Alcohol Cue-Induced Ventral Striatum Activity Predicts Subsequent Alcohol Self-Administration.

BACKGROUND: Human laboratory paradigms are a pillar in medication development for alcohol use disorders (AUD). Neuroimaging paradigms, in which individuals are exposed to cues that elicit neural correlates of alcohol craving (e.g., mesocorticolimbic activation), are increasingly utilized to test the effects of AUD medications. Elucidation of the translational effects of these neuroimaging paradigms on human laboratory paradigms, such as self-administration, is warranted. The current study is a secondary analysis examining whether alcohol cue-induced activation in the ventral striatum is predictive of subsequent alcohol self-administration in the laboratory. METHODS: Non-treatment-seeking heavy drinkers of East Asian descent (n = 41) completed a randomized, placebo-controlled, double-blind, crossover experiment on the effects of naltrexone on neuroimaging and human laboratory paradigms. Participants completed 5 days of study medication (or placebo); on day 4, they completed a neuroimaging alcohol taste cue-reactivity task. On the following day (day 5), participants completed a 60-minute alcohol self-administration paradigm. RESULTS: Multilevel Cox regressions indicated a significant effect of taste cue-elicited ventral striatum activation on latency to first drink, Wald χ2  = 2.88, p = 0.05, such that those with higher ventral striatum activation exhibited shorter latencies to consume their first drink. Similarly, ventral striatum activation was positively associated with total number of drinks consumed, F(1, 38) = 5.90, p = 0.02. These effects were significant after controlling for alcohol use severity, OPRM1 genotype, and medication. Other potential regions of interest (anterior cingulate, thalamus) were not predictive of self-administration outcomes. CONCLUSIONS: Neuroimaging alcohol taste cue paradigms may be predictive of laboratory paradigms such as self-administration. Elucidation of the relationships among different paradigms will inform how these paradigms may be used synergistically in experimental medicine and medication development.

Central Nervous System Correlates of "Objective" Neuropathy in Alcohol Use Disorder.

BACKGROUND: Among the neurological consequences of alcoholism is peripheral neuropathy. Relative to human immunodeficiency virus (HIV) or diabetes-related neuropathies, neuropathy associated with alcohol use disorders (AUD) is understudied. In both the diabetes and HIV literature, emerging evidence supports a central nervous system (CNS) component to peripheral neuropathy. METHODS: In seeking a central substrate for AUD-related neuropathy, the current study was conducted in 154 individuals with AUD (43 women, age 21 to 74 years) and 99 healthy controls (41 women, age 21 to 77 years) and explored subjective symptoms (self-report) and objective signs (perception of vibration, deep tendon ankle reflex, position sense, 2-point discrimination) of neuropathy separately. In addition to regional brain volumes, risk factors for AUD-related neuropathy, including age, sex, total lifetime ethanol consumed, nutritional indices (i.e., thiamine, folate), and measures of liver integrity (i.e., γ-glutamyltransferase), were evaluated. RESULTS: The AUD group described more subjective symptoms of neuropathy and was more frequently impaired on bilateral perception of vibration. From 5 correlates, the number of AUD-related seizures was most significantly associated with subjective symptoms of neuropathy. There were 15 correlates of impaired perception of vibration among the AUD participants: Of these, age and volume of frontal precentral cortex were the most robust predictors. CONCLUSIONS: This study supports CNS involvement in objective signs of neuropathy in AUD.

Risk profiles for heavy drinking in adolescence: differential effects of gender.

