@article{HeinzelLorenzBrockhausetal.2014, author = {Heinzel, Stephan and Lorenz, Robert C. and Brockhaus, Wolf-Ruediger and Wuestenberg, Torsten and Kathmann, Norbert and Heinz, Andreas and Rapp, Michael Armin}, title = {Working memory load-dependent brain response predicts behavioral training gains in older adults}, series = {The journal of neuroscience}, volume = {34}, journal = {The journal of neuroscience}, number = {4}, publisher = {Society for Neuroscience}, address = {Washington}, issn = {0270-6474}, doi = {10.1523/JNEUROSCI.2463-13.2014}, pages = {1224 -- 1233}, year = {2014}, abstract = {In the domain of working memory (WM), a sigmoid-shaped relationship between WM load and brain activation patterns has been demonstrated in younger adults. It has been suggested that age-related alterations of this pattern are associated with changes in neural efficiency and capacity. At the same time, WM training studies have shown that some older adults are able to increase their WM performance through training. In this study, functional magnetic resonance imaging during an n-back WM task at different WM load levels was applied to compare blood oxygen level-dependent (BOLD) responses between younger and older participants and to predict gains in WM performance after a subsequent 12-session WM training procedure in older adults. We show that increased neural efficiency and capacity, as reflected by more "youth-like" brain response patterns in regions of interest of the frontoparietal WM network, were associated with better behavioral training outcome beyond the effects of age, sex, education, gray matter volume, and baseline WM performance. Furthermore, at low difficulty levels, decreases in BOLD response were found after WM training. Results indicate that both neural efficiency (i. e., decreased activation at comparable performance levels) and capacity (i. e., increasing activation with increasing WM load) of a WM-related network predict plasticity of the WM system, whereas WM training may specifically increase neural efficiency in older adults.}, language = {en} } @article{BookerJacobRappetal.2016, author = {Booker, Anke and Jacob, Louis E. C. and Rapp, Michael Armin and Bohlken, Jens and Kostev, Karel}, title = {Risk factors for dementia diagnosis in German primary care practices}, series = {International psychogeriatrics}, volume = {28}, journal = {International psychogeriatrics}, publisher = {Cambridge Univ. Press}, address = {New York}, issn = {1041-6102}, doi = {10.1017/S1041610215002082}, pages = {1059 -- 1065}, year = {2016}, abstract = {Background: Dementia is a psychiatric condition the development of which is associated with numerous aspects of life. Our aim was to estimate dementia risk factors in German primary care patients. Methods: The case-control study included primary care patients (70-90 years) with first diagnosis of dementia (all-cause) during the index period (01/2010-12/2014) (Disease Analyzer, Germany), and controls without dementia matched (1:1) to cases on the basis of age, sex, type of health insurance, and physician. Practice visit records were used to verify that there had been 10 years of continuous follow-up prior to the index date. Multivariate logistic regression models were fitted with dementia as a dependent variable and the potential predictors. Conclusions: Risk factors for dementia found in this study are consistent with the literature. Nevertheless, the associations between statin, PPI and antihypertensive drug use, and decreased risk of dementia need further investigations.}, language = {en} } @misc{BookerJacobRappetal.2016, author = {Booker, Anke and Jacob, Louis E. C. and Rapp, Michael Armin and Bohlken, Jens and Kostev, Karel}, title = {Risk factors for dementia diagnosis in German primary care practices}, series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {449}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-413441}, pages = {7}, year = {2016}, abstract = {Background: Dementia is a psychiatric condition the development of which is associated with numerous aspects of life. Our aim was to estimate dementia risk factors in German primary care patients. Methods: The case-control study included primary care patients (70-90 years) with first diagnosis of dementia (all-cause) during the index period (01/2010-12/2014) (Disease Analyzer, Germany), and controls without dementia matched (1:1) to cases on the basis of age, sex, type of health insurance, and physician. Practice visit records were used to verify that there had been 10 years of continuous follow-up prior to the index date. Multivariate logistic regression models were fitted with dementia as a dependent variable and the potential predictors. Results: The mean age for the 11,956 cases and the 11,956 controls was 80.4 (SD: 5.3) years. 