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The present study employs a new framework to categorise the heterogeneous findings on the relationship between impaired reward processing and negative and affective symptoms of schizophrenia. Based on previous behavioural and neuroimaging studies we postulate that "wanting" (i.e. anticipation) of a reward is specifically related to apathy, whereas "liking" (i.e. hedonic impact) is related to anhedonia and depression--symptoms commonly observed in schizophrenia. Fifteen patients with schizophrenia or schizoaffective disorder treated with atypical antipsychotic drugs and fifteen healthy controls performed a probabilistic monetary incentive delay task while undergoing functional magnetic resonance imaging. At the group level we found no significant differences between patients and controls in neural activation during anticipation or receipt of a reward. However, in patients with schizophrenia specific relationships between ventral-striatal activation and symptoms were observed. Ventral-striatal activation during reward anticipation was negatively correlated with apathy, while activation during receipt of reward was negatively correlated with severity of depressive symptoms. These results suggest that the link between negative symptoms and reward anticipation might specifically relate to apathy, i.e. a lack of motivation and drive. Impaired hedonic reward processing might contribute to the development of depressive symptoms in patients with schizophrenia, but it is not directly associated with self-rated anhedonia. These results indicate the necessity of more specifically differentiating negative and affective symptoms in schizophrenia in order to understand the role of the reward system in their pathogenesis. [ABSTRACT FROM AUTHOR]

Here we describe labeling with barcodes and enrichment for biochemical analysis by sequencing (LABEL-seq), an assay for massively parallel profiling of pooled protein variants in human cells. By leveraging the intracellular self-assembly of an RNA-binding domain (RBD) with a stable, variant-encoding RNA barcode, LABEL-seq facilitates the direct measurement of protein properties and functions using simple affinity enrichments of RBD protein fusions, followed by high-throughput sequencing of co-enriched barcodes. Measurement of ~20,000 variant effects for ~1,600 BRaf variants revealed that variation at positions frequently mutated in cancer minimally impacted intracellular abundance but could dramatically alter activity, protein-protein interactions and druggability. Integrative analysis identified networks of positions with similar biochemical roles and enabled modeling of variant effects on cell proliferation and small molecule-promoted degradation. Thus, LABEL-seq enables direct measurement of multiple biochemical properties in a native cellular context, providing insights into protein function, disease mechanisms and druggability., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: Respiratory diseases encompass a diverse range of conditions that significantly impact global morbidity and mortality. While common diseases like asthma and COPD exhibit moderate symptoms, less prevalent conditions such as pulmonary hypertension and cystic fibrosis profoundly affect quality of life and mortality. The prevalence of these diseases has surged by approximately 40% over the past 3 decades. Despite advancements in pharmacotherapy, challenges in drug administration, adherence, and adverse effects persist. This study aimed to develop and perform an interim validation of a Capacity-Motivation-Opportunity (CMO) model tailored for respiratory outpatients to enhance pharmaceutical care, which is the direct, responsible provision of medication-related care for the purpose of achieving definite outcomes that improve a patient's quality of life, and overall wellbeing., Methodology: This cross-sectional, multicenter study was conducted from March 2022 to March 2023. It comprised four phases: 1) forming an expert panel of 15 hospital pharmacists, 2) selecting respiratory pathologies based on prevalence and severity, 3) developing the CMO model's pillars, and 4) integrating and conducting an interim validation of the model. The Capacity pillar focused on patient stratification and personalized care; the Motivation pillar aligned therapeutic goals through motivational interviewing; and the Opportunity pillar promoted the use of information and communication technologies (ICTs) for telemedicine., Results: The model included eight respiratory diseases based on expert assessment. For the Capacity pillar, 22 variables were defined for patient stratification, leading to three priority levels for personalized pharmaceutical care. In a preliminary test involving 201 patients across six hospitals, the stratification tool effectively classified patients according to their needs. The Motivation pillar adapted motivational interviewing techniques to support patient adherence and behavior change. The Opportunity pillar established teleconsultation protocols and ICT tools to enhance patient monitoring and care coordination., Conclusion: The CMO model, tailored for respiratory patients, provides a comprehensive framework for improving pharmaceutical care. By focusing on patient-centered care, aligning therapeutic goals, and leveraging technology, this model addresses the multifaceted needs of individuals with respiratory conditions. Future studies are necessary to validate this model in other healthcare systems and ensure its broad applicability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zarate-Tamames, Garin, Calvin-Lamas, Jornet, Martinez-Simon, Garcia-Gil, Garcia-Rebolledo and Morillo-Verdugo.)

