Background:The major aim of this study was to investigate whether the motivational salience of food cues (as reflected by their attention-grabbing properties) differs between obese and normal-weight subjects in a manner consistent with altered reward system function in obesity. Methodology/Principal Findings: A total of 18 obese and 18 normal-weight, otherwise healthy, adult women between the ages of 18 and 35 participated in an eye-tracking paradigm in combination with a visual probe task. Eye movements and reaction time to food and non-food images were recorded during both fasted and fed conditions in a counterbalanced design. Eating behavior and hunger level were assessed by self-report measures. Obese individuals had higher scores than normalweight individuals on self-report measures of responsiveness to external food cues and vulnerability to disruptions in control of eating behavior. Both obese and normal-weight individuals demonstrated increased gaze duration for food compared to nonfood images in the fasted condition. In the fed condition, however, despite reduced hunger in both groups, obese individuals maintained the increased attention to food images, whereas normal-weight individuals had similar gaze duration for food and non-food images. Additionally, obese individuals had preferential orienting toward food images at the onset of each image. Obese and normal-weight individuals did not differ in reaction time measures in the fasted or fed condition. Conclusions/Significance: Food cue incentive salience is elevated equally in normal-weight and obese individuals during fasting. Obese individuals retain incentive salience for food cues despite feeding and decreased self-report of hunger. Sensitization to food cues in the environment and their dysregulation in obese individuals may play a role in the development and/or maintenance of obesity.

Dopamine has long been implicated in impulsivity, but the precise mechanisms linking human variability in dopamine signaling to differences in impulsive traits remain largely unknown. Using a dual PET scan approach in healthy human volunteers with amphetamine and the D2/D3 ligand 18F-fallypride, we found that higher levels of trait impulsivity were predicted by diminished midbrain D2/D3 autoreceptor binding and greater amphetamine-induced DA release in the striatum, which was in turn associated with stimulant craving. Path analysis confirmed that the impact of decreased midbrain D2/D3 autoreceptor availability on trait impulsivity is mediated in part through its effect on stimulated striatal dopamine release.

1. Spontaneous fluctuations of membrane potential, patterns of spontaneous firing, dendritic branching patterns, and intracortical and striatal axonal arborizations were compared for two types of corticostriatal neurons in the medial agranular cortex of urethan-anesthetized rats: 1) pyramidal tract (PT) cells identified by antidromic activation from the medullary pyramid and 2) crossed corticostriatal (CST) neurons identified by antidromic activation from the contralateral neostriatum. The ipsilateral corticostriatal projections of intracellularly stained PT neurons as well as contralateral corticostriatal neurons were confirmed after labeling by intracellular injection of biocytin. 2. All well-stained PT neurons had intracortical and intrastriatal collaterals. The more common type (6 of 8) was a large, deep layer V neuron that had an extensive intracortical axon arborization but a limited axon arborization in the neostriatum. The less common type of PT neuron (2 of 8) was a medium-sized, superficial layer V neuron that had a limited intracortical axon arborization but a larger and more dense intrastriatal axonal arborization. Both subclasses of PT neurons had anatomic and physiological properties associated with slow PT cells in cats and monkeys and conduction velocities < 10 m/s. All of the PT cells but one were regular spiking cells. The exception cell fired intrinsic bursts. 3. Intracellularly stained CST neurons were located in the superficial half of layer V and the deep part of layer III. Their layer I apical dendrites were few and sparsely branched. Their axons gave rise to an extensive arbor of local axon collaterals that distributed in the region of the parent neuron, frequently extending throughout the more superficial layers, including layer I. Axon collaterals were also traced to the corpus callosum, as expected from their contralateral projections, and they contributed axon collaterals to the ipsilateral neostriatum. In the neostriatum, these axons formed extended arborizations sparsely occupying a large volume of striatal tissue. All CST neurons were regular spiking cells. 4. Both types of cells displayed spontaneous membrane fluctuations consisting of a polarized state (-60 to -90 mV) that was interrupted by 0.1- to 3.0-s periods of depolarization (-55 to -45 mV) accompanied by action potentials. The membrane potential was relatively constant in each state, and transitions between the depolarized and hyperpolarized states were sometimes periodic with a frequency of 0.3-1.5 Hz. A much faster (30-45 Hz) subthreshold oscillation of the membrane potential was observed only in the depolarized state and triggered action potentials that locked to the depolarizing peaks of this rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)

Psychopathy is a personality disorder that is strongly linked to criminal behavior. Using [18F]fallypride PET and BOLD fMRI, we show that impulsive-antisocial psychopathic traits selectively predict nucleus accumbens dopamine release and reward anticipation-related neural activity in response to pharmacological and monetary reinforcers, respectively. These findings suggest that neurochemical and neurophysiological hyperreactivity of the dopaminergic reward system may comprise a neural substrate for impulsivity, antisocial behavior and substance abuse in psychopathy.

