBecketal.2015,
  author    = {Friedel, Eva and Schlagenhauf, Florian and Beck, Anne and Dolan, Raymond J. and Huys, Quentin J. M. and Rapp, Michael A. and Heinz, Andreas},
  title     = {The effects of life stress and neural learning signals on fluid intelligence},
  series = {European archives of psychiatry and clinical neuroscience : official organ of the German Society for Biological Psychiatry},
  volume    = {265},
  journal   = {European archives of psychiatry and clinical neuroscience : official organ of the German Society for Biological Psychiatry},
  number    = {1},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {0940-1334},
  doi       = {10.1007/s00406-014-0519-3},
  pages     = {35 -- 43},
  year      = {2015},
  abstract  = {Fluid intelligence (fluid IQ), defined as the capacity for rapid problem solving and behavioral adaptation, is known to be modulated by learning and experience. Both stressful life events (SLES) and neural correlates of learning [specifically, a key mediator of adaptive learning in the brain, namely the ventral striatal representation of prediction errors (PE)] have been shown to be associated with individual differences in fluid IQ. Here, we examine the interaction between adaptive learning signals (using a well-characterized probabilistic reversal learning task in combination with fMRI) and SLES on fluid IQ measures. We find that the correlation between ventral striatal BOLD PE and fluid IQ, which we have previously reported, is quantitatively modulated by the amount of reported SLES. Thus, after experiencing adversity, basic neuronal learning signatures appear to align more closely with a general measure of flexible learning (fluid IQ), a finding complementing studies on the effects of acute stress on learning. The results suggest that an understanding of the neurobiological correlates of trait variables like fluid IQ needs to take socioemotional influences such as chronic stress into account.},
  language  = {en}
}
@article{FriedelSeboldKuitunenPauletal.2017,
  author    = {Friedel, Eva and Sebold, Miriam Hannah and Kuitunen-Paul, S{\"o}ren and Nebe, Stephan and Veer, Ilya M. and Zimmermann, Ulrich S. and Schlagenhauf, Florian and Smolka, Michael N. and Rapp, Michael A. and Walter, Henrik and Heinz, Andreas},
  title     = {How Accumulated Real Life Stress Experience and Cognitive Speed Interact on Decision-Making Processes},
  series = {Frontiers in human neuroscienc},
  volume    = {11},
  journal   = {Frontiers in human neuroscienc},
  publisher = {Frontiers Research Foundation},
  address   = {Lausanne},
  issn      = {1662-5161},
  doi       = {10.3389/fnhum.2017.00302},
  pages     = {1 -- 9},
  year      = {2017},
  abstract  = {Rationale: Advances in neurocomputational modeling suggest that valuation systems for goal-directed (deliberative) on one side, and habitual (automatic) decision-making on the other side may rely on distinct computational strategies for reinforcement learning, namely model-free vs. model-based learning. As a key theoretical difference, the model-based system strongly demands cognitive functions to plan actions prospectively based on an internal cognitive model of the environment, whereas valuation in the model-free system relies on rather simple learning rules from operant conditioning to retrospectively associate actions with their outcomes and is thus cognitively less demanding. Acute stress reactivity is known to impair model-based but not model-free choice behavior, with higher working memory capacity protecting the model-based system from acute stress. However, it is not clear which impact accumulated real life stress has on model-free and model-based decision systems and how this influence interacts with cognitive abilities. Methods: We used a sequential decision-making task distinguishing relative contributions of both learning strategies to choice behavior, the Social Readjustment Rating Scale questionnaire to assess accumulated real life stress, and the Digit Symbol Substitution Test to test cognitive speed in 95 healthy subjects. Results: Individuals reporting high stress exposure who had low cognitive speed showed reduced model-based but increased model-free behavioral control. In contrast, subjects exposed to accumulated real life stress with high cognitive speed displayed increased model-based performance but reduced model-free control. Conclusion: These findings suggest that accumulated real life stress exposure can enhance reliance on cognitive speed for model-based computations, which may ultimately protect the model-based system from the detrimental influences of accumulated real life stress. The combination of accumulated real life stress exposure and slower information processing capacities, however, might favor model-free strategies. Thus, the valence and preference of either system strongly depends on stressful experiences and individual cognitive capacities.},
  language  = {en}
}
@article{GarbusowNebeSommeretal.2019,
  author    = {Garbusow, Maria and Nebe, Stephan and Sommer, Christian and Kuitunen-Paul, S{\"o}ren and Sebold, Miriam Hannah and Schad, Daniel and Friedel, Eva and Veer, Ilya M. and Wittchen, Hans-Ulrich and Rapp, Michael A. and Ripke, Stephan and Walter, Henrik and Huys, Quentin J. M. and Schlagenhauf, Florian and Smolka, Michael N. and Heinz, Andreas},
  title     = {Pavlovian-To-Instrumental Transfer and Alcohol Consumption in Young Male Social Drinkers},
  series = {Journal of Clinical Medicine},
  volume    = {8},
  journal   = {Journal of Clinical Medicine},
  number    = {8},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2077-0383},
  doi       = {10.3390/jcm8081188},
  pages     = {14},
  year      = {2019},
