Sabine Frank

Processing of food pictures: Influence of hunger, gender and calorie content

In most cases obesity, a major risk factor for diabetes mellitus type 2 and other associated chronic diseases, is generated by excessive eating. For a better understanding of eating behavior, it is necessary to determine how it is modulated by factors such as the calorie content of food, satiety and gender. Twelve healthy normal weighted participants (six female) were investigated in a functional magnetic resonance imaging (fMRI) study. In order to prevent the influence of social acceptability, an implicit one-back task was chosen for stimulus presentation. We presented food (high- and low-caloric) and non-food pictures in a block design and subjects had to indicate by button press whether two consecutive pictures were the same or not. Each subject performed the task in a hungry and satiated state on two different days. High-caloric pictures compared to low-caloric pictures led to increased activity in food processing and reward related areas, like the orbitofrontal and the insular cortex. In addition, we found activation differences in visual areas (occipital lobe), despite the fact that the stimuli were matched for their physical features. Detailed investigation also revealed gender specific effects in the fusiform gyrus. Women showed higher activation in the fusiform gyrus while viewing high-caloric pictures in the hungry state. This study shows that the calorie content of food pictures modulates the activation of brain areas related to reward processing and even early visual areas. In addition, satiation seems to influence the processing of food pictures differently in men and women. Even though an implicit task was used, activation differences could also be observed in the orbitofrontal cortex, known to be activated during explicit stimulation with food related stimuli.

Food related processes in the insular cortex

The insular cortex is a multimodal brain region with regional cytoarchitectonic differences indicating various functional specializations. As a multisensory neural node, the insular cortex integrates perception, emotion, interoceptive awareness, cognition, and gustation. Regarding the latter, predominantly the anterior part of the insular cortex is regarded as the primary taste cortex. In this review, we will specifically focus on the involvement of the insula in food processing and on multimodal integration of food-related items. Influencing factors of insular activation elicited by various foods range from calorie-content to the internal physiologic state, body mass index or eating behavior. Sensory perception of food-related stimuli including seeing, smelling, and tasting elicits increased activation in the anterior and mid-dorsal part of the insular cortex. Apart from the pure sensory gustatory processing, there is also a strong association with the rewarding/hedonic aspects of food items, which is reflected in higher insular activity and stronger connections to other reward-related areas. Interestingly, the processing of food items has been found to elicit different insular activation in lean compared to obese subjects and in patients suffering from an eating disorder (anorexia nervosa (AN), bulimia nervosa (BN)). The knowledge of functional differences in the insular cortex opens up the opportunity for possible noninvasive treatment approaches for obesity and eating disorders. To target brain functions directly, real-time functional magnetic resonance imaging neurofeedback offers a state-of-the-art tool to learn to control the anterior insular cortex activity voluntarily. First evidence indicates that obese adults have an enhanced ability to regulate the anterior insular cortex.

Meta-analysis of real-time fMRI neurofeedback studies using individual participant data: How is brain regulation mediated?

An increasing number of studies using real-time fMRI neurofeedback have demonstrated that successful regulation of neural activity is possible in various brain regions. Since these studies focused on the regulated region(s), little is known about the target-independent mechanisms associated with neurofeedback-guided control of brain activation, i.e. the regulating network. While the specificity of the activation during self-regulation is an important factor, no study has effectively determined the network involved in self-regulation in general. In an effort to detect regions that are responsible for the act of brain regulation, we performed a post-hoc analysis of data involving different target regions based on studies from different research groups. We included twelve suitable studies that examined nine different target regions amounting to a total of 175 subjects and 899 neurofeedback runs. Data analysis included a standard first- (single subject, extracting main paradigm) and second-level (single subject, all runs) general linear model (GLM) analysis of all participants taking into account the individual timing. Subsequently, at the third level, a random effects model GLM included all subjects of all studies, resulting in an overall mixed effects model. Since four of the twelve studies had a reduced field of view (FoV), we repeated the same analysis in a subsample of eight studies that had a well-overlapping FoV to obtain a more global picture of self-regulation. The GLM analysis revealed that the anterior insula as well as the basal ganglia, notably the striatum, were consistently active during the regulation of brain activation across the studies. The anterior insula has been implicated in interoceptive awareness of the body and cognitive control. Basal ganglia are involved in procedural learning, visuomotor integration and other higher cognitive processes including motivation. The larger FoV analysis yielded additional activations in the anterior cingulate cortex, the dorsolateral and ventrolateral prefrontal cortex, the temporo-parietal area and the visual association areas including the temporo-occipital junction. In conclusion, we demonstrate that several key regions, such as the anterior insula and the basal ganglia, are consistently activated during self-regulation in real-time fMRI neurofeedback independent of the targeted region-of-interest. Our results imply that if the real-time fMRI neurofeedback studies target regions of this regulation network, such as the anterior insula, care should be given whether activation changes are related to successful regulation, or related to the regulation process per se. Furthermore, future research is needed to determine how activation within this regulation network is related to neurofeedback success.

