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Die appetitiven Pawlow���schen Lernmechanismen der Konditionierung, Extinktion und des Reinstatements sind von entscheidender Bedeutung f��r das Verst��ndnis der Entstehung, Aufrechterhaltung, Therapie und R��ckfallph��nomene von Abh��ngigkeitserkrankungen. Bislang mangelt es an Studien, die appetitive Konditionierungs- und Extinktionsprozesse im Humanmodell untersuchen, w��hrend Reinstatement-Effekte g��nzlich unerforscht sind. Dieser Mangel wird gew��hnlich auf die Schwierigkeit zur��ckgef��hrt, ein geeignetes psychophysiologisches Ma�� zu finden, das sensitiv konditionierte Reaktionen beim Menschen erfasst. Die vorliegende Dissertation zielte daher darauf ab, die behavioralen, physiologischen und neuronalen Korrelate appetitiver Pawlow���scher Lernprozesse in gesunden Probanden zu erkunden. Studie I untersuchte die Eignung von Eyetracking-Ma��en zur Abbildung konditionierter Reaktionen in appetitiven Lernparadigmen und verglich diese mit weiteren psychophysiologischen Ma��en. Zus��tzlich wurde gepr��ft, ob sich Lernprozesse anhand des Pupillenverhaltens mit Hilfe computationaler Modellierung ableiten lassen. Konditionierte Reaktionen zeigten sich durch st��rkere Pupillendilatation, l��ngere Blickverweildauer und eine k��rzere Lidschlagdauer auf den belohnungsank��ndigenden Stimulus. Das Pearce-Hall-Modell mit aufmerksamkeitsgewichtetem Pr��diktionsfehler konnte die Pupillenreaktion am besten vorhersagen. In Studie II wurde untersucht, ob sich der appetitive Reinstatement-Effekt als Modell des R��ckfallgeschehens psychophysiologisch abbilden l��sst und welche neuronalen Strukturen diesem Lernprozess zugrunde liegen. Ein erfolgreiches Reinstatement konnte anhand der Hautleitf��higkeitsreaktion festgestellt werden und wurde auf neuronaler Ebene durch eine erh��hte Amygdala-Aktivierung gezeigt. Die vmPFC-Aktivit��t korrelierte negativ mit dem beobachteten Reinstatement-Effekt der Hautleitf��higkeit. Diese Ergebnisse belegen den Wert von Eyetracking-Ma��en als robuste und sensitive Indizes appetitiver Konditionierungsprozesse und weisen der Amygdala und dem vmPFC gegenl��ufige Funktionen bei Pawlow���schen R��ckfallprozessen zu. Damit tragen die Ergebnisse zu einem gr����eren Verst��ndnis von appetitiven Lernprozessen beim Menschen bei und liefern wertvolle neue Ma��e und Erkenntnisse, um Abh��ngigkeitserkrankungen besser zu untersuchen und zu verstehen., Appetitive Pavlovian learning mechanisms like conditioning, extinction and reinstatement are of fundamental importance for the understanding of the etiology, maintenance, treatment and relapse of addiction disorders. The investigation of appetitive conditioning and extinction in humans remains sparse, while reinstatement has thus far never been successfully modeled in humans. This paucity is commonly attributed to the lack of an adequate psychophysiological measure that sensitively reflects conditioned responding. The aim of this thesis was to explore the behavioral, physiological and neural correlates of appetitive Pavlovian learning processes in healthy participants. Study I evaluated the applicability of eye-tracking measures for representing conditioned responding and compared them to further psychophysiological measures. Additionally, this study investigated whether learning mechanisms could be inferred from the pupil response using computational modeling techniques. Conditioned responding was reflected through greater pupil dilation, longer gaze duration and shorter eye blink duration on the reward-predicting stimulus. A Pearce-Hall attention-weighted model most accurately predicted the trial-by-trial pupil response. Study II examined whether appetitive reinstatement could be psychophysiologically modeled in humans and what neural structures underlie this learning process. Successful reinstatement was indicated through an enhanced skin conductance response and correlated positively with amygdala activation, while vmPFC activation correlated negatively with the reinstatement effect observed in the skin conductance response. These results emphasize the value of eye-tracking measures as robust and sensitive indices for measuring appetitive conditioning processes and assign amygdala and vmPFC opposing roles in the return of Pavlovian reinstatement processes. These results thereby contribute to our knowledge of appetitive learning mechanisms in humans and provide valuable new measures and insights for exploring and understanding addiction disorders.