39.0\% of them were male and 1.9\% had private health insurance. In the multivariate regression model, the following variables were linked to a significant extent with an increased risk of dementia: diabetes (OR: 1.17; 95\% CI: 1.10-1.24), lipid metabolism (1.07; 1.00-1.14), stroke incl. TIA (1.68; 1.57-1.80), Parkinson's disease (PD) (1.89; 1.64-2.19), intracranial injury (1.30; 1.00-1.70), coronary heart disease (1.06; 1.00-1.13), mild cognitive impairment (MCI) (2.12; 1.82-2.48), mental and behavioral disorders due to alcohol use (1.96; 1.50-2.57). The use of statins (OR: 0.94; 0.90-0.99), proton-pump inhibitors (PPI) (0.93; 0.90-0.97), and antihypertensive drugs (0.96, 0.94-0.99) were associated with a decreased risk of developing dementia. Conclusions: Risk factors for dementia found in this study are consistent with the literature. Nevertheless, the associations between statin, PPI and antihypertensive drug use, and decreased risk of dementia need further investigations.}, language = {en} } @article{LorenzGleichBecketal.2014, author = {Lorenz, Robert C. and Gleich, Tobias and Beck, Anne and Poehland, Lydia and Raufelder, Diana and Sommer, Werner and Rapp, Michael Armin and Kuehn, Simone and Gallinat, J{\"u}rgen}, title = {Reward anticipation in the adolescent and aging brain}, series = {Human brain mapping : a journal devoted to functional neuroanatomy and neuroimaging}, volume = {35}, journal = {Human brain mapping : a journal devoted to functional neuroanatomy and neuroimaging}, number = {10}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1065-9471}, doi = {10.1002/hbm.22540}, pages = {5153 -- 5165}, year = {2014}, abstract = {Processing of reward is the basis of adaptive behavior of the human being. Neural correlates of reward processing seem to be influenced by developmental changes from adolescence to late adulthood. The aim of this study is to uncover these neural correlates during a slot machine gambling task across the lifespan. Therefore, we used functional magnetic resonance imaging to investigate 102 volunteers in three different age groups: 34 adolescents, 34 younger adults, and 34 older adults. We focused on the core reward areas ventral striatum (VS) and ventromedial prefrontal cortex (VMPFC), the valence processing associated areas, anterior cingulate cortex (ACC) and insula, as well as information integration associated areas, dorsolateral prefrontal cortex (DLPFC), and inferior parietal lobule (IPL). Results showed that VS and VMPFC were characterized by a hyperactivation in adolescents compared with younger adults. Furthermore, the ACC and insula were characterized by a U-shape pattern (hypoactivation in younger adults compared with adolescents and older adults), whereas the DLPFC and IPL were characterized by a J-shaped form (hyperactivation in older adults compared with younger groups). Furthermore, a functional connectivity analysis revealed an elevated negative functional coupling between the inhibition-related area rIFG and VS in younger adults compared with adolescents. Results indicate that lifespan-related changes during reward anticipation are characterized by different trajectories in different reward network modules and support the hypothesis of an imbalance in maturation of striatal and prefrontal cortex in adolescents. Furthermore, these results suggest compensatory age-specific effects in fronto-parietal regions. Hum Brain Mapp 35:5153-5165, 2014. (c) 2014 Wiley Periodicals, Inc.