  abstract  = {In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, p(SVC) = 0.04, x = 26, y = -6, z = -12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (r(s) = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies.},
  language  = {en}
}
@misc{GarbusowNebeSommeretal.2019,
  author    = {Garbusow, Maria and Nebe, Stephan and Sommer, Christian and Kuitunen-Paul, S{\"o}ren and Sebold, Miriam Hannah and Schad, Daniel and Friedel, Eva and Veer, Ilya M. and Wittchen, Hans-Ulrich and Rapp, Michael A. and Ripke, Stephan and Walter, Henrik and Huys, Quentin J. M. and Schlagenhauf, Florian and Smolka, Michael N. and Heinz, Andreas},
  title     = {Pavlovian-To-Instrumental Transfer and Alcohol Consumption in Young Male Social Drinkers},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe},
  number    = {841},
  issn      = {1866-8364},
  doi       = {10.25932/publishup-47328},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-473280},
  pages     = {14},
  year      = {2019},
  abstract  = {In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, p(SVC) = 0.04, x = 26, y = -6, z = -12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (r(s) = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies.},
  language  = {en}
}
@article{GarbusowSchadSeboldetal.2016,
  author    = {Garbusow, Maria and Schad, Daniel and Sebold, Miriam Hannah and Friedel, Eva and Bernhardt, Nadine and Koch, Stefan P. and Steinacher, Bruno and Kathmann, Norbert and Geurts, Dirk E. M. and Sommer, Christian and Mueller, Dirk K. and Nebe, Stephan and Paul, Soeren and Wittchen, Hans-Ulrich and Zimmermann, Ulrich S. and Walter, Henrik and Smolka, Michael N. and Sterzer, Philipp and Rapp, Michael A. and Huys, Quentin J. M. and Schlagenhauf, Florian and Heinz, Andreas},
  title     = {Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence},
  series = {Addiction biology},
  volume    = {21},
  journal   = {Addiction biology},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {1355-6215},
  doi       = {10.1111/adb.12243},
  pages     = {719 -- 731},
  year      = {2016},
  abstract  = {In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.},
  language  = {en}
}
@article{GarbusowSchadSommeretal.2014,
  author    = {Garbusow, Maria and Schad, Daniel and Sommer, Christian and Juenger, Elisabeth and Sebold, Miriam Hannah and Friedel, Eva and Wendt, Jean and Kathmann, Norbert and Schlagenhauf, Florian and Zimmermann, Ulrich S. and Heinz, Andreas and Huys, Quentin J. M. and Rapp, Michael A.},
  title     = {Pavlovian-to-instrumental transfer in alcohol dependence: a pilot study},
  series = {Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography},
  volume    = {70},
  journal   = {Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography},
  number    = {2},
  publisher = {Karger},
  address   = {Basel},
  issn      = {0302-282X},
  doi       = {10.1159/000363507},
  pages     = {111 -- 121},
  year      = {2014},
  abstract  = {Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping ongoing thought and behavior. The influence of pavlovian stimuli on ongoing behavior is paradigmatically measured by pavlovian-to-instrumental transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced PIT. Methods: Thirty-two recently detoxified alcohol-dependent patients and 32 age- and gender-matched healthy controls performed a PIT task with instrumental go/no-go approach behaviors. The task involved both pavlovian stimuli associated with monetary rewards and losses, and images of drinks. Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect, and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs. Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol-dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.},
  language  = {en}
}
@inproceedings{HaegeleFriedelSchlagenhaufetal.2014,
  author    = {Haegele, Claudia and Friedel, Eva and Schlagenhauf, Florian and Sterzer, Philipp and Beck, Anne and Bermpohl, Felix and Rapp, Michael A. and Stoy, Meline and Stroehle, Andreas and Dolan, Raymond J. and Heinz, Andreas},
  title     = {Reward expectation and affective responses across psychiatric disorders - A dimensional approach},
  series = {Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry},
  volume    = {75},
  booktitle = {Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry},
  number    = {9},
  publisher = {Elsevier},
  address   = {New York},
  issn      = {0006-3223},
  pages     = {91S -- 92S},
  year      = {2014},
  language  = {en}
}
@article{SchadGarbusowFriedeletal.2018,
  author    = {Schad, Daniel and Garbusow, Maria and Friedel, Eva and Sommer, Christian and Sebold, Miriam Hannah and H{\"a}gele, Claudia and Bernhardt, Nadine and Nebe, Stephan and Kuitunen-Paul, S{\"o}ren and Liu, Shuyan and Eichmann, Uta and Beck, Anne and Wittchen, Hans-Ulrich and Walter, Henrik and Sterzer, Philipp and Zimmermann, Ulrich S. and Smolka, Michael N. and Schlagenhauf, Florian and Huys, Quentin J. M. and Heinz, Andreas and Rapp, Michael A.},
  title     = {Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk},
  series = {European archives of psychiatry and clinical neuroscience : official organ of the German Society for Biological Psychiatry},
  volume    = {269},
  journal   = {European archives of psychiatry and clinical neuroscience : official organ of the German Society for Biological Psychiatry},
  number    = {3},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {0940-1334},
  doi       = {10.1007/s00406-017-0860-4},
  pages     = {295 -- 308},
  year      = {2018},
  abstract  = {The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = -3.86, p < .001), but not in healthy controls (t = -0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t((30)) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.},
  language  = {en}
}