Alcohol use in young adults associated with cortical gyrification.

BACKGROUND: Young adulthood has the highest rates of alcohol use and high-risk drinking behavior. This period is also a critical neurodevelopmental stage, with neural insults having a profound neurotoxic effect on the brain. Cortical gyrification is thought, in part, to reflect early brain maturation (e.g., hypogyrification in fetal alcohol syndrome). There is also evidence that cortical gyrification is sensitive to later-life events (e.g., fluctuations in malnutrition in young adults). However, no study has examined how alcohol use in young adulthood is associated with cortical gyrification. METHODS: We examined the associations between cortical gyrification with lifetime alcohol use and past year hangover symptoms in young adults (N = 78). RESULTS: Lifetime alcohol use was associated with hypogyria in multiple cortical regions (rs ≤ -.27, ps ≤ .0159; right orbitofrontal, right temporal pole, and left lateral occipital). Further, past year hangover symptoms were associated with hypogyria (rs ≤ -.27, ps ≤ .0034), overlapping with lifetime alcohol use (right orbitofrontal and left lateral occipital). Hangover symptoms were also uniquely associated with hypogyria of other cortical regions (rs ≤ -.30, ps ≤ .0002; right parahippocampal gyrus, left inferior temporal/parahippocampal gyrus and right anterior insula). CONCLUSIONS: Thus, results suggest that young adulthood is a critical period for targeted prevention and intervention, especially for individuals exhibiting heavy alcohol consumption and high-risk drinking behavior.

Is clinician assessment accurate or is routine pan-body CT needed in the stable intoxicated trauma patient?

BACKGROUND: We sought to determine if clinician suspicion of injury was useful in predicting injuries found on pan-body computed tomography (PBCT) in clinically intoxicated patients. METHODS: We prospectively enrolled awake, intoxicated patients with low-energy mechanism of injury. For each of four body regions (head/face, neck, thorax and abdomen/pelvis), clinician suspicion for injury was recorded as "low index" or "more than a low index". The reference standard was the presence of any pre-defined significant finding (SF) on CT. Sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratios were calculated. RESULTS: Enrollment of 103 patients was completed. Sensitivity, specificity, LR+ and LR-for clinician index of suspicion were: 56%, 68%, 1.75, 0.64 (head/face), 50%, 92%, 6.18, 0.54 (neck), 10%, 96%, 2.60, 0.94 (thorax) and 67%, 93%, 9.56, 0.36 (abdomen/pelvis). CONCLUSION: Clinician judgement was most useful to guide need for CT imaging in the neck and abdomen/pelvis. Routine PBCT may not be necessary. SUMMARY: For awake, stable intoxicated patients after falls and assaults, clinician index of suspicion was most useful to guide the need for CT imaging in the neck and abdomen/pelvis. Our findings support selective use of CT if the index of suspicion is low. Routine PBCT may not be necessary.

Violence-related traumatic brain injury.

Objectives: The purpose of this study was to determine the unique characteristics of violence-related traumatic brain injuries (TBI). Methods: All consecutive patients who underwent head CT due to an acute head injury (n = 3023) at the Emergency Department of Tampere University Hospital (Aug 2010-Jul 2012) were included. A detailed retrospective data collection was conducted in relation to demographics, injury-related data, premorbid health, clinical characteristics, and neuroimaging findings. Results: Patients with violence-related TBIs (n = 222) were compared to patients who sustained a TBI by other mechanisms (n = 2801). Statistically significant differences were found on age, gender, prior circulatory system disease, prior mental or behavioral disorders, chronic alcohol abuse, regular substance abuse, regular medication, alcohol intoxication at the time of injury, narcotics intoxication at the time of injury, and acute traumatic lesion on head CT. The groups did not differ on clinical signs of TBI severity. Conclusions: Young adult males with premorbid mental health history and chronic alcohol abuse are most prone to sustain a TBI due to a violence-related incident. Incidents are often related to alcohol intoxication. However, violence was not consistently associated with more severe TBIs than other mechanisms of injury.

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.

Time of Injury and Relation to Alcohol Intoxication in Moderate-to-Severe Traumatic Brain Injury: A Decade-Long Prospective Study.

