Prefrontal response and frontostriatal functional connectivity to monetary reward in abstinent alcohol-dependent young adults

Although altered function in neural reward circuitry is widely proposed in models of addiction, more recent conceptual views have emphasized the role of disrupted response in prefrontal regions. Changes in regions such as the orbitofrontal cortex, medial prefrontal cortex, and dorsolateral prefrontal cortex are postulated to contribute to the compulsivity, impulsivity, and altered executive function that are central to addiction. In addition, few studies have examined function in these regions during young adulthood, when exposure is less chronic than in typical samples of alcohol-dependent adults. To address these issues, we examined neural response and functional connectivity during monetary reward in 24 adults with alcohol dependence and 24 psychiatrically healthy adults. Adults with alcohol dependence exhibited less response to the receipt of monetary reward in a set of prefrontal regions including the medial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex. Adults with alcohol dependence also exhibited greater negative correlation between function in each of these regions and that in the nucleus accumbens. Within the alcohol-dependent group, those with family history of alcohol dependence exhibited lower mPFC response, and those with more frequent drinking exhibited greater negative functional connectivity between the mPFC and the nucleus accumbens. These findings indicate that alcohol dependence is associated with less engagement of prefrontal cortical regions, suggesting weak or disrupted regulation of ventral striatal response. This pattern of prefrontal response and frontostriatal connectivity has consequences for the behavior patterns typical of addiction. Furthermore, brain-behavior findings indicate that the potential mechanisms of disruption in frontostriatal circuitry in alcohol dependence include family liability to alcohol use problems and more frequent use of alcohol. In all, these findings build on the extant literature on reward-circuit function in addiction and suggest mechanisms for disrupted function in alcohol dependence. © 2014 Forbes et al

Urocortin-1 within the Centrally-Projecting Edinger-Westphal Nucleus Is Critical for Ethanol Preference

Converging lines of evidence point to the involvement of neurons of the centrally projecting Edinger-Westphal nucleus (EWcp) containing the neuropeptide Urocortin-1 (Ucn1) in excessive ethanol (EtOH) intake and EtOH sensitivity. Here, we expanded these previous findings by using a continuous-access, two-bottle choice drinking paradigm (3%, 6%, and 10% EtOH vs. tap water) to compare EtOH intake and EtOH preference in Ucn1 genetic knockout (KO) and wild-type (WT) mice. Based on previous studies demonstrating that electrolytic lesion of the EWcp attenuated EtOH intake and preference in high-drinking C57BL/6J mice, we also set out to determine whether EWcp lesion would differentially alter EtOH consumption in Ucn1 KO and WT mice. Finally, we implemented well-established place conditioning procedures in KO and WT mice to determine whether Ucn1 and the corticotropin-releasing factor type-2 receptor (CRF-R2) were involved in the rewarding and aversive effects of EtOH (2 g/kg, i.p.). Results from these studies revealed that (1) genetic deletion of Ucn1 dampened EtOH preference only in mice with an intact EWcp, but not in mice that received lesion of the EWcp, (2) lesion of the EWcp dampened EtOH intake in Ucn1 KO and WT mice, but dampened EtOH preference only in WT mice expressing Ucn1, and (3) genetic deletion of Ucn1 or CRF-R2 abolished the conditioned rewarding effects of EtOH, but deletion of Ucn1 had no effect on the conditioned aversive effects of EtOH. The current findings provide strong support for the hypothesis that EWcp-Ucn1 neurons play an important role in EtOH intake, preference, and reward

Self-reported attentional and motor impulsivity are related to age at first methamphetamine use

IntroductionMethamphetamine (MA) users report higher levels of impulsivity relative to healthy controls, which may either result from, or precede, their substance use. Further, there is evidence that female MA users may be more impulsive than male MA users prior to MA use. Thus, the goal of the current study was to determine whether different subtraits of self-reported impulsivity are significantly related to age at first MA use, controlling for total years of MA use.MethodsA community sample of MA users was recruited for this study (N=157; 113 males, 44 females). The Barratt Impulsiveness Scale (BIS-11) was used to assess self-reported impulsivity on three subscales (Attentional, Motor, Non-planning). Age at first MA use served as the dependent variable in a series of multiple regression models with BIS-11 subscales, sex, and their interaction as independent variables, controlling for total years of MA use.ResultsAttentional and Motor impulsivity were significantly related to age at first MA use when controlling for total years of MA use (Attentional: p=0.008; Motor: p=0.003).ConclusionsIndividuals who reported higher Attentional and Motor impulsivity started using MA at an earlier age, which could suggest that impulsivity levels may be an important marker of vulnerability towards MA use. These findings indicate that prevention efforts may be targeted towards individuals who report high levels of Attentional and Motor impulsivity, as they may be at greatest risk for earlier initiation of MA use

