Hand Movement Speed and Accuracy in Detoxified Alcoholics

Detoxified alcoholics (n = 192) were found to be 9.3% slower than age-matched controls (n = 112) with regard to the composite speed (movement time, MT) with which they were able to strike targets of various sizes and distances with a hand-held stylus at onset of a light stimulus (Fitts's Task). Females (n = 102) were 8% slower than males (n = 202), and blacks (n = 103) about 15.6% slower than whites (n = 201). Gender was the only significant factor with regard to errors (target misses), with women committing 28% fewer errors than men. Women, in contrast to men, appear to trade speed for accuracy in this task. Favorable socioeconomic/medical status and target misses were directly related to movement speed. Thus, when the MT data were corrected for lifestyle variables, the significance of the alcohol effects on MT disappeared, but gender differences persisted. The alcohol effect became statistically significant, the ethnic group differences remained statistically significant, and the gender effect became insignificant when MT scores were corrected for accuracy of performance (target misses). The slope of the linear function relating MT to target difficulty was similar for all subgroups. Prior knowledge of the direction of movement was found to affect MT performance more in white than in black subjects. With regard to reaction times, ethnic group and alcohol use effects remained statistically significant after corrections for lifestyle and errors were made, with values for blacks about 5% slower than values for whites, and values for alcoholics about 4.6% slower than those for controls. Prior knowledge of the direction of movement significantly improved (shortened) reaction time in all subgroups (14%-19%).     

Motor functioning and alcohol dependence

BACKGROUND: Autopsy and neuroimaging research in stably abstinent alcoholics illuminated structural and functional abnormalities in brain areas that organize and coordinate motor functioning. Researchers that used behavioural tasks to measure motor functioning found that abstinent alcoholics perform worse than healthy controls. These researchers however did not analyze timed responses into their cognitive and motor components. They thus were unable to decide which aspects of information processing are impaired. We here used a Fitts' task to examine differences in cognitive and motor components between abstinent alcoholics and healthy controls. METHODS: Fifty-two abstinent alcoholics and 52 healthy controls participated in this research design. Fine motor functioning was assessed by means of the Fitts' task. RESULTS: Abstinent alcoholics needed more time to perform timed responses than healthy controls. As both reaction and movement times were higher in abstinent alcoholics, both cognitive and motor processes seem to be impaired. When the task became more difficult (small targets instead of large targets) abstinent alcoholics needed proportionally more time to give the correct response than healthy controls. This phenomenon solely applied to movement times. CONCLUSIONS: These research data indicate that abstinent alcoholics are somewhat impaired on a behavioral level. The execution of timed responses indeed was lengthier in abstinent alcoholics than in healthy controls. As both cognitive and motor processes were impaired, we here assume that both central and peripheral processes are affected by progressive alcohol intake. Abstinent alcoholics also have more difficulties to adapt their motor responses to changing task conditions.     

Impaired Visual Search in Alcoholics

Visual search performance was studied in detoxified long-term alcoholics, short-term alcoholics, and nonalcoholic controls. Measures of search time and errors indicated that alcoholics had significantly longer search times than controls and that long-term alcoholics had comparatively longer search times and more shape errors in the left visual hemispace than the other groups. The results are consistent with the hypothesis that alcoholism results in subtle frontal lobe and right hemisphere dysfunctions.     

Event-Related Potential Characteristics in Children of Alcoholics from High Density Families

Sons and daughters (ages 8-14) of male alcoholics without psychiatric problems were compared with sons and daughters of controls employing two auditory paradigms to elicit event-related potentials (ERPs). All of the children of alcoholics were from high density families (each father had an average of 3.7 first and second-degree relatives meeting criteria for alcoholism). Subjects were presented with high- and low-pitched tones with global probabilities of 25% and 75% of total trials, respectively. Subjects were instructed to count silently the number of "high" tones (rare targets) but not the number of "low" tones (non-targets) and report the number heard. In a second auditory paradigm (Choice Reaction task), subjects were asked to perform a different motor response to each high or low tone. The amplitude of the P300 component was influenced significantly by event probability (decreased amplitudes were associated with increased event probability). A greater rate of decrease in P300 amplitude occurred among the high risk children as event probability increased. In addition, greater negativity beginning at approximately N250 was observed for both tasks at the frontal electrode for the high risk children as compared to controls. This enhanced frontal negativity is interpreted in terms of a maturational lag hypothesis.     