BACKGROUND: Knowledge about the causes and time of injury for traumatic brain injury (TBI) is important for the development of efficient prevention policies. We aimed to study time of injury and relation to alcohol intoxication for moderate-to-severe TBI in a level 1 trauma center in Norway. METHODS: From October 2004 to September 2014, 493 consecutive patients (≥16 years) with moderate (Glasgow Coma Scale [GCS] score 9-13) and severe TBI (GCS score 3-8) were prospectively included in the Trondheim TBI Study (222 patients with moderate and 270 patients with severe TBI). RESULTS: Mean age was 47 years (standard deviation 21 years). Positive blood alcohol concentration (BAC) was found in 29%, and median BAC was 41.5 mmol/L (interquartile range 28.7-54.3), equal to 1.91‰. Admissions were more frequent on Saturdays (relative risk [RR] 2.67, 95% confidence interval [CI] 1.87-3.80) and Sundays (RR 2.10, 95% CI 1.45-3.03) compared with Mondays, and positive BAC was more common on weekends than weekdays (43% vs. 16%). Furthermore, admissions were more frequent in June (RR 2.26, 95% CI 1.44-3.55), July (RR 2.07, 95% CI 1.31-3.28), and December (RR 2.07, 95% CI 1.31-3.28) compared with January. The number of patients with positive BAC was greatest in December (RR 5.75, 95% CI 1.99-16.63), and 70% of these were caused by falls. CONCLUSIONS: Our findings demonstrate that moderate-to-severe TBI admissions display a clear weekly and seasonal variation and that alcohol is an important modifiable risk factor for moderate-to-severe TBI.

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 (conditioned stimulus; 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 2, 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.

Clinical Outcome of Epidural Hematoma Treated Surgically in the Era of Modern Resuscitation and Trauma Care.

OBJECTIVE: Patients from contemporary populations with traumatic brain injury (TBI) resulting from epidural hematoma (EDH) may differ regarding age, comorbidities, and coagulation status. We therefore analyzed predictors for the clinical outcome of patients with EDH treated surgically regarding modern approaches to resuscitation and trauma care. METHODS: A retrospective observational analysis was carried out. All patients included underwent surgery. The indication for surgery followed international guidelines. Retrospective data evaluation considered data reflecting the effectiveness of trauma care, baseline characteristics, and radiologic findings. In this analysis, we divided patients into 2 groups (isolated EDH vs. EDH plus other intracranial traumatic injuries). The neurologic outcome was assessed at discharge using the Glasgow Outcome Scale. RESULTS: Two hundred and sixty-eight patients with epidural hematoma, of whom 131 underwent surgery, were treated between January 1997 and December 2012 in our level-1 trauma center. The overall mortality was 6.8% (mortality for patients with Glasgow Outcome Scale score <9, 15%). As expected, factors with a highly significant (P < 0.01) impact on outcome were concomitant with other intracranial injuries, brain midline shift, and higher Injury Severity Score. Alcohol intoxication was a significant (P < 0.05) predictor of an unfavorable outcome. Anticoagulants and Glasgow Coma Scale score at admission had no significant impact on the outcome. CONCLUSIONS: The outcome for EDH is more favorable than decades ago, most probably reflecting a well-established chain of trauma care. Therefore, EDH is a treatable disease with a high probability of a favorable outcome.

Effects of the Acute and Chronic Ethanol Intoxication on Acetate Metabolism and Kinetics in the Rat Brain.

BACKGROUND: Ethanol (EtOH) intoxication inhibits glucose transport and decreases overall brain glucose metabolism; however, humans with long-term EtOH consumption were found to have a significant increase in [1-11 C]-acetate uptake in the brain. The relationship between the cause and effect of [1-11 C]-acetate kinetics and acute/chronic EtOH intoxication, however, is still unclear. METHODS: [1-11 C]-acetate positron emission tomography (PET) with dynamic measurement of K1 and k2 rate constants was used to investigate the changes in acetate metabolism in different brain regions of rats with acute or chronic EtOH intoxication. RESULTS: PET imaging demonstrated decreased [1-11 C]-acetate uptake in rat brain with acute EtOH intoxication, but this increased with chronic EtOH intoxication. Tracer uptake rate constant K1 and clearance rate constant k2 were decreased in acutely intoxicated rats. No significant change was noted in K1 and k2 in chronic EtOH intoxication, although 6 of 7 brain regions showed slightly higher k2 than baseline. These results indicate that acute EtOH intoxication accelerated acetate transport and metabolism in the rat brain, whereas chronic EtOH intoxication status showed no significant effect. CONCLUSIONS: In vivo PET study confirmed the modulatory role of EtOH, administered acutely or chronically, in [1-11 C]-acetate kinetics and metabolism in the rat brain. Acute EtOH intoxication may inhibit the transport and metabolism of acetate in the brain, whereas chronic EtOH exposure may lead to the adaptation of the rat brain to EtOH in acetate utilization. [1-11 C]-acetate PET imaging is a feasible approach to study the effect of EtOH on acetate metabolism in rat brain.

