23 research outputs found

    Obesity is associated with insufficient behavioral adaptation

    Get PDF
    Obesity is one of the major health concerns nowadays according to the World Health Organisation (WHO global status report on noncommunicable diseases 2010). Thus, there is an urgent need for understanding obesity-associated alterations in food-related and general cognition and their underlying structural and functional correlates within the central nervous system (CNS). Neuroscientific research of the past decade has mainly focussed on obesity-related differences within homeostatic and hedonic processing of food stimuli. Therein, alterations during anticipation and consumption of food-reward stimuli in obese compared with lean subjects have been highlighted. This points at an altered adaptation of eating behavior in obese individuals. This thesis investigates if adaptation of behavior is attenuated in obese compared to lean individuals in learning-related processes beyond the food domain. In five consecutive experimental studies, we show that obese participants reveal reduced adaptation of behavior within and outside the food context. With the help of MRI, we relate these behavioral findings to alterations in structure and function of the fronto-striatal dopaminergic system in obesity. In more detail, reduced behavioral adaptation seems to be associated with attenuated utilization of negative prediction errors in obese individuals. Within the brain, this relates to reduced functional coupling between subcortical dopaminergic target regions (ventral striatum) and executive cortical structures (supplementary motor area) in obesity, as revealed by fMRI analysis

    Dopamine release, diffusion and uptake : A computational model for synaptic and volume transmission

    Get PDF
    Computational modeling of dopamine transmission is challenged by complex underlying mechanisms. Here we present a new computational model that (I) simultaneously regards release, diffusion and uptake of dopamine, (II) considers multiple terminal release events and (III) comprises both synaptic and volume transmission by incorporating the geometry of the synaptic cleft. We were able to validate our model in that it simulates concentration values comparable to physiological values observed in empirical studies. Further, although synaptic dopamine diffuses into extra-synaptic space, our model reflects a very localized signal occurring on the synaptic level, i.e. synaptic dopamine release is negligibly recognized by neighboring synapses. Moreover, increasing evidence suggests that cognitive performance can be predicted by signal variability of neuroimaging data (e.g. BOLD). Signal variability in target areas of dopaminergic neurons (striatum, cortex) may arise from dopamine concentration variability. On that account we compared spatio-temporal variability in a simulation mimicking normal dopamine transmission in striatum to scenarios of enhanced dopamine release and dopamine uptake inhibition. We found different variability characteristics between the three settings, which may in part account for differences in empirical observations. From a clinical perspective, differences in striatal dopaminergic signaling contribute to differential learning and reward processing, with relevant implications for addictive- and compulsive-like behavior. Specifically, dopaminergic tone is assumed to impact on phasic dopamine and hence on the integration of reward-related signals. However, in humans DA tone is classically assessed using PET, which is an indirect measure of endogenous DA availability and suffers from temporal and spatial resolution issues. We discuss how this can lead to discrepancies with observations from other methods such as microdialysis and show how computational modeling can help to refine our understanding of DA transmission. Author summary The dopaminergic system of the brain is very complex and affects various cognitive domains like memory, learning and motor control. Alterations have been observed e.g. in Parkinson's or Huntington's Disease, ADHD, addiction and compulsive disorders, such as pathological gambling and also in obesity. We present a new computational model that allows to simulate the process of dopamine transmission from dopaminergic neurons originated in source brain regions like the VTA to target areas such as the striatum on a synaptic and on a larger, volume-spanning level. The model can further be used for simulations of dopamine related diseases or pharmacological interventions. In general, computational modeling helps to extend our understanding, gained from empirical research, to situations were in vivo measurements are not feasible.Peer reviewe

    Slave to habit?: obesity is associated with decreased behavioural sensitivity to reward devaluation.

    Get PDF
    The motivational value of food is lower during satiety compared to fasting. Dynamic changes in motivational value promote food seeking or meal cessation. In obesity this mechanism might be compromised since obese subjects ingest energy beyond homeostatic needs. Thus, lower adaptation of eating behaviour with respect to changes in motivational value might cause food overconsumption in obesity. To test this hypothesis, we implemented a selective satiation procedure to investigate the relationship between obesity and the size of the behavioural devaluation effect in humans. Lean to obese men (mean age 25.9, range 19‚Äď30 years; mean BMI 29.1, range 19.2‚Äď45.1 kg/m2) were trained on a free operant paradigm and learned to associate cues with the possibility to win different food rewards by pressing a button. After the initial training phase, one of the rewards was devalued by consumption. Response rates for and wanting of the different rewards were measured pre and post devaluation. Behavioural sensitivity to reward devaluation, measured as the magnitude of difference between pre and post responses, was regressed against BMI. Results indicate that (1) higher BMI compared to lower BMI in men led to an attenuated behavioural adjustment to reward devaluation, and (2) the decrease in motivational value was associated with the decrease in response rate between pre and post. Change in explicitly reported motivational value, however, was not affected by BMI. Thus, we conclude that high BMI in men is associated with lower behavioural adaptation with respect to changes in motivational value of food, possibly resulting in automatic overeating patterns that are hard to control in daily life