Abnormalities across different domains of neuropsychological functioning may constitute a risk factor for heavy drinking during adolescence and for developing alcohol use disorders later in life. However, the exact nature of such multi-domain risk profiles is unclear, and it is further unclear whether these risk profiles differ between genders. We combined longitudinal and cross-sectional analyses on the large IMAGEN sample (N ≈ 1000) to predict heavy drinking at age 19 from gray matter volume as well as from psychosocial data at age 14 and 19-for males and females separately. Heavy drinking was associated with reduced gray matter volume in 19-year-olds' bilateral ACC, MPFC, thalamus, middle, medial and superior OFC as well as left amygdala and anterior insula and right inferior OFC. Notably, this lower gray matter volume associated with heavy drinking was stronger in females than in males. In both genders, we observed that impulsivity and facets of novelty seeking at the age of 14 and 19, as well as hopelessness at the age of 14, are risk factors for heavy drinking at the age of 19. Stressful life events with internal (but not external) locus of control were associated with heavy drinking only at age 19. Personality and stress assessment in adolescents may help to better target counseling and prevention programs. This might reduce heavy drinking in adolescents and hence reduce the risk of early brain atrophy, especially in females. In turn, this could additionally reduce the risk of developing alcohol use disorders later in adulthood.

Neural mechanisms of risky decision making in adolescents reporting frequent alcohol and/or marijuana use.

Because adolescence is a period of heightened exploration of new behaviors, there is a natural increase in risk taking including initial use of alcohol and marijuana. In order to better understand potential differences in neurocognitive functioning among adolescents who use drugs, the current study aimed to identify the neural substrates of risky decision making that differ among adolescents who are primary users of alcohol or marijuana, primary users of both alcohol and marijuana, and controls who report primary use of neither drug. Participants completed the Balloon Analogue Risk Task (BART) while undergoing functional magnetic resonance imaging. Comparison of brain activation during risky decisions versus non-risky decisions across all subjects revealed greater response to risky decisions in dorsal anterior cinguate cortex (dACC), anterior insula, ventral striatum, and lateral prefrontal cortex. Group comparisons across non-using controls, primary marijuana, primary alcohol, and alcohol and marijuana users revealed several notable differences in the recruitment of brain regions. Adolescents who use both alcohol and marijauna show decreased response during risky decision making compared to controls in insula, striatum, and thalamus, and reduced differentiation of increasing risk in dACC, insula, striatum, and superior parietal lobe compared to controls. These results provide evidence of differential engagement of risky decision making circuits among adolescents with varying levels of alcohol and marijuana use, and may provide useful targets for longitudinal studies that explicitly address causality of these differences.

Prospective changes in neural alcohol cue reactivity in at-risk adolescents.

Adolescence represents an ideal time for elucidating the etiology of cue reactivity profiles. This study examined the influence of three risk factors consistently associated with heavy adolescent drinking on alcohol cue reactivity. Youth were first assessed while still naïve to alcohol (12-14 years old) and followed after transitioning into alcohol use (17-21 years old). The effects of family history of substance use disorder, sex, and history of early of dating (i.e., before 14 years of age) on BOLD response contrast to alcohol picture cues were examined in a linear mixed model, controlling for age and alcohol use patterns at follow-up. Activation to alcohol picture cues differed as a function of risk factor and time. At baseline, family history positive youth showed greater activation to alcohol cues than family history negative peers in the right middle occipital and anterior cingulate gyri. Youth with a history of early-dating showed greater activation to alcohol cues, compared to non-early daters, in the left anterior cingulate/white matter region. Girls showed greater activation to alcohol than boys at baseline in left middle frontal gyrus. At follow-up, after drinking started, patterns reversed for each risk factor. These results indicate that even prior to initiating alcohol use, adolescents showed differences in activation to alcohol cues based on their family history, dating history, and sex.

Genome-wide association study of subcortical brain volume in PTSD cases and trauma-exposed controls.

