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

GABA and Glutamate Levels in Occlusal Splint-Wearing Males with Possible Bruxism

Objective The inhibitory neurotransmitter γ-aminobutyric acid (GABA) plays an important role in the pathophysiology of anxiety behavioural disorders such as panic disorder and post-traumatic stress disorder and is also implicated in the manifestation of tooth-grinding and clenching behaviours generally known as bruxism. In order to test whether the stress-related behaviours of tooth-grinding and clenching share similar underlying mechanisms involving GABA and other metabolites as do anxiety-related behavioural disorders, we performed a Magnetic Resonance Spectroscopy (MRS) study for accurate, in vivo metabolite quantification in anxiety-related brain regions. Design MRS was performed in the right hippocampus and right thalamus involved in the hypothalamic−pituitary−adrenal axis system, together with a motor planning region (dorsal anterior cingulate cortex/pre-supplementary motor area) and right dorsolateral prefrontal cortex (DLPFC). Eight occlusal splint-wearing men (OCS) with possible tooth-grinding and clenching behaviours and nine male controls (CON) with no such behaviour were studied. Results Repeated-measures ANOVA showed significant Group × Region interaction for GABA+ (p = 0.001) and glutamate (Glu) (p = 0.031). Between-group post hoc ANOVA showed significantly lower levels of GABA+ (p = 0.003) and higher levels of Glu (p = 0.002) in DLPFC of OCS subjects. These GABA+ and Glu group differences remained significant (GABA+, p = 0.049; Glu, p = 0.039) after the inclusion of anxiety as a covariate. Additionally, GABA and Glu levels in the DLPFC of all subjects were negatively related (Pearson's r = −0.75, p = 0.003). Conclusions These findings indicate that the oral behaviours of tooth-grinding and clenching, generally known as bruxism, may be associated with disturbances in brain GABAergic and glutamatergic systems

Corticostriatal and dopaminergic response to beer flavor with both fMRI and [11C]raclopride Positron Emission Tomography

Background Cue-evoked drug seeking behavior likely depends on interactions between frontal activity and ventral striatal (VST) dopamine transmission. Using [11C]raclopride (RAC) positron emission tomography (PET), we previously demonstrated that beer flavor (absent intoxication) elicited VST dopamine (DA) release in beer drinkers, inferred by RAC displacement. Here, a subset of subjects from this previous RAC-PET study underwent a similar paradigm during functional magnetic resonance imaging (fMRI) to test how orbitofrontal cortex (OFC) and VST BOLD responses to beer flavor are related to VST DA release and motivation to drink. Methods Male beer drinkers (n=28, age=24±2, drinks/week=16±10) from our previous PET study participated in a similar fMRI paradigm wherein subjects tasted their most frequently consumed brand of beer and Gatorade® (appetitive control). We tested for correlations between blood oxygenation level dependent (BOLD) activation in fMRI and VST DA responses in PET, and drinking-related variables. Results Compared to Gatorade, beer flavor increased wanting and desire to drink, and induced BOLD responses in bilateral OFC and right VST. Wanting and desire to drink correlated with both right VST and medial OFC BOLD activation to beer flavor. Like the BOLD findings, beer flavor (relative to Gatorade) again induced right VST DA release in this fMRI subject subset, but there was no correlation between DA release and the magnitude of BOLD responses in frontal regions of interest. Conclusions Both imaging modalities showed a right lateralized VST response (BOLD and DA release) to a drug-paired conditioned stimulus, whereas fMRI BOLD responses in the VST and medial OFC also reflected wanting and desire to drink. The data suggest the possibility that responses to drug-paired cues may be rightward biased in the VST (at least in right-handed males), and that VST and OFC responses in this gustatory paradigm reflect stimulus wanting

Ghrelin is not Related to Hunger or Calories Consumed at Breakfast in Lean and Obese Women

poster abstractBackground: The mechanisms that result in greater caloric intake in obese individuals are incompletely understood. Ghrelin administration increases ad lib food intake in humans. We investigated the relationship of ghrelin to calorie consumption and hunger at breakfast on two separate occasions in lean and obese women. Methods: 23 lean (BMI 22.3±0.5 kg/m2, 26.5±1.0 yr) and 25 obese (BMI 36.9±0.7 kg/m2, 27.8±1.1 yr) women participated in a noncontiguous 2 day study. The minimum and maximum days between visits were 6 and 43 days. Participants were given the same breakfast on both days (turkey sausage, French toast with margarine/syrup, fruit cup, coffee, tea, diet soda, or water) with portions adjusted to provide 20% of the daily energy requirement for weight maintenance. Subjects were instructed to eat until full. Hunger was evaluated on a Satiety Labeled Intensity Magnitude Scale (SLIM) before and after the meal. Anchors were “greatest imaginable fullness” at 0 and “greatest imaginable hunger” at 100. Blood samples were collected over 120 minutes for measurement of active ghrelin. Results: Lean subjects consumed an equivalent number of calories on both days (380.0±14.6 vs 378.2±14.9 kcal), as did the obese (419.4±16.2 vs 428.8±15.4 kcal). On average for both days, obese consumed significantly more breakfast calories than lean (424.1±11.1 vs 379.1±10.3 kcal; P<0.01), but the same percentage of calories provided (85.7±1.8 vs 86.1±1.7 %kcal). Lean subjects rated hunger before breakfast the same on both days (69.2±1.6 vs 71.7±1.4), as did the obese (69.8±1.6 vs 69.6±1.8), and there was no difference between the groups. Lean subjects rated hunger after breakfast the same on both days (27.8±1.9 vs 30.3±2.4), as did the obese (25.0±1.7 vs 24.3±1.8). The reduction in hunger score following breakfast was significant for both groups (P<0.0001), with the obese reporting significantly less hunger/more fullness after breakfast than the lean (P=0.02). Fasting ghrelin was significantly greater in the lean than obese women (549.9±58.9 vs 231.0±29.1 pg/ml; P<0.0001). Ghrelin was significantly reduced at 60 min following breakfast in the lean (375.8±49.2 pg/ml; P=0.028) but not the obese (212.2±26.4 pg/ml). Ghrelin was not related to hunger score prior to breakfast, and there was no relationship between reduction in ghrelin and hunger score in the lean or obese. Conclusion: Caloric intake (as a percentage provided) and hunger scores before breakfast on two occasions were the same for both lean and obese women. Fasting ghrelin was significantly different between lean and obese women but did not predict hunger score or calories consumed. Our findings do not support a role for ghrelin in driving food intake at breakfast