Aims: Increased sympathetic activation in patients with heart failure (HF) and sleep-disordered breathing (SDB) provokes cardiac decompensation and protein degradation and could lead to muscle wasting and muscle weakness. The aim of this study was to investigate the differences in body composition, muscle function, and the susceptibility of preclinical congestion among patients with HF and SDB compared with those without SDB. Methods and results: We studied 111 outpatients with stable HF who were enrolled into the Studies Investigating Co-morbidities Aggravating Heart Failure. Echocardiography, short physical performance battery (SPPB), cardiopulmonary exercise testing, dual-energy X-ray absorptiometry, bioelectrical impedance analysis (BIA), tests of muscle strength, and polygraphy were performed. SDB was defined as apnoea/hypopnoea index (AHI) >5 per hour of sleep. Central sleep apnoea (CSA) and obstructive sleep apnoea (OSA) were defined as AHI >50% of central or obstructive origin, respectively. A total of 74 patients (66.7%) had any form of SDB [CSA (24 patients, 32.4%), OSA (47 patients, 63.5%)]. Patients with SDB showed increased muscle weakness (chair stand), reduced muscle strength, and lower values of SPPB score (P 0.05) but had increased amounts of water (total body water, intracellular, and extracellular) measured using BIA (P

BACKGROUND Body weight loss is a frequent complication after stroke, and its adverse effect on clinical outcome has been shown in several clinical trials. The purpose of this prospective longitudinal single-centre observational study was to investigate dynamical changes of body composition and body weight after ischemic stroke and an association with functional outcome. METHODS Sixty-seven consecutive patients (age 69 ± 11 years, body mass index 27.0 ± 4.1 kg/m , 42% female patient, mean ± SD) with acute ischemic stroke with mild to moderate neurological deficit (National Institute of Health Stroke Scale median 4, ranged 0-12) were analysed in the acute phase (4 ± 2 days) and at 12 months (389 ± 26 days) follow-up. Body composition was examined by dual energy X-ray absorptiometry. Cachexia was defined according to the consensus definition by body weight loss ≥5% within 1 year and additional clinical signs. Lean tissue wasting was considered if a ratio of upper and lower limbs lean mass sum to squared height (kg/m ) was ≤5.45 kg/m for female patient and ≤7.25 kg/m for male patient. RESULTS According to the body weight changes after 12 months, 42 (63%) patients had weight gain or stable weight, 11 (16%) patients had moderate weight loss, and 14 (21%) patients became cachectic. A relative decline of 19% of fat tissue and 6.5% of lean tissue was observed in cachectic patients, while no changes of lean tissue were observed in non-cachectic patients after 12 months. The modified Rankin Scale was 48% higher (2.1 ± 1.6, P

Background: Body weight loss is a frequent complication after stroke, and its adverse effect on clinical outcome has been shown in several clinical trials. The purpose of this prospective longitudinal single-centre observational study was to investigate dynamical changes of body composition and body weight after ischemic stroke and an association with functional outcome. Methods: Sixty-seven consecutive patients (age 69 ± 11 years, body mass index 27.0 ± 4.1 kg/m2, 42% female patient, mean ± SD) with acute ischemic stroke with mild to moderate neurological deficit (National Institute of Health Stroke Scale median 4, ranged 0–12) were analysed in the acute phase (4 ± 2 days) and at 12 months (389 ± 26 days) follow-up. Body composition was examined by dual energy X-ray absorptiometry. Cachexia was defined according to the consensus definition by body weight loss ≥5% within 1 year and additional clinical signs. Lean tissue wasting was considered if a ratio of upper and lower limbs lean mass sum to squared height (kg/m2) was ≤5.45 kg/m2 for female patient and ≤7.25 kg/m2 for male patient. Results: According to the body weight changes after 12 months, 42 (63%) patients had weight gain or stable weight, 11 (16%) patients had moderate weight loss, and 14 (21%) patients became cachectic. A relative decline of 19% of fat tissue and 6.5% of lean tissue was observed in cachectic patients, while no changes of lean tissue were observed in non-cachectic patients after 12 months. The modified Rankin Scale was 48% higher (2.1 ± 1.6, P < 0.05), Barthel Index was 22% lower (71 ± 39, P < 0.01), and handgrip strength was 34% lower (21.9 ± 13.0, P < 0.05) in cachectic compared to non-cachectic patients after 12 months. The low physical performance if defined by Barthel Index