An fMRI Study of Responses to Sexual Stimuli as a Function of Gender and Sensation Seeking: A Preliminary Analysis

Although sexual cues produce stronger neural activation in men than in women, mechanisms underlying this differential response are unclear. We examined the relationship of sensation seeking and the brain’s response to sexual stimuli across gender in 27 subjects (14 men, M = 25.2 years, SD = 3.6, 85.2% Caucasian) who underwent functional magnetic resonance imaging (fMRI) while viewing sexual and nonsexual images. Whole-brain corrected significant clusters of regional activation were extracted and associated with gender, sensation seeking, and sexual behaviors. Men responded more to sexual than nonsexual images in the anterior cingulate/medial prefrontal cortex (ACC/mPFC), anterior insula/lateral orbitofrontal cortex, bilateral amygdala, and occipital regions. Sensation seeking related positively to ACC/mPFC (r = 0.65, p = 0.01) and left amygdala (r = 0.66, p = 0.01) response in men alone, with both of these correlations being significantly larger in men than in women (ps < 0.03). The relationship between brain responses and self-reported high-risk and low-risk sexual behaviors showed interesting, albeit nonsignificant, gender-specific trends. These findings suggest the relationship between sexual responsivity, sensation seeking, and sexual behavior is gender specific. This study indicates a need to identify the gender-specific mechanisms that underlie sexual responsivity and behaviors. In addition, it demonstrates that the nature of stimuli used to induce positive mood in imaging and other studies should be carefully considered

Pairing Neutral Cues with Alcohol Intoxication: New Findings in Executive and Attention Networks

Rationale: Alcohol-associated stimuli capture attention, yet drinkers differ in the precise stimuli that become paired with intoxication. Objectives: Extending our prior work to examine the influence of alcoholism risk factors, we paired abstract visual stimuli with intravenous alcohol delivered covertly and examined brain responses to these Pavlovian conditioned stimuli in fMRI when subjects were not intoxicated. Methods: Sixty healthy drinkers performed task-irrelevant alcohol conditioning that presented geometric shapes as conditioned stimuli. Shapes were paired with a rapidly rising alcohol limb (CS+) using intravenous alcohol infusion targeting a final peak breath alcohol concentration of 0.045 g/dL or saline (CS−) infusion at matched rates. On day two, subjects performed monetary delay discounting outside the scanner to assess delay tolerance and then underwent event-related fMRI while performing the same task with CS+, CS−, and an irrelevant symbol. Results: CS+ elicited stronger activation than CS− in frontoparietal executive/attention and orbitofrontal reward-associated networks. Risk factors including family history, recent drinking, sex, and age of drinking onset did not relate to the [CS+ > CS−] activation. Delay-tolerant choice and [CS+ > CS−] activation in right inferior parietal cortex were positively related. Conclusions: Networks governing executive attention and reward showed enhanced responses to stimuli experimentally paired with intoxication, with the right parietal cortex implicated in both alcohol cue pairing and intertemporal choice. While different from our previous study results in 14 men, we believe this paradigm in a large sample of male and female drinkers offers novel insights into Pavlovian processes less affected by idiosyncratic drug associations

A preliminary study of the human brain response to oral sucrose and its association with recent drinking

BACKGROUND: A preference for sweet tastes has been repeatedly shown to be associated with alcohol preference in both animals and humans. In this study, we tested the extent to which recent drinking is related to blood oxygen level-dependent (BOLD) activation from an intensely sweet solution in orbitofrontal areas known to respond to primary rewards. METHODS: Sixteen right-handed, non-treatment-seeking, healthy volunteers (mean age: 26 years; 75% male) were recruited from the community. All underwent a taste test using a range of sucrose concentrations, as well as functional magnetic resonance imaging (fMRI) during pseudorandom, event-driven stimulation with water and a 0.83 M concentration of sucrose in water. RESULTS: [Sucrose > water] provoked a significant BOLD activation in primary gustatory cortex and amygdala, as well as in the right ventral striatum and in bilateral orbitofrontal cortex. Drinks/drinking day correlated significantly with the activation as extracted from the left orbital area (r = 0.52, p = 0.04 after correcting for a bilateral comparison). Using stepwise multiple regression, the addition of rated sucrose liking accounted for significantly more variance in drinks/drinking day than did left orbital activation alone (multiple R = 0.79, p = 0.002). CONCLUSIONS: Both the orbitofrontal response to an intensely sweet taste and rated liking of that taste accounted for significant variance in drinking behavior. The brain response to sweet tastes may be an important phenotype of alcoholism risk