Background: Borderline personality disorder (BPD) and complex posttraumatic stress disorder (cPTSD) share clinical similarities, complicating diagnosis and treatment. Research on the neurobiology of BPD and monotraumatic PTSD has shown that a prefrontal-limbic imbalance in emotional and reward processing is a hallmark of both disorders, but studies examining this network in cPTSD are lacking. Therefore, this study aimed to directly compare neural processing of emotion and reward during decision making in cPTSD and BPD., Methods: Using functional magnetic resonance imaging, we measured neural activity in female patients (27 patients with cPTSD, 21 patients with BPD and 37 healthy controls) during a Desire-Reason Dilemma task featuring distracting fearful facial expressions., Results: We found no differences in neural activation when comparing cPTSD and BPD. However, when grouping patients based on symptom severity instead on diagnosis, we found that increased symptoms of cPTSD were associated with increased activation of dorsolateral prefrontal cortex during reward rejection, whereas increased symptoms of BPD were associated with decreased activation in prefrontal and limbic regions during reward rejection with distracting negative emotional stimuli., Conclusion: This is the first study to investigate and compare emotional processing and reward-based decision making in cPTSD and BPD. Although we found no neural differences between disorders, we identified symptom-related neural patterns. Specifically, we found that elevated cPTSD symptoms were related to greater sensitivity to reward stimuli, whereas heightened BPD symptoms were related to increased susceptibility to emotional stimuli during goal-directed decision making. These findings enhance our understanding of neural pathomechanisms in trauma-related disorders., Competing Interests: Declaration of competing interest The authors report no financial relationships with commercial interests and no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Once a threat no longer exists, extinction of conditioned fear becomes adaptive in order to reduce allotted resources towards cues that no longer predict the threat. In anxiety and stress disorders, fear extinction learning may be affected. Animal findings suggest that the administration of oxytocin (OT) modulates extinction learning in a timepoint-dependent manner, facilitating extinction when administered prior to fear conditioning, but impairing it when administered prior to extinction learning. The aim of the present study was to examine if these findings translate into human research. Using a randomized, double-blind, placebo-controlled, 2-day fear conditioning and extinction learning design, behavioral (self-reported anxiety), physiological (skin conductance response), neuronal (task-based and resting-state functional magnetic resonance imaging), and hormonal (cortisol) data were collected from 124 naturally cycling (taking no hormonal contraceptives) healthy females. When administered prior to conditioning (Day 1), OT, similar to rodent findings, did not affect fear conditioning, but modulated the intrinsic functional connectivity of the anterior insula immediately after fear conditioning. In contrast to animal findings, OT impaired, not facilitated, extinction learning on the next day and increased anterior insula activity. When administered prior to extinction learning (day 2), OT increased the activity in the bilateral middle temporal gyrus, and similar to animal findings, reduced extinction learning. The current findings suggest that intranasal OT impedes fear extinction learning in humans regardless of the timepoint of administration, providing new insights and directions for future translational research and clinical applications., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Patients with anorexia nervosa (AN) show overgeneralization of memory (OGM) when generating autobiographical episodes related to food and body shape. These memories are central for the construction of a coherent self-concept, interpersonal relationships, and problem-solving abilities. The current study aims to investigate changes in autobiographical memory following weight gain., Methods: OGM was assessed with an adapted version of the Autobiographical Memory Test including food-, body-, depression-related, and neutral cues. N = 41 female patients with AN (28 restricting-, 13 binge-eating/purging-subtype; mean disease duration: 4.5 years; mean BMI: 14.5 kg/m 2 ) and N = 27 healthy controls (HC) were included at baseline. After inpatient treatment (mean duration: 11 weeks), 24 patients with AN and 24 age-matched HC were reassessed. Group differences were assessed using independent samples t-tests for cross-sectional comparisons and repeated measures ANOVAs for longitudinal data., Results: At baseline, patients with AN generated significantly fewer specific memories than HC, independent of word category (F( 1 . 66 ) = 27.167, p < 0.001). During inpatient stay, the average weight gain of patients with AN was 3.1 body mass index points. At follow-up, patients with AN showed a significant improvement in the number of specific memories for both depression-related and neutral cues, but not for food- and body-related cues., Conclusions: Generalised OGM (i.e., independent of word category) in patients with AN before weight restoration may be a general incapacity to recall autobiographical memory. After weight gain, the previously well-studied pattern of eating disorder-related OGM emerges. The clinical relevance of the continuing disorder-related OGM in patients with AN after weight gain is discussed., (© 2024 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Background: Schizophrenia is associated with hypoactivation of reward sensitive brain areas during reward anticipation. However, it is unclear whether these neural functions are similarly impaired in other disorders with psychotic symptomatology or individuals with genetic liability for psychosis. If abnormalities in reward sensitive brain areas are shared across individuals with psychotic psychopathology and people with heightened genetic liability for psychosis, there may be a common neural basis for symptoms of diminished pleasure and motivation., Methods: We compared performance and neural activity in 123 people with a history of psychosis (PwP), 81 of their first-degree biological relatives, and 49 controls during a modified Monetary Incentive Delay task during fMRI., Results: PwP exhibited hypoactivation of the striatum and anterior insula (AI) during cueing of potential future rewards with each diagnostic group showing hypoactivations during reward anticipation compared to controls. Despite normative task performance, relatives demonstrated caudate activation intermediate between controls and PwP, nucleus accumbens activation more similar to PwP than controls, but putamen activation on par with controls. Across diagnostic groups of PwP there was less functional connectivity between bilateral caudate and several regions of the salience network (medial frontal gyrus, anterior cingulate, AI) during reward anticipation., Conclusions: Findings implicate less activation and connectivity in reward processing brain regions across a spectrum of disorders involving psychotic psychopathology. Specifically, aberrations in striatal and insular activity during reward anticipation seen in schizophrenia are partially shared with other forms of psychotic psychopathology and associated with genetic liability for psychosis.

Objective: Anorexia nervosa (AN) and obesity are weight-related disorders with imbalances in energy homeostasis that may be due to hormonal dysregulation. Given the importance of the hypothalamus in hormonal regulation, we aimed to identify morphometric alterations to hypothalamic subregions linked to these conditions and their connection to appetite-regulating hormones., Methods: Structural magnetic resonance imaging (MRI) was obtained from 78 patients with AN, 27 individuals with obesity and 100 normal-weight healthy controls. Leptin, ghrelin, and insulin blood levels were measured in a subsample of each group. An automated segmentation method was used to segment the hypothalamus and its subregions. Volumes of the hypothalamus and its subregions were compared between groups, and correlational analysis was employed to assess the relationship between morphometric measurements and appetite-regulating hormone levels., Results: While accounting for total brain volume, patients with AN displayed a smaller volume in the inferior-tubular subregion (ITS). Conversely, obesity was associated with a larger volume in the anterior-superior, ITS, posterior subregions (PS), and entire hypothalamus. There were no significant volumetric differences between AN subtypes. Leptin correlated positively with PS volume, whereas ghrelin correlated negatively with the whole hypothalamus volume in the entire cohort. However, appetite-regulating hormone levels did not mediate the effects of body mass index on volumetric measures., Conclusion: Our results indicate the importance of regional structural hypothalamic alterations in AN and obesity, extending beyond global changes to brain volume. Furthermore, these alterations may be linked to changes in hormonal appetite regulation. However, given the small sample size in our correlation analysis, further analyses in a larger sample size are warranted., Public Significance: Using an automated segmentation method to investigate morphometric alterations of hypothalamic subregions in AN and obesity, this study provides valuable insights into the complex interplay between hypothalamic alterations, hormonal appetite regulation, and body weight, highlighting the need for further research to uncover underlying mechanisms., (© 2024 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Kinase inhibitors are effective cancer therapies, but resistance often limits clinical efficacy. Despite the cataloging of numerous resistance mutations, our understanding of kinase inhibitor resistance is still incomplete. Here, we comprehensively profiled the resistance of ∼3,500 Src tyrosine kinase mutants to four different ATP-competitive inhibitors. We found that ATP-competitive inhibitor resistance mutations are distributed throughout Src's catalytic domain. In addition to inhibitor contact residues, residues that participate in regulating Src's phosphotransferase activity were prone to the development of resistance. Unexpectedly, we found that a resistance-prone cluster of residues located on the top face of the N-terminal lobe of Src's catalytic domain contributes to autoinhibition by reducing catalytic domain dynamics, and mutations in this cluster led to resistance by lowering inhibitor affinity and promoting kinase hyperactivation. Together, our studies demonstrate how drug resistance profiling can be used to define potential resistance pathways and uncover new mechanisms of kinase regulation., Competing Interests: Declaration of interests Authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Dysfunctional glucose sensing in homeostatic brain regions such as the hypothalamus is interlinked with the pathogenesis of obesity and type 2 diabetes mellitus. However, the physiology and pathophysiology of glucose sensing and neuronal homeostatic regulation remain insufficiently understood. To provide a better understanding of glucose signaling to the brain, we assessed the responsivity of the hypothalamus (i.e., the core region of homeostatic control) and its interaction with mesocorticolimbic brain regions in 31 normal-weight, healthy participants. We employed a single-blind, randomized, crossover design of the intravenous infusion of glucose and saline during fMRI. This approach allows to investigate glucose signaling independent of digestive processes. Hypothalamic reactivity and connectivity were assessed using a pseudo-pharmacological design and a glycemia-dependent functional connectivity analysis, respectively. In line with previous studies, we observed a hypothalamic response to glucose infusion which was negatively related to fasting insulin levels. The observed effect size was smaller than in previous studies employing oral or intragastric administration of glucose, demonstrating the important role of the digestive process in homeostatic signaling. Finally, we were able to observe hypothalamic connectivity with reward-related brain regions. Given the small amount of glucose employed, this points toward a high responsiveness of these regions to even a small energy stimulus in healthy individuals. Our study highlights the intricate relationship between homeostatic and reward-related systems and their pronounced sensitivity to subtle changes in glycemia.