Depending on the traumatic event, a significant fraction of trauma survivors subsequently develop PTSD. The additional variability in PTSD risk is expected to arise from genetic susceptibility. Unfortunately, several genome-wide association studies (GWAS) have failed to identify a consistent genetic marker for PTSD. The heritability of intermediate phenotypes such as regional brain volumes is often 80% or higher. We conducted a GWAS of subcortical brain volumes in a sample of recent military veteran trauma survivors (n = 157), grouped into PTSD (n = 66) and non-PTSD controls (n = 91). Covariates included PTSD diagnosis, sex, intracranial volume, ancestry, childhood trauma, SNP×PTSD diagnosis, and SNP×childhood trauma. We identified several genetic markers in high linkage disequilibrium (LD) with rs9373240 (p = 2.0 × 10-7, FDR q = 0.0375) that were associated with caudate volume. We also observed a significant interaction between rs9373240 and childhood trauma (p-values = 0.0007-0.002), whereby increased trauma exposure produced a stronger association between SNPs and increased caudate volume. We identified several SNPs in high LD with rs34043524, which is downstream of the TRAM1L1 gene that were associated with right lateral ventricular volume (p = 1.73 × 10-7; FDR q = 0.032) and were also associated with lifetime alcohol abuse or dependence (p = 2.49 × 10-7; FDR q = 0.0375). Finally, we identified several SNPs in high LD with rs13140180 (p = 2.58 × 10-7; FDR q = .0016), an intergenic region on chromosome 4, and several SNPs in the TMPRSS15 associated with right nucleus accumbens volume (p = 2.58 × 10-7; FDR q = 0.017). Both TRAM1L1 and TMPRSS15 have been previously implicated in neuronal function. Key results survived genome-wide multiple-testing correction in our sample. Leveraging neuroimaging phenotypes may offer a shortcut, relative to clinical phenotypes, in mapping the genetic architecture and neurobiological pathways of PTSD.

Neuroimaging of chronic alcohol misuse.

Alcohol is one of the most commonly abused substances worldwide. It results in a wide range of diseases and disorders affecting many organ systems. Alcohol-related nutritional deficiencies and electrolyte disturbance leave chronic abusers at risk of a range of demyelinating conditions to which the radiologist and clinician should always be alert. These include Wernicke's encephalopathy, Korsakoff's syndrome, Marchiafava-Bignami disease and osmotic demyelination. Cerebral volume loss is also a commonly encountered neuroimaging phenomenon in chronic alcohol abusers. Neuroimaging with CT and MR, with a focus on FLAIR and diffusion-weighted MR sequences, play an important role in the diagnosis and often monitoring of these conditions. We present an educational review of these entities in terms of their clinical features, neuropathology and imaging features along with a case example of each condition.

Psychiatric, Demographic, and Brain Morphological Predictors of Relapse After Treatment for an Alcohol Use Disorder.

BACKGROUND: Relapse in alcohol use disorders (AUD) is related to a complex interplay among multiple biological, psychiatric, psychological, and psychosocial factors, which may change dynamically during and after treatment. At treatment entry for AUD, morphological abnormalities in anterior frontal regions and the insula have been observed in those who ultimately relapse following treatment. The goal of this study was to determine whether anterior frontal and insula measures of brain thickness, surface area, and volume predict posttreatment drinking status (i.e., relapser or abstainer) over an extended period after outpatient treatment for AUD, while concurrently considering common psychiatric, psychological, and psychosocial factors previously associated with relapse. METHODS: Alcohol-dependent individuals (n = 129) were followed for 18 months after treatment to determine posttreatment drinking status (abstainers [n = 47] or relapsers [n = 82]). Brain morphometrics were derived from FreeSurfer. Receiver operating characteristic (ROC) curve analysis was used to identify the regional brain thickness, surface area, and volume (all scaled to intracranial volume), demographic, psychiatric, other substance use (e.g., cigarette smoking), and alcohol consumption variables, obtained at entry into treatment, that best predicted posttreatment drinking status. Survival analyses determined variables that were related to duration of abstinence after treatment. RESULTS: ROC analyses indicated that mood disorders, education, and volumes of the right caudal anterior cingulate cortex (ACC), right rostral ACC, and total right frontal gray matter were significant predictors of posttreatment drinking status. Among relapsers, survival analyses showed smokers and individuals with a comorbid medical condition relapsed earlier after treatment. Additionally, a greater frequency of smokers relapsed within 6 months of AUD treatment. CONCLUSIONS: Results reinforce that relapse in AUD is a function of multiple biological, psychiatric, psychological, and psychosocial factors. Effective treatment of depressive disorders and cigarette smoking concurrent with AUD-focused interventions may promote better treatment outcomes.