Involvement of the left anterior insula and frontopolar gyrus in odor discrimination

Discriminating between successively presented odors requires brief storage of the first odor's perceptual trace, which then needs to be subsequently compared to the second odor in the pair. This study explores the cortical areas involved in odor discrimination and compares them with findings from studies of working‐memory, traditionally investigated with n‐back paradigms. Sixteen right‐handed subjects underwent H2 15O positron emission tomography during counterbalanced conditions of odorless sniffing, repeated single odor detection, multiple odor detection, and conscious successive discrimination between odor pairs. Eight odorants were delivered using a computer‐controlled olfactometer through a birhinal nasal cannula. Conscious successive odor discrimination evoked significantly greater activity in the left anterior insula and frontopolar gyrus when compared to reported sensory detection of the identical odors. Additional activation was found in the left lateral orbital/inferior frontal and middle frontal gyri when discrimination was compared to the odorless condition. The left anterior insula is likely involved in the evaluation of odor properties. Consistent with other studies, frontopolar and middle frontal gyrus activation is more likely related to working memory during odor discrimination

Negative urgency and ventromedial prefrontal cortex responses to alcohol cues: FMRI evidence of emotion-based impulsivity

BACKGROUND: Recent research has highlighted the role of emotion-based impulsivity (negative and positive urgency personality traits) for alcohol use and abuse, but has yet to examine how these personality traits interact with the brain's motivational systems. Using functional magnetic resonance imaging (fMRI), we tested whether urgency traits and mood induction affected medial prefrontal responses to alcohol odors (AcO). METHODS: Twenty-seven social drinkers (mean age = 25.2, 14 males) had 6 fMRI scans while viewing negative, neutral, or positive mood images (3 mood conditions) during intermittent exposure to AcO and appetitive control (AppCo) aromas. RESULTS: Voxel-wise analyses (p AppCo] activation throughout medial prefrontal cortex (mPFC) and ventromedial PFC (vmPFC) regions. Extracted from a priori mPFC and vmPFC regions and analyzed in Odor (AcO, AppCo) × Mood factorial models, AcO activation was greater than AppCo in left vmPFC (p AppCo] activation. Negative urgency also mediated the relationship between vmPFC activation and both (i) subjective craving and (ii) problematic drinking. CONCLUSIONS: The trait of negative urgency is associated with neural responses to alcohol cues in the vmPFC, a region involved in reward value and emotion-guided decision-making. This suggests that negative urgency might alter subjective craving and brain regions involved in coding reward value

The policy procedure of the FOMC: a critique

Federal Open Market Committee

Associations between regional brain physiology and trait impulsivity, motor inhibition, and impaired control over drinking

Trait impulsivity and poor inhibitory control are well-established risk factors for alcohol misuse, yet little is known about the associated neurobiological endophenotypes. Here we examined correlations among brain physiology and self-reported trait impulsive behavior, impaired control over drinking, and a behavioral measure of response inhibition. A sample of healthy drinkers (n = 117) completed a pulsed arterial spin labeling (PASL) scan to quantify resting regional cerebral blood flow (rCBF), as well as measures of self-reported impulsivity (Eysenck I7 Impulsivity scale) and impaired control over drinking. A subset of subjects (n = 40) performed a stop signal task during blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging to assess brain regions involved in response inhibition. Eysenck I7 scores were inversely related to blood flow in the right precentral gyrus. Significant BOLD activation during response inhibition occurred in an overlapping right frontal motor/premotor region. Moreover, impaired control over drinking was associated with reduced BOLD response in the same region. These findings suggest that impulsive personality and impaired control over drinking are associated with brain physiology in areas implicated in response inhibition. This is consistent with the idea that difficulty controlling behavior is due in part to impairment in motor restraint systems

Correlation between Ventromedial Prefrontal Cortex Activation to Food Aromas and Cue-driven Eating: An fMRI Study