Preferences for different combinations of costs and benefits are a key source of variability in economic decision-making. However, the neurochemical basis of individual differences in these preferences is poorly understood. Studies in both animals and humans have demonstrated that direct manipulation of the neurotransmitter dopamine (DA) significantly impacts cost/benefit decision-making, but less is known about how naturally occurring variation in DA systems may relate to individual differences in economic behavior. In the present study, 25 healthy volunteers completed a dual-scan PET imaging protocol with [18F]fallypride and d-amphetamine to measure DA responsivity, and separately completed the Effort Expenditure for Rewards Task, a behavioral measure of cost/benefit decision-making in humans. We found that individual differences in DA function in the left striatum and ventromedial prefrontal cortex were correlated with a willingness to expend greater effort for larger rewards, particularly when probability of reward receipt was low. Additionally, variability in DA responses in the bilateral insula was negatively correlated with willingness to expend effort for rewards, consistent with evidence implicating this region in the processing of response costs. These findings highlight the role of DA signaling in striatal, prefrontal and insular regions as key neurochemical mechanisms underlying individual differences in cost/benefit decision-making.

Novelty-seeking personality traits are a major risk factor for the development of drug abuse and other unsafe behaviors. Rodent models of temperament indicate that high novelty responding is associated with decreased inhibitory autoreceptor control of midbrain dopamine neurons. It has been speculated that individual differences in dopamine functioning also underlie the personality trait of novelty seeking in humans. However, differences in the dopamine system of rodents and humans, as well as the methods for assessing novelty responding/seeking across species leave unclear to what extent the animal models inform our understanding of human personality. In the present study we examined the correlation between novelty-seeking traits in humans and

Antibodies to the intracellular calcium binding protein parvalbumin were shown to label specifically a distinct group of neostriatal GABAergic neurons. These neurons corresponded to the intensely staining subclass of neostriatal GABAergic neurons that have previously been shown to be a class of aspiny interneurons in the neostriatum. The parvalbumin neurons were aspiny neurons with varicose dendrites distributed throughout the neostriatum in a pattern identical to the intensely stained GABA neurons, and both populations of neurons showed increased numbers in the lateral part of the neostriatum. Double labeling of single neurons with both the GABA and parvalbumin antisera showed that all parvalbumin neurons were positive for GABA, but some GABA labelled neurons were not immunoreactive for parvalbumin. These parvalbumin-negative GABAergic neurons were morphologically similar to the spiny projection neurons, which are GABAergic but usually are not so heavily stained. The relationship of the GABA-containing parvalbumin neurons to the striatal mosaic organization was determined by using immunocytochemistry for another calcium binding protein, calbindin D28K, to label the matrix compartment of the striatum. The distribution of parvalbumin-positive neurons relative to the calbindin-positive matrix and calbindin-poor patches was determined by using pairs of adjacent sections stained with the calbindin and parvalbumin antisera. This analysis showed that the somata of the parvalbumin neurons were present in both patch and matrix compartments, and their axons and dendrites crossed the boundaries between compartments. A quantitative analysis of the number of neurons in each compartment revealed that the neurons showed no preferential distribution in either compartment, but instead were present according to the area occupied by that compartment.(ABSTRACT TRUNCATED AT 250 WORDS)

Background Diminished dopaminergic neurotransmission contributes to decreased reward and negative eating behaviors in obesity. Bariatric surgery is the most effective therapy for obesity and rapidly reduces hunger and improves satiety through unknown mechanisms. We hypothesized that dopaminergic neurotransmission would be enhanced after Roux-en-Y-Gastric Bypass (RYGB) and Vertical Sleeve Gastrectomy (VSG) surgery and that these changes would influence eating behaviors and contribute to the positive outcomes from bariatric surgery. Methods Five females with obesity were studied preoperatively and at ~ 7 weeks after RYGB or VSG surgery. Subjects underwent positron emission tomography (PET) imaging with a dopamine type 2 (DA D2) receptor radioligand whose binding is sensitive to competition with endogenous dopamine. Regions of interest (ROI) relevant to eating behaviors were delineated. Fasting enteroendocrine hormones were quantified at each time point. Results Body weight decreased as expected after surgery. DA D2 receptor availability decreased after surgery. Regional decreases (mean ± SEM) were, caudate 10±3%, putamen 9±4%, ventral striatum 8±4%, hypothalamus 9±3%, substantia nigra 10±2%, medial thalamus 8±2%, and amygdala 9±3%. These were accompanied by significant decreases in plasma insulin (62%) and leptin (41%). Conclusions The decreases in DA D2 receptor availability after RYGB and VSG most likely reflect increases in extracellular dopamine levels. Enhanced dopaminergic neurotransmission may contribute to improved eating behavior (e.g. reduced hunger and improved satiety) following these bariatric procedures.