Auditory P3 in female alcoholics

BACKGROUND: The P3 (P300) has been considered to be a phenotypical marker of the risk for alcoholism. Although reductions in visual P3 in male and female alcoholics have been replicated, studies of auditory target P3 have been inconsistent. Our objective was to study the magnitude of auditory P3 reduction in female alcoholics and to establish the association between P3 reduction and alcoholism while taking into account comorbid depression and psychoactive drug dependence. The characteristics of P3 reduction were further examined by studying the reduction in family history-positive and -negative individuals. METHODS: Auditory target P3s recorded from 61 scalp electrodes in female alcoholics (n = 71) were compared with P3s from female controls (n = 159) ranging in age from 18 to 50 years. The amplitudes and latencies were statistically analyzed, by using repeated-measures ANOVA, in six regional electrode arrays and at representative electrode sites, with age and comorbid depression as covariates. The effects of family density and clinical variables such as depression and drug dependence were also examined with correlation analysis. RESULTS: Alcoholic women had significantly lower P3 amplitudes in all six regions and at midline electrode sites. The reductions were not associated with comorbid depression, as shown by low correlations and similar P3 amplitudes at Pz in female alcoholics with and without depression. The P3 amplitudes in women with a high family density were smaller than those in women with a low family density of alcohol dependence. Drug dependency did not influence P3 amplitude, as shown by similar responses in drug-dependent and non-drug-dependent alcoholic women. CONCLUSIONS: These findings highlight the significance of P3 reductions associated with alcoholism in women, independently of comorbid depression. Family density effects further support the evidence that these findings are heritable. These results suggest that P3 can be considered as a phenotypical marker of vulnerability to alcoholism in women.     

Neuropsychological deficits in sober alcoholics: influences of chronicity and recent alcohol consumption

BACKGROUND: The relationships between severity of neuropsychological (NP) deficits and quantity and duration of alcoholic drinking remain controversial. Eckardt et al. (1998) proposed that NP deficits can be observed only if chronicity of alcohol abuse equals or exceeds 10 years. In this study we tested the hypothesis of Eckardt et al. and reexamined the relationship of NP performance and alcohol consumption. METHODS: One hundred sixty-two alcoholics and 165 controls completed a NP test battery at least 3 weeks after the alcoholics attained sobriety. Chronicity varied from 4 to 9 years for 55 alcoholics and from 10 to 33 years for the remaining 107. RESULTS: Compared to controls, both groups of alcoholics were impaired on the Shipley Vocabulary and Abstraction tests and on two versions of the Digit Symbol test, but there was no difference between the two alcoholic groups on any measure. Regression analyses that controlled for age and education showed that chronicity predicted less than 0.5% of the variance on NP measures. By contrast, a measure of recent alcohol consumption, the Quantity-Frequency Index, contributed significantly (approximately 5% of the variance) to the prediction of alcoholics' NP performance. CONCLUSIONS: These data provide weak support for a dose effect relationship between degree of NP impairment and level of alcoholic drinking in the past 6 months but no evidence for an influence of chronicity.     

Systolic Blood Pressure and Neuropsychological Test Performance of Alcoholics

This study examined resting systolic blood pressure (SBP) as a mediator of neuropsychological (NP) test performance in nonhypertensive alcoholics and controls. A median-split was used to assign alcoholics and controls to low and high SBP groups. Results showed that: (1) When SBP level was not considered, alcoholics only performed worse than controls on the WAIS Comprehension subtest. (2) Alcoholics and controls in the high SBP groups had fewer correct items on the WAIS Comprehension and Raven's, Set I tests than subjects in the low SBP groups. (3) Significant Diagnostic Group by SBP Group interaction was found for the Sentence Writing test. For this test only controls in the High SBP Group did worse than controls in the Low SBP Group. (4) Individual group comparisons for all NP tests showed that alcoholics in the High SBP Group were more impaired than controls in the Low SBP Group on the WAIS Comprehension, Shipley Abstraction Age and Stark Visual-Spatial tests; but alcoholics in the Low SBP Group did not differ from, or outperformed, controls in the High SBP Group on the WAIS Comprehension, Shipley Abstraction Age, Raven's, Set I, and Stark Visual-Spatial tests. These data demonstrate that both alcoholism and high SBP adversely and differentially affect the NP test performance of alcoholics and controls.     

