Comparisons of Korsakoff and non-Korsakoff alcoholics on neuropsychological tests of prefrontal brain functioning

BACKGROUND: Evidence suggests that alcoholics exhibit particular deficits in brain systems involving the prefrontal cortex, but few studies have directly compared patients with and without Korsakoff's syndrome on measures of prefrontal integrity. METHODS: Neuropsychological tasks sensitive to dysfunction of frontal brain systems were administered, along with standard tests of memory, intelligence, and visuospatial abilities, to 50 healthy, abstinent, nonamnesic alcoholics, 6 patients with alcohol-induced persisting amnestic disorder (Korsakoff's syndrome), 6 brain-damaged controls with right hemisphere lesions, and 82 healthy nonalcoholic controls. RESULTS: Korsakoff patients were impaired on tests of memory, fluency, cognitive flexibility, and perseveration. Non-Korsakoff alcoholics showed some frontal system deficits as well, but these were mild. Cognitive deficits in non-Korsakoff alcoholics were related to age, duration of abstinence (less than 5 years), duration of abuse (more than 20 years), and amount of alcohol intake. CONCLUSIONS: Abnormalities of frontal system functioning are most apparent in alcoholics with Korsakoff's syndrome. In non-Korsakoff alcoholics, factors contributing to cognitive performance are age, duration of abstinence, duration of alcoholism, and amount of alcohol consumed.     

Motor Performance in Detoxified Alcoholics

Detoxified male and female alcoholics (aged 20-49 years) and age-matched controls performed a series of 15-sec target-tapping tasks in which they alternatively marked two target strips with a felt marker as rapidly and as accurately as possible. Consistent with "Fitts' Law" (Fitts PM: J Exp Psych 47:381-391, 1954), a highly linear relationship between movement time and task difficulty was observed in all four groups. Overall, the alcoholics were slower and made more errors than the controls, although the pattern of deficit differed for males and females. Accuracy, but not speed, was impaired in male alcoholics. The production of undershoot errors was increased more in alcoholics than nonalcoholics in targets of narrower width, whereas the production of overshoot errors was increased more in alcoholics as target separation decreased. Female alcoholics displayed impairment in speed of movement, but not accuracy. However, both alcoholic groups displayed elevated error rates for the more difficult targets. It is thus possible that detoxified alcoholics might mimic the speed functions of nonalcoholic individuals at the occasional cost of an erroneous response at a difficult target.     

The neuropsychological consequences of abstinence among older alcoholics: a cross-sectional study

BACKGROUND: The older alcoholic has been distinguished from the younger alcoholic with regard to both the acute effects of alcohol and also the recovery of functioning with abstinence. Few studies, however, have included samples of exclusively older subjects. In this investigation we examined the recovery of functioning in an older cohort of recovering alcoholics (age range 55-83) to determine which neuropsychological functions improve and which remain impaired with abstinence. METHODS: We used a cross-sectional design, comparing three demographically matched groups on a battery of neuropsychological tests: (a) older alcoholics who had been abstinent for greater than 6 months, (b) older alcoholics who had been abstinent for less than 6 months, and (c) a control group of older subjects without alcohol abuse histories. RESULTS: In almost all tasks, the alcoholics who were abstinent for less than 6 months performed worse than the control group. In contrast, the alcoholics who had been abstinent for more than 6 months differed from the control group on learning and recall of a word list, immediate and delayed recall of a complex figure, initial letter fluency, and clock drawing. CONCLUSIONS: Memory and executive skills appear to be resistant to recovery or at least slower to recover with abstinence in the older alcoholic. The impairment with visuospatial skills reported in prior investigations of alcoholics may be related to compromised executive functions, which interfere with the encoding of more complex visuospatial information and thus affect recall of such information. Studies that involve larger samples of older alcoholics are needed to understand their ability to recover cognitive functioning with abstinence.     

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.     