Analysis of alcohol use disorders from the Nathan Kline Institute-Rockland Sample: Correlation of brain cortical thickness with neuroticism.

BACKGROUND: Although differences in both neuroanatomical measures and personality traits, in particular neuroticism, have been associated with alcohol use disorders (AUD), whether lifetime AUD diagnosis alters the relationship between neuroticism and neuroanatomical structures remains to be determined. METHODS: Data from 65 patients with lifetime AUD diagnoses and 65 healthy comparisons (HC) group-matched on age, sex and race were extracted from the Nathan Kline Institute - Rockland Sample data set. Each subject completed personality trait measures and underwent MRI scanning. Cortical thickness measures at 68 Desikan-Killiany Atlas regions were obtained using FreeSurfer 5.3.0. Regression analyses were performed to identify brain regions at which the neuroticism-cortical thickness relationship was altered by lifetime AUD status. RESULTS: As expected, AUDs had higher neuroticism scores than HCs. Correlations between neuroticism and cortical thickness in the left insula and right fusiform differed significantly across groups. Higher neuroticism score in AUD and the interaction between the insular cortical thickness-neuroticism correlation and AUD status were confirmed in a replication study using the Human Connectome Project data set. CONCLUSIONS: Results confirmed the relationship between neuroticism and AUD and suggests that specific cortical regions, particularly the left insula, represent anatomic substrates underlying this association in AUD.

Neural predictors of alcohol use and psychopathology symptoms in adolescents.

Adolescence is a period marked by increases in risk taking, sensation seeking, and emotion dysregulation. Neurobiological models of adolescent development propose that lagging development in brain regions associated with affect and behavior control compared to regions associated with reward and emotion processing may underlie these behavioral manifestations. Cross-sectional studies have identified several functional brain networks that may contribute to risk for substance use and psychopathology in adolescents. Determining brain structure measures that prospectively predict substance use and psychopathology could refine our understanding of the mechanisms that contribute to these problems, and lead to improved prevention efforts. Participants (N = 265) were healthy substance-naïve adolescents (ages 12-14) who underwent magnetic resonance imaging and then were followed annually for up to 13 years. Cortical thickness and surface area measures for three prefrontal regions (dorsolateral prefrontal cortex, inferior frontal gyrus, and orbitofrontal cortex) and three cortical regions from identified functional networks (anterior cingulate cortex, insular cortex, and parietal cortex) were used to predict subsequent binge drinking, externalizing symptoms, and internalizing symptoms. Thinner dorsolateral prefrontal cortex and inferior frontal cortex in early adolescence predicted more binge drinking and externalizing symptoms, respectively, in late adolescence (ps < .05). Having a family history of alcohol use disorder predicted more subsequent binge drinking and externalizing symptoms. Thinner parietal cortex, but not family history, predicted more subsequent internalizing symptoms (p < .05). This study emphasizes the temporal association between maturation of the salience, inhibition, and executive control networks in early adolescence and late adolescent behavior outcomes. Our findings indicate that developmental variations in these brain regions predate behavioral outcomes of substance use and psychopathology, and may therefore serve as prospective biomarkers of vulnerability.

Elevated Glutamate Levels in the Left Dorsolateral Prefrontal Cortex Are Associated with Higher Cravings for Alcohol.