}, language = {en} } @article{HeinzelLorenzQuynhLamDuongetal.2017, author = {Heinzel, Stephan and Lorenz, Robert C. and Quynh-Lam Duong, and Rapp, Michael Armin and Deserno, Lorenz}, title = {Prefrontal-parietal effective connectivity during working memory in older adults}, series = {Neurobiology of Aging}, volume = {57}, journal = {Neurobiology of Aging}, publisher = {Elsevier}, address = {New York}, issn = {0197-4580}, doi = {10.1016/j.neurobiolaging.2017.05.005}, pages = {18 -- 27}, year = {2017}, abstract = {Theoretical models and preceding studies have described age-related alterations in neuronal activation of frontoparietal regions in a working memory (WM)load-dependent manner. However, to date, underlying neuronal mechanisms of these WM load-dependent activation changes in aging remain poorly understood. The aim of this study was to investigate these mechanisms in terms of effective connectivity by application of dynamic causal modeling with Bayesian Model Selection. Eighteen healthy younger (age: 20-32 years) and 32 older (60-75 years) participants performed an n-back task with 3 WM load levels during functional magnetic resonance imaging (fMRI). Behavioral and conventional fMRI results replicated age group by WM load interactions. Importantly, the analysis of effective connectivity derived from dynamic causal modeling, indicated an age-and performance-related reduction in WM load-dependent modulation of connectivity from dorsolateral prefrontal cortex to inferior parietal lobule. This finding provides evidence for the proposal that age-related WM decline manifests as deficient WM load-dependent modulation of neuronal top-down control and can integrate implications from theoretical models and previous studies of functional changes in the aging brain.}, language = {en} } @misc{GarbusowSommerNebeetal.2018, author = {Garbusow, Maria and Sommer, C. and Nebe, S. and Sebold, Miriam Hannah and Kuitunen-Paul, S{\"o}ren and Wittchen, H. U. and Smolka, M. and Zimmermann, U. and Rapp, Michael Armin and Huys, Q. and Schlagenhauf, Florian and Heinz, A.}, title = {Pavlovian-instrumental transfer in the course of alcohol use disorder}, series = {European psychiatry : the journal of the Association of European Psychiatrists}, volume = {48}, journal = {European psychiatry : the journal of the Association of European Psychiatrists}, publisher = {Elsevier}, address = {ISSY-LES-MOULINEAUX}, issn = {0924-9338}, pages = {S546 -- S546}, year = {2018}, 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 on- going thought and behavior. The influence of Pavlovian stimuli on on-going 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 Pavlovian-Instrumental transfer. Methods: 32 recently detoxified alcohol-dependent patients and 32 age and gender matched healthy controls performed a PIT task with instrumental go/no-go approach behaviours. 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} } @article{HeinzelLorenzPelzetal.2016, author = {Heinzel, Stephan and Lorenz, Robert C. and Pelz, Patricia and Heinz, Andreas and Walter, Henrik and Kathmann, Norbert and Rapp, Michael Armin and Stelzel, Christine}, title = {Neural correlates of training and transfer effects in working memory in older adults}, series = {NeuroImage : a journal of brain function}, volume = {134}, journal = {NeuroImage : a journal of brain function}, publisher = {Elsevier}, address = {San Diego}, issn = {1053-8119}, doi = {10.1016/j.neuroimage.2016.03.068}, pages = {236 -- 249}, year = {2016}, abstract = {As indicated by previous research, aging is associated with a decline in working memory (WM) functioning, related to alterations in fronto-parietal neural activations. At the same time, previous studies showed that WM training in older adults may improve the performance in the trained task (training effect), and more importantly, also in untrained WM tasks (transfer effects). However, neural correlates of these transfer effects that would improve understanding of its underlying mechanisms, have not been shown in older participants as yet. In this study, we investigated blood-oxygen-level-dependent (BOLD) signal changes during n-back performance and an untrained delayed recognition (Sternberg) task following 12 sessions (45 min each) of adaptive n-back training in older adults. The Sternberg task used in this study allowed to test for neural training effects independent of specific task affordances of the trained task and to separate maintenance from updating processes. Thirty-two healthy older participants (60-75 years) were assigned either to an n-back training or a no-contact control group. Before (t1) and after (t2) training/waiting period, both the n-back task and the Sternberg task were conducted while BOLD signal was measured using functional Magnetic Resonance Imaging (fMRI) in all participants. In addition, neuropsychological tests were performed outside the scanner. WM