Perceptual learning in detoxified alcoholic men: contributions from explicit memory, executive function, and age

BACKGROUND: Visuospatial and visuoperceptual deficits have consistently been observed in detoxified alcoholics; however, the severity of impairment varies with test and task type. Identifying the component processes and factors that underlie a particular deficit may reveal why some visuospatial and visuoperceptual tasks are more compromised than others and may lead to the specification of neural systems that are particularly vulnerable in alcoholism. METHODS: We examined visuoperception and perceptual learning with a picture fragment identification task in 51 recently detoxified nonamnesic alcoholic men (aged 29-66 years) compared with 63 normal control men (aged 21-70 years). Executive function and explicit declarative memory were also assessed. RESULTS: Despite deficits in the primary components of visuoperception and explicit memory for visuospatial stimuli, the alcoholics showed normal perceptual learning. Although the alcoholics and controls performed at comparable levels on the perceptual learning task, multiple regression analyses indicated that the factors accounting for perceptual learning variance differed between and within groups. Visuoperceptual abilities consistently predicted perceptual learning in the control subjects but not the alcoholic subjects. Explicit memory contributed to perceptual learning performance in both the alcoholic and control groups. Frontal executive ability consistently predicted perceptual learning in the alcoholic subjects, but it had predictive ability only in the control subjects as time elapsed. Age was significantly correlated with perceptual learning performance in both groups. Lifetime alcohol consumption, but not alcoholism duration, was an independent predictor of 1-hr perceptual learning. CONCLUSIONS: These correlational analyses suggest that controls invoke basic visuospatial processes to perform a perceptual learning task, whereas alcoholics invoke higher-order cognitive processes (i.e., frontal executive systems) to perform the same task at normal levels. Use of more demanding cognitive systems by the alcoholics may be less efficient and more costly to processing capacity than those invoked by controls.     

Global–Local Interference is Related to Callosal Compromise in Alcoholism: A Behavior-DTI Association Study

Background: Visuospatial ability is a multifactorial process commonly impaired in chronic alcoholism. Identification of which features of visuospatial processing are affected and which are spared in alcoholism, however, has not been clearly determined. We used a global–local paradigm to assess component processes of visuospatial ability and MR diffusion tensor imaging (DTI) to examine whether alcoholism‐related microstructural degradation of the corpus callosum contributes to disruption of selective lateralized visuospatial and attention processes. Methods: A hierarchical letter paradigm was devised, where large global letters were composed of small local letters. The task required identification of target letters among distractors presented at global, local, both, or neither level. Attention was either selectively directed to global or local levels or divided between levels. Participants were 18 detoxified chronic alcoholics and 22 age‐matched healthy controls. DTI provided quantitative assessment of the integrity of corpus callosal white matter microstructure. Results: Alcoholics generally had longer reaction times than controls but obtained similar accuracy scores. Both groups processed local targets faster than global targets and showed interference from targets at the unattended level. Alcoholics exhibited moderate compromise in selectively attending to the global level when the global stimuli were composed of local targets. Such local interference was less with longer abstinence. Callosal microstructural integrity compromise predicted degree of interference from stimulus incongruency in the alcoholic group. This relationship was not observed for lateral or third ventricular volumes, which are measures of nonspecific cortical volume deficits. Conclusion: Global–local feature perception was generally spared in abstinent chronic alcoholics, but impairments were observed when directing attention to global features and when global and local information interfered at stimulus or response levels. Furthermore, the interference‐callosal integrity relationship in alcoholics indicates that compromised visuospatial functions include those requiring bilateral integration of information.     

Studies of Alpha-2-Adrenoceptor Function in Abstinent Alcoholics

Hormonal, haemodynamic and subjective psychological responses to the intravenous infusion of clonidine were investigated in nine male alcoholics who had been abstinent for 5 weeks, and were compared with those of nine healthy controls. The growth hormone response to clonidine was significantly blunted in the abstinent alcoholics. Both baseline cortisol levels and the clonidine-induced cortisol decrease were significantly greater in the alcoholics than in controls. Blood pressure, pulse rate and psychological responses to clonidine were similar in both groups. These results indicate that some aspects of alpha-2-adrenoceptor sensitivity are persistently abnormal in alcoholics at least 5 weeks into abstinence.     