Event-Related Potentials in Alcoholic Men: P3 Amplitude Reflects Family History But Not Alcohol Consumption

Multilead event-related potentials (ERPs), elicited by auditory and visual stimuli requiring a button press response and by a startling noise requiring no response, were recorded from male alcoholics and age-matched male controls (26-60 years old). Single-trial analyses of blink responses to the startling stimuli indicated that alcoholics startle less frequently but with equivalent amplitude as the controls. In contrast, single-trial analyses of P3 indicated that alcoholics generate a P3 as often as controls, but that their individual P3s are smaller. Alcoholics who reported a positive family history of problem drinking had larger startle blink amplitudes and smaller auditory and visual P3s than did alcoholics who reported a negative family history. Hierarchical regression analysis was used to demonstrate that smaller P3s in family history positive alcoholics were independent of lifetime alcohol consumption.     

Alcohol-related ERP changes recorded from different modalities: a topographic analysis

BACKGROUND: There is controversy in the literature regarding the relationship between event-related-potential (ERP) abnormalities in abstinent alcoholics and stimulus-processing modality (i.e., visual versus auditory). The first purpose of this study was to address questions about whether ERP abnormalities observed in alcoholics are modality specific. The second purpose was to employ current source density (CSD) analyses to investigate topographic differences between alcoholics and controls within each modality. METHODS: Data were collected from 30 sober male alcoholics and 39 normal males in a typical auditory oddball task and in a visual oddball paradigm with novel stimuli, with an extensive set of 61 scalp electrodes. Visual and quantitative assessment of CSD maps as well as analyses of variances on both raw and normalized ERP data were performed. RESULTS: Positive findings were limited to the N1 and P3 components. The visual N1 amplitude was significantly smaller in alcoholics than in controls at the parietal region; no significant group differences in N1 were found in the auditory modality. Alcoholics had widespread reductions in P3 amplitudes in both modalities compared with controls, although in the frontal region this effect was partially due to the influence of age. These P3 reductions in alcoholics were statistically more pronounced in the posterior compared with the anterior regions regardless of modality. Topographically, sources in CSD maps were weaker in alcoholics than in controls; in the frontal and central regions, the weakness was more pronounced in the auditory modality but, in parietal and occipital regions, it was more pronounced in the visual modality. CONCLUSIONS: The results suggest that, in abstinent alcoholics, abnormalities in auditory ERPs may be localized to more anterior sources, while abnormalities in visual ERPs may be localized to more posterior sources. ERP topographic features are more sensitive than amplitude measurements in assessing alcoholic-related modality effects.     

Reduced Cerebral Grey Matter Observed in Alcoholics Using Magnetic Resonance Imaging

Twenty-eight chronic alcoholics and 36 age- and sex-matched non-alcoholic controls were examined with magnetic resonance imaging and brain morphometric analyses. Results confirmed large increases in subarachnoid cerebrospinal fluid (CSF) volume and mild ventricular enlargement in the alcoholics and revealed associated volume reductions of localized cortical and subcortical cerebral structures. Volume losses in the diencephalon, the caudate nucleus, dorsolateral frontal and parietal cortex, and mesial temporal lobe structures were the most prominent. Significant correlations between increments in cortical and ventricular CSF and decrements in the volume of cortical and subcortical grey matter were noted. Although there was little evidence for relationships between performance on neuropsychological tests and volume of grey matter structures, significant correlations between some cognitive measures and subcortical and cortical fluid volumes were found. The parallels between this pattern of affected structures and recent neuropathological findings are discussed.     