performance improved with training and behavioral transfer to tests measuring executive functions, processing speed, and fluid intelligence was found. In the training group, BOLD signal in the right lateral middle frontal gyrus/caudal superior frontal sulcus (Brodmann area, BA 6/8) decreased in both the trained n-back and the updating condition of the untrained Sternberg task at t2, compared to the control group. fMRI findings indicate a training-related increase in processing efficiency of WM networks, potentially related to the process of WM updating. Performance gains in untrained tasks suggest that transfer to other cognitive tasks remains possible in aging. (C) 2016 Elsevier Inc. All rights reserved.}, language = {en} } @article{BaltaBeylergilBeckDesernoetal.2017, author = {Balta Beylergil, Sinem and Beck, Anne and Deserno, Lorenz and Lorenz, Robert C. and Rapp, Michael Armin and Schlagenhauf, Florian and Heinz, Andreas and Obermayer, Klaus}, title = {Dorsolateral prefrontal cortex contributes to the impaired behavioral adaptation in alcohol dependence}, series = {NeuroImage: Clinical : a journal of diseases affecting the nervous system}, volume = {15}, journal = {NeuroImage: Clinical : a journal of diseases affecting the nervous system}, publisher = {Elsevier}, address = {Oxford}, issn = {2213-1582}, doi = {10.1016/j.nicl.2017.04.010}, pages = {80 -- 94}, year = {2017}, abstract = {Substance-dependent individuals often lack the ability to adjust decisions flexibly in response to the changes in reward contingencies. Prediction errors (PEs) are thought to mediate flexible decision-making by updating the reward values associated with available actions. In this study, we explored whether the neurobiological correlates of PEs are altered in alcohol dependence. Behavioral, and functional magnetic resonance imaging (fMRI) data were simultaneously acquired from 34 abstinent alcohol-dependent patients (ADP) and 26 healthy controls (HC) during a probabilistic reward-guided decision-making task with dynamically changing reinforcement contingencies. A hierarchical Bayesian inference method was used to fit and compare learning models with different assumptions about the amount of task-related information subjects may have inferred during the experiment. Here, we observed that the best-fitting model was a modified Rescorla-Wagner type model, the "double-update" model, which assumes that subjects infer the knowledge that reward contingencies are anti-correlated, and integrate both actual and hypothetical outcomes into their decisions. Moreover, comparison of the best-fitting model's parameters showed that ADP were less sensitive to punishments compared to HC. Hence, decisions of ADP after punishments were loosely coupled with the expected reward values assigned to them. A correlation analysis between the model-generated PEs and the fMRI data revealed a reduced association between these PEs and the BOLD activity in the dorsolateral prefrontal cortex (DLPFC) of ADP. A hemispheric asymmetry was observed in the DLPFC when positive and negative PE signals were analyzed separately. The right DLPFC activity in ADP showed a reduced correlation with positive PEs. On the other hand, ADP, particularly the patients with high dependence severity, recruited the left DLPFC to a lesser extent than HC for processing negative PE signals. These results suggest that the DLPFC, which has been linked to adaptive control of action selection, may play an important role in cognitive inflexibility observed in alcohol dependence when reinforcement contingencies change. Particularly, the left DLPFC may contribute to this impaired behavioral adaptation, possibly by impeding the extinction of the actions that no longer lead to a reward.}, language = {en} } @article{SturmWildermuthStolzetal.2019, author = {Sturm, Heidrun and Wildermuth, Ronja and Stolz, Regina and Bertram, L. and Eschweiler, G. W. and Thomas, C. and Rapp, Michael Armin and Joos, S.