Cognitive performance in long-term abstinent elderly alcoholics

BACKGROUND: To date, there is a wealth of literature describing the deleterious effects of active alcoholism on cognitive function. There is also a growing body of literature on the extent of cognitive recovery that can occur with abstinence. However, there is still a dearth of published findings on cognitive functioning in very long-term abstinence alcoholics, especially in the elderly population. METHODS: The current study examines 91 elderly abstinent alcoholics (EAA) (49 men and 42 women) with an average age of 67.3 years, abstinent for an average of 14.8 years (range 0.5 to 45 years), and age and gender comparable light/nondrinking controls. The EAA group was divided into 3 subgroups: individuals that attained abstinence before age 50 years, between the ages 50 and 60 years, and after age 60 years. Attention, verbal fluency, abstraction/cognitive flexibility, psychomotor, immediate memory, delayed memory, reaction time, spatial processing, and auditory working memory were assessed. The AMNART and cranium size were used as estimates of brain reserve capacity, and the association of all variables with alcohol use measures was examined. RESULTS: Overall, the EAA groups performed comparably to controls on the assessments of cognitive function. Only the abstinent in group before 50 years of age performed worse than controls, and this was only in the domain of auditory working memory. EAAs had larger craniums than their controls. This effect was strongest for those who drank the longest and had the shortest abstinence. Such individuals also performed better cognitively. CONCLUSIONS: Our data showed that elderly alcoholics that drank late into life, but with at least 6 months abstinence can exhibit normal cognitive functioning. Selective survivorship and selection bias probably play a part in these findings. Cognitively healthier alcoholics, with more brain reserve capacity, may be more likely to live into their 60s, 70s, or 80s of age with relatively intact cognition, and to volunteer for studies such as this. Our results do not imply that all elderly alcoholics with long-term abstinence will attain normal cognition.     

Patterns of Cognitive Impairment among Alcoholics: Are There Subtypes?

The mild generalized dysfunction hypothesis of alcohol abuse's deleterious effects on cognitive processes has gained support from a number of studies in which detoxified alcoholics have a lower mean performance level than peer controls on a variety of neuropsychological tests. This approach might obscure consistent but different patterns of preserved and impaired cognitive performance among subgroups of alcoholics, suggestive of alternative hypotheses. To test this possibility, neuropsychological test data from two large, independent samples of alcoholics (sample 1, n = 143; sample 2, n = 130) and controls (sample 1, n = 97; sample 2, n = 83) were subjected to separate centroid hierarchical cluster analyses. For both samples, the majority of alcoholics (94% and 94%) exhibited a pattern of impaired verbal and nonverbal performance and deficits in memory and perceptual motor skill, with normal motor skill. The alcoholics who did not fit this pattern showed more severe or wide-ranging impairments. These findings indicate that empirical support for the mild generalized dysfunction hypothesis of alcoholics' cognitive deficits is not an artifact of averaging.     

Impairment on a simulated gambling task in long-term abstinent alcoholics

BACKGROUND: Recent research indicates that currently active or recently detoxified substance abusers make more disadvantageous decisions on a simulated gambling task (SGT). This study expands on the current literature by using the SGT to examine decision making in long-term abstinent alcoholics (mean of 6.6 years' abstinence) who do not have antisocial personality disorder or a history of conduct disorder. METHODS: A total of 102 subjects (58 controls and 44 abstinent alcoholics) were tested on the SGT, in which subjects choose cards from 4 different decks that vary in terms of the magnitude of the immediate win (large or small) and the magnitude of long-term loss (large or small). The association of SGT performance with alcohol use variables, with the number of externalizing symptoms, and with personality measures of social deviance was examined. RESULTS: Compared with controls, long-term abstinent alcohol-dependent subjects had more externalizing symptoms, had personality profiles associated with a proneness to social deviance, and made more disadvantageous decisions on the SGT. The magnitude of disadvantageous decision making was associated with the duration of peak alcohol use but was associated with only one measure (low socialization) of socially deviant personality traits. CONCLUSIONS: The results suggest that alcoholics can achieve long-term abstinence despite persistent deficits in decision making and abnormal personality profiles. The decision-making deficits either may be the result of long-term alcoholism or may reflect a factor predisposing to alcoholism that persists with abstinence. The possibility is raised that alcoholics who cannot achieve long-term abstinence are even more impaired on their decision making and have more abnormal personality profiles than the abstinent alcoholics studied here.     