    Obesity is associated with insufficient behavioral adaptation

    Get PDF
    Obesity is one of the major health concerns nowadays according to the World Health Organisation (WHO global status report on noncommunicable diseases 2010). Thus, there is an urgent need for understanding obesity-associated alterations in food-related and general cognition and their underlying structural and functional correlates within the central nervous system (CNS). Neuroscientific research of the past decade has mainly focussed on obesity-related differences within homeostatic and hedonic processing of food stimuli. Therein, alterations during anticipation and consumption of food-reward stimuli in obese compared with lean subjects have been highlighted. This points at an altered adaptation of eating behavior in obese individuals. This thesis investigates if adaptation of behavior is attenuated in obese compared to lean individuals in learning-related processes beyond the food domain. In five consecutive experimental studies, we show that obese participants reveal reduced adaptation of behavior within and outside the food context. With the help of MRI, we relate these behavioral findings to alterations in structure and function of the fronto-striatal dopaminergic system in obesity. In more detail, reduced behavioral adaptation seems to be associated with attenuated utilization of negative prediction errors in obese individuals. Within the brain, this relates to reduced functional coupling between subcortical dopaminergic target regions (ventral striatum) and executive cortical structures (supplementary motor area) in obesity, as revealed by fMRI analysis

    Obesity is associated with insufficient behavioral adaptation

    No full text
    Obesity is one of the major health concerns nowadays according to the World Health Organisation (WHO global status report on noncommunicable diseases 2010). Thus, there is an urgent need for understanding obesity-associated alterations in food-related and general cognition and their underlying structural and functional correlates within the central nervous system (CNS). Neuroscientific research of the past decade has mainly focussed on obesity-related differences within homeostatic and hedonic processing of food stimuli. Therein, alterations during anticipation and consumption of food-reward stimuli in obese compared with lean subjects have been highlighted. This points at an altered adaptation of eating behavior in obese individuals. This thesis investigates if adaptation of behavior is attenuated in obese compared to lean individuals in learning-related processes beyond the food domain. In five consecutive experimental studies, we show that obese participants reveal reduced adaptation of behavior within and outside the food context. With the help of MRI, we relate these behavioral findings to alterations in structure and function of the fronto-striatal dopaminergic system in obesity. In more detail, reduced behavioral adaptation seems to be associated with attenuated utilization of negative prediction errors in obese individuals. Within the brain, this relates to reduced functional coupling between subcortical dopaminergic target regions (ventral striatum) and executive cortical structures (supplementary motor area) in obesity, as revealed by fMRI analysis

    Failing to learn from negative prediction errors: Obesity is associated with alterations in a fundamental neural learning mechanism

    No full text
    Prediction errors (PEs) encode the difference between expected and actual action outcomes in the brain via dopaminergic modulation. Integration of these learning signals ensures efficient behavioral adaptation. Obesity has recently been linked to altered dopaminergic fronto-striatal circuits, thus implying impairments in cognitive domains that rely on its integrity. 28 obese and 30 lean human participants performed an implicit stimulus-response learning paradigm inside an fMRI scanner. Computational modeling and psycho physiological interaction (PPI) analysis was utilized for assessing PE-related learning and associated functional connectivity. We show that human obesity is associated with insufficient incorporation of negative PEs into behavioral adaptation even in a non-food context, suggesting differences in a fundamental neural learning mechanism. Obese subjects were less efficient in using negative PEs to improve implicit learning performance, despite proper coding of PEs in striatum. We further observed lower functional coupling between ventral striatum and supplementary motor area in obese subjects subsequent to negative PEs. Importantly, strength of functional coupling predicted task performance and negative PE utilization. These findings show that obesity is linked to insufficient behavioral adaptation specifically in response to negative PEs, and to associated alterations in function and connectivity within the fronto-striatal system. Recognition of neural differences as a central characteristic of obesity hopefully paves the way to rethink established intervention strategies: Differential behavioral sensitivity to negative and positive PEs should be considered when designing intervention programs. Measures relying on penalization of unwanted behavior may prove less effective in obese subjects than alternative approaches. (C) 2017 Elsevier Ltd. All rights reserved

    Retraining automatic action tendencies in obesity

    No full text
    Eating behavior in obesity resembles addictive disorders in that individuals have difficulties inhibiting problematic eating behavior. They show an approach bias - a tendency to approach rather than avoid problematic stimuli. Here, we investigate the existence of such a bias towards healthy and unhealthy food in individuals with normal-weight and obesity. We further aimed to assess whether it is possible to retrain a bias, and whether training would differentially affect our two weight groups. 60 participants completed a training form of the Approach-Avoidance Task (AAT) on three consecutive days. Using a joystick, they were implicitly trained to approach healthy and to avoid unhealthy food pictures. Prior to training, individuals with obesity showed stronger approach tendencies towards food pictures than normal-weight individuals. In individuals with obesity, approach tendencies could be diminished for unhealthy food through one training session and stayed weakened for the following days. In normal-weight participants, approach tendencies towards healthy food could be enhanced over the days of training. Findings indicate that automatic approach tendencies can be changed through training, thus offering possibilities for obesity treatment. Future studies should expand on these findings, for example by including pictures of neutral objects or a no-training control condition