Delayed P3A in Abstinent Elderly Male Chronic Alcoholics

Significant central nervous system toxicity in frontal brain regions has been demonstrated with chronic alcohol consumption both on autopsy and using neuropsychological testing. This study examined the latency of an objective and reproducible brain event-related potential measure of frontal cortex function in chronic elderly male alcoholics who were abstinent 3 months-2 years, a patient group in whom the central nervous system effects of chronic alcohol abuse are thought to be largest and most persistent. We examined the latency of the P3A event-related potential component, which reflects a frontal maximum orienting response to novel stimuli. Twelve elderly abstinent chronic alcoholic males and 11 elderly male controls were studied in an auditory and a visual paradigm, each of which included target, nontarget, and novel rare nontarget conditions. In both modalities, the P3A response to the novel rare nontarget stimuli was significantly delayed in the chronic alcoholics. P3B delays to the target stimuli were also present in the alcoholics, with the P3A and P3B effects being independent of each other. For both P3A and P3B, the effects were larger and more consistent in the visual compared with the auditory modality. Our conclusions are as follows: (1) both P3A and P3B latency delays are evident in elderly abstinent chronic alcoholics; (2) separate mechanisms are responsible for these effects; (3) these effects are more sensitively detected in the visual versus the auditory modality; and (4) delayed P3A latency may be an objective and reproducible index of the frontal cortex effects of chronic alcohol abuse.     

The Role of Antisocial, Affective, and Childhood Behavioral Characteristics in Alcoholics' Neuropsychological Performance

Chronic alcoholics demonstrate cognitive deficits when compared with nonalcoholics. These deficits are typically attributed to the direct effects of ethanol and its metabolites on the central nervous system (CNS). There are other factors, however, that differentiate alcoholics from controls, such as personality or behavioral characteristics. These factors may affect neuropsychological performance and thus alter the interpretation of alcoholic cognitive deficits as resulting solely from alcohol's toxic effects. To investigate this question, male and female alcoholics and peer nonalcoholic controls were compared on personality, behavioral, and cognitive measures. Alcoholics had greater numbers of antisocial behaviors, childhood behavioral disorder symptoms (CBD), and affective symptomatology, and had poorer neuropsychological performance than controls. The three personality and behavioral factors were positively intercorrelated with each other, and were negatively related to cognitive performance. The CBD factor proved to be the most consistent predictor of neuropsychological performance for both alcoholics and controls, and males and females. While the behavioral factors differentiated alcoholics from controls and predicted performance, significant differences between the groups in cognitive performance still remained when these factors were taken into account.     

Visual P3a in male alcoholics and controls

The goal of this study was to assess the P3a component of event-related potentials in a population of abstinent, chronic alcoholics. A three-stimulus visual oddball paradigm was used to elicit robust P3a components in a large group of well-characterized male alcoholics (n = 44) and controls (n = 28). The task required subjects to make a difficult perceptual discrimination between randomly presented, frequently occurring vertical lines (.80) and infrequent target lines that were tilted 2 degrees to the right of vertical (.10) by only responding with a button press to the target stimuli. A nontarget infrequent horizontal line occurred (.10) randomly to which no response was made. The target stimulus elicited robust late P3b components with a parietal maximum amplitude, and the nontarget stimulus elicited reliable P3a components with a fronto-central maximum amplitude distribution. Group differences in P3a were assessed using repeated measures ANCOVA analyses in five scalp regions. Alcoholic subjects produced smaller P3a amplitudes over the central, parietal, temporal, and occipital areas compared with controls. Current source density analyses supported these findings with extension of the differences between the groups to the frontal region. The results suggest that the P3a may be important in the evaluation of alcoholism and its heritability. Theoretical implications are discussed.     

Increased distractibility by task-irrelevant sound changes in abstinent alcoholics

