Luke E. Stoeckel

Widespread reward-system activation in obese women in response to pictures of high-calorie foods.

Behavioral studies have suggested that exaggerated reactivity to food cues, especially those associated with high-calorie foods, may be a factor underlying obesity. This increased motivational potency of foods in obese individuals appears to be mediated in part by a hyperactive reward system. We used a Philips 3T magnet and fMRI to investigate activation of reward-system and associated brain structures in response to pictures of high-calorie and low-calorie foods in 12 obese compared to 12 normal-weight women. A regions of interest (ROI) analysis revealed that pictures of high-calorie foods produced significantly greater activation in the obese group compared to controls in medial and lateral orbitofrontal cortex, amygdala, nucleus accumbens/ventral striatum, medial prefrontal cortex, insula, anterior cingulate cortex, ventral pallidum, caudate, putamen, and hippocampus. For the contrast of high-calorie vs. low-calorie foods, the obese group also exhibited a larger difference than the controls did in all of the same regions of interest except for the putamen. Within-group contrasts revealed that pictures of high-calorie foods uniformly stimulated more activation than low-calorie foods did in the obese group. By contrast, in the control group, greater activation by high-calorie foods was seen only in dorsal caudate, whereas low-calorie foods were more effective than high-calorie foods in the lateral orbitofrontal cortex, medial prefrontal cortex, and anterior cingulate cortex. In summary, compared to normal-weight controls, obese women exhibited greater activation in response to pictures of high-calorie foods in a large number of regions hypothesized to mediate motivational effects of food cues.

Effective connectivity of a reward network in obese women

Exaggerated reactivity to food cues in obese women appears to be mediated in part by a hyperactive reward system that includes the nucleus accumbens, amygdala, and orbitofrontal cortex. The present study used functional magnetic resonance imaging (fMRI) to investigate whether differences between 12 obese and 12 normal-weight women in reward-related brain activation in response to food images can be explained by changes in the functional interactions between key reward network regions. A two-step path analysis/General Linear Model approach was used to test whether there were group differences in network connections between nucleus accumbens, amygdala, and orbitofrontal cortex in response to high- and low-calorie food images. There was abnormal connectivity in the obese group in response to both high- and low-calorie food cues compared to normal-weight controls. Compared to controls, the obese group had a relative deficiency in the amygdalas modulation of activation in both orbitofrontal cortex and nucleus accumbens, but excessive influence of orbitofrontal cortexs modulation of activation in nucleus accumbens. The deficient projections from the amygdala might relate to suboptimal modulation of the affective/emotional aspects of a foods reward value or an associated cues motivational salience, whereas increased orbitofrontal cortex to nucleus accumbens connectivity might contribute to a heightened drive to eat in response to a food cue. Thus, it is possible that not only greater activation of the reward system, but also differences in the interaction of regions in this network may contribute to the relatively increased motivational value of foods in obese individuals.

fMRI reactivity on a delay discounting task predicts weight gain in obese women

Obesity can be accompanied by abnormalities in executive function and related neural circuitry. A useful task for studying executive function is delay discounting (DD), in which an individual chooses between sooner and delayed, but greater, amounts of money or other commodities. We previously found that obese compared to normal-weight women made more immediate choices on a monetary DD task, or had greater delay discounting. In the present study, we performed functional magnetic resonance imaging (fMRI) of obese women during performance of a DD of money task. Confirming the results of previous studies, we found that more difficult compared to easy DD trials resulted in activation in putative executive function areas of the brain, the middle and inferior frontal gyri, and medial prefrontal cortex. Most interestingly, we also found that less activation in executive function areas such as the inferior, middle, and superior frontal gyri on difficult vs. easy DD trials predicted a greater rate of weight gain over the subsequent 1.3-2.9 years. These results suggest that suboptimal functioning of executive function areas such as prefrontal cortex contributes to the progression of obesity.

Optimizing real time fMRI neurofeedback for therapeutic discovery and development

While reducing the burden of brain disorders remains a top priority of organizations like the World Health Organization and National Institutes of Health, the development of novel, safe and effective treatments for brain disorders has been slow. In this paper, we describe the state of the science for an emerging technology, real time functional magnetic resonance imaging (rtfMRI) neurofeedback, in clinical neurotherapeutics. We review the scientific potential of rtfMRI and outline research strategies to optimize the development and application of rtfMRI neurofeedback as a next generation therapeutic tool. We propose that rtfMRI can be used to address a broad range of clinical problems by improving our understanding of brain–behavior relationships in order to develop more specific and effective interventions for individuals with brain disorders. We focus on the use of rtfMRI neurofeedback as a clinical neurotherapeutic tool to drive plasticity in brain function, cognition, and behavior. Our overall goal is for rtfMRI to advance personalized assessment and intervention approaches to enhance resilience and reduce morbidity by correcting maladaptive patterns of brain function in those with brain disorders.

