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Background Cue-evoked drug-seeking behavior likely depends on interactions between frontal activity and ventral striatal ( VST) dopamine (DA) transmission. Using [11C]raclopride ( RAC) positron emission tomography ( PET), we previously demonstrated that beer flavor (absent intoxication) elicited VST 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 blood oxygenation level-dependent ( 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/wk = 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 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. [ABSTRACT FROM AUTHOR]

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 ( p FWE <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 I 7 ) 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. [ABSTRACT FROM AUTHOR]

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 I 7 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 I 7 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. [ABSTRACT FROM AUTHOR]

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 < 0.001) confirmed [AcO > AppCo] activation throughout medial prefrontal cortex ( mPFC) and ventromedial PFC (vmPFC) regions. Extracted from a priori mPFC and vm PFC regions and analyzed in Odor ( Ac O, App Co) × Mood factorial models, Ac O activation was greater than App Co in left vm PFC ( p < 0.001), left mPFC ( p = 0.002), and right vm PFC ( p = 0.01) regions. Mood did not interact significantly with activation, but the covariate of trait negative urgency accounted for significant variance in left vm PFC ( p = 0.01) and right vm PFC ( p = 0.01) [ Ac O > App Co] activation. Negative urgency also mediated the relationship between vm PFC 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 vm PFC, 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. [ABSTRACT FROM AUTHOR]

Background: Small, priming doses of alcohol enhance desire to drink, and thus play a role in the loss of control of alcohol consumption. Using functional magnetic resonance imaging (fMRI), we previously showed that alcoholic drink odors (AO; subjects’ drinks of choice) induce greater nucleus accumbens (NAc) activity than non-appetitive odors (NApO; grass, leather) in subjects at risk for alcoholism. Here we hypothesized that priming exposure to alcohol would enhance responses to AO in the NAc and orbitofrontal cortex in comparison to NApO (grass, leather) and to the appetitive control odors (ApCO) of chocolate and grape. Methods: Ten hazardous drinkers (mean age = 22.7; SD = 2.9, average drinks per drinking day = 5.9, SD = 2.3; drinking days/90 days = 50.4, SD = 13.7) were scanned on a 1.5T GE Signa MR scanner during intravenous infusion of lactated Ringer’s or 6% ethanol in lactated Ringer’s that was pharmacokinetically modeled to achieve a constant breath alcohol concentration (BrAC) of 50 mg% throughout imaging. During scanning, subjects sniffed AO, NApO, and ApCO. Results: Alcohol infusion enhanced the contrast between AO and NApO in the NAc, and in orbitofrontal, medial frontal, and precuneus/posterior cingulate regions. The contrast between AO and appetitive control odors (ApCO; chocolate and grape) was similarly larger in the orbital, medial frontal, precuneus, and posterior cingulate/retrosplenial areas, with the most robust finding being a potentiated response in the posterior cingulate/retrosplenial area. The orbital region is similar to an area previously shown to manifest satiety-related decreases in activity induced by food cues. Conclusions: The results suggest that priming exposure to alcohol renders a limbic network more responsive to alcohol cues, potentially enhancing desire to drink. [ABSTRACT FROM AUTHOR]

Background: Striatal dopamine (DA) has been implicated in alcohol use disorders, but it is still unclear whether or not alcohol can induce dopamine release in social drinkers. Furthermore, no data exist on dopamine responses to alcohol in dependent drinkers. We sought to characterize the DA responses to alcohol intoxication in moderately large samples of social drinkers (SD) and nontreatment-seeking alcoholics (NTS).Methods: Twenty-four SD and twenty-one NTS received two [(11)C]raclopride (RAC) PET scans; one at rest, and one during an intravenous alcohol infusion, with a prescribed ascent to a target breath alcohol concentration (BrAC), at which it was then "clamped." The alcohol clamp was started 5min after scan start, with a linear increase in BrAC over 15min to the target of 80mg%, the legal threshold for intoxication. Target BrAC was maintained for 30min. Voxel-wise binding potential (BPND) was estimated with MRTM2.Results: IV EtOH induced significant increases in DA in the right ventral striatum in NTS, but not SD. No decreases in DA were observed in either group.Conclusions: Alcohol intoxication results in distinct anatomic profiles of DA responses in SD and NTS, suggesting that in NTS, the striatal DA system may process effects of alcohol intoxication differently than in SD. [ABSTRACT FROM AUTHOR]

Background: The P3 component of the event-related potential (ERP) has been particularly useful in alcohol research for identifying endophenotypes of alcohol-use disorder (AUD) risk in sober subjects. However, practice and/or fatigue reduce P3 amplitude, limiting the ability to ascertain acute and adaptive effects of alcohol exposure. Here, we report acute alcohol effects on P3 amplitude and latency using an adaptive stop signal task (aSST).Methods: One hundred forty-eight non-dependent moderate to heavy social drinkers, ages 21 to 27, participated in two single-blind, alcohol or placebo, counterbalanced sessions approximately 1 week apart. During each session, subjects performed an adaptive stop signal task (aSST) at 1) baseline, 2) upon reaching the target 60 mg/dL breath alcohol concentration or at the equivalent time during the placebo session, and 3) approximately 135 min later while the breath alcohol concentration was clamped. Here, we report on differences between baseline and first subsequent measurements across the experimental sessions. During each aSST run, the stop signal delay (SSD, the time between stop and go signals) adjusted trial-by-trial, based on the subject's performance.Results: The aSST reliably generated a STOP P3 component that did not change significantly with repeated task performance. The pre-infusion SSD distribution was bimodal, with mean values several hundred msec apart (FAST: 153 msec and SLOW: 390 msec). This suggested different response strategies: FAST SSD favoring "going" over "stopping", and SLOW SSD favoring "stopping" over "going". Exposure to alcohol at 60 mg/dL differentially affected the amplitude and latency of the STOP P3 according to SSD group. Alcohol significantly reduced P3 amplitude in the SLOW SSD compared to the FAST SSD group, but significantly increased P3 latency in the FAST SSD compared to the SLOW SSD group.Conclusions: The aSST is a robust and sensitive task for detecting alcohol-induced changes in inhibition behavior as measured by the P3 component in a within-subject design. Alcohol was associated with P3 component changes, which varied by SSD group, suggesting a differential effect as a function of task strategy. Overall, the data support the potential utility of the aSST in the detection of alcohol response-related AUD risk. [ABSTRACT FROM AUTHOR]