Urinary bladder volume measured in whole-body CT scans is a useful marker for alcohol intoxication.

PURPOSE: The aim of this study was to investigate whether urinary bladder volume (UBV) and blood alcohol concentration (BAC) correlate in a cohort of emergency trauma patients. Furthermore, the feasibility of semi-automated 3D-CT volumetry for urinary bladder volumetry calculations in whole-body CT examinations was elucidated. MATERIAL AND METHODS: Whole-body CT scans of 831 individuals treated in the emergency department with suspected multiple injuries were included. Manual 3D-CT volumetry of the urinary bladder was performed and the mechanism of injury, patient demographics, BAC, serum creatinine, and hematocrit were retrospectively analyzed. Semi-automated calculation of UBV was performed in 30 patients. Statistical analysis included ROC analysis to calculate cut-off values, sensitivity, and specificity. The Mann-Whitney test and Spearman's correlation coefficient were used to detect significant correlations between UBV and BAC. RESULTS: Manual 3D-CT volumetry showed maximum sensitivity and specificity with a cut-off value for urinary bladder volume of 416.3 mL (sensitivity 50.9%; specificity 76.3%; AUC 0.678). With a cut-off value of 4.2 mL/µmol for the creatinine quotient (quotient of serum creatinine and UBV), the sensitivity was 64.2% (specificity 67.0%; AUC 0.681). Semi-automated 3D-CT volumetry resulted in lower UBV values compared to those obtained with manual 3D-CT volumetry. CONCLUSION: Semi-automated 3D-CT volumetry is a reliable method to quantify UBV. UBV correlates with positive BAC results. A UBV above 416 mL seen on an initial whole-body CT must raise suspicion of alcohol intoxication. The creatinine quotient is an even more sensitive and specific parameter for the detection of alcohol intoxication.

Diffusion Kurtosis Imaging Detects Microstructural Changes in the Brain after Acute Alcohol Intoxication in Rats.

The aim of this study was to test the technical feasibility of diffusion kurtosis imaging (DKI) in the brain after acute alcohol intoxication. Diffusion tensor imaging (DTI) and DKI during 7.0 T MRI were performed in the frontal lobe and thalamus before and 30 min, 2 h, and 6 h after ethyl alcohol administration. Compared with controls, mean kurtosis values of the frontal lobe and thalamus first decreased by 44% and 38% within 30 min (p < 0.01 all) and then increased by 14% and 46% at 2 h (frontal lobe, p > 0.05; thalamus, p < 0.01) and by 29% and 68% at 6 h (frontal lobe, p < 0.05; thalamus, p < 0.01) after acute intake. Mean diffusivity decreased significantly in both the frontal lobe and the thalamus at various stages. However, fractional anisotropy decreased only in the frontal lobe, with no detectable change in the thalamus. This demonstrates that DKI possesses sufficient sensitivity for tracking pathophysiological changes at various stages associated with acute alcohol intoxication and may provide additional information that may be missed by conventional DTI parameters.

Alcohol-Related Visits to US Emergency Departments, 2001-2011.