Background: Patients with Anorexia Nervosa (AN) show a moderate deficit in overall neuropsychological functioning. Since previous studies on memory performance mainly employed cross-sectional designs, the present study aims to investigate changes in verbal memory following weight-gain., Methods: Verbal memory was assessed with the Wechsler Memory Scale-Revised (WMS-R; 'logical memory'-story-recall-subtest) and the California Verbal Learning Test-II (CVLT-II; 'verbal learning'). Included were 31 female patients with AN (18 restricting-, 13 purging-subtype; average disease duration: 5.1 years; average baseline BMI: 14.4 kg/m 2 ) and 24 medication-free normal-weight healthy women adjusted for age at baseline (T0). In a post-treatment assessment of approx. 6 weeks with weight increase (T1), 18 patients with AN and 20 healthy women were assessed again. Group differences in verbal memory (i.e., WMS-R, CVLT-II) were assessed for the baseline comparisons with a multivariate ANOVA and longitudinal data were analysed with repeated measures (RM) ANOVAs., Results: At baseline, patients with AN as compared to healthy women displayed deficits in logical memory. In the follow-up assessment, patients with AN improved their logical memory significantly compared to healthy controls (p < 0.006). Furthermore, groups did not differ in verbal learning neither before nor after inpatient treatment., Conclusions: Enhanced logical memory in patients with AN following weight-gain is probably due to the impaired memory as compared to healthy controls at T0. A survivorship bias could explain the improved memory performance in longitudinal data in contrast to cross-sectional studies. Patients with AN with poorer memory performance before inpatient treatment are at higher risk to drop out and need support., (© 2022 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Background: Anorexia nervosa (AN) is characterized by an overgeneralization of food/body-related autobiographical memories (AM). This is regarded as an emotion regulation strategy with adverse long-term effects implicated in disorder maintenance and treatment resistance. Therefore, we aimed to examine neural correlates of food/body-related AM-recall in AN., Methods: Twenty-nine female patients with AN and 30 medication-free age-sex-matched normal-weight healthy controls (HC) underwent functional magnetic resonance imaging while recalling AMs in response to food/body-related and neutral cue words. To control for general knowledge retrieval, participants engaged in a semantic generation and riser detection task., Results: In comparison to HC, patients with AN generated fewer and less specific AMs in response to food/body-related words, but not for neutral cue words. Group comparisons revealed reduced activation in regions associated with self-referential processing and memory retrieval (precuneus and angular gyrus) during the retrieval of specific food/body-related AM in patients with AN. Brain connectivity in regions associated with memory functioning and executive control was reduced in patients with AN during the retrieval of specific food/body-related AM. Finally, resting-state functional connectivity analysis revealed no differences between groups, arguing against a general underlying disconnection of brain networks implicated in memory and emotional processing in AN., Conclusions: These results indicate impaired neural processing of food/body-related AM in AN, with a reduced involvement of regions involved in self-referential processing. Our findings are discussed as possible neuronal correlates of emotional avoidance in AN and provide new insights of AN-pathophysiology underscoring the importance of targeting dysfunctional emotion regulation strategies during treatment.

Background: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data., Methods: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251)., Results: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients., Conclusions: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Despite a great diagnostic overlap, complex posttraumatic stress disorder (CPTSD) has been recognised by the ICD-11 as a new, discrete entity and recent empirical evidence points towards a distinction from simple posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD). The development and maintenance of these disorders is sustained by neurobiological alterations and studies using functional magnetic resonance imaging (fMRI) may further contribute to a clear differentiation of CPTSD, PTSD and BPD. However, there are no existing fMRI studies directly comparing CPTSD, PTSD and BPD. In addition to a summarization of diagnostic differences and similarities, the current review aims to provide a qualitative comparison of neuroimaging findings on affective, attentional and memory processing in CPTSD, PTSD and BPD. Our narrative review alludes to an imbalance in limbic-frontal brain networks, which may be partially trans-diagnostically linked to the degree of trauma symptoms and their expression. Thus, CPTSD, PTSD and BPD may underlie a continuum where similar brain regions are involved but the direction of activation may constitute its distinct symptom expression. The neuronal alterations across these disorders may conceivably be better understood along a symptom-based continuum underlying CPTSD, PTSD and BPD. Further research is needed to amend for the heterogeneity in experimental paradigms and sample criteria., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: To systematically review the problem of appetite loss after major abdominal surgery., Summary of Background Data: Appetite loss is a common problem after major abdominal surgery. Understanding of etiology and treatment options is limited., Methods: We searched Medline, Cochrane Central Register of Controlled Trials, and Web of Science for studies describing postoperative appetite loss. Data were extracted to clarify definition, etiology, measurement, surgical influence, pharmacological, and nonpharmacological treatment. PROSPERO registration ID: CRD42021224489., Results: Out of 6144 articles, we included 165 studies, 121 of which were also analyzed quantitatively. A total of 19.8% were randomized, controlled trials (n = 24) and 80.2% were nonrandomized studies (n = 97). The studies included 20,506 patients undergoing the following surgeries: esophageal (n = 33 studies), gastric (n = 48), small bowel (n = 6), colon (n = 27), rectal (n = 20), hepatobiliary (n = 6), and pancreatic (n = 13). Appetite was mostly measured with the Quality of Life Questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ C30, n = 54). In a meta-analysis of 4 randomized controlled trials gum chewing reduced time to first hunger by 21.2 hours among patients who had bowel surgery. Other reported treatment options with positive effects on appetite but lower levels of evidence include, among others, intravenous ghrelin administration, the oral Japanese herbal medicine Rikkunshito, oral mosapride citrate, multidisciplin-ary-counseling, and watching cooking shows. No studies investigated the effect of well-known appetite stimulants such as cannabinoids, steroids, or megestrol acetate on surgical patients., Conclusions: Appetite loss after major abdominal surgery is common and associated with increased morbidity and reduced quality of life. Recent studies demonstrate the influence of reduced gastric volume and ghrelin secretion, and increased satiety hormone secretion. There are various treatment options available including level IA evidence for postoperative gum chewing. In the future, surgical trials should include the assessment of appetite loss as a relevant outcome measure., Competing Interests: The other authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Growing evidence points towards dysfunction of the ventral striatum as a neural substrate of motivational impairments in schizophrenia. Ventral striatal activity during reward anticipation is generally reduced in patients with schizophrenia and specifically correlates with apathy. However, little is known about the cortico-striatal functional connectivity in patients with schizophrenia during reward anticipation and its relation to negative symptoms., Objectives: The aim of this study was to identify categorical group differences in ventral striatal functional connectivity during reward anticipation between patients with schizophrenia and healthy controls, and dimensional associations between cortico-striatal functional connectivity and negative symptom severity., Method: A total of 40 patients with schizophrenia (10 females) and 33 healthy controls (8 females) were included from two previously published studies. All participants performed a variant of the Monetary Incentive Delay Task while undergoing event-related fMRI. Functional connectivity was assessed using psychophysical interactions (PPI) with the left and right ventral striatum as seeds and the contrast [High Reward Anticipation - No Reward Anticipation]. Negative symptoms were assessed using the Brief Negative Symptom Scale., Results: Compared to controls, patients with schizophrenia showed increased functional connectivity between the left ventral striatum and the left precuneus and right parahippocampal gyrus, two hubs of the default mode network (cluster-level threshold: FWE, p < .05). In addition, we found a negative association between apathy scores on the BNSS and increased functional connectivity between the left ventral striatum and the left ventral anterior insula / putamen and the left inferior frontal gyrus / dorsal anterior insula (cluster-level threshold: FWE, p < .05)., Conclusions: Our results indicate that the patterns of increased functional connectivity between the ventral striatum and the dorsal default mode network during reward anticipation could act as a compensatory mechanism to regulate the activity of the ventral striatum. Our results also showed that functional connectivity patterns from the ventral striatum, much like its local activity, is specifically related to apathy, and not diminished expression., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Food intake in obesity has been found to be reward-based and less contingent on homeostatic needs. Accordingly, previous studies investigating neural processing of food cues observed aberrant processing in reward- and control-related brain regions in obesity. To further investigate the relation between homeostasis and food intake, this study investigated the influence of glucose metabolism on the neuronal response during the regulation of food craving in participants with obesity., Methods: Twenty-five normal-weight and 25 women with obesity were examined on two occasions after receiving either water or glucose directly into the stomach using a nasogastric tube. Participants were blinded to the type of infusion and were required to refrain from eating for 16 h before each visit. An event-related fMRI paradigm was used to investigate the effect of intestinal glucose load on the neuronal response during the regulation of food craving., Results: A 2 × 2 mixed-model ANOVA revealed that craving regulation was associated with increased activation in fronto-parietal regions in participants with obesity when compared to healthy controls. However, this effect was observed independently from homeostatic satiety. A regression analysis revealed that the reduction of food craving was related to increased activation in the lingual gyrus in individuals with obesity following the infusion of water., Conclusions: In participants with obesity, the neuronal response during the regulation of food craving is associated with increased neural cognitive top-down control and increased visual food processing. Since this observation was independent from satiety status, our results indicate a reduced influence of homeostasis on neural processing during food craving in obesity. This study was registered on clinicaltrials.org: NCT03075371., (© 2021. The Author(s).)