}, title = {Diverging awareness of postoperative delirium and cognitive dysfunction in German Health Care Providers}, series = {Clinical interventions in agins}, volume = {14}, journal = {Clinical interventions in agins}, publisher = {DOVE Medical Press}, address = {Albany}, issn = {1178-1998}, doi = {10.2147/CIA.S230800}, pages = {2125 -- 2135}, year = {2019}, abstract = {Purpose: Postoperative cognitive dysfunction (POCD) appears in up to 30\% of patients suffering from postoperative delirium (POD). Both are associated with higher mortality and postoperative complications, prolonged hospital stays, and increased costs. Multi-modal models with pre-admission risk reduction counselling, perioperative monitoring, and training of multidisciplinary patient care providers have been shown to decrease the prevalence of both. The aim of our study is to understand how far those measures are known and implemented in routine care and to detect potential gaps in the current practice regarding risk communication and information flow between involved caregivers for patients at risk for POD/POCD. Patients and Methods: As part of a multicenter study, seven semi-structured focus group (FG) discussions with nurses and physicians from tertiary care hospitals (surgery, anesthesiology, and orthopedics, n=31) and general practitioners (GPs) in private practice (n=7) were performed. Transcribed discussions were analyzed using qualitative content analysis. Results: POD is present above all in the daily work of nurses, whereas physicians do not perceive it as a relevant problem. Physicians report that no regular risk assessment or risk communication was performed prior to elective surgery. Information about POD often gets lost during hand-offs and is not regularly reported in discharge letters. Thus, persisting cognitive dysfunction is often missed. The importance of standardized documentation and continuous education concerning risks, screening, and treatment was emphasized. The often-suggested pre-OP medication adjustment was seen as less important; in contrast, avoiding withdrawal was regarded as far more important. Conclusion: Altogether, it seems that standards and available best practice concepts are rarely implemented. In contrast to physicians, nurses are highly aware of delirium and ask for standardized procedures and more responsibility. Therefore, raising awareness regarding risks, screening tools, and effective preventive measures for POD/POCD seems an urgent goal. Nurses should have a central role in coordination and care of POD to prevent the risk for POCD.}, language = {en} } @article{DesernoBeckHuysetal.2015, author = {Deserno, Lorenz and Beck, Anne and Huys, Quentin J. M. and Lorenz, Robert C. and Buchert, Ralph and Buchholz, Hans-Georg and Plotkin, Michail and Kumakara, Yoshitaka and Cumming, Paul and Heinze, Hans-Jochen and Grace, Anthony A. and Rapp, Michael Armin and Schlagenhauf, Florian and Heinz, Andreas}, title = {Chronic alcohol intake abolishes the relationship between dopamine synthesis capacity and learning signals in the ventral striatum}, series = {European journal of neuroscience}, volume = {41}, journal = {European journal of neuroscience}, number = {4}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0953-816X}, doi = {10.1111/ejn.12802}, pages = {477 -- 486}, year = {2015}, abstract = {Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug-related stimuli towards drug-related stimuli. Such hijacked' dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs) during a probabilistic reversal learning task in recently detoxified alcohol-dependent patients and healthy controls (N=27). All participants also underwent 6-[F-18]fluoro-DOPA positron emission tomography to assess ventral striatal dopamine synthesis capacity. Neither ventral striatal activation by RPEs nor striatal dopamine synthesis capacity differed between groups. However, ventral striatal coding of RPEs correlated inversely with craving in patients. Furthermore, we found a negative correlation between ventral striatal coding of RPEs and dopamine synthesis capacity in healthy controls, but not in alcohol-dependent patients. Moderator analyses showed that the magnitude of the association between dopamine synthesis capacity and RPE coding depended on the amount of chronic, habitual alcohol intake. Despite the relatively small sample size, a power analysis supports the reported results. Using a multimodal imaging approach, this study suggests that dopaminergic modulation of neural learning signals is disrupted in alcohol dependence in proportion to long-term alcohol intake of patients. Alcohol intake may perpetuate itself by interfering with dopaminergic modulation of neural learning signals in the ventral striatum, thus increasing craving for habitual drug intake.}, language = {en} }