AIMS: Alcohol intoxication is a source of significant illness and injury commonly resulting in emergency department (ED) visits. We characterize recent trends in alcohol-related visits to US EDs using nationally representative data. METHODS: We conducted a retrospective review of data on national ED visits among patients aged 18 years or older with alcohol intoxication between 2001 and 2011 using the National Hospital Ambulatory Medical Care Survey (NHAMCS). Demographic and resource utilization trends in alcohol-related visits were examined. We also assessed ED length of stay (LOS) across the study period, as well as the total hours spent on ED care for alcohol-related complaints. RESULTS: Between 2001-2002 and 2010-2011, alcohol-related visits increased from 2,459,748 to 3,856,346 (P = 0.049). Utilization of resources such as laboratory tests, medications and radiography increased, with the use of advanced imaging (i.e. computed tomography and magnetic resonance imaging) increasing 232.2% (P < 0.001) from 2001-2002 to 2010-2011. Overall LOS increased 16.1% (P = 0.028), while LOS among patients admitted to the hospital increased 24.9% (P = 0.076). Total alcohol-related hours spent in EDs nationwide increased from 5.6 million in 2001 to 11.6 million in 2011, an increase of 108.5% (P < 0.001) compared with an increase in overall ED hours of 54.0% (P < 0.001). CONCLUSION: Alcohol-related ED visits are increasing at a greater rate than overall ED visits and represent a growing burden on hospital resources.

Mind the gap: a case of severe methanol intoxication.

We report a case of a 37-year-old woman with non-insulin-dependent diabetes on sitagliptin, an alcohol abuser who was brought unresponsive to the emergency department of our hospital. On arrival, the patient was intubated and mechanically ventilated due to a low Glasgow Coma score of 3/15. Initial laboratory testing identified profound high anion gap metabolic acidosis. Owing to the dubious circumstances and the depth of acidosis, methanol and ethylene glycol intoxication was suspected. Further evaluation revealed a significantly increased serum osmolal gap. Pending volatile compound screen, fomepizole was started and urgent haemodialysis undertaken. Subsequent brain MRI identified changes in putamen of bilateral basal ganglia, suggestive of methanol intoxication. The patient was later found to have an initial methanol level of 237 mg/dL. She was successfully extubated on day 2 of hospitalisation, with residual cognitive and visual deficits.

Beer self-administration provokes lateralized nucleus accumbens dopamine release in male heavy drinkers.

RATIONALE: Although striatal dopamine (DA) is important in alcohol abuse, the nature of DA release during actual alcohol drinking is unclear, since drinking includes self-administration of both conditioned flavor stimuli (CS) of the alcoholic beverage and subsequent intoxication, the unconditioned stimulus (US). OBJECTIVES: Here, we used a novel self-administration analog to distinguish nucleus accumbens (NAcc) DA responses specific to the CS and US. METHODS: Right-handed male heavy drinkers (n = 26) received three positron emission tomography (PET) scans with the D2/D3 radioligand [(11)C]raclopride (RAC) and performed a pseudo self-administration task that separately administered a flavor CS of either a habitually consumed beer or the appetitive control Gatorade®, concomitant with the US of ethanol intoxication (0.06 g/dL intravenous (IV) administration) or IV saline. Scan conditions were Gatorade flavor + saline (Gat&Sal), Gatorade flavor + ethanol (Gat&Eth), and beer flavor + ethanol (Beer&Eth). RESULTS: Ethanol (US) reduced RAC binding (inferring DA release) in the left (L) NAcc [Gat&Sal > Gat&Eth]. Beer flavor (CS) increased DA in the right (R) NAcc [Gat&Eth > Beer&Eth]. The combination of beer flavor and ethanol (CS + US), [Gat&Sal > Beer&Eth], induced DA release in bilateral NAcc. Self-reported intoxication during scanning correlated with L NAcc DA release. Relative to saline, infusion of ethanol increased alcoholic drink wanting. CONCLUSIONS: Our findings suggest lateralized DA function in the NAcc, with L NAcc DA release most reflecting intoxication, R NAcc DA release most reflecting the flavor CS, and the conjoint CS + US producing a bilateral NAcc response.

Early detection of left ventricular systolic dysfunction using two-dimensional speckle tracking strain evaluation in healthy subjects after acute alcohol intoxication.

