Lance O. Bauer

Alcohol cue reactivity, negative-mood reactivity, and relapse in treated alcoholic men

Relapsed alcoholic individuals frequently report that negative emotional states trigger their return to drinking. A parametric laboratory study was conducted to assess the separate and combined effects of exposure to alcohol-related stimuli and induced negative moods in abstinent alcoholic persons. The authors also sought to determine if reactivity to alcohol cues or reactivity to negative mood induction predicted relapse soon after treatment. Men with alcoholism (N = 50) undergoing inpatient treatment participated in a guided imagery procedure designed to induce negative moods and were then exposed to either their favorite alcoholic beverage or to spring water. Results indicated that both alcoholic beverage presentation and negative affect imagery led to increased subjective reporting of desire to drink. These effects were additive but not multiplicative (i.e., the interaction of mood state with beverage type was not significant). Reported urge to drink during the trial that combined negative mood imagery with alcoholic beverage exposure predicted time to relapse after inpatient discharge.

Linkage disequilibrium between the beta frequency of the human EEG and a GABAA receptor gene locus.

Human brain oscillations represent important features of information processing and are highly heritable. A common feature of beta oscillations (13–28 Hz) is the critical involvement of networks of inhibitory interneurons as pacemakers, gated by γ-aminobutyric acid type A (GABAA) action. Advances in molecular and statistical genetics permit examination of quantitative traits such as the beta frequency of the human electroencephalogram in conjunction with DNA markers. We report a significant linkage and linkage disequilibrium between beta frequency and a set of GABAA receptor genes. Uncovering the genes influencing brain oscillations provides a better understanding of the neural function involved in information processing.

Beta power in the EEG of alcoholics

BACKGROUND In this study, the magnitude and spatial distribution of beta power in the resting electroencephalogram (EEG) were examined to address the possibility of an excitation-inhibition imbalance in the central nervous system of alcoholics. METHODS Log transformed absolute power in the Beta 1 (12.5-16 Hz), Beta 2 (16.5-20 Hz), and Beta 3 (20.5-28 Hz) bands in the eyes-closed EEG of 307 alcohol-dependent subjects and 307 unaffected age- and gender-matched control subjects were compared using a multivariate repeated measures design. Effect of gender, age, and drinking variables was examined separately. RESULTS Increased Beta 1 (12.5-16 Hz) and Beta 2 (16.5-20 Hz) absolute power was observed in alcohol-dependent subjects at all loci over the scalp. The increase was most prominent in the central region. Increased Beta 3 (20.5-28 Hz) power was frontal in the alcoholics. Age and clinical variables did not influence the increase. Male alcoholics had significantly higher beta power in all three bands. In female alcoholics the increase did not reach statistical significance. CONCLUSIONS Beta power in all three bands of resting EEG is elevated in alcoholics. This feature is more prominent in male alcoholics. The increased beta power in the resting EEG may be an electrophysiological index of the imbalance in the excitation-inhibition homeostasis in the cortex.

Quantitative trait loci analysis of human event-related brain potentials: P3 voltage

The P3 event-related brain potential (ERP) is a positive-going voltage change of scalp-recorded electroencephalographic activity that occurs between 300-500 ms after stimulus onset. It is elicited when a stimulus is perceived, memory operations are engaged, and attentional resources are allocated toward its processing. Because this ERP component reflects fundamental cognitive processing, it has found wide utility as an assessment of human mental function in basic and clinical studies. In particular, P3 attributes are heritable and have demonstrated considerable promise as a means to identify individuals at genetic risk for alcoholism. We have conducted a quantitative linkage analysis on a large sample from families with a high density of affected individuals. The analyses suggest that several regions of the human genome contain genetic loci related to the generation of the P3 component of the ERP, which are possible candidate loci underlying the functional organization of human neuroelectric activity.

P300 decrements in teenagers with conduct problems: implications for substance abuse risk and brain development

BACKGROUND The purpose of this study was to evaluate the effects of conduct disorder problems, family history, gender, and age on P300 electroencephalographic potentials in teenagers. METHODS The 257 subjects, aged 15 to 20 years, were assigned to one of twelve groups defined by the crossing of three between-subjects factors: 1) gender; 2) ranking below vs above the median number of conduct disorder problems for their gender; and 3) no family history of alcohol or drug dependence vs familial alcohol dependence vs familial heroin or cocaine dependence. RESULTS P300 amplitude was smaller among subjects reporting a greater number of conduct problems prior to age 15 vs those reporting fewer problems of this type. No family history effects were detected. Another set of analyses examined the effects of age on conduct problem-related decrements in P300. Smaller P300 amplitudes within the posterior scalp region were associated with a greater number of conduct problems among subjects younger than 16.5 years. Among subjects greater than this median age, the effects of these behaviors were only apparent over the frontal scalp. CONCLUSIONS It is concluded that P300 decrements previously attributed to familial alcohol/substance dependence might be the result of a coincident increase in the prevalence of conduct disorder problems. The analysis of age interactions suggests that P300 amplitude decrements observed at posterior scalp sites among subjects with more conduct problems disappear at approximately 16 to 17 years of age. After that age, decrements in frontal brain function may begin to emerge in the subset of conduct problem subjects who are at risk for developing adult antisocial personality disorder.

Frontal P300 decrements, alcohol dependence, and antisocial personality disorder.