Assessments of Function and Biochemistry of the Anterior Cingulate Cortex in Schizophrenia

BACKGROUND Neuroimaging and electrophysiologic studies have consistently provided evidence of impairment in anterior cingulate cortex/medial frontal cortex function in people with schizophrenia. In this study, we sought to clarify the nature of this abnormality by combining proton magnetic resonance spectroscopy (1H-MRS) with functional magnetic resonance imaging (fMRI) at 3T. METHODS We used single-voxel MRS acquired in the dorsal anterior cingulate cortex and fMRI during performance of a Stroop color-naming task to investigate the neurochemistry and functional response of the anterior cingulate cortex/medial frontal cortex in 26 stable, medicated subjects with schizophrenia and 23 matched healthy control subjects. RESULTS In schizophrenia subjects, we found decreased blood oxygen level-dependent signal in the medial frontal wall, with significant clusters restricted to more dorsal regions compared with healthy subjects. In addition, we observed a trend-level decrease in N-acetylaspartate/creatine (NAA/Cr) levels and a significant positive correlation between NAA/Cr level and the blood oxygen level-dependent signal in schizophrenia subjects that did not exist in healthy subjects. Furthermore, in this group of medicated subjects, we did not find evidence of decreased glutamate + glutamine(Glx)/Cr levels, but there was a significant negative correlation between Glx/Cr levels and negative symptoms. CONCLUSIONS Our results suggest that abnormal NAA levels, which may reflect a neuronal dysfunction related to schizophrenia, affect neuronal physiology, as evidenced by reduced blood oxygen level-dependent response.

Motivational state modulates the hedonic value of food images differently in men and women.

We investigated visual alimentary alliesthesia in non-fasted (N = 369) and fasted participants (N = 257) viewing photographs of food. Fasted participants were asked to not eat for 12 h before the session. Each participant was shown food and non-food images and rated each image on valence (i.e., pleasantness). The strongest evidence of alliesthesia was found in women. Fasting enhanced the pleasantness of food images for each of the food categories in women, although this alliesthesia effect was smaller in response to dessert foods compared to the less-pleasantly-rated food categories. In addition, non-fasting women exhibited significant positive correlations between hunger ratings and valence ratings of three of the five food categories. There was no significant difference in valence ratings of food between fasting vs. non-fasting men, but non-fasting men showed correlations between hunger and valence that were similar to those observed among the women. No evidence was found of hunger- or fasting-induced enhancement of hedonic ratings of non-foods in women or men, indicating the specificity of the alliesthesia effect for the food images only.

Greater Impulsivity is Associated with Decreased Brain Activation in Obese Women during a Delay Discounting Task

Impulsivity and poor inhibitory control are associated with higher rates of delay discounting (DD), or a greater preference for smaller, more immediate rewards at the expense of larger, but delayed rewards. Of the many functional magnetic resonance imaging (fMRI) studies of DD, few have investigated the correlation between individual differences in DD rate and brain activation related to DD trial difficulty, with difficult DD trials expected to activate putative executive function brain areas involved in impulse control. In the current study, we correlated patterns of brain activation as measured by fMRI during difficult vs. easy trials of a DD task with DD rate (k) in obese women. Difficulty was defined by how much a reward choice deviated from an individual’s ‘indifference point’, or the point where the subjective preference for an immediate and a delayed reward was approximately equivalent. We found that greater delay discounting was correlated with less modulation of activation in putative executive function brain areas, such as the middle and superior frontal gyri and inferior parietal lobule, in response to difficult compared to easy DD trials. These results support the suggestion that increased impulsivity is associated with deficient functioning of executive function areas of the brain.

Magnetic Resonance Imaging Volume of the Angular Gyri Predicts Financial Skill Deficits in People with Amnestic Mild Cognitive Impairment

OBJECTIVES: To better understand how brain atrophy in amnestic mild cognitive impairment (MCI) as measured using magnetic resonance imaging (MRI) volumetrics could affect instrumental activities of daily living (IADLs) such as financial abilities.

Patterns of Brain Activation when Mothers View Their Own Child and Dog: An fMRI Study

Neural substrates underlying the human-pet relationship are largely unknown. We examined fMRI brain activation patterns as mothers viewed images of their own child and dog and an unfamiliar child and dog. There was a common network of brain regions involved in emotion, reward, affiliation, visual processing and social cognition when mothers viewed images of both their child and dog. Viewing images of their child resulted in brain activity in the midbrain (ventral tegmental area/substantia nigra involved in reward/affiliation), while a more posterior cortical brain activation pattern involving fusiform gyrus (visual processing of faces and social cognition) characterized a mothers response to her dog. Mothers also rated images of their child and dog as eliciting similar levels of excitement (arousal) and pleasantness (valence), although the difference in the own vs. unfamiliar child comparison was larger than the own vs. unfamiliar dog comparison for arousal. Valence ratings of their dog were also positively correlated with ratings of the attachment to their dog. Although there are similarities in the perceived emotional experience and brain function associated with the mother-child and mother-dog bond, there are also key differences that may reflect variance in the evolutionary course and function of these relationships.

Peptide YY levels are associated with appetite suppression in response to long-chain fatty acids

Release of peptide YY(3-36) (PYY(3-36)) has been proposed to contribute to postprandial satiety. Using a randomized, double-blind design, we examined the effects of a 417 kcal beverage with 95% of the calories from long-chain fatty acids compared to a 21 kcal lipid-free control beverage on the temporal profiles of total plasma PYY levels and appetite ratings in 12 normal-weight human subjects. Ratings were taken before ingestion of the beverage and 15, 30, 60, 120, and 180 min later. Blood samples were taken from the subjects when ratings were made. The lipid beverage increased plasma PYY relative to the control beverage at 60-180 min after ingestion. Subjects were divided into High and Low PYY groups (N=6 in each group) on the basis of a median split. In the High PYY group, the lipid beverage was more effective in suppressing hunger and enhancing satiety than in the Low PYY group, in which the lipid beverage had no effects on appetite. Within the High PYY group, changes in mean relative hunger suppression (changes in hunger specifically attributable to the lipid load) across the 3-h test closely paralleled changes in plasma PYY after ingestion of the lipid beverage relative to the control beverage. The close temporal correspondence between these variables supports the proposed role of this peptide in the intermediate-term control of intake, possibly acting to regulate appetite during the intermeal interval.