OBJECTIVES: We evaluated the ability of two-dimensional speckle tracking strain echocardiography to detect left ventricular (LV) systolic dysfunction as compared with LV ejection fraction (EF) in healthy subjects following acute alcohol intoxication. METHODS AND RESULTS: In total, 25 healthy subjects were investigated using echocardiography 4-6 hours after the onset of alcohol intoxication at a regional festive gathering, and then compared to 23 healthy control subjects without alcohol consumption. Heart rate, blood pressure, blood alcohol level, LV volumes, EF, shortening fraction, E/A ratio, as well as global longitudinal strain (LS) were recorded. Mean blood alcohol level was 1.3 ± 0.3 g.L(-1) . Mean systolic blood pressure and heart rate were slightly increased in the alcohol group compared to controls (147.5 ± 21.8 mmHg vs 127.0 ± 9.9 mmHg, P = 0.003, and 79.7 ± 10.7 bpm vs 70.6 ± 7.6 bpm, P < 0.001, respectively). While there was no significant difference in terms of LVEF (62.9 ± 4.4% vs 64.8 ± 5.9%, P = 0.18) or shortening fraction (34.7 ± 5.9% vs 36.0 ± 4.3%, P = 0.54), global LS was significantly impaired (-17.8 ± 2.0% vs -21.2 ± 1.8%, P < 0.001). In addition, subjects who consumed alcohol had increased LV end-diastolic (108.3 ± 20.1 mL vs 95.5 ± 14.6 mL, P = 0.037) and end-systolic volumes (41.6 ± 11.4 mL vs 33.7 ± 6.9 mL, P = 0.024), along with depressed aortic time-velocity integral (19.9 ± 3.2 mL vs 21.9 ± 2.5 mL, P = 0.034). According to multivariate linear regression analyses, blood alcohol level was the only factor significantly associated with global LS (ß=-3.6 ± 1.0, P = 0.005). CONCLUSION: Alcohol intoxication around festive days induces acute LV contraction abnormalities, which may be detected using global LS by speckle tracking at an earlier stage and more accurately than LVEF decreases.

Moderate doses of alcohol disrupt the functional organization of the human brain.

Acute alcohol administration decreases overall brain glucose metabolism, which serves as a marker of brain activity. The behavioral effects of alcohol, however, are likely to reflect not only changes in regional brain activity but also the patterns of brain functional organization. Here we assessed the effects of a moderate dose of alcohol on the patterns of brain activity and cerebral differentiation. We measured brain glucose metabolism in 20 healthy controls with positron emission tomography and fluorodeoxyglucose during baseline and during alcohol intoxication (0.75 g/kg). We used the coefficient of variation (CV) to assess changes in brain metabolic homogeneity, which we used as a marker for cerebral differentiation. We found that alcohol decreased the CV in the brain and this effect was independent of the decrements in overall glucose metabolism. Our study revealed marked disruption in brain activity during alcohol intoxication including decreases in global and regional brain differentiation, a loss of right versus left brain metabolic laterality and a shift in the predominance of activity from cortical to limbic brain regions. The widespread nature of the changes induced by a moderate dose of alcohol is likely to contribute to the marked disruption of alcohol on behavior, mood, cognition and motor activity.

[About the so-called "Geserick sign"]. / Zur klinischen Bedeutung des "Geserick-Zeichens".

Geserick et al. were the first who reported about fractures of the medial and basal wall of the orbita, originating from blunt occipital trauma leading to consecutive contrecoup lesions of the bulbus/orbita complex. A case history with (survived) occipital craniocerebral trauma and monocle hematoma (48-year-old drunken homeless person, found unconscious in a small street of the redlight quarter) is presented. The question was whether the injuries were caused by falling or inflicted by an assailant.

Identifying spatial relationships in neural processing using a multiple classification approach.

The application of statistical classification methods to in vivo functional neuroimaging data makes it possible to explore spatial patterns in task-related changes in neural processing. Cluster analysis is one group of descriptive statistical procedures that can assist in identifying classes of brain regions that exhibit similar task-related functionality. In practice, a limitation of cluster analysis is that the performances of clustering algorithms rely on unknown characteristics of the data, making it difficult to determine which procedure best suits a particular analysis. We present a multiple classification approach that incorporates numerous algorithms, evaluates the associated classifications, and either selects a plausible partition relative to the others considered or pools the results from the numerous methods. The multiple classification approach utilizes a new performance criterion, called the relative information (RI) measure, to evaluate the quality of the candidate partitions and as the basis for producing a composite classification image. Employing multiple classifications, rather than a single algorithm, our methodology increases the chance of detecting the functional relationships within the data and, therefore, produces more reliable results. We apply our methodology to a PET study to explore spatial relationships in measured brain function associated with increasing blood alcohol concentration levels, and we perform a simulation study to evaluate the performance of RI.