Background: Chronic alcoholism is accompanied by "frontal" neuropsychological deficits that include an inability to maintain focus of attention. This might be associated with pronounced involuntary attention shifting to task-irrelevant stimulus changes and, thereafter, an impaired reorienting to the relevant task. The neural abnormalities that underlie such deficits in alcoholics were explored with event-related potential (ERP) components that disclosed different phases of detection and orienting to stimulus changes.
Methods: Twenty consecutive abstinent male alcoholics (DSM-IV) and 20 age-matched male controls (healthy social drinkers) were instructed to discriminate equiprobable 100 and 200 msec tones in a reaction-time task (RT) and to ignore occasional, either slight (7%) or wide (70%), frequency changes (hypothesized to increase RT) during an ERP measurement.
Results: In the alcoholics, we found pronounced distractibility, evidenced by a RT lag ( p < 0.01) caused by deviants, that correlated (Spearman ρ= 0.5) with a significantly enhanced ( p < 0.01) amplitude of mismatch negativity (MMN) to deviants. Significantly increased RT lag for trials subsequent to deviants (slight p < 0.001, wide p < 0.05) in the alcoholics suggested impaired reorienting to the relevant task. The MMN enhancement also predicted poorer hit rates in the alcoholics (Spearman ρ= 0.6–0.7). Both the MMN enhancement and pronounced distractibility correlated (Spearman ρ= 0.4) with an early onset of alcoholism.
Conclusions: Attentional deficits in the abstinent alcoholics were indicated by the increased distractibility by irrelevant sound changes. The MMN enhancement suggested that this reflects impaired neural inhibition of involuntary attention shifting, being most pronounced in early-onset alcoholics.     

Isokinetic Muscle Strength and Its Association with Neuropsychological Capacity in Cirrhotic Alcoholics

Alcoholic cirrhotics (n = 49), nonalcoholic cirrhotics (n = 42), and normal controls ( n = 50) were compared on measures of isokinetic muscle strength and neuropsychological capacity. Alcoholic cirrhotics were deficient on measures of eccentric and concentric muscle movements, compared with normal controls but were not different from nonalcoholic cirrhotics. Nor were differences observed between the two cirrhotic groups on neuropsychological tests of cognitive and psychomotor capacity, suggesting that cirrhosis rather than alcoholism per se is responsible for the manifest deficits. Psychomotor capacity correlated negatively with isokinetic strength in cirrhotic subjects. These findings suggest that muscle weakness, due either directly to advanced liver disease or mediated by subclinical hepatic encephalopathy, accounts for a portion of the variance on the neuropsychological test performance of cirrhotic alcoholics.     

Executive dysfunction and clinical outcome in chronic alcoholics

BACKGROUND: The purpose of this study was to investigate which of 12 neuropsychological tests predict alcoholic patients' alcohol-specific and/or alcoholic-nonspecific outcome. Our hypothesis was that the ecologically valid neuropsychological tests that measure executive function are better predictors of alcoholics' functional outcome. METHODS: We administered 12 neuropsychological tests to chronic alcoholics. Included in the tests were tasks of Reaction Time, Symbol Digit Modalities, Figure Position, Digit Span, Block Design, Trail Making, and six subtests of a battery called the Behavioral Assessment of the Dysexecutive Syndrome (BADS). Previous investigators have suggested that the BADS has ecological validity. Twenty-two male alcoholics were compared with 15 nonalcoholic control subjects on these neuropsychological measures 7 weeks after detoxification. Two functional outcome indices, i.e., resumption of drinking and occupation, were evaluated 18 months after discharge. RESULTS: The total profile score and the score on three of the six subtests of the BADS were lower in alcoholics than in nonalcoholic controls. Alcoholics' performance on the BADS predicted alcohol-nonspecific outcome (occupation) but not alcohol-specific (drinking) outcome. In contrast, other neuropsychological tests did not predict either of the two outcome indices. CONCLUSIONS: The BADS total profile score is related to alcohol-nonspecific outcome but not to alcohol-specific outcome.     

Event-related brain potentials in male hypogonadism.