Altered brain activity in severely obese women may recover after Roux-en Y gastric bypass surgery

Objective:Neuroimaging studies have demonstrated alterations in brain activity in obese (OB) subjects that might be causally linked to their disorder. Roux-en Y gastric bypass (RYGB) surgery induces a marked and sustained weight loss and may affect brain activity. The aim of this study was to compare brain activity pattern between severely OB women (n=11), normal-weight women (NW, n=11) and previously severely OB women who had undergone RYGB surgery (RYGB, n=9) on average 3.4±0.8 years (all >1 year) before the experiment.Design:Brain activity was assessed by functional magnetic resonance imaging during a one-back task containing food- and non-food-related pictures and during resting state. Hunger and satiety were repeatedly rated on a visual analog scale during the experiment.Results:As compared with NW and also with RYGB women, OB women showed (1) a higher cerebellar and a lower fusiform gyrus activity during the visual stimulation independently of the picture category, (2) a higher hypothalamic activation during the presentation of low- vs high-caloric food pictures, (3) a higher hippocampal and cerebellar activity during the working memory task and (4) a stronger functional connectivity in frontal regions of the default mode network during resting state. There were no differences in brain activity between the NW and RYGB women, both during picture presentation and during resting state. RYGB women generally rated lower on hunger and higher on satiety, whereas there were no differences in these ratings between the OB and NW women.Conclusion:Data provide evidence for an altered brain activity pattern in severely OB women and suggest that RYGB surgery and/or the surgically induced weight loss reverses the obesity-associated alterations.

Leptin Therapy in a Congenital Leptin-Deficient Patient Leads to Acute and Long-Term Changes in Homeostatic, Reward, and Food-Related Brain Areas

CONTEXT Mutations that lead to congenital leptin deficiency cause severe obesity, hyperphagia, and impaired satiety due to malfunctions of peripheral and brain-related mechanisms. DESIGN AND PATIENT In a leptin-deficient adolescent girl, we investigated brain-related changes before and at two time points after leptin therapy (3 d and 6 months). Functional magnetic resonance imaging was performed during visual stimulation with food (high and low caloric) and nonfood pictures. RESULTS Results show acute and long-term effects in the amygdala, the orbitofrontal cortex, and the substantia nigra/ventral tegmental area for the comparison of food and nonfood pictures. For the comparison of high and low caloric pictures, pure acute effects in the ventral striatum and the orbitofrontal cortex could be observed as well as acute and long-term effects in the hypothalamus. CONCLUSION This study gives additional insight in the influence of leptin therapy on brain functions in leptin deficiency.

The Obese Brain Athlete: Self-Regulation of the Anterior Insula in Adiposity

The anterior insular cortex (AIC) is involved in emotional processes and gustatory functions which can be examined by imaging techniques. Such imaging studies showed increased activation in the insula in response to food stimuli as well as a differential activation in lean and obese people. Additionally, studies investigating lean subjects established the voluntary regulation of the insula by a real-time functional magnetic resonance imaging-brain computer interface (rtfMRI-BCI) approach. In this exploratory study, 11 lean and 10 obese healthy, male participants were investigated in a rtfMRI-BCI protocol. During the training sessions, all obese participants were able to regulate the activity of the AIC voluntarily, while four lean participants were not able to regulate at all. In successful regulators, functional connectivity during regulation vs. relaxation between the AIC and all other regions of the brain was determined by a seed voxel approach. Lean in comparison to obese regulators showed stronger connectivity in cingular and temporal cortices during regulation. We conclude, that obese people possess an improved capacity to self-regulate the anterior insula, a brain system tightly related to bodily awareness and gustatory functions.

Long-term stabilization effects of leptin on brain functions in a leptin-deficient patient.