Background: Restrictive food intake in anorexia nervosa (AN) has been related to an overactive cognitive control network inhibiting intuitive motivational responses to food stimuli. However, the influence of short-term homeostatic signaling on the neural regulation of cue-induced food craving in AN is still unclear., Methods: Twenty-five women with AN and 25 matched normal-weight women were examined on two occasions after receiving either glucose or water directly into their stomach using a nasogastric tube. Participants were blinded to the type of infusion. An event-related functional magnetic resonance imaging paradigm was used to investigate the effect of intestinal glucose load on neural processing during either simple viewing or distraction from food stimuli., Results: Neural differences between patients with AN and normal-weight participants were found during the distraction from food stimuli, but not during the viewing condition. When compared to controls, patients with AN displayed increased activation during food distraction in the left parietal lobule/precuneus and fusiform gyrus after water infusion and decreased activation in ventromedial prefrontal and cingulate regions after intestinal glucose load., Conclusions: Independent of the cephalic phase and the awareness of caloric intake, homeostatic influences trigger disorder-specific reactions in AN. Food distraction in patients with AN is associated with either excessive higher-order cognitive control during physiological hunger or decreased internally directed attention after intestinal glucose load. These findings suggest that food distraction plays an important role in the psychopathology of AN. This study was registered on clinicaltrials.gov with identifier: NCT03075371.

Objectives: Excess sugar consumption, particularly in the form of sweetened beverages, has been identified as a pivotal contributor to the epidemic of obesity and associated metabolic disorders. However, the impact of sugar-sweetened beverages on food craving is still inconclusive. Therefore, the present study aimed to specifically investigate the effects of an intestinal glucose load on neural processing of food cues. Methods: Using a single-blind fMRI design, 26 normal-weight women were scanned on two occasions, after receiving either a glucose or water infusion directly into the stomach using a nasogastric tube, without being aware of the type of infusion. Participants had to either view neutral and food images, or were asked to distract themselves from these images by solving an arithmetic task. Results: In response to viewing high-caloric food cues, we observed increased activation in reward-related brain areas. During food distraction, fronto-parietal brain regions were recruited, which are commonly related to attentional deployment and hedonic valuation. Furthermore, activity in the dorsolateral prefrontal cortex showed increased functional connectivity with the insula and was correlated with subjective craving levels to food cues. Despite an increase of blood glucose levels in response to the glucose compared to the water infusion, neither subjective food craving nor neural regulation of food craving showed significant differences. Conclusions: These findings support a decreased satiation effect of sweet beverages, as intestinal glucose ingestion and signalling showed no significant effect on cortical brain circuits associated with food craving. This trial was registered at clinicaltrials.gov as NCT03075371.

BACKGROUNDGiven the heightened tolerance to self-starvation in anorexia nervosa (AN), a hypothalamic dysregulation of energy and glucose homeostasis has been hypothesized. Therefore, we investigated whether hypothalamic reactivity to glucose metabolism is impaired in AN.METHODSTwenty-four participants with AN, 28 normal-weight participants, and 24 healthy participants with obesity underwent 2 MRI sessions in a single-blind, randomized, case-controlled crossover study. We used an intragastric infusion of glucose and water to bypass the cephalic phase of food intake. The responsivity of the hypothalamus and the crosstalk of the hypothalamus with reward-related brain regions were investigated using high-resolution MRI.RESULTSNormal-weight control participants displayed the expected glucose-induced deactivation of hypothalamic activation, whereas patients with AN and participants with obesity showed blunted hypothalamic reactivity. Furthermore, patients with AN displayed blunted reactivity in the nucleus accumbens and amygdala. Compared with the normal-weight participants and control participants with obesity, the patients with AN failed to show functional connectivity between the hypothalamus and the reward-related brain regions during water infusion relative to glucose infusion. Finally, the patients with AN displayed typical baseline levels of peripheral appetite hormones during a negative energy balance.CONCLUSIONThese results indicate that blunted hypothalamic glucose reactivity might be related to the pathophysiology of AN. This study provides insights for future research, as it is an extended perspective of the traditional primary nonhomeostatic understanding of the disease.FUNDINGThis study was supported by a grant from the DFG (SI 2087/2-1).