BACKGROUND The purpose of this study was to examine the independent and interactive effects of alcohol dependence, antisocial personality disorder (ASPD), and age on brain function. METHODS P300 event-related potentials (ERPs) were recorded from 393 alcohol-dependent and 170 non-alcohol-dependent adults while they performed a visual oddball task. The two subject groups were further subdivided based upon age and the presence/absence of ASPD. RESULTS Alcohol dependence was associated with a significant P300 amplitude decrement at anterior electrode sites only. Antisocial personality disorder was also associated with reduced P300 amplitudes at anterior electrode sites; however, the effects were only significant among subjects 30 years of age or younger. To validate this association between ASPD and P300 amplitude a correlational analysis was performed; the correlation between anterior P300 amplitude and the total number of childhood conduct disorder and adult ASPD symptoms was significant. CONCLUSIONS The P300 amplitude decrement found at anterior electrode sites among subjects with ASPD is consistent with the results of numerous ERP, neuroimaging, or neuropsychologic studies of anterior brain function. Our study is unique in suggesting that the effects of ASPD on anterior brain function are best detected during early adulthood. The study also suggests that the detrimental neurophysiologic effects of alcohol dependence predominantly involve the anterior brain.

Predicting Relapse to Alcohol and Drug Abuse via Quantitative Electroencephalography

A sensitive and specific screening test that would identify the subset of substance-abusing patients at highest risk for relapse would constitute an important advance for treatment planning. This study examined the relative value of quantitative electroencephalography as a rapid, inexpensive, and noninvasive measure of relapse potential. The subjects were 107 substance-dependent patients enrolled in residential treatment programs. All were unmedicated and free of the complicating effects of major medical and neurological disorders. Structured clinical interview data and a 5-minute recording of the resting, eyes-closed electroencephalogram were obtained after patients had verifiably maintained abstinence for 1–5 months. Patients were then monitored for relapse or successful abstinence by research staff for an ensuing 6-month period. ANCOVAs of EEG power spectral density within pre-defined frequency bands revealed an enhanced amount of high frequency (19.5–39.8 Hz) β activity among the 48 patients who later relapsed compared to both 59 patients who maintained abstinence and 22 additional subjects with no history of substance dependence. Importantly, in subsequent logistic regression analyses, fast β power was found to be superior to severity of illness, depression level, and childhood conduct problems in predicting relapse. With fast β power as the sole predictor, the sensitivity, specificity, and positive and negative predictive value parameters for discriminating outcomes were 0.61, 0.85, 0.75, and 0.74, respectively. Additional ANCOVAs revealed that the EEG difference between relapse-prone and abstinence-prone groups was related to the interaction of two premorbid factors, viz., childhood Conduct Disorder and paternal alcoholism. The enhancement of fast β electroencephalographic activity in patients who will later relapse most likely originates from a premorbid and subtle dysfunction involving frontal brain regions.

Linkage and linkage disequilibrium mapping of ERP and EEG phenotypes.

Linkage analyses of highly heritable electrophysiological phenotypes (EEG, ERP) that can potentially identify individuals at risk for alcoholism were performed on a large sample of families with a high density of alcohol dependence as part of the Collaborative Study on the Genetics of Alcoholism (COGA); these genetic findings are summarized. Quantitative trait loci (QTLs) were identified for several ERP characteristics (P300, N100, N400) and for the beta frequencies of the EEG where we report linkage and linkage disequilibrium at a GABA(A) receptor gene on chromosome 4. Genetic analyses of ERPs suggest that several regions of the human genome contain genetic loci related to the generation of N100, N400 and P300, which are possible candidate loci underlying the functional organization of human neuroelectric activity. The advent of genomics and proteomics and a fuller understanding of gene regulation, will open new horizons on the critical electrical events so essential for human brain function.

Frontal P300 decrements, childhood conduct disorder, family history, and the prediction of relapse among abstinent cocaine abusers.

P300 event related brain potentials were studied in 49 cocaine dependent patients, abstinent for 1-5 months, and 20 healthy, non-drug-dependent controls. Patients were assigned to one of two subgroups based on the presence/absence of a DSM-IIIR diagnosis of antisocial personality disorder (ASPD). Analyses of P300s recorded during a visual selective attention task revealed reduced amplitudes at frontal electrode sites among patients with ASPD, relative to the ASPD negative patient and control groups. The frontal P300 decrement was significantly correlated with the number of childhood conduct disorder symptoms, but not with the presence/absence of a family history of alcoholism. A secondary analysis examined the relationship between P300 amplitude among cocaine dependent patients and their future behavior, i.e., relapse versus continued abstinence. Discriminant function analysis revealed that P300 amplitude alone accurately identified 70.6% of the patients who later relapsed, and 53.3% of the patients who did not.

Quantitative electroencephalographic differences associated with alcohol, cocaine, heroin and dual-substance dependence

Resting electroencephalographic (EEG) activity was evaluated in 88 drug-dependent inpatients, abstinent 1-6 months, and 14 non-drug-dependent controls. The patients were assigned to one of four groups using DSM-III-R criteria: alcohol-dependent (n = 12), cocaine-dependent (n = 21), heroin-dependent (n = 19), or dual alcohol- and cocaine-dependent (n = 36). The analysis revealed significant differences between the five subject groups in high- and low-frequency beta power, but not in other frequency bands. Beta power was significantly greater in the alcohol-dependent and cocaine-dependent groups relative to non-drug-dependent controls. These group differences did not correlate with quantity/frequency measures of alcohol or cocaine use, family history, personality, mood, or demographic characteristics. The similar increases in EEG beta found in alcohol- and cocaine-dependent patients do not suggest a direct drug effect. Rather, they suggest the existence of a common premorbid variable or a complex interaction between alcohol/drug use and other variables.