Cortisol dysregulation and cognitive impairment in abstinent male alcoholics

BACKGROUND: Alcoholics have impaired cortisol response to stress, indicating dysregulation in the extrahypothalamic systems responsible for activating cortisol secretion in response to stressor exposure. There is a growing literature indicating a relationship between hypothalamic-pituitary-adrenocortical axis activity and neurocognitive functioning. This study examined the hypothesis that dysregulation of the hypothalamic-pituitary-adrenocortical axis may be associated with some neuropsychological impairments in alcoholics. METHODS: Serum cortisol was obtained during cognitive testing and after exposure to cold pressor and mental arithmetic stress in 48 male alcoholics abstinent for 32 +/- 6.7 days and in 30 controls; cortisol was also obtained from 18 of the alcoholic patients during withdrawal. Neurocognitive tasks included the Wechsler Memory Scale and Wisconsin Card Sorting Test. Relationships among alcoholics' cognitive test scores, cortisol levels, and drinking practices were examined by correlation and regression analyses. RESULTS: Verbal memory deficits were more severe in alcoholics who had more withdrawals and ingested a higher typical quantity of alcohol during the prior year ( p< 0.05). Higher levels of cortisol during withdrawal, an index of withdrawal severity, were associated with more errors on the Wisconsin Card Sorting Test ( p< 0.005). As previously reported, the alcoholics had lower cortisol levels after stress compared with controls. Lower poststress cortisol levels were associated with poorer logical memory on the Wechsler Memory Scale and more errors on the Wisconsin Card Sorting Test ( p< 0.05). Among controls, memory deficits occurred only in relation to higher poststress cortisol levels. CONCLUSIONS: Poorer cognitive performance in alcoholics was related to more withdrawals, heavier alcohol consumption, and higher cortisol levels during a recent withdrawal. Alcoholics' cognitive impairment was also related to attenuated stress cortisol responses. Altered stress regulation of the hypothalamic-pituitary-adrenal axis should be studied further as a potential factor related to impaired cognitive function in recovering alcoholics.     

Calcium Status and Calcium-Regulating Hormones in Alcoholics

To elucidate effects of chronic ethanol consumption on clinical chemical parameters reflecting overall calcium homeostasis 34 hospitalized male alcoholics and 35 age-matched controls were studied during the winter season. Serum concentrations of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 were reduced by 28% (p less than 0.01) and 24% (p less than 0.02) among the alcoholics as compared to the controls, respectively. Dietary intake of vitamin D3 did not differ significantly between the groups. The calcium level was below lower limit of reference in nine alcoholics (26%). Serum concentrations of parathyroid hormone and phosphorus were within normal ranges in both groups, and no differences were observed in levels of magnesium, vitamin D-binding protein, calcitonin, or alkaline phosphatase. In conclusion, it is possible that the activities of enzymes crucial in vitamin D3 metabolism may be altered in alcoholics.     

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.     

Response to Diazepam in Sons of Alcoholics

Alcohol exerts several of its actions via the chloride channel associated with the central GABA-benzodiazepine receptor complex. To explore a possible role for this receptor complex in risk for alcoholism, and to determine whether risk for alcoholism is associated with risk for benzodiazepine abuse, the authors administered intravenous diazepam to 18 sons of male alcoholics (SOAs) and 18 control subjects. Four logarithmically increasing doses of diazepam and matched volumes of placebo were given in randomized order on separate days about 1 week apart. SOAs were significantly more likely than controls to report euphoric responses to diazepam. At some diazepam doses, SOAs were more likely to report feeling "high" and "intoxicated." SOAs and controls did not differ in feeling "drugged." SOAs and controls may differ in expectations regarding the subjective effects of drugs and/or in the function of the central GABA-benzodiazepine receptor complex. These findings also add further evidence for increased pleasurable effects, and thus possibly increased risk for benzodiazepine abuse, in a subgroup of SOAs.     