Severity of alcohol dependence is negatively related to hypothalamic and prefrontal cortical gray matter density in heavy drinking smokers

BackgroundWhile research has examined brain structure in individuals who use alcohol or nicotine, heavy drinking smokers comprise a unique subpopulation of substance users for whom less is known about the relationship between alcohol or nicotine use and structural brain abnormalities.ObjectivesThe present study examined gray matter morphometry in a sample of 39 heavy drinking smokers (24 males, 15 females) in relation to alcohol and nicotine dependence and quantity of use.MethodsTraditional voxel-based morphometry techniques were employed for preprocessing of imaging data. One multiple regression analysis for alcohol and nicotine dependence severity and another for alcohol and nicotine quantity of use were conducted, while controlling for age, gender, and total intracranial volume (ICV).ResultsAlcohol dependence severity was significantly negatively associated with gray matter density in the hypothalamus (p < 0.001, uncorrected) and the right superior frontal gyrus (p < 0.001, uncorrected), while controlling for nicotine dependence severity, age, gender, and ICV. There were no significant relationships observed with respect to nicotine dependence severity, the quantity of alcohol use, or the quantity of nicotine use variables and gray matter density.ConclusionsThese findings suggest that within heavy drinking smokers, alcohol dependence severity is significantly related to alterations in brain structure, while this effect is not seen for the quantity of alcohol or nicotine use, or severity of nicotine dependence. The current findings help clarify the contribution of alcohol and nicotine effects on brain structure, which could aid in understanding their neurocognitive consequences in heavy drinking smokers

Review: Pharmacogenetics of alcoholism treatment: Implications of ethnic diversity

Background and objectivesPharmacogenetic studies of alcohol use disorder (AUD) have suggested that the efficacy of treatments for AUD is, in part, influenced by the genetic background of an individual. Since the frequency of alleles associated with pharmacotherapy for AUD varies by ancestral background, the effectiveness of medications used to treat AUD may vary among different populations. The purpose of this review is to summarize the existing pharmacogenetic studies of treatments for AUD in individuals of European, East Asian, African, and American Indian/Alaska Native ancestry.MethodsElectronic databases were searched for pharmacogenetic studies of AUD treatment that included individuals of diverse ancestral backgrounds.ResultsPharmacogenetic studies of AUD reviewed here have primarily investigated genetic variation thought to play a role in the response to naltrexone, ondansetron, and topiramate. There is support that the A118G polymorphism should be further investigated in individuals of East Asian ancestry.Discussion and conclusionsGiven the lack of pharmacogenetic research on response to AUD medication in ethnic minority populations and the mixed results, there is a critical need for future studies among individuals of different ancestries. More efforts should be devoted to standardizing procedures such that results can be more readily integrated into a body of literature that can directly inform clinical practice.Scientific significanceThis review highlights the importance for future research to aim for inclusiveness in pharmacogenetic studies of AUD and increase diversity of clinical trials in order to provide the best treatment outcomes for individuals across different racial and ethnic groups. (Am J Addict 2017;26:516-525)

Reduced cerebellar brain activity during reward processing in adolescent binge drinkers

AbstractDue to ongoing development, adolescence may be a period of heightened vulnerability to the neurotoxic effects of alcohol. Binge drinking may alter reward-driven behavior and neurocircuitry, thereby increasing risk for escalating alcohol use. Therefore, we compared reward processing in adolescents with and without a history of recent binge drinking. At their baseline study visit, all participants (age=14.86±0.88) were free of heavy alcohol use and completed a modified version of the Wheel of Fortune (WOF) functional magnetic resonance imaging task. Following this visit, 17 youth reported binge drinking on ≥3 occasions within a 90 day period and were matched to 17 youth who remained alcohol and substance-naïve. All participants repeated the WOF task during a second visit (age=16.83±1.22). No significant effects were found in a region of interest analysis of the ventral striatum, but whole-brain analyses showed significant group differences in reward response at the second study visit in the left cerebellum, controlling for baseline visit brain activity (p/α<0.05), which was negatively correlated with mean number of drinks consumed/drinking day in the last 90 days. These findings suggest that binge drinking during adolescence may alter brain activity during reward processing in a dose-dependent manner

Studies on some seed traits of Iris pumila L., Adonis vernalis L., Primula veris Huds. and Alkanna tinctoria (L.) Tausch.