Food aromas are signals associated with both food's availability and pleasure. Previous research from this laboratory has shown that food aromas under fasting conditions evoke robust activation of medial prefrontal brain regions thought to reflect reward value (Bragulat, et al. 2010). In the current study, eighteen women (eleven normal-weight and seven obese) underwent a two-day imaging study (one after being fed, one while fasting). All were imaged on a 3T Siemens Trio-Tim scanner while sniffing two food (F; pasta and beef) odors, one non-food (NF; Douglas fir) odor, and an odorless control (CO). Prior to imaging, participants rated hunger and perceived odor qualities, and completed the Dutch Eating Behavior Questionnaire (DEBQ) to assess “Externality” (the extent to which eating is driven by external food cues). Across all participants, both food and non-food odors (compared to CO) elicited large blood oxygenation level dependent (BOLD) responses in olfactory and reward-related areas, including the medial prefrontal and anterior cingulate cortex, bilateral orbitofrontal cortex, and bilateral piriform cortex, amygdala, and hippocampus. However, food odors produced greater activation of medial prefrontal cortex, left lateral orbitofrontal cortex and inferior insula than non-food odors. Moreover, there was a significant correlation between the [F > CO] BOLD response in ventromedial prefrontal cortex and “Externality” sub-scale scores of the DEBQ, but only under the fed condition; no such correlation was present with the [NF > CO] response. This suggests that in those with high Externality, ventromedial prefrontal cortex may inappropriately valuate external food cues in the absence of internal hunger

Effects of dietary protein and fiber at breakfast on appetite, ad libitum energy intake at lunch, and neural responses to visual food stimuli in overweight adults

Increasing either protein or fiber at mealtimes has relatively modest effects on ingestive behavior. Whether protein and fiber have additive or interactive effects on ingestive behavior is not known. Fifteen overweight adults (5 female, 10 male; BMI: 27.1 ± 0.2 kg/m²; aged 26 ± 1 year) consumed four breakfast meals in a randomized crossover manner (normal protein (12 g) + normal fiber (2 g), normal protein (12 g) + high fiber (8 g), high protein (25 g) + normal fiber (2 g), high protein (25 g) + high fiber (8 g)). The amount of protein and fiber consumed at breakfast did not influence postprandial appetite or ad libitum energy intake at lunch. In the fasting-state, visual food stimuli elicited significant responses in the bilateral insula and amygdala and left orbitofrontal cortex. Contrary to our hypotheses, postprandial right insula responses were lower after consuming normal protein vs. high protein breakfasts. Postprandial responses in other a priori brain regions were not significantly influenced by protein or fiber intake at breakfast. In conclusion, these data do not support increasing dietary protein and fiber at breakfast as effective strategies for modulating neural reward processing and acute ingestive behavior in overweight adults.R01 MH102224 - NIMH NIH HHS; UL1 TR001108 - NCATS NIH HHS; UL1TR001108 - NCATS NIH HH

Externalizing personality traits, empathy, and gray matter volume in healthy young drinkers

Externalizing psychopathology has been linked to prefrontal abnormalities. While clinically diagnosed subjects show altered frontal gray matter, it is unknown if similar deficits relate to externalizing traits in non-clinical populations. We used voxel-based morphometry (VBM) to retrospectively analyze the cerebral gray matter volume of 176 young adult social to heavy drinkers (mean age=24.0±2.9, male=83.5%) from studies of alcoholism risk. We hypothesized that prefrontal gray matter volume and externalizing traits would be correlated. Externalizing personality trait components-Boredom Susceptibility-Impulsivity (BS/IMP) and Empathy/Low Antisocial Behaviors (EMP/LASB)-were tested for correlations with gray matter partial volume estimates (gmPVE). Significantly large clusters (pFWE<0.05, family-wise whole-brain corrected) of gmPVE correlated with EMP/LASB in dorsolateral and medial prefrontal regions, and in occipital cortex. BS/IMP did not correlate with gmPVE, but one scale of impulsivity (Eysenck I7) correlated positively with bilateral inferior frontal/orbitofrontal, and anterior insula gmPVE. In this large sample of community-dwelling young adults, antisocial behavior/low empathy corresponded with reduced prefrontal and occipital gray matter, while impulsivity correlated with increased inferior frontal and anterior insula cortical volume. These findings add to a literature indicating that externalizing personality features involve altered frontal architecture