Background: Bipolar disorder I (BD-I) is defined by episodes of mania, depression and euthymic states. These episodes are among other symptoms characterized by altered reward processing and negative symptoms (NS), in particular apathy. However, the neural correlates of these deficits are not well understood., Methods: We first assessed the severity of NS in 25 euthymic BD-I patients compared with 25 healthy controls (HC) and 27 patients with schizophrenia (SZ). Then, we investigated ventral (VS) and dorsal striatal (DS) activation during reward anticipation in a Monetary Incentive Delayed Task and its association with NS., Results: In BD-I patients NS were clearly present and the severity of apathy was comparable to SZ patients. Apathy scores in the BD-I group but not in the SZ group correlated with sub-syndromal depression scores. At the neural level, we found significant VS and DS activation in BD-I patients and no group differences with HC or SZ patients. In contrast to patients with SZ, apathy did not correlate with striatal activation during reward anticipation. Explorative whole-brain analyses revealed reduced extra-striatal activation in BD-I patients compared with HC and an association between reduced activation of the inferior frontal gyrus and apathy., Conclusion: This study found that in BD-I patients apathy is present to an extent comparable to SZ, but is more strongly related to sub-syndromal depressive symptoms. The findings support the view of different pathophysiological mechanisms underlying apathy in the two disorders and suggest that extra-striatal dysfunction may contribute to impaired reward processing and apathy in BD-I.

Abnormalities and alterations in brain function are commonly associated with the etiology and maintenance of anorexia nervosa (AN). Different symptom categories of AN have been correlated with distinct neurobiological patterns in previous studies. The aim of this literature review is to provide a narrative overview of the investigations into neural correlates of disorder-specific stimuli in patients with AN. Although findings vary across studies, a summary of neuroimaging results according to stimulus category allows us to account for methodological differences in experimental paradigms. Based on the available evidence, the following conclusions can be made: (a) the neural processing of visual food cues is characterized by increased top-down control, which enables restrictive eating, (b) increased emotional and reward processing during gustatory stimulation triggers disorder-specific thought patterns, (c) hunger ceases to motivate food foraging but instead reinforces disorder-related behaviors, (d) body image processing is related to increased emotional and hedonic reactions, (e) emotional stimuli provoke increased saliency associated with decreased top-down control and (f) neural hypersensitivity during interoceptive processing reinforces avoidance behavior. Taken together, studies that investigated symptom-specific neural processing have contributed to a better understanding of the underlying mechanisms of AN.

Plasmonic nanocomposites based on well-dispersed silver nanocubes in poly(vinylpyrrolidone) are presented that are solution-processed into layers of varying volume fractions of nanocubes. We show that the high-energy modes of the nanocubes are almost insensitive to plasmonic coupling within the nanocube assemblies, leading to a linear increase in light absorption in the UV region with the nanocube densities. Concerning the main dipolar resonance mode at 450 nm, it is strongly affected by the formation of these assemblies, leading to an increased absorption in the UV region as well as a large absorption band in the visible region. Simulations of the optical response of the nanocube assemblies as a function of nanocube spacing and electric field polarization reveal that optical features in the visible region are due to intercube couplings at short intercube distances and parallel electric field orientation. In contrast, the additional plasmonic band in the UV region has its origin in residual dipolar oscillations of the nanocubes in combination with weak dipolar coupling for both parallel and transversal field polarizations. The combination of these effects leads to an enlarged absorption band in the UV region with nearly perfect light absorption of 98.8% at a high silver volume fraction of 8% that is accompanied by a very weak specular reflection of only 0.28%. Although such perfect absorption is usually observed only when nanocubes are assembled on a gold surface, nearly perfect absorption herein is achieved on a large palette of substrates including glass, plastic, and cheap metals such as aluminum, making it a promising approach for solution-processed robust and cheap quasi-perfect absorption coatings.

Introduction: The etiology of bulimic-type eating (BTE) disorders such as binge eating disorder (BED) and bulimia nervosa (BN) is still largely unknown. Brain networks subserving the processing of rewards, emotions, and cognitive control seem to play a crucial role in the development and maintenance of eating disorders. Therefore, further investigations into the neurobiological underpinnings are needed to discern abnormal connectivity patterns in BTE disorders., Methods: The present study aimed to investigate functional as well as seed-based connectivity within well-defined brain networks. Twenty-seven individuals with BED, 29 individuals with BN, 28 overweight, and 30 normal-weight control participants matched by age, gender, and education underwent resting-state functional magnetic resonance imaging. Functional connectivity was assessed by spatial group independent component analysis and a seed-based correlation approach by examining the default mode network (DMN), salience network (SN), and executive network (EN)., Results: Group comparisons revealed that BTE disorder patients exhibit aberrant functional connectivity in the dorsal anterior cingulate cortex (dACC) within the SN, as well as in the medial prefrontal cortex within the DMN. Furthermore, BED and BN groups differed from each other in functional connectivity within each network. Seed-based correlational analysis revealed stronger synchronous dACC-retrosplenial cortex activity in the BN group., Conclusion: Our findings demonstrate abnormalities in brain networks involved in salience attribution, self-referential processing, and cognitive control in bulimic-type eating disorders. Together with our observation of functional connectivity differences between BED and BN, this study offers a differentiated account of both similarities and differences regarding brain connectivity in BED and BN., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Aim: Previous studies indicate the effectiveness of motor imagery training in stroke patients. To determine whether patients showing chronic visuospatial neglect symptoms may profit from motor imagery training, it is important to assess how the brain implements motor imagery when cortical systems involved in attentional control are impaired., Method: Therefore, in this pilot study, nine chronic neglect patients with right-hemispheric stroke performed motor imagery of a finger opposition task during functional magnetic resonance imaging (fMRI)., Results: Imagery of unaffected hand movements was related to activations in the left primary somatosensory and premotor cortices as well as in the left supplementary motor area. During the imagery of the affected hand, patients displayed activations in the left premotor cortex and supplementary motor area as well as left dorsolateral prefrontal cortex. Furthermore, time since onset and visual imagery capacity were negatively related to activation in the supplementary motor area during the imagery of the affected hand., Conclusions: These initial results demonstrate motor imagery capacity in patients with chronic neglect via compensatory neural processing during motor imagery of the affected hand in ipsilateral brain regions, since we found that the supplementary motor area appears to be specifically related to neglect severity. Although our results must be treated with caution due to the small sample size and missing control group, they indicate that neglect is not necessarily an exclusion criterion for motor imagery training per se.