BACKGROUND: Quantifying craving longitudinally during the course of withdrawal, early abstinence, and relapse is essential for optimal management of alcohol use disorder (AUD). In an effort to identify biological correlates of craving, we used proton magnetic resonance spectroscopy (1H-MRS) to investigate the correlation between craving and glutamate levels in the left dorsolateral prefrontal cortex (LDLPFC) of patients with AUD. METHODS: Participants underwent 1H-MRS of the LDLPFC with 2-dimensional J-resolved (2DJ) averaged PRESS. MRS data were processed with LCModel and cerebrospinal fluid (CSF)-corrected to generate metabolite concentrations. The Penn Alcohol Craving Scale (PACS) and the 30-day time line follow-back (TLFB 30) were used to quantify craving for alcohol and drinking patterns, respectively. RESULTS: There was a statistically significant positive correlation between CSF-corrected glutamate ([Glu]) levels and PACS scores (n = 14; p = 0.005). When PACS scores were dichotomized (< or ≥median = 16), [Glu] levels were significantly higher in the high- versus low-craving group (p = 0.007). In addition, there was a significant negative correlation between CSF-corrected N-acetyl aspartic acid ([NAA]) levels and mean number of drinks per drinking day in the past month (n = 13; TLFB 30; p = 0.012). When mean TLFB 30 was dichotomized (< or ≥median = 7.86), [NAA] levels were significantly lower in subjects that consumed more alcoholic beverages. There was no significant correlation between [Glu] and [NAA] levels with other measures of drinking behavior and or depression symptom severity. CONCLUSIONS: While limited by small sample size, these data suggest that glutamate levels in LDLPFC are associated with alcohol craving intensity in patients with AUD. Further study with larger sample size is needed to replicate this finding and evaluate the merits of glutamate spectroscopy as a biological correlate of alcohol craving intensity and a guide to treatment interventions.

Population-based study of alcoholic cerebellar degeneration: The Atahualpa Project.

BACKGROUND: There are no population studies estimating the burden of alcoholic cerebellar degeneration (ACD). We aimed to assess prevalence and correlates of ACD among chronic alcohol drinkers living in rural Ecuador. METHODS: Characteristics of alcohol intake were evaluated in community-dwelling men aged ≥40years enrolled in the Atahualpa Project. Cerebellar dysfunction evaluation used the Brief Ataxia Rating Scale (BARS). Association between alcohol intake and the BARS was assessed in generalized linear models adjusted for relevant confounders. In subjects who had CT, the relationship between cerebellar atrophy and the BARS was evaluated. RESULTS: Of the 313 men identified during a door-to-door survey, 246 (79%) were enrolled. All admitted continuous drinking for ≥10years. Of these, 41% started drinking below legal age (18years), 72% were current drinkers, and 83% engaged in binge drinking. Average alcohol intake was 330±351g/week. Mean BARS score was 1.4±2 points, with 14.6% (95% C.I.: 10.8%-19.6%) of individuals having ≥4 points and considered to have clinically relevant ACD. The BARS was associated with years of drinking (p=0.036), amount of alcohol intake (p<0.0001), and binge drinking (p=0.026). Predictive models showed significant relationships between BARS score margins and years of drinking and the amount of alcohol intake, independent of other variables. There was no association between cerebellar atrophy on CT and the BARS in 214 participants. CONCLUSIONS: Prevalence of clinically relevant ACD in this population is low. There are both independent and synergistic effects of years of drinking, amount of alcohol intake and binge drinking in the severity of cerebellar dysfunction.

To drink or not to drink: Harmful drinking is associated with hyperactivation of reward areas rather than hypoactivation of control areas in men.