In this study we summarize the results of a five-years period concerning seed traits examinations on Iris pumila, Adonis vernalis, Primula veris and Alkanna tinctoria, with special attention to seed dimensions, seed mass and other traits concerning plant fitness, to their variability and the relationship among them. We found tight correlation between seed weight and seed dimensions in Adonis and Primula, at the same time no correlation exists among the same characters in Alkanna tinctoria. Consequently, the seed weight and seed dimensions can be used as synonyms in the form of „seed size" only after preliminary detection of correlations among them. The variability of seed traits is higher in natural categories (individuals, morphs) than in seed mass categories as speculative groups. When we need homogeneous plant stand (e.g. for an introduction experiment) it is suggested to use seeds pre-selected in this way. For ex situ conservation, where the central goal is to maintain the genetic variability, seeds originated from different individuals are preferred. &nbsp

Studies on some seed traits of Iris pumila L., Adonis vernalis L., Primula veris Huds. and Alkanna tinctoria (L.) Tausch.

In this study we summarize the results of a five-years period concerning seed traits examinations on Iris pumila, Adonis vernalis, Primula veris and Alkanna tinctoria, with special attention to seed dimensions, seed mass and other traits concerning plant fitness, to their variability and the relationship among them. We found tight correlation between seed weight and seed dimensions in Adonis and Primula, at the same time no correlation exists among the same characters in Alkanna tinctoria. Consequently, the seed weight and seed dimensions can be used as synonyms in the form of „seed size" only after preliminary detection of correlations among them. The variability of seed traits is higher in natural categories (individuals, morphs) than in seed mass categories as speculative groups. When we need homogeneous plant stand (e.g. for an introduction experiment) it is suggested to use seeds pre-selected in this way. For ex situ conservation, where the central goal is to maintain the genetic variability, seeds originated from different individuals are preferred. &nbsp

Development, Initial Testing and Challenges of an Ecologically Valid Reward Prediction Error FMRI Task for Alcoholism.

AimsTo advance translational studies of the role of reward prediction error (PE) in alcohol use disorder, the present study sought to develop and conduct an initial test of an alcohol-specific PE task paradigm using functional magnetic resonance imaging in humans.MethodsAlcohol dependent or social drinkers received small tastes of their preferred alcohol beverage or control beverage, with preceding visual cues indicating whether alcohol (or water) would be delivered. To assess both positive and negative PE signals, expectancies were systematically violated in both positive (i.e. expecting water and receiving alcohol) and negative (i.e. expecting alcohol and receiving water) directions. Exploratory trial-by-trial analyses were conducted to explore temporal fluctuations of activation within a priori-defined regions of interest that have been implicated in cue reactivity and PE processing.ResultsAcross the entire sample of participants, positive PE-related brain activation was found in a large cluster comprised of frontal lobe regions, as well as insular cortex, and motor/sensory cortices. Compared to social drinking subjects, alcohol dependent subjects had greater positive PE-related brain activity in left superior parietal lobule, lateral occipital cortex and postcentral gyrus. Exploratory trial-by-trial analyses indicated differences in activation specific to type of taste, mostly at earlier trials.ConclusionsThis task-development oriented pilot study found that PE signaling may not be detected in expected brain regions when image analyses average across all PE trials of the task. Rather, a trial-by-trial analysis approach may help detect sparse, temporally distinct PE signaling in expected reward processing regions.Short summaryThis fMRI study of reward prediction error found greater positive prediction error-related activity (i.e. expecting water taste, receiving alcohol taste) in alcohol dependent individuals relative to social drinkers in parietal and occipital cortices. Trial-by-trial analyses may be able to better detect sparse prediction error signaling in expected reward processing regions