Adaptive coding of information is a fundamental principle of brain functioning. It allows for efficient representation over a large range of inputs and thereby alleviates the limited coding range of neurons. In the present study, we investigated for the first time potential alterations in context-dependent reward adaptation and its association with symptom dimensions in the schizophrenia spectrum. We studied 27 patients with first-episode psychosis, 26 individuals with schizotypal personality traits and 25 healthy controls. We used functional MRI in combination with a variant of the monetary incentive delay task and assessed adaptive reward coding in two reward conditions with different reward ranges. Compared to healthy controls, patients with first-episode psychosis and healthy individuals with schizotypal personality traits showed a deficit in increasing the blood oxygen level-dependent response slope in the right caudate for the low reward range compared to the high reward range. In other words, the two groups showed inefficient neural adaptation to the current reward context. In addition, we found impaired adaptive coding of reward in the caudate nucleus and putamen to be associated with total symptom severity across the schizophrenia spectrum. Symptom severity was more strongly associated with neural deficits in adaptive coding than with the neural coding of absolute reward outcomes. Deficits in adaptive coding were prominent across the schizophrenia spectrum and even detectable in unmedicated (healthy) individuals with schizotypal personality traits. Furthermore, the association between total symptom severity and impaired adaptive coding in the right caudate and putamen suggests a dimensional mechanism underlying imprecise neural adaptation. Our findings support the idea that impaired adaptive coding may be a general information-processing deficit explaining disturbances within the schizophrenia spectrum over and above a simple model of blunted absolute reward signals.

Objective: Weight loss maintenance is one of the biggest challenges in behavioral weight loss programs. The present study aimed to examine metabolic influences on the mesolimbic reward system in people with successful and unsuccessful long-term weight loss maintenance., Methods: Thirty-three women with obesity at least 6 months after the completion of a diet were recruited: seventeen women were able to maintain their weight loss, whereas sixteen showed weight regain. Using functional magnetic resonance imaging in combination with the assessment of appetite-regulating hormones, neural reward processing during hunger and satiety was investigated. An incentive delay task was employed to investigate the expectation and receipt of both food-related and monetary reward., Results: Only participants with successful weight loss maintenance showed a satiety-induced attenuation of brain activation during the receipt of a food-related reward. Furthermore, in successful weight loss maintenance, the attenuation of active ghrelin levels was related to brain activation in response to food-related reward anticipation during satiety., Conclusions: The findings suggest that an attenuated influence of satiety signaling on the neural processing of food-related reward contributes to unsuccessful weight loss maintenance. Thus, intact satiety signaling to the mesolimbic reward system may serve as a promising target for tackling weight cycling., (© 2018 The Obesity Society.)

Anhedonia, or the inability to experience pleasure, is commonly observed in schizophrenia. It has been suggested that patients with schizophrenia are unable to predict future pleasurable events, but show intact experience of in-the-moment pleasure. Therefore, the Temporal Experience of Pleasure Scale (TEPS), a self-report measure allowing the assessment of anticipatory and consummatory pleasure, has been developed. To validate the German version of the TEPS, we recruited 59 healthy control participants and 51 patients with schizophrenia or schizoaffective disorder who completed the TEPS as well as a battery of psychometric tests to assess psychopathology, in particular self-rated anhedonia and clinician-rated apathy as well as overall measures of negative symptoms. We found acceptable to good internal consistency and a factor structure comparable to the original version. Scores of the TEPS were related to measures of anhedonia and apathy, but not with other measures of psychopathology. The present results suggest that the German version of the TEPS shows adequate reliability and validity to assess the construct of anhedonia. However, differential aspects of anticipatory and consummatory pleasure should be further investigated in clinical samples., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The protein hormone adiponectin promotes metabolic and psychological health. The aim of the study was to track changes in adiponectin levels in response to weight gain and to assess associations between adiponectin and psychological aspects in patients with anorexia nervosa (AN)., Methods: To investigate if adiponectin levels depend on AN severity, data were assessed from 11 inpatients with a very low body mass index (BMI) and a high chronicity (high severity group; HSS), and nine with less severe symptoms (LSS). During the course of treatment, serum adiponectin concentrations were assessed on a weekly basis along with BMI. Psychological variables (i.e., depression, anxiety, stress, and AN-specific symptoms) were obtained by means of electronic diaries. Longitudinal regressions and correlations were calculated to evaluate the temporal course of adiponectin and its relationship with psychological self-ratings., Results: At the beginning adiponectin was not increased in HSS patients (p = .56), and only marginally elevated in LSS patients (p = 0.07) compared with controls. In HSS patients, adiponectin increased along with BMI during the first treatment phase (i.e., when the BMI of patients was below 16 kg/m2) and thereafter decreased with further weight gain. In LSS patients, adiponectin was not associated with BMI increase. Furthermore, adiponectin was strongly negatively correlated with psychological self-ratings when the BMI of patients was above 16 kg/m2, i.e., higher levels of adiponectin were related to lower ratings of depression, anxiety, and AN-specific symptoms., Discussion: The study connects previous varying results by indicating that the course of adiponectin is dependent on BMI and symptom severity. Similarly, associations of adiponectin and psychological health depended on BMI.

Background: Heightened sensitivity towards reward and insensitivity towards disadvantageous consequences may constitute a driving factor underlying unrestricted food intake and consequent weight gain in people with overweight and obesity. Therefore, the present study applied a behavioral economics approach to investigate the potential contribution of poor reward-related decision making to unsuccessful long-term weight loss maintenance (i.e. weight cycling). Based on previous research, it was expected that successful long-term weight loss maintainers would show a better performance in a gambling task than their less successful counterparts., Methods: Reward-related decision making was assessed post hoc using the Game of Dice Task in a total of 33 overweight and obese women who had either (a) successfully maintained initial weight loss of at least 10% of their body weight over one year or (b) had regained weight until at least their initial body weight prior to weight reduction (i.e. showed weight cycling)., Results: The groups did not differ in terms of age, current body weight, magnitude of initial weight reduction, educational level, and global intelligence level. As hypothesized, however, the group of successful long-term weight loss maintainers performed significantly better (i.e. showed less impulsive, more advantageous choices) in the Game of Dice Task than their less successful counterparts., Conclusions: The findings suggest that poor reward-related decision making is associated with weight cycling which is considered a key concern in weight loss treatments for overweight and obesity. Furthermore, the findings speak in favor of specific psychological interventions that are designed to bolster reward-related decision making., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Food intake is guided by homeostatic needs and by the reward value of food, yet the exact relation between the two remains unclear. The aim of this study was to investigate the influence of different metabolic states and hormonal satiety signaling on responses in neural reward networks., Methods: Twenty-three healthy participants underwent functional magnetic resonance imaging while performing a task distinguishing between the anticipation and the receipt of either food- or monetary-related reward. Every participant was scanned twice in a counterbalanced fashion, both during a fasted state (after 24 hours fasting) and satiety. A functional connectivity analysis was performed to investigate the influence of satiety signaling on activation in neural reward networks. Blood samples were collected to assess hormonal satiety signaling., Results: Fasting was associated with sensitization of the striatal reward system to the anticipation of food reward irrespective of reward magnitude. Furthermore, during satiety, individual ghrelin levels were associated with increased neural processing during the expectation of food-related reward., Conclusions: Our findings show that physiological hunger stimulates food consumption by specifically increasing neural processing during the expectation (i.e., incentive salience) but not the receipt of food-related reward. In addition, these findings suggest that ghrelin signaling influences hedonic-driven food intake by increasing neural reactivity during the expectation of food-related reward. These results provide insights into the neurobiological underpinnings of motivational processing and hedonic evaluation of food reward., Trial Registration: ClinicalTrials.gov NCT03081585., Funding: This work was supported by the German Competence Network on Obesity, which is funded by the German Federal Ministry of Education and Research (FKZ 01GI1122E).

