David Mathar

Obesity-Related Differences between Women and Men in Brain Structure and Goal-Directed Behavior

Gender differences in the regulation of body-weight are well documented. Here, we assessed obesity-related influences of gender on brain structure as well as performance in the Iowa Gambling Task. This task requires evaluation of both immediate rewards and long-term outcomes and thus mirrors the trade-off between immediate reward from eating and the long-term effect of overeating on body-weight. In women, but not in men, we show that the preference for salient immediate rewards in the face of negative long-term consequences is higher in obese than in lean subjects. In addition, we report structural differences in the left dorsal striatum (i.e., putamen) and right dorsolateral prefrontal cortex for women only. Functionally, both regions are known to play complimentary roles in habitual and goal-directed control of behavior in motivational contexts. For women as well as men, gray matter volume correlates positively with measures of obesity in regions coding the value and saliency of food (i.e., nucleus accumbens, orbitofrontal cortex) as well as in the hypothalamus (i.e., the brains central homeostatic center). These differences between lean and obese subjects in hedonic and homeostatic control systems may reflect a bias in eating behavior toward energy-intake exceeding the actual homeostatic demand. Although we cannot infer from our results the etiology of the observed structural differences, our results resemble neural and behavioral differences well known from other forms of addiction, however, with marked differences between women and men. These findings are important for designing gender-appropriate treatments of obesity and possibly its recognition as a form of addiction.

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/m(2)) 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.

Brain regulation of food craving: Relationships with weight status and eating behavior

Objectives:Food craving is a driving force for overeating and obesity. However, the relationship between brain mechanisms involved in its regulation and weight status is still an open issue. Gaps in the studied body mass index (BMI) distributions and focusing on linear analyses might have contributed to this lack of knowledge. Here, we investigated brain mechanisms of craving regulation using functional magnetic resonance imaging in a balanced sample including normal-weight, overweight and obese participants. We investigated associations between characteristics of obesity, eating behavior and regulatory brain function focusing on nonlinear relationships.Subjects/Methods:Forty-three hungry female volunteers (BMI: 19.4–38.8 kg m−2, mean: 27.5±5.3 s.d.) were presented with visual food stimuli individually pre-rated according to tastiness and healthiness. The participants were instructed to either admit to the upcoming craving or regulate it. We analyzed the relationships between regulatory brain activity as well as functional connectivity and BMI or eating behavior (Three-Factor Eating Questionnaire, scales: Cognitive Restraint, Disinhibition).Results:During regulation, BMI correlated with brain activity in the left putamen, amygdala and insula in an inverted U-shaped manner. Functional connectivity between the putamen and the dorsolateral prefrontal cortex (dlPFC) correlated positively with BMI, whereas that of amygdala with pallidum and lingual gyrus was nonlinearly (U-shaped) associated with BMI. Disinhibition correlated negatively with the strength of functional connectivity between amygdala and dorsomedial prefrontal (dmPFC) cortex as well as caudate.Conclusions:This study is the first to reveal quadratic relationships of food-related brain processes and BMI. Reported nonlinear associations indicate inverse relationships between regulation-related motivational processing in the range of normal weight/overweight compared with the obese range. Connectivity analyses suggest that the need for top-down (dlPFC) adjustment of striatal value representations increases with BMI, whereas the interplay of self-monitoring (dmPFC) or eating-related strategic action planning (caudate) and salience processing (amygdala) might be hampered with high Disinhibition.

Is it Worth the Effort? Novel Insights into Obesity-Associated Alterations in Cost-Benefit Decision-Making

Cost-benefit decision-making entails the process of evaluating potential actions according to the trade-off between the expected reward (benefit) and the anticipated effort (costs). Recent research revealed that dopaminergic transmission within the fronto-striatal circuitry strongly modulates cost-benefit decision-making. Alterations within the dopaminergic fronto-striatal system have been associated with obesity, but little is known about cost-benefit decision-making differences in obese compared with lean individuals. With a newly developed experimental task we investigate obesity-associated alterations in cost-benefit decision-making, utilizing physical effort by handgrip-force exertion and both food and non-food rewards. We relate our behavioral findings to alterations in local gray matter volume assessed by structural MRI. Obese compared with lean subjects were less willing to engage in physical effort in particular for high-caloric sweet snack food. Further, self-reported body dissatisfaction negatively correlated with the willingness to invest effort for sweet snacks in obese men. On a structural level, obesity was associated with reductions in gray matter volume in bilateral prefrontal cortex. Nucleus accumbens volume positively correlated with task induced implicit food craving. Our results challenge the common notion that obese individuals are willing to work harder to obtain high-caloric food and emphasize the need for further exploration of the underlying neural mechanisms regarding cost-benefit decision-making differences in obesity.

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

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.

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

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.

Retraining automatic action tendencies in obesity

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 in gamblers and controls

Accumulating evidence points at similarities between substance use disorders and pathological gambling on the behavioral and neural level. In substance addiction, dysregulation of striatal dopamine transmission has been consistently revealed. Due to the neurotoxicity of stimulating substances, it is still debated if this constitutes mainly a consequence of recurrent substance abuse or a vulnerability marker for addiction disorders. For gambling addiction, no clear association with striatal dopamine levels has been unveiled so far. With its presumably negligible dopaminergic toxicity, possible differences in striatal dopamine transmission in gambling addiction might therefore constitute a vulnerability marker. Spontaneous eye blink rate (sEBR) is controversially discussed as a potential proxy measure for striatal dopamine levels. 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 addiction 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 association between dopamine transmission and sEBR is still debated, our findings reveal that sEBR is sensitive to inter-individual differences in addiction severity in problem gamblers.