Polysomnographic and spectral sleep EEG in primary alcoholics: an interaction between alcohol dependence and African-American ethnicity

BACKGROUND: Disturbances of sleep EEG are prominent in alcoholic patients, persist into recovery, and recently have been found to predict those alcoholics who are most likely to relapse. Increasing evidence indicates that there are ethnic differences in sleep EEG and that African-Americans may be at elevated risk for disordered sleep. METHODS: This study compared polysomnographic and spectral sleep EEG measures in male primary alcoholic inpatients (n = 31) and age-matched comparison controls (n = 31) stratified by African-American and Euro-American ethnicity. RESULTS: African-American alcoholic patients showed more severe sleep abnormalities than Euro-American alcoholics, and the interaction between alcohol dependence and ethnicity uniquely contributed to prolonged sleep latency (p < 0.001), loss of delta sleep (p < 0.001), and short rapid eye movement (REM) latency (p < 0.001). Spectral EEG analyses confirmed polysomnographic findings of disordered sleep architecture in alcoholics. Compared with controls, alcoholics had lower delta (0.75-4.5 Hz) activity over the whole night (p < 0.05), reductions in mean spectral power (0.75-40 Hz, p < 0.05), and decreases of delta (p < 0.01) and theta (4.5-7.5 Hz,p = 0.05) activity during the first period of non-REM sleep, with African-American alcoholics having the lowest theta of the four groups. CONCLUSIONS: In view of the possible connection between relapse and poor sleep and the role of sleep in the maintenance of health, these data have implications for treatment and morbidity outcomes in African-American alcoholics.     

Some Aspects of Antioxidant Status in Blood from Alcoholics

The effect of ethanol consumption on serum concentration of alpha-tocopherol, erythrocyte activities of superoxide dismutase, glutathione peroxidase, and catalase were studied in 34 male alcoholics and 35 age-matched controls. Serum concentration of alpha-tocopherol was 30% lower in the alcoholics as compared to the controls (p less than 0.001). No significant difference was found in erythrocyte activities of Cu-Zn-containing superoxide dismutase, glutathione peroxidase, or catalase between the groups. Of the 12 alcoholics with subnormal serum alpha-tocopherol, 50% had concomitant neurological clinical scores and cerebellar atrophy, and their neurological scores were significantly higher (82%) than for alcoholics with normal alpha-tocopherol levels (p less than 0.03). However, no significant correlation was observed between levels of alpha-tocopherol and neurological clinical scores or cerebellar atrophy. When entering the study, alcoholics and controls were each randomized into two separate groups, receiving vitamin E supplementation (100 mg/day) or placebo capsules for 10 days, respectively. In the four subgroups, alpha-tocopherol levels increased only in alcoholics receiving vitamin E supplementation (23%) (p less than 0.001). The reduced serum levels of alpha-tocopherol in alcoholics may be normalized by vitamin E supplementation.     

Glucose turnover rate and peripheral insulin sensitivity in alcoholic patients without liver damage

Glucose intolerance is frequently found in alcoholic patients and an impaired insulin response has been documented in them. To look for alternative mechanisms that could explain this intolerance, a glucose turnover using tritiated glucose and an euglycemic glucose clamp were performed to measure the glucose production rate and peripheral insulin sensitivity, respectively. Two groups of recently abstinent chronic male alcoholic patients without evidence of liver damage were studied. The glucose turnover technique showed a higher basal glucose production rate in alcoholics, compared with normal volunteers (2.83 +/- 0.29 vs. 1.84 +/- 0.22 mg/kg/min); an intravenous ethanol load significantly increased this rate. The euglycemic glucose clamp did not show peripheral insulin resistance in alcoholics, compared with controls.     