Rationale: Alcohol dependence is associated with impaired response inhibition and heightened cue reactivity towards alcohol-related stimuli. Several brain areas, but mainly prefrontal structures, have been linked to response inhibition in addiction. This study aimed at combining both aspects: salience of drug-associated cues and response inhibition using a go/no-go task with alcohol-associated stimuli during functional magnetic resonance imaging (fMRI)., Objectives: Nineteen abstinent alcohol-dependent patients (ADP) and 21 healthy control subjects (HC) were compared on blood oxygen level-dependent (BOLD) responses during successful inhibition of no-go stimuli and successful reactions to go stimuli., Results: ADP and HC did not significantly differ in their behavioural performance in the task. However, both groups performed worse during the inhibition of alcoholic-associated stimuli compared to neutral stimuli. On the neural level, ADP displayed enhanced BOLD activity relative to HC during successful response inhibition in several areas involved in visual processing, cognitive and impulse control, including occipital structures, anterior cingulate gyrus, medial frontal gyrus and medial orbitofrontal cortex., Conclusions: We interpret these findings as a possible compensation strategy for impaired cognitive processing. Furthermore, the results underline the impact of salience of alcohol-related stimuli on response inhibition, which seems to affect both ADP and HC.

The fast and computationally inexpensive Modified Transfer Matrix Method (MTM) is employed to simulate the optical response of kesterite Cu 2 ZnSnSe 4 solar cells. This method can partially take into account the scattering effects due to roughness at the interfaces between the layers of the stack. We analyzed the optical behavior of the whole cell structure by varying the thickness of the TCO layer (iZnO + ITO) between 50 and 1200 nm and the buffer CdS layer between 0 and 100 nm. We propose optimal combinations of the TCO/CdS thicknesses that can locally maximize the device photocurrent. We provide experimental data that qualitatively confirm our theoretical predictions.

Clinical observations and similarities to addiction suggest heightened reward sensitivity to food in patients with bulimic-type eating (BTE) disorders. Therefore, we investigated the expectation and receipt of food reward compared with monetary reward in patients with BTE. Fifty-six patients with BTE (27 patients with binge eating disorder and 29 with bulimia nervosa) and 55 matched healthy control participants underwent event-related functional magnetic resonance imaging while performing both food and monetary incentive delay tasks. BTE patients exhibited reduced brain activation in the posterior cingulate cortex during the expectation of food and increased activity in the medial orbitofrontal cortex, anterior medial prefrontal cortex and posterior cingulate cortex during the receipt of food reward. These findings were relevant to food because we found no significant group differences related to monetary reward. In the patients, higher brain activity in the medial orbitofrontal cortex during the receipt of food reward was related to higher levels of trait food craving and external eating. BTE patients exhibited increased hedonic processing during the receipt of food reward. These findings corroborate the notion that an altered responsiveness of the reward network to food stimuli is associated with BTE., (© The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

Background: Impaired inhibitory control is considered a behavioural phenotype in patients with bulimia nervosa. However, the underlying neural correlates of impaired general and food-specific behavioural inhibition are largely unknown. Therefore, we investigated brain activation during the performance of behavioural inhibition to general and food-related stimuli in adults with bulimia nervosa., Methods: Women with bulimia and healthy control women underwent event-related fMRI while performing a general and a food-specific no-go task., Results: We included 28 women with bulimia nervosa and 29 healthy control women in our study. On a neuronal level, we observed significant group differences in response to general no-go stimuli in women with bulimia nervosa with high symptom severity; compared with healthy controls, the patients showed reduced activation in the right sensorimotor area (postcentral gyrus, precentral gyrus) and right dorsal striatum (caudate nucleus, putamen)., Limitations: The present results are limited to adult women with bulimia nervosa. Furthermore, it remains unclear whether impaired behavioural inhibition in patients with this disorder are a cause or consequence of chronic illness., Conclusion: Our findings suggest that diminished frontostriatal brain activation in patients with bulimia nervosa contribute to the severity of binge eating symptoms. Gaining further insight into the neural mechanisms of behavioural inhibition problems in individuals with this disorder may inform brain-directed treatment approaches and the development of response inhibition training approaches to improve inhibitory control in patients with bulimia nervosa. The present study does not support greater behavioural and neural impairments to food-specific behavioural inhibition in these patients.

Recent models of the development of addiction propose a transition from a pleasure-driven to a heavily automatized behaviour, marked by a loss of cognitive control. This study investigated the deficits in different components of cognitive functions including behavioural inhibition in response to alcohol-related stimuli in alcohol-dependent patients (ADP) and healthy controls (HC). The aims of the study were to identify which particular cognitive functions are impaired in ADP. Furthermore, we analysed the association between cognitive deficits and relapse rates and the reversibility of cognitive deficits under abstinence in a 6-month follow-up period. Ninety-four recently detoxified ADP and 71 HC completed the cognitive tasks as well as questionnaire measures assessing drinking behaviour and personality traits. Compared with HC, ADP showed poorer performance in response initiation, response inhibition, complex-sustained attention and executive functions. Impairment in response inhibition was a significant predictor for relapse, yet the strongest predictor was the interaction between the number of previous detoxifications and response-inhibition deficits. The results of a moderation analysis showed that patients with many previous detoxifications and large deficits in response inhibition showed the highest relapse risk. These findings indicate that interventions should take into account inhibitory deficits especially in ADP with a high number of previous detoxifications., (© 2015 Society for the Study of Addiction.)

Dysfunctional patterns of activation in brain reward networks have been suggested as a core element in the pathophysiology of schizophrenia. However, it remains unclear whether this dysfunction is specific to schizophrenia or can be continuously observed across persons with different levels of nonclinical and clinical symptom expression. Therefore, we sought to investigate whether the pattern of reward system dysfunction is consistent with a dimensional or categorical model of psychosis-like symptom expression. 23 patients with schizophrenia and 37 healthy control participants with varying levels of psychosis-like symptoms, separated into 3 groups of low, medium, and high symptom expression underwent event-related functional magnetic resonance imaging while performing a Cued Reinforcement Reaction Time task. We observed lower activation in the ventral striatum during the expectation of high vs no reward to be associated with higher symptom expression across all participants. No significant difference between patients with schizophrenia and healthy participants with high symptom expression was found. However, connectivity between the ventral striatum and the medial orbitofrontal cortex was specifically reduced in patients with schizophrenia. Dysfunctional local activation of the ventral striatum depends less on diagnostic category than on the degree of symptom expression, therefore showing a pattern consistent with a psychosis continuum. In contrast, aberrant connectivity in the reward system is specific to patients with schizophrenia, thereby supporting a categorical view. Thus, the results of the present study provide evidence for both continuous and discontinuous neural substrates of symptom expression across patients with schizophrenia and the general population., (© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Food is an innate reward stimulus related to energy homeostasis and survival, whereas money is considered a more general reward stimulus that gains a rewarding value through learning experiences. Although the underlying neural processing for both modalities of reward has been investigated independently from one another, a more detailed investigation of neural similarities and/or differences between food and monetary reward is still missing. Here, we investigated the neural processing of food compared with monetary-related rewards in 27 healthy, normal-weight women using functional magnetic resonance imaging. We developed a task distinguishing between the anticipation and the receipt of either abstract food or monetary reward. Both tasks activated the ventral striatum during the expectation of a reward. Compared with money, greater food-related activations were observed in prefrontal, parietal and central midline structures during the anticipation and lateral orbitofrontal cortex (lOFC) during the receipt of food reward. Furthermore, during the receipt of food reward, brain activation in the secondary taste cortex was positively related to the body mass index. These results indicate that food-dependent activations encompass to a greater extent brain regions involved in self-control and self-reflection during the anticipation and phylogenetically older parts of the lOFC during the receipt of reward., (© The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