Context Congenital leptin deficiency, caused by a very rare mutation in the gene encoding leptin, leads to severe obesity, hyperphagia and impaired satiety. The only systemic treatment is the substitution with metreleptin leading to weight reduction based on hormonal changes. Several studies have also shown alterations in brain function after metreleptin therapy. In a previous study, we were able to show changes in homeostatic (hypothalamus) and reward-related brain areas (striatum, orbitofrontal cortex (OFC), substantia nigra/ventral tegmental area, amygdala) 3 days and 6 months after therapy start in a leptin-deficient adolescent girl. To further access the time course of functional brain activation changes, we followed the patient for 2 years after initiation of the therapy. Design, Patient Functional magnetic resonance imaging during visual stimulation with food (high- and low-caloric) and non-food pictures was performed 1 and 2 years after therapy start in the previously described patient. Results The comparison of ‘food vs. non-food’ pictures showed a stabilization of the long-term effects in the amygdala and in the OFC. Therefore, no significant differences were observed between 6 months compared to 12 and 24 months in these regions. Additionally, a reduction of the frontopolar cortex activity over the whole time span was observed. For the comparison of high- and low-caloric pictures, long-term effects in the hypothalamus showed an assimilating pattern for the response to the food categories whereas only acute effects after 3 months were observed in hedonic brain regions. Conclusion This follow-up study shows that the long lasting benefit of metreleptin therapy is also associated with activation changes in homeostatic, hedonic and frontal control regions in congenital leptin deficiency.

Fat intake modulates cerebral blood flow in homeostatic and gustatory brain areas in humans

BACKGROUND The hypothalamus is the central homeostatic control region of the brain and, therefore, highly influenced by nutrients such as glucose and fat. Immediate and prolonged homeostatic effects of glucose ingestion have been well characterized. However, studies that used stimulation with fat have mainly investigated immediate perceptional processes. Besides homeostatic processes, the gustatory cortex, including parts of the insular cortex, is crucial for the processing of food items. OBJECTIVE The aim of this study was to investigate the effect of high- compared with low-fat meals on the hypothalamus and the insular cortex. DESIGN Eleven healthy men participated in a single-blinded, functional MRI study of high- and low-fat meals on 2 measurement days. Cerebral blood flow (CBF) was measured before and 30 and 120 min after intake of high- and low-fat yogurts. Hunger was rated and blood samples were taken before each CBF measurement. RESULTS High-fat yogurt induced a pronounced decrease in CBF in the hypothalamus, and the corresponding CBF change correlated positively with the insulin change. Furthermore, insular activity increased after 120 min in the low-fat condition only. The CBF change in both regions correlated positively in the high-fat condition. CONCLUSIONS The decrease in hypothalamic activity and the interaction with the insular cortex elicited by fat may contribute to an efficient energy homeostasis. Therefore, fat might be a modulator of homeostatic and gustatory brain regions and their interaction. This trial was registered at clinicaltrials.gov as NCT01516021.

Controversies in fat perception.

Nutritional fat is one of the most controversial topics in nutritional research, particularly against the background of obesity. Studies investigating fat taste perception have revealed several associations with sensory, genetic, and personal factors (e.g. BMI). However, neuronal activation patterns, which are known to be highly sensitive to different tastes as well as to BMI differences, have not yet been included in the scheme of fat taste perception. We will therefore provide a comprehensive survey of the sensory, genetic, and personal factors associated with fat taste perception and highlight the benefits of applying neuroimaging research. We will also give a critical overview of studies investigating sensory fat perception and the challenges resulting from multifaceted methodological approaches. In conclusion, we will discuss a multifactorial approach to fat perception to gain a better understanding of the underlying mechanisms that cause varying fat sensitivity which could be responsible for overeating. Such knowledge might be beneficial in new treatment strategies for obesity and overweight.

Dopamine Depletion Reduces Food-Related Reward Activity Independent of BMI

Reward sensitivity and possible alterations in the dopaminergic-reward system are associated with obesity. We therefore aimed to investigate the influence of dopamine depletion on food-reward processing. We investigated 34 female subjects in a randomized placebo-controlled, within-subject design (body mass index (BMI)=27.0 kg/m2 ±4.79 SD; age=28 years ±4.97 SD) using an acute phenylalanine/tyrosine depletion drink representing dopamine depletion and a balanced amino acid drink as the control condition. Brain activity was measured with functional magnetic resonance imaging during a ‘wanting’ and ‘liking’ rating of food items. Eating behavior-related traits and states were assessed on the basis of questionnaires. Dopamine depletion resulted in reduced activation in the striatum and higher activation in the superior frontal gyrus independent of BMI. Brain activity during the wanting task activated a more distributed network than during the liking task. This network included gustatory, memory, visual, reward, and frontal regions. An interaction effect of dopamine depletion and the wanting/liking task was observed in the hippocampus. The interaction with the covariate BMI was significant in motor and control regions but not in the striatum. Our results support the notion of altered brain activity in the reward and prefrontal network with blunted dopaminergic action during food-reward processing. This effect is, however, independent of BMI, which contradicts the reward-deficiency hypothesis. This hints to the hypothesis suggesting a different or more complex mechanism underlying the dopaminergic reward function in obesity.