BACKGROUND: The maintenance of harmful alcohol use can be considered a reiterated decision in favour of alcohol in concrete drinking occasions. These decisions are often made despite an intention to quit or reduce alcohol consumption. We tested if a hyperactive reward system and/or an impaired cognitive control system contribute to such unfavourable decision-making. METHODS: In this fMRI study, men with modest to harmful drinking behaviour, which was measured using the Alcohol Use Disorders Identification Test (AUDIT), repeatedly made decisions between alcoholic and nonalcoholic drinks. Based on prior individual ratings, decision pairs were created with an alcoholic decision option considered more desirable but less beneficial by the participant. By correlating AUDIT scores with brain activation during decision-making, we determined areas explicitly related to pro-alcohol decisions in men with greater drinking severity. RESULTS: Thirty-eight men participated in our study. Behaviourally, we found a positive correlation between AUDIT scores and the number of decisions for desired alcoholic drinks compared with beneficial nonalcoholic drinks. The fMRI results show that AUDIT scores were positively associated with activation in areas associated with reward and motivation processing (i.e., ventral striatum, amygdala, medial prefrontal cortex) during decisions favouring a desired, nonbeneficial alcoholic drink. Conversely, we did not find hypoactivation in areas associated with self-control (dorsolateral prefrontal cortex). These effects were not present when participants chose a desired, nonbenefical, nonalcoholic drink. LIMITATIONS: The men participating in our study had to be abstinent and would potentially consume an alcoholic drink at the end of the experiment. Hence, we did not define manifest alcohol dependence as an inclusion criterion and instead focused on less severely affected individuals. CONCLUSION: Our results indicate that with growing drinking severity, decisions for alcoholic drinks are associated with increasing activity in reward-associated neural systems, rather than decreasing activity in self-control-associated systems.

Go/No Go task performance predicts cortical thickness in the caudal inferior frontal gyrus in young adults with and without ADHD.

Response inhibition deficits are widely believed to be at the core of Attention-Deficit Hyperactivity Disorder (ADHD). Several studies have examined neural architectural correlates of ADHD, but research directly examining structural correlates of response inhibition is lacking. Here we examine the relationship between response inhibition as measured by a Go/No Go task, and cortical surface area and thickness of the caudal inferior frontal gyrus (cIFG), a region implicated in functional imaging studies of response inhibition, in a sample of 114 young adults with and without ADHD diagnosed initially during childhood. We used multiple linear regression models to test the hypothesis that Go/No Go performance would be associated with cIFG surface area or thickness. Results showed that poorer Go/No Go performance was associated with thicker cIFG cortex, and this effect was not mediated by ADHD status or history of substance use. However, independent of Go/No Go performance, persistence of ADHD symptoms and more frequent cannabis use were associated with thinner cIFG. Go/No Go performance was not associated with cortical surface area. The association between poor inhibitory functioning and thicker cIFG suggests that maturation of this region may differ in low performing participants. An independent association of persistent ADHD symptoms and frequent cannabis use with thinner cIFG cortex suggests that distinct neural mechanisms within this region may play a role in inhibitory function, broader ADHD symptomatology, and cannabis use. These results contribute to Research Domain Criteria (RDoC) by revealing novel associations between neural architectural phenotypes and basic neurobehavioral processes measured dimensionally.

From mother to child: orbitofrontal cortex gyrification and changes of drinking behaviour during adolescence.

Adolescence is a common time for initiation of alcohol use and alcohol use disorders. Importantly, the neuro-anatomical foundation for later alcohol-related problems may already manifest pre-natally, particularly due to smoking and alcohol consumption during pregnancy. In this context, cortical gyrification is an interesting marker of neuronal development but has not been investigated as a risk factor for adolescent alcohol use. On magnetic resonance imaging scans of 595 14-year-old adolescents from the IMAGEN sample, we computed whole-brain mean curvature indices to predict change in alcohol-related problems over the following 2 years. Change of alcohol use-related problems was significantly predicted from mean curvature in left orbitofrontal cortex (OFC). Less gyrification of OFC was associated with an increase in alcohol use-related problems over the next 2 years. Moreover, lower gyrification in left OFC was related to pre-natal alcohol exposure, whereas maternal smoking during pregnancy had no effect. Current alcohol use-related problems of the biological mother had no effect on offsprings' OFC gyrification or drinking behaviour. The data support the idea that alcohol consumption during pregnancy mediates the development of neuro-anatomical phenotypes, which in turn constitute a risk factor for increasing problems due to alcohol consumption in a vulnerable stage of life. Maternal smoking during pregnancy or current maternal alcohol/nicotine consumption had no significant effect. The OFC mediates behaviours known to be disturbed in addiction, namely impulse control and reward processing. The results stress the importance of pre-natal alcohol exposure for later increases in alcohol use-related problems, mediated by structural brain characteristics.