Background/aims: Little is known about the association of binge drinking with impulsivity related to trait- or state-like aspects of behavior. The aim of the present study was therefore to investigate whether binge drinkers show an impairment of inhibitory control in comparison to non-binge drinkers when confronted with alcohol-associated or control stimuli, and whether this is reflected in self-reported impulsivity., Methods: A go/no-go task with pictures of alcoholic and nonalcoholic beverages as well as control stimuli was administered to binge drinkers and a gender-matched group of non-binge drinkers. All participants also completed the Barratt Impulsiveness Scale (BIS-11)., Results: We found an alcohol-specific impairment of response inhibition for binge drinkers only, while the groups did not differ with regard to overall response inhibition to the experimental stimuli or self-reported impulsiveness (BIS-11). In addition, the number of commission errors in response to alcohol-associated stimuli was the only significant predictor of binge drinking., Conclusion: The findings of the present study suggest that when young adults have established binge drinking as a common drinking pattern, impairment of inhibition in response to alcoholic stimuli is the only significant predictor of binge drinking, but not general impulsive behavior., (© 2014 S. Karger AG, Basel.)

There is growing evidence that reward processing is disturbed in schizophrenia. However, it is uncertain whether this dysfunction predates or is secondary to the onset of psychosis. Studying 21 unmedicated persons at risk for psychosis plus 24 healthy controls (HCs) we used a incentive delay paradigm with monetary rewards during functional magnetic resonance imaging. During processing of reward information, at-risk individuals performed similarly well to controls and recruited the same brain areas. However, while anticipating rewards, the high-risk sample exhibited additional activation in the posterior cingulate cortex, and the medio- and superior frontal gyrus, whereas no significant group differences were found after rewards were administered. Importantly, symptom dimensions were differentially associated with anticipation and outcome of the reward. Positive symptoms were correlated with the anticipation signal in the ventral striatum (VS) and the right anterior insula (rAI). Negative symptoms were inversely linked to outcome-related signal within the VS, and depressive symptoms to outcome-related signal within the medial orbitofrontal cortex (mOFC). Our findings provide evidence for a reward-associated dysregulation that can be compensated by recruitment of additional prefrontal areas. We propose that stronger activations within VS and rAI when anticipating a reward reflect abnormal processing of potential future rewards. Moreover, according to the aberrant salience theory of psychosis, this may predispose a person to positive symptoms. Additionally, we report evidence that negative and depressive symptoms are differentially associated with the receipt of a reward, which might demonstrate a broader vulnerability to motivational and affective symptoms in persons at-risk for psychosis.

The anticipation of the pleasure derived from food intake drives the motivation to eat, and hence facilitate overconsumption of food, which ultimately results in obesity. Brain imaging studies provide evidence that mesolimbic brain regions underlie both general as well as food-related anticipatory reward processing. In light of this knowledge, the present study examined the neural responsiveness of the ventral striatum (VS) in participants with a broad BMI spectrum. The study differentiated between general (i.e., monetary) and food-related anticipatory reward processing. We recruited a sample of volunteers with greatly varying body weights, ranging from a low BMI (below 20 kg/m(2)) over a normal (20-25 kg/m(2)) and overweight (25-30 kg/m(2)) BMI, to class I (30-35 kg/m(2)) and class II (35-40 kg/m(2)) obesity. A total of 24 participants underwent functional magnetic resonance imaging while performing both a food and monetary incentive delay task, which allows to measure neural activation during the anticipation of rewards. After the presentation of a cue indicating the amount of food or money to be won, participants had to react correctly in order to earn "snack points" or "money coins," which could then be exchanged for real food or money, respectively, at the end of the experiment. During the anticipation of both types of rewards, participants displayed activity in the VS, a region that plays a pivotal role in the anticipation of rewards. Additionally, we observed that specifically anticipatory food reward processing predicted the individual BMI (current and maximum lifetime). This relation was found to be mediated by impaired hormonal satiety signaling, i.e., increased leptin levels and insulin resistance. These findings suggest that heightened food reward motivation contributes to obesity through impaired metabolic signaling.

Decision-making research has thoroughly investigated how people choose from a set of externally provided options. However, in ill-structured real-world environments, possible options for action are not defined by the situation but have to be generated by the agent. Here, we apply behavioral analysis (Study 1) and functional magnetic resonance imaging (Study 2) to investigate option generation and subsequent choice. For this purpose, we employ a new experimental task that requires participants to generate options for simple real-world scenarios and to subsequently decide among the generated options. Correlational analysis with a cognitive test battery suggests that retrieval of options from long-term memory is a relevant process during option generation. The results of the fMRI study demonstrate that option generation in simple real-world scenarios recruits the anterior prefrontal cortex. Furthermore, we show that choice behavior and its neural correlates differ between self-generated and externally provided options. Specifically, choice between self-generated options is associated with stronger recruitment of the dorsal anterior cingulate cortex. This impact of option generation on subsequent choice underlines the need for an expanded model of decision making to accommodate choice between self-generated options.

Purpose: To report the cross-over venous catheter technique in case of left-sided central venous (internal jugular, subclavian and innominate veins) occlusion and right-sided central vein patency., Methods: A 60-year-old right breast cancer patient presented with a local recurrence requiring chemotherapy. He presented with a left-sided catheter-related central venous occlusion and radiodermatitis of the right chest and neck. The nonsymptomatic side of insertion was defined as the patient's left side. Successful percutaneous left-to-right external jugular vein (EJV) cross-over access tips and tricks are reported. They include performing (a) the EJV access at the lower neck, (b) the 0.032 hydrophilic guidewire (GW) catheterization of the venous curves, (c) the GW anchor technique into the inferior vena cava, (d) the GW + Glidecath catheter stiffening technique and (e) the over-the-stiff wire implantable catheter push., Results: The cross-over technique was successful by using real-time ultrasonography/X-ray monitoring and interventional radiology tools (hydrophilic 0.032 in. and stiff 0.0035 in. GW and "J-shaped" Glidecath catheter) and the five-step technique., Conclusions: In case of left innominate vein occlusion and necessity of left neck venous access, percutaneous EJV access should be attempted under real-time ultrasound/X-ray monitoring when other standard (subclavian venous port and internal jugular vein) routes are no longer available.