Obesity is associated with insufficient behavioral adaptation

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

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.

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 19–30 years; mean BMI 29.1, range 19.2–45.1 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

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

Tyrosine effects on RL & temporal discounting

data and code of https://www.biorxiv.org/content/10.1101/2022.02.09.479693v

Obesity is associated with insufficient behavioral adaptation

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

Tyrosine effects on RL & temporal discounting

data and code of https://www.biorxiv.org/content/10.1101/2022.02.09.479693v