The Role of Cirrhosis in Memory Functioning of Alcoholics

The effects of alcoholism and liver disease on memory functioning in alcoholics were studied by comparing four groups: normal healthy controls, alcoholics without liver disease, alcoholics with biopsy-confirmed cirrhosis, and nonalcoholics with postnecrotic cirrhosis. Memory capacity was evaluated employing the Benton Visual Retention Test (BVRT), the Rey-Osterreith Complex Figure Test, Digit Span, and the Brown Peterson four-word short-term memory test. A 2 x 2 ANOVA revealed significant main effects for both alcohol and cirrhosis on Digits Forward and the total score on the Brown Peterson test. Additionally, there were significant main effects for cirrhosis on the BVRT. The Brown Peterson test was analyzed using a repeated measures 2 x 2 ANOVA. Significant effects for cirrhosis were observed at all three interpolation periods. The effects for alcohol approached significance at the 30-sec (most difficult) interpolation period. Analysis of error patterns on the Brown Peterson test indicated that overall omission errors were most commonly made among all groups. Significant effects were found for alcohol on omissions and intrusion, while the cirrhosis factor yielded significant effects for phonemic, perseverative, and omission errors. This study demonstrates the importance of liver disease underlying the etiology of memory impairments in alcoholics. The results confirm our earlier findings that neuropsychologic deficits seen in alcoholics may be the result of the combination of alcohol abuse and liver disease.     

Speed and efficiency but not accuracy or timing deficits of limb movements in alcoholic men and women

BACKGROUND: Lesions of the cerebellum, a concomitant of alcoholism, can disrupt quality and regularity of movement. Whether evidence for such dysfunction lingers in patients with uncomplicated alcoholism, which is known to affect cerebellar structural integrity, is controversial. METHODS: We used quantitative measures to examine component processes of five classes of movement associated with regional cerebellar function: limb ataxia (alternated finger tapping and variants of the finger-to-nose and heel-to-shin tests), paced tapping, eye-hand coordinated tracing, timed response reflecting preparation and execution time, and postural stability. The subjects examined were 39 abstinent alcoholics (13 men and 26 women) and 21 age-matched controls (9 men and 12 women). For limb ataxia, the dependent measures were the trajectory deviation from the subject's own average movement path and the speed of travel from beginning points to endpoints. RESULTS: Repeated-measures analysis of variance comparing movement speed of finger to nose and heel to shin yielded significant interactions in all conditions (p < 0.007); this indicated that the alcoholics were relatively slower in the upper- than lower-limb tasks. Movements by the alcoholic men were significantly slower but less deviant from an ideal trajectory in all upper-limb conditions than those of the control men (p < 0.002). Although measures of lower-limb movement trajectory did not distinguish the groups, tests of ataxia of stance and gait did. The groups did not differ, however, on tests of timed tapping or sinusoid tracing. CONCLUSIONS: Alcohol-related postural instability in abstinent alcoholics is functional evidence supporting the postulated damage to the anterior superior vermis. Altered speed or accuracy trade-offs, with alcoholics moving slower to attain equivalent or even smaller trajectory deviations, are symptomatic of cerebellar hemisphere dysfunction that is characterized by deliberation of otherwise automatic movements.     

Release of Glucagon in Male Alcoholics with Vagal Neuropathy

There is evidence supporting involvement of the parasympathetic nervous system in the control of glucagon secretion. We have investigated the possible role of vagal neuropathy in alcoholics as a cause of alcoholic hypoglycemia. Slow infusions of insulin (2.4 U/hr) were carried out in ten male alcoholics, four with and six without evidence of vagal neuropathy, and in six male controls. The fall in blood glucose levels and the rise in serum glucagon levels in the alcoholics with or without vagal neuropathy were not significantly different from controls. We conclude that vagal neuropathy in alcoholics has no effect on the glucagon response to hypoglycemia.     