Several studies based on psychometric tests have determined an impairment of cognitive functions in patients with androgen deficiency. However, little is known about event-related potentials (ERPs) alterations in male hypogonadism. We investigated alterations of ERP in male hypogonadism before and 3 months after gonadotropin treatment. ERPs were elicited in 20 untreated male patients with idiopathic hypogonadotropic hypogonadism (IHH) (mean age: 21.1+/-1.4 years) and in a group of 30 male controls with comparable mean age and educational level. ERP recordings were repeated 3 months after hCG/hMG treatment. Untreated hypogonadal patients had longer mean P300 latencies and increased P300 amplitudes when compared to those in controls (321.6+/-18.5 vs 299.3+/-20.1 msec, p=0.0002; 12.15+/-4.47 vs 9.38+/-3.02 microV, p=0.011, respectively). The mean P300 latencies did not change significantly 3 months after gonadotropin treatment, while P300 amplitudes were decreased significantly. P300 latencies did not correlate with serum testosterone and other hormone levels. We conclude that prolongation of P300 latencies and increased P300 amplitudes are associated with male hypogonadism, but P300 prolongation is not reversed 3 months after gonadotropin treatment. These findings confirm the occurrence of cognitive defects in hypogonadal patients and would support the hypothesis that perinatal androgen deficiency contributes to an insufficient cognitive development.     

No Electrocortical Evidence of Automatic Mismatch Dysfunction in Children of Alcoholics

The mismatch negativity (MMN) event-related potential (ERP) component is an automatic, attention-independent brain response to auditory stimulus change, which has been reported to be smaller in alcoholics relative to nonalcoholic controls. To determine whether MMN decrements might be a trait marker of alcoholism that is also present in nonalcoholic individuals at high risk for developing alcoholism, we investigated MMN in 9-to 18-year-old children of alcoholics ( n = 20) and control children ( n = 20) in three different stimulus conditions using a passive auditory oddball paradigm. There were no statistically significant between-group differences observed in amplitude, scalp topography, and peak latency of MMN. These findings, if replicated, suggest that reported MMN decrements in alcoholics most likely represent a state marker, and not a trait marker, of alcoholism. Also, inasmuch as another ERP component, the P300, is attention-dependent and reported to be smaller in children of alcoholics, the present results implicate that deviations in attentive, but not in automatic, information processing are associated with alcoholism vulnerability.     

血管性认知功能障碍神经心理及事件相关电位的研究

目的探讨非痴呆型血管性认知功能障碍(vascular cognitive impairment no dementia,VCIND)患者神经心理学及事件相关电位P300的特点。方法对64例VCIND患者(VCIND组)及42例其他疾病患者(对照组)行事件相关电位P300检查,使用简易智能状态检查量表(MMSE)、画钟测验(CDT)评定入选者认知功能状态,并进行相关分析。结果与对照组比较,VCIND组患者的CDT、MMSE评分明显降低,差异有统计学意义(P0.01),MMSE评分亚项中的时间定向、地点定向、注意/计算力、短程记忆、言语复述、阅读能力、书写能力、图形描画均明显降低,差异有统计学意义(P0.05,P0.01);P300潜伏期明显延长(P0.01),MMSE评分与P300潜伏期呈负相关(r=-0.615,P0.05)。结论事件相关电位P300检测有助于VCIND的早期诊断。     

Family History of Alcoholism Does Not Predict Neuropsychological Performance in Alcoholics

We examined the relationship of history of alcoholism in first-degree relatives to neuropsychological performance of alcoholics abstinent from several weeks to several years. Eighty-four men were assigned to four groups based on "strength" of family history of alcoholism. The groups were: (1) "strong history," a parent plus another first-degree relative positive; (2) "moderate," parent only positive; (3) "weak," nonparent first-degree relative only positive; and (4) "negative," no first-degree relative positive. There were no significant between-group differences in NP performance. In other analyses there were no NP differences between alcoholics classified positive or negative purely on basis of paternal alcoholism, and no differences between subjects who had multigenerational versus unigenerational versus negative familial histories of alcoholism. It is concluded that genetic loading for alcoholism does not significantly affect the NP status of abstinent alcoholic groups equated for education, drinking history, and medical risk.     

Neurocognitive Deficits in Alcoholics and Social Drinkers: A Continuum?