Implicit learning, executive function and hedonic activity in chronic polydrug abusers, currently abstinent polydrug abusers and controls

AIMS: The study seeks to evaluate impairments of implicit learning and executive function in chronic polydrug abusers. It was hypothesized that implicit learning and executive function correlate with anhedonia. DESIGN: A cross-sectional group comparison. SETTINGS: Department of Psychiatry, University of Tübingen, Germany. Participants A total of 25 male polydrug abusers with opiate dependence, n = 26 polydrug abusers abstinent for more than 3 months and n = 26 non-drug-using healthy males. SETTING: Abstinent polydrug abusers were recruited from a community treatment centre, current polydrug abusers from local drug counselling services and controls through advertisements. MEASUREMENTS: A psychological battery assessing implicit learning (serial reaction-time task), various executive functions (latent inhibition, delayed matching-to-sample, Trail Making Test, acquisition and modification of conditioned responses, figural reasoning) and verbal logic memory was administered. Hedonic thoughts and activities as well as depressive symptoms were assessed through questionnaires. FINDINGS: In chronic polydrug abusers, there were moderate impairments of implicit learning, of acquisition, reversal and extinction of conditioned responses, of latent inhibition as well as anhedonia, while working memory was spared. In the abstinent group, cognitive performance was normal except for latent inhibition and more anhedonia and depression than in controls. CONCLUSIONS: The findings suggest that current polydrug abusers suffer from impairment of many cognitive functions and from anhedonia. During abstinence, there is near normal cognitive function but still anhedonia. Anhedonia was correlated with implicit learning but not with executive function.     

The interplay between cognitive and motor functioning in healthy older adults: findings from dual-task studies and suggestions for intervention

Reaching late adulthood is accompanied by losses in physical and mental resources, but lifestyle choices seem to have a considerable influence on the aging trajectory. This review deals with the interplay between cognitive and motor functioning in old age, focusing on two different lines of research, namely (a) dual-task studies requiring participants to perform a cognitive and a motor task simultaneously, and (b) intervention studies investigating whether increases in physical fitness also lead to improvements in cognitive performance. Dual-task studies indicate that healthy older adults show greater performance reductions in both domains than young adults when performing a cognitive and a motor task simultaneously. In addition, older adults often tend to protect their motor functioning at the expense of the cognitive task when the situation involves a threat to balance. This can be considered an adaptive behavior since fall-related injuries can have severe consequences. Fitness intervention studies which increased the aerobic fitness of previously sedentary older adults have demonstrated impressive performance improvements in the cognitive domain, especially for tasks involving executive control processes. These findings are interesting in light of cognitive intervention studies, which often fail to find significant transfer effects to tasks that have not been trained directly. The authors argue that future research should compare the effects of cognitive and aerobic fitness interventions in older adults, and they present a study design in which cognition and fitness are trained sequentially as well as simultaneously. Finally, methodological issues involved in this type of research and potential applications to applied settings are discussed.     

Impulsive responding in alcoholics

BACKGROUND: Impaired decision-making is one diagnostic characteristic of alcoholism. Quantifying decision-making with rapid and robust laboratory-based measures is thus desirable for the testing of novel treatments for alcoholism. Previous research has demonstrated the utility of delay discounting (DD) tasks for quantifying differences in decision-making in substance abusers and normal controls. In DD paradigms subjects choose between a small, immediate reward and a larger, delayed reward. METHODS: We used a novel computerized DD task to demonstrate that abstinent alcoholics (AA, n=14) choose the larger, delayed option significantly less often than control subjects (n=14; p<0.02). This difference in choice tendency was independent of subject age, gender, years of education, or socio-economic status. RESULTS: All subjects discounted as a function of reward delay and amount, with alcoholics demonstrating steeper discounting curves for both variables. This tendency to discount delayed rewards was positively correlated with subjective reports of both alcohol addiction severity (Drug Use Screening Inventory-Revised, Domain 1, p<0.01), and impulsivity (Barratt Impulsivity Scale-11, p<0.004). Novel aspects of this new paradigm include an element of time pressure, an additional experimental condition that evaluated motor impulsivity by assessing the ability to inhibit a pre-potent response, and another control condition to requiring non-subjective choice. CONCLUSIONS: Non-alcoholic controls and alcoholics did not differ on motor impulsivity or non-subjective choice, suggesting that the differing choice behavior of the two groups was due mainly to differences in cognitive impulsivity.     