Regional Cerebral Metabolism in Female Alcoholics of Moderate Severity Does Not Differ From That of Controls

It is generally believed that women are more vulnerable to alcohol's toxic effects than men. Studies in male alcoholics have consistently shown reductions in brain glucose metabolism. However, such studies have not been done in female alcoholics. The purpose of this study was to evaluate if similar or worse brain metabolic abnormalities occurred in female alcoholics. For this purpose, we measured regional brain metabolism with positron emission tomography and [¹⁸F]fluorodeoxyglucose in 10 recently detoxified female alcoholics and compared it with that in 12 age-matched female controls. There were no differences between alcoholics and control females in regional brain glucose metabolism whether we used regions of interest analysis or statistical parameter maps methods. These results do not support a higher toxicity for the effects of alcohol in the female brain, as assessed with regional brain glucose metabolism, because metabolic values in female alcoholics did not differ from those of controls, whereas metabolic values in male alcoholics are generally lower than those in controls. However, this study is confounded by the fact that the severity of alcohol use in these female alcoholics was less than that of the male alcoholics previously investigated in positron emission tomography studies. Future studies in male subjects with alcoholism of moderate severity are required to address gender differences in sensitivity to alcohol effects in brain metabolism.     

Premature Aging in Male Alcoholics: “Accelerated Aging” or “Increased Vulnerability”?

This study involved an evaluation of two versions of the "premature aging" theory of chronic alcoholism: the accelerated aging and increased vumerabHty versions. The major dependent measures used were the tests included in Reitan's brain age quotient (BAO), a series of neuropsychological tests known to be sensitive to the effects of alcoholism and aging. Subjects were 40 chronic alcoholic inpatients and 40 matched controls, divided into age groups by; decade, ranging from the 30s to the 60s. It was proposed that an j interaction between age and presence or absence of alcoholism, with BAO test differences between alcoholics and controls widening as age increases, would support the increased vulnerability version, while the absence of such aw interaction would support the accel-] erated aging version. The results dearty favored the accelerated aging version, with merited BAO test differences between alcoholics, and controls appearing even in the 30-year-old groups. It was concluded that chronic ateohoftcs tend to perform at levels found for nonalconoiics 10 years their senior, but the discrepancy between, alcoholics and nonalcohoics does not increase with age.     

Effect of Diazepam on Plasma γ-Aminobutyric Acid in Sons of Alcoholic Fathers

A subgroup of abstinent alcoholics display low levels of plasma γ-aminobutyric acid (GABA). Two previous studies of plasma GABA in sons of alcoholic fathers (SOAs) have yielded conflicting results. The aim of the current study was to measure plasma GABA both at baseline and after challenge with diazepam, a GABA_A receptor agonist, in a group of SOAs already shown to display decreased eye movement, memory, and sedative effects of diazepam. Twenty-seven SOAs and 23 male control subjects received four logarithmically increasing doses of diazepam or placebo in randomized order on 2 days at least 1 week apart. Plasma GABA was measured at baseline and after the last dose. There were no significant differences between SOAs and controls in baseline plasma GABA levels. In the whole sample, there were significant correlations between baseline plasma GABA and both high novelty-seeking and low-harm avoidance scores on the Tridimensional Personality Questionnaire. Both SOAs and controls displayed decreases in plasma GABA over time on both testing days, but there was no effect of diazepam on plasma GABA and no significant difference between groups in plasma GABA response to diazepam. These results suggest that neither low plasma GABA at baseline nor altered plasma GABA response to diazepam is associated with increased genetic risk for alcoholism.     