Our research program has investigated neurocognitive deficits in sober alcoholics for several decades. We have shown that both male and female adult alcoholics – compared with peer nonalcoholic controls – have deficits on tests of learning, memory, abstracting, problem-solving, perceptual analysis and synthesis, speed of information processing, and efficiency. The deficits are equivalent to those found in patients with known brain dysfunction of a mild to moderate nature. Attempts to identify factors other than alcoholism to account for these differences have been unsuccessful. The deficits appear to remit slowly over 4 to 5 years. Relapse of recovering alcoholics is predicted by behavioral (e.g., depressive symptoms and neurocognitive performance) and biological measures (e.g., event-related potentials) obtained at the end of treatment. Results of recent studies support the hypothesis of a continuum of neurocognitive deficits ranging from the severe deficits found in Korsakoff patients to moderate deficits found in alcoholics and moderate to mild deficits in heavy social drinkers (more than 21 drinks/week). Individual differences in the presence and magnitude of neurocognitive deficits in social drinkers and alcoholics are hypothesized to be due, in part, to individual differences in vulnerability of the brain to alcohol or its metabolites' toxic effects.     

Interpersonal Problem-Solving in Male and Female Alcoholics

This study compared the performance of alcoholics (18 male, 16 female) with community controls (15 male, 12 female) on the Adaptive Skills Battery (ASB), a test of interpersonal problem-solving. The ASB consists of 30 situations. Fifteen situations require subjects' typical responses and 15, their optimal responses. Male and female alcoholics were inferior to controls in their typical responses [F(1,57) = 45.22, p = 0.0001], but did not differ on the optimal responses (F less than 1). Further analyses indicated that decreased feelings of self-efficacy could not account for the alcoholic deficit. Females were superior to males in the optimal response condition [(F(1,56) = 9.90, p = 0.003]. No significant group x sex interactions were obtained. Performance on the ASB was not correlated with performance on traditional measures of problem-solving. Post-hoc correlational analyses revealed differential patterns between depression scores and performance for alcoholics and controls. These data suggest that (1) female and male alcoholics exhibit similar interpersonal problem-solving deficits, (2) alcoholic self-efficacy expectancies cannot account for the impairment, (3) the ASB appears to assess aspects of problem-solving not typically examined, and (4) the role of depression in alcoholic performance deserves continued empirical evaluation.     

The effects of age on late components of the ERP and reaction time

The effects of age on late component (N100, P200, N200, and P300) event-related potentials (ERP) and reaction time (RT) were investigated in 50 normal subjects, 18 to 70 years of age. A conventional auditory oddball paradigm was employed. An equal number of subjects, as well as an equal number of males and females, were examined in each decade. There were no significant associations found between ERP amplitude and age. A significant positive correlation was found between age and N200/P300 latency. There were no significant effects of age on RT in the overall group. However, females had slower RT and decreased P200 and N200 amplitude as compared with males. Moreover, males had significant correlations between N200 latency and RT, whereas females showed significant correlations between P300 amplitude and RT. ERP/RT effects should be further explicated between gender, as well as across age.     

ERP and RT Delays in Long‐Term Abstinent Alcoholics in Processing of Emotional Facial Expressions During Gender and Emotion Categorization Tasks

Background: There is considerable evidence that alcoholics differ from nonalcoholics in the processing of stimuli that have emotional content. The current study examines those differences that are present in multi‐year abstinent individuals. Methods: We compared reaction time (RT), accuracy, and Event Related Potentials (ERP) measures in long‐term abstinent alcoholics (LTAA, n = 52) with that in age‐ and gender‐comparable nonalcoholic controls (NAC, n = 47). Subjects were presented with male and female faces exhibiting happy, neutral, or sad facial expressions and were instructed to identify the picture gender in 1 task and the emotion being expressed in a subsequent task. Results: LTAA had slower RTs than NAC when instructed to identify emotion, while RT was comparable when identifying gender. There were no differences between groups on task accuracy. P160 latency was increased in LTAA for both tasks compared to NAC, though P160 amplitude did not differ between groups. The P160 effect was about 5 × as large as the RT effect and was statistically independent of the RT effect, while the RT effect was no longer present after removing variance because of the P160 effect. Conclusions: Our data demonstrate slower early processing of emotional facial stimuli in alcoholics that is unresolved by long‐term abstinence and is most sensitively indexed by delayed P160 latency in LTAA.