Imaging of frequent emergency department users with alcohol use disorders.

BACKGROUND: Patients with altered level of consciousness secondary to alcohol use disorders (AUDs) often undergo imaging in the emergency department (ED), although the frequency and yield of this practice over time are unknown. STUDY OBJECTIVES: We describe the use of imaging, the associated ionizing radiation exposure, cumulative costs, and identified acute and chronic injuries and abnormalities among frequent users of the ED with AUDs. METHODS: This is a retrospective case series of individuals identified through an administrative database having 10 or more annual ED visits in 2 consecutive years who were prospectively followed for a third year. International Classification of Diseases, 9(th) Revision, Clinical Modification and Current Procedural Terminology codes were used to select individuals with alcohol-related diagnoses, track imaging procedures, and calculate cost. Diagnoses, imaging results, and radiation exposure per computed tomography (CT) study were abstracted from the medical record. RESULTS: Fifty-one individuals met inclusion criteria and had a total of 1648 imaging studies over the 3-year period. Subjects had a median of 5 (interquartile range [IQR] 2-10) CT scans, 20 (IQR 10-33) radiographs, 28.3 mSv (IQR 8.97-61.71) ionizing radiation, 0.2% (IQR 0.07-0.4) attributable risk of cancer, and $2979 (IQR 1560-5440) in charges using a national rate. The incidence of acute fracture or intracranial head injury was 55%, and 39% of the cohort had a history of moderate or severe traumatic brain injury. CONCLUSION: The remarkable use of imaging and occurrence of injury among these highly vulnerable and frequently encountered individuals compels further study to refine clinical practices through the development of evidence-based, effective interventions.

The effects of acute alcohol administration on the human brain: insights from neuroimaging.

Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'.

Functional neuroimaging studies of alcohol cue reactivity: a quantitative meta-analysis and systematic review.

A comprehensive understanding of the neurobiology of alcohol cue reactivity is critical in identifying the neuropathology of alcohol use disorders (AUD) and developing treatments that may attenuate alcohol craving and reduce relapse risk. Functional neuroimaging studies have identified many brain areas in which alcohol cues elicit activation. However, extant studies have included relatively small numbers of cases, with AUD of varying severity, and have employed many different cue paradigms. We used activation likelihood estimation, a quantitative, coordinate-based meta-analytic method, to analyze the brain areas activated by alcohol-related cues across studies, and to examine whether these areas were differentially activated between cases and controls. Secondarily, we reviewed correlations between behavioral measures and cue-elicited activation, as well as treatment effects on such activation. Data analyzed were from 28 studies of 679 cases and 174 controls. Among cases, alcohol cues elicited robust activation of limbic and prefrontal regions, including ventral striatum, anterior cingulate and ventromedial prefrontal cortex. As compared to controls, cases demonstrated greater activation of parietal and temporal regions, including posterior cingulate, precuneus and superior temporal gyrus. Cue-elicited activation of ventral striatum was most frequently correlated with behavioral measures and most frequently reduced by treatment, but these results were often derived from region-of-interest analyses that interrogated only limbic regions. These findings support long-standing theories of mesolimbic involvement in alcohol cue processing, but suggest that cue-elicited activation of other brain areas may more clearly differentiate cases from controls. Prevention and treatment for AUD should consider interventions that may reduce cue-elicited activation of these areas.

Regional cerebral glucose metabolism and blood flow in a patient with Marchiafava-Bignami disease.

We report functional neuroimaging studies of a 54-year-old man with Marchiafava-Bignami disease (MBD). Glucose metabolic images obtained by [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography showed diffusely reduced whole brain metabolism and strongly decreased metabolism in the frontal and parietal lobes, orbital gyrus, and thalamus. Cerebral perfusion images showed a similarly decreased radioactivity pattern as the metabolic images. Functional neuroimages would be useful for understanding the pathophysiologic processes of MBD.