Influence of obesity on accurate and rapid arm movement performed from a standing posture

INTRODUCTION: Obesity yields a decreased postural stability. The potentially negative impact of obesity on the control of upper limb movements, however, has not been documented. This study sought to examine if obesity imposes an additional balance control constraint limiting the speed and accuracy with which an upper limb goal-directed movement performed from an upright standing position can be executed. METHOD: Eight healthy lean subjects (body mass index (BMI) between 20.9 and 25.0 kg/m(2)) and nine healthy obese subjects (BMI between 30.5 and 48.6 kg/m(2)) pointed to a target located in front of them from an upright standing posture. The task was to aim at the target as fast and as precisely as possible after an auditory signal. The difficulty of the task was varied by using different target sizes (0.5, 1.0, 2.5 and 5.0 cm width). Hand movement time (MT) and velocity profiles were measured to quantify the aiming. Centre of pressure and segmental kinematics were analysed to document postural stability. RESULTS: When aiming, the forward centre of pressure (CP) displacement was greater for the obese group than for the normal BMI group (4.6 and 1.9 cm, respectively). For the obese group, a decrease in the target size was associated with an increase in backward CP displacement and CP peak speed whereas for the normal BMI group backward CP displacements and CP peak speed were about the same across all target sizes. Obese participants aimed at the target moving their whole body forward whereas the normal BMI subjects predominantly made an elbow extension and shoulder flexion. For both groups, MT increased with a decreasing target size. Compare to the normal BMI group, this effect was exacerbated for the obese group. For the two smallest targets, movements were on average 115 and 145 ms slower for the obese than for the normal BMI group suggesting that obesity added a balance constraint and limited the speed with which an accurate movement could be done. SUMMARY: Obesity, because of its effects on the control of balance, also imposes constraints on goal-directed movements. From a clinical perspective, obese individuals might be less efficient and more at risk of injuries than normal weight individuals in a large number of work tasks and daily activities requiring upper limb movements performed from an upright standing position.     

Determinants of Blood Acetaldehyde Level during Ethanol Oxidation in Chronic Alcoholics

We analyzed the blood alcohol and acetaldehyde concentrations in nine alcoholics and four healthy nonalcoholic controls during and after an intravenous infusion of a high and a low dose of alcohol. In the alcoholics, the mean rates of plasma ethanol disappearance were significantly higher than in nonalcoholic controls. In the control subjects, the blood acetaldehyde levels were, in general, below the detection limit (less than 0.5 microM), but in sharp contrast to this, an elevated blood acetaldehyde during ethanol infusion was found in 6/9 alcoholics. Peak blood acetaldehyde values were higher after the high than the low dose of alcohol. Fructose infusion significantly enhanced the rate of plasma ethanol disappearance both in controls and in alcoholics, and this was usually associated with a significant elevation of blood acetaldehyde level. The maximal specific activities (expressed as milliunits/mg og protein) of alcohol, lactate, and aldehyde dehydrogenases in liver were significantly lower in alcoholics than in controls. Even more importantly, the peak blood acetaldehyde correlated negatively with the activity of hepatic "low-Km" aldehyde dehydrogenase. Our results suggest that the main reason for blood acetaldehyde elevation seen in these chronic alcoholics is their impaired capacity to metabolize acetaldehyde. This may be further accentuated by the increased rate of ethanol oxidation.     

Mechanisms of cell death in cholinergic basal forebrain neurons in chronic alcoholics

Tau immunoreactivity was examined in post mortem tissue from patients in three groups: neurologically-asymptomatic and neuropathologically normal alcoholics, alcoholics with Wernicke's Encephalopathy (WE) and age matched non-alcoholic controls. Tau-positive granular and fibrillary inclusions were frequently observed within the magnocellular neurons of the cholinergic nucleus basalis, within occasional nucleus basalis neurons in non-WE alcoholics, but not in controls. Tau immunoreactivity was not however observed in cortical, brainstem, diencephalic or non-cholinergic forebrain structures. Peroxidase activity was also examined within the nucleus basalis using diaminobenzidine as an indicator. The majority of neurons in the basal forebrain showed increased peroxidase activity in all WE alcoholics and in some nucleus basalis neurons of non-WE alcoholics, but was rarely seen in controls. Neighboring astrocytes also showed increased peroxidase activity. These results suggest a link between peroxidase activity and the abnormal accumulation of phosphorylated tau. The presence of tau in the nucleus basalis of alcoholics with WE suggests a thiamine-dependent mechanism in tau accumulation and cell death in the cholinergic basal forebrain.