Regional brain metabolism during alcohol intoxication.

BACKGROUND: Ethanol has a broad range of actions on many neurotransmitter systems. The depressant actions of ethanol in the brain are related in part to facilitation of gamma-aminobutyric acid (GABA) neurotransmission via its interaction with the benzodiazepine/GABA receptor complex. The purpose of this study was to evaluate the effects of ethanol on regional brain metabolism in 10 healthy right-handed men. The results were compared with those we previously published in a different group of 16 normal male subjects who received intravenous lorazepam, a benzodiazepine drug that also enhances GABA neurotransmission. METHODS: The subjects were scanned with positron emission tomography and [F-18] fluorodeoxyglucose twice: 40 min after the end of placebo (diet soda) or ethanol (0.75 g/kg) oral administration. Image data sets were analyzed by using both the region of interest and the statistical parametric mapping (SPM) approach. SPM was used to generate a difference image between baseline and ethanol, which we compared to the difference image between baseline and lorazepam (30 microg/kg). RESULTS: Ethanol significantly increased self-reports of "high" (p < or = 0.0001), dizziness (p < or = 0.004), and intoxication (p < or = 0.0001). Ethanol significantly decreased whole brain (-25 +/- 6%, p < or = 0.0001) and regional metabolism. Normalization of the regional measures by whole brain metabolism (relative measures) showed that ethanol decreased relative metabolic activity in occipital cortex (-4.9 +/- 4.1%, p < or = 0.006), whereas it increased relative metabolic act in left temporal cortex (+3.5 +/- 2.9%, p < or = 0.006) and left basal ganglia (+9 +/- 6.3%, p < or = 0.0009). SPM analyses revealed the same pattern of responses as the relative measures, showing decreases in occipital cortex and increases in left temporal cortex. Comparison of the relative measures and the SPM analyses obtained with lorazepam data revealed a similar pattern of effects, with relative decreases in occipital cortex (-7.8 +/- 4.8%) and relative increases in left temporal cortex (+3.8 +/- 5.7%). Lorazepam, but not ethanol, also decreased thalamic metabolism (-11.2 +/- 7.2%). CONCLUSIONS: These results support similar though not identical mechanisms for the effects of alcohol and benzodiazepines on brain glucose metabolism. The fact that lorazepam, but not alcohol, reduced thalamic metabolism, an effect associated with sleepiness, could explain the higher sedative effects of lorazepam than of alcohol.

Cocaine abusers show a blunted response to alcohol intoxication in limbic brain regions.

UNLABELLED: Cocaine and alcohol are frequently used simultaneously and this combination is associated with enhanced toxicity. We recently showed that active cocaine abusers have a markedly enhanced sensitivity to benzodiazepines. Because both benzodiazepines and alcohol facilitate GABAergic neurotransmission we questioned whether cocaine abusers would also have an enhanced sensitivity to alcohol that could contribute to the toxicity. In this study we compared the effects of alcohol (0.75 g/kg) on regional brain glucose metabolism between cocaine abusers (n = 9) and controls (n = 10) using PET and FDG. Alcohol significantly decreased whole brain metabolism and this effect was greater in controls (26+/-6%) than in abusers (17+/-10%) even though they had equivalent levels of alcohol in plasma. Analysis of the regional measures showed that cocaine abusers had a blunted response to alcohol in limbic regions, cingulate gyrus, medial frontal and orbitofrontal cortices. CONCLUSIONS: The blunted response to alcohol in cocaine abusers contrasts with their enhanced sensitivity to benzodiazepines suggesting that targets other than GABA-benzodiazepine receptors are involved in the blunted sensitivity to alcohol and that the toxicity from combined cocaine-alcohol use is not due to an enhanced sensitivity to alcohol in cocaine abusers. The blunted response to alcohol in limbic regions and in cortical regions connected to limbic areas could result from a decreased sensitivity of reward circuits in cocaine abusers.