    A potential link between gambling addiction severity and central dopamine levels: Evidence from spontaneous eye blink rates

    No full text
    Accumulating evidence points at similarities between substance use disorders (SUD) and gambling disorder on the behavioral and neural level. In SUD, attenuation of striatal D2/3-receptor availability is a consistent finding, at least for stimulating substances. For gambling disorder, no clear association with striatal D2/3-receptor availability has been unveiled so far. With its presumably negligible dopaminergic toxicity, possible differences in receptor availability in gambling disorder might constitute a vulnerability marker. Spontaneous eye blink rate (sEBR) is discussed as a potential proxy measure for striatal dopamine D2/3-receptor availability. Here we examined sEBR in 21 male problem gamblers and 20 healthy control participants. In addition, participants completed a screening questionnaire for overall psychopathology and self-reported measures of alcohol and nicotine consumption. We found no significant difference in sEBR between gamblers and controls. However, in gamblers, sEBR was negatively associated with gambling severity and positively associated with psychopathology. A final exploratory analysis revealed that healthy controls with low sEBR displayed higher alcohol and nicotine consumption than healthy participants with high sEBR. Although the exact association between dopamine transmission and sEBR is still debated, our findings reveal that sEBR is sensitive to inter-individual differences in gambling disorder severity in problem gamblers

    Dopaminergic modulation of the exploration/exploitation trade-off in human decision-making

    No full text
    International audienceInvolvement of dopamine in regulating exploration during decision-making has long been hypothesized, but direct causal evidence in humans is still lacking. Here, we use a combination of computational modeling, pharmacological intervention and functional magnetic resonance imaging to address this issue. Thirty-one healthy male participants performed a restless four-armed bandit task in a within-subjects design under three drug conditions: 150 mg of the dopamine precursor L-dopa, 2 mg of the D2 receptor antagonist haloperidol, and placebo. Choices were best explained by an extension of an established Bayesian learning model accounting for perseveration, directed exploration and random exploration. Modeling revealed attenuated directed exploration under L-dopa, while neural signatures of exploration, exploitation and prediction error were unaffected. Instead, L-dopa attenuated neural representations of overall uncertainty in insula and dorsal anterior cingulate cortex. Our results highlight the computational role of these regions in exploration and suggest that dopamine modulates how this circuit tracks accumulating uncertainty during decision-making

    The catecholamine precursor Tyrosine reduces autonomic arousal and decreases decision thresholds in reinforcement learning and temporal discounting

    No full text
    Supplementation with the catecholamine precursor L-Tyrosine might enhance cognitive performance, but overall findings are mixed. Here, we investigate the effect of a single dose of tyrosine (2g) vs. placebo on two catecholamine-dependent trans-diagnostic traits: model-based control during reinforcement learning (2-step task) and temporal discounting, using a double-blind, placebo-controlled, within-subject design (n = 28 healthy male participants). We leveraged drift diffusion models in a hierarchical Bayesian framework to jointly model participants' choices and response times in both tasks. Furthermore, comprehensive autonomic monitoring (heart rate, heart rate variability, pupillometry, spontaneous eye-blink rate) was performed both pre- and post-supplementation, to explore potential physiological effects of supplementation. Across tasks, tyrosine consistently reduced participants' RTs without deteriorating task-performance. Diffusion modeling linked this effect to attenuated decision-thresholds in both tasks and further revealed increased model-based control (2-step task) and (if anything) attenuated temporal discounting. On the physiological level, participants' pupil dilation was predictive of the individual degree of temporal discounting. Tyrosine supplementation reduced physiological arousal as revealed by increases in pupil dilation variability and reductions in heart rate. Supplementation-related changes in physiological arousal predicted individual changes in temporal discounting. Our findings provide first evidence that tyrosine supplementation might impact psychophysiological parameters, and suggest that modeling approaches based on sequential sampling models can yield novel insights into latent cognitive processes modulated by amino-acid supplementation. Author summary Model-based control during reinforcement learning and temporal discounting have emerged as two candidates delivering on the promise of the Research Domain Criteria as trans-diagnostic characteristics that seem to go awry in a broad range of psychiatric illnesses. Both processes rely on catecholamine transmission and thus may benefit from L-tyrosine supplementation. Here, we tested this in a placebo controlled within-subjects design. On a physiological level, tyrosine intake reduced participants' arousal as revealed by increases in pupil dilation variability and reductions in heart rate compared with placebo. With respect to task performance, we found that following tyrosine intake participants' response times decreased consistently in both tasks without deteriorating task performance. Hierarchical drift diffusion modeling linked this with attenuated decision-thresholds in both tasks. Despite this reduced speed-accuracy trade-off, tyrosine seemed to increase goal-directed control as evident in increased reliance on model-based computations during reinforcement learning and if anything reduced temporal discounting of rewards. Our findings highlight that deeper insights into cognitive effects of supplementation can be gained from applying comprehensive computational models
    corecore