Family history of alcoholism and the human brain response to oral sucrose

A heightened hedonic response to sweet tastes has been associated with increased alcohol preference and alcohol consumption in both humans and animals. The principal goal of this study was to examine blood oxygenation level dependent (BOLD) activation to high- and low-concentration sweet solutions in subjects who are either positive (FHP) or negative (FHN) for a family history of alcoholism. Seventy-four non-treatment seeking, community-recruited, healthy volunteers (22.8 ± 1.6 SD years; 43% men) rated a range of sucrose concentrations in a taste test and underwent functional magnetic resonance imaging (fMRI) during oral delivery of water, 0.83 M, and 0.10 M sucrose. Sucrose compared to water produced robust activation in primary gustatory cortex, ventral insula, amygdala, and ventral striatum. FHP subjects displayed greater bilateral amygdala activation than FHN subjects in the low sucrose concentration (0.10 M). In secondary analyses, the right amygdala response to the 0.10 M sucrose was greatest in FHP women. When accounting for group differences in drinks per week, the family history groups remained significantly different in their right amygdala response to 0.10 M sucrose. Our findings suggest that the brain response to oral sucrose differs with a family history of alcoholism, and that this response to a mildly reinforcing primary reward might be an endophenotypic marker of alcoholism risk

DISTO data on Kpp

The data from the DISTO Collaboration on the exclusive pp -> p K+ Lambda production acquired at T_p = 2.85 GeV have been re-analysed in order to search for a deeply bound K- pp (= X) state, to be formed in the binary process pp -> K+ X. The preliminary spectra of the DeltaM_{K+} missing-mass and of the M_{p Lambda} invariant-mass show, for large transverse-momenta of protons and kaons, a distinct broad peak with a mass M_X = 2265 +- 2 MeV/c^2 and a width Gamma_X = 118 +- 8 MeV/c^2.Comment: 8 pages, 4 figures. Talk presented at the "10th International Conference on Hypernuclear and Strange Particle Physics" (HYP-X), Tokai, Ibaraki, Japan, September 14th-18th, 2009. To appear in the proceeding

Tangent functional connectomes uncover more unique phenotypic traits

Functional connectomes (FCs) contain pairwise estimations of functional couplings based on pairs of brain regions activity. FCs are commonly represented as correlation matrices that are symmetric positive definite (SPD) lying on or inside the SPD manifold. Since the geometry on the SPD manifold is non-Euclidean, the inter-related entries of FCs undermine the use of Euclidean-based distances. By projecting FCs into a tangent space, we can obtain tangent functional connectomes (tangent-FCs). Tangent-FCs have shown a higher predictive power of behavior and cognition, but no studies have evaluated the effect of such projections with respect to fingerprinting. We hypothesize that tangent-FCs have a higher fingerprint than regular FCs. Fingerprinting was measured by identification rates (ID rates) on test-retest FCs as well as on monozygotic and dizygotic twins. Our results showed that identification rates are systematically higher when using tangent-FCs. Specifically, we found: (i) Riemann and log-Euclidean matrix references systematically led to higher ID rates. (ii) In tangent-FCs, Main-diagonal regularization prior to tangent space projection was critical for ID rate when using Euclidean distance, whereas barely affected ID rates when using correlation distance. (iii) ID rates were dependent on condition and fMRI scan length. (iv) Parcellation granularity was key for ID rates in FCs, as well as in tangent-FCs with fixed regularization, whereas optimal regularization of tangent-FCs mostly removed this effect. (v) Correlation distance in tangent-FCs outperformed any other configuration of distance on FCs or on tangent-FCs across the fingerprint gradient (here sampled by assessing test-retest, Monozygotic and Dizygotic twins). (vi)ID rates tended to be higher in task scans compared to resting-state scans when accounting for fMRI scan length.Comment: 29 pages, 10 figures, 2 table

Depolarization of a Stored Proton Beam in Presence of an Internal Gas Target

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

Indication of a deeply bound compact K-pp state formed in the pp -> p Lambda K+ reaction at 2.85 GeV

We have analyzed data of the DISTO experiment on the exclusive pp -> p Lambda K+ reaction at 2.85 GeV to search for a strongly bound compact K-pp (= X) state to be formed in the pp -> K+ + X reaction. The observed spectra of the K+ missing-mass and the p Lambda invariant-mass with high transverse momenta of p and K+ revealed a broad distinct peak with a mass M_X = 2265 +- 2 (stat) +- 5 (syst) MeV/c2 and a width Gamma_X = 118 +- 8 (stat) +- 10 (syst) MeV.Comment: 4 pages, 4 figure

A Measurement of pp Spin Correlation Coefficients at 6˚ <= θ[cm] <= 90˚ Between 200 and 450 MeV

This research was sponsored by the National Science Foundation Grant NSF PHY-931478