Chronic Alcoholism in Males: Cognitive Deficit as a Function of Age of Onset, Age, and Duration

Performance on a cognitive rule-learning task was studied in detoxified alcoholics having early/late onset and short-/long-term drinking histories, and in matched nonalcoholic controls. There were pronounced cognitive deficits in early onset and long-term alcoholics. Impairment was severest in the early onset group, even though they were on the average 15 years younger than the late onset group. Early onset alcoholics were relatively more impaired on both the abstract and the verbal Shipley measures. This group also manifested a relative deficit in ability to show positive transfer across problems. Chronicity of alcoholism also interfered with acquisition of an abstract relationship between concrete stimulus attributes. Age negatively influenced ability to perform abstractions, but not commonly tested verbal skills. The findings suggest that an early onset of alcoholism, regardless of duration of problem drinking, is particularly predictive of cognitive impairment.     

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.     

A Comparison of the Effects of Long-Term Alcohol Abuse and Aging on the Performance of Verbal and Nonverbal Divided Attention Tasks

The purpose of this study was to assess two versions of the hypothesis that alcohol abuse results in premature aging of the brain and of cognitive functioning. The performances of detoxified long-term alcoholic was compared with that of nonalcoholic controls on three divided attention tasks known to be sensitive to aging. While both forms of the premature aging hypothesis predicted that alcoholics should perform more poorly than controls, the hypotheses differed in their predictions of the interactions between the effects of alcohol and normal aging. The results showed that while all three tasks were sensitive to age, only two were affected by long-term alcohol abuse. On one of the tests affected by both age and alcohol abuse, the performance of both young and old alcoholics was equally impaired whereas on the other, only the older alcoholics had significant difficulties. Based on these findings it was concluded that there was only partial overlap between the effects of alcohol and aging, and that neither of the two forms of the premature aging hypothesis could predict the observed pattern of results.     

Hypoperfusion of the Cerebellum and Aging Effects on Cerebral Cortex Blood Flow in Abstinent Alcoholics: A SPECT Study

BACKGROUND: This study evaluated hypotheses concerning alcoholism, aging, and the relationship between cerebral hypoperfusion and residual deficits in the functioning of cerebellar and neocortical brain systems. METHODS: The participants were 10 healthy abstinent alcoholics (9 men, 1 woman) and 12 nonalcoholic controls (10 men, 2 women) ranging in age from 35 to 67 years. Cerebral blood flow was observed through the use of regionally specific computer-derived quantitative analysis of single photon emission computed tomography (SPECT) perfusion images. Cerebellar perfusion was measured and compared with cerebral cortex perfusion in age-equivalent subgroups of alcoholics and controls (under 55 years; 55 years and over). RESULTS: In abstinent alcoholics under age 55, cerebellar perfusion ratios were significantly reduced compared with the controls. In alcoholics and nonalcoholic controls 55 years old and older, this relationship was reversed, probably as a result of diminished cortical perfusion with aging in the alcoholics and of cerebellar decline in the controls. CONCLUSIONS: The findings support hypotheses that the residual effects of alcoholism include cerebellar brain abnormalities and that aging combined with long-term alcoholism leads to cerebral cortical decline.     

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 fronto-cerebellar functional connectivity in chronic alcoholic patients

Background: Alcohol dependence is associated with neurocognitive deficits related to neuropathological changes in structure, metabolism, and function of the brain. Impairments of motor functioning in alcoholics have been attributed to well‐characterized neuropathological brain abnormalities in cerebellum. Methods: Using functional magnetic resonance imaging (fMRI), we studied in vivo the functional connectivity between cerebellar and cortical brain regions. Participants were 10 uncomplicated chronic alcoholic patients studied after 5 to 7 days of abstinence when signs of withdrawal had abated and 10 matched healthy controls. We focused on regions of prefrontal, frontal, temporal, and parietal cortex that exhibited an fMRI response associated with nondominant hand finger tapping in the patients but not in the controls. We predicted that fronto‐cerebellar functional connectivity would be diminished in alcoholics compared with controls. Results: Functional connectivity in a circuit involving premotor areas (Brodmann Area 6) and Lobule VI of the superior cerebellum was reduced in the patients compared with the controls. Functional connectivity was also reduced in a circuit involving prefrontal cortex (Brodmann Area 9) and Lobule VIII of the inferior cerebellum. Reductions in connectivity were specific to fronto‐cerebellar circuits and were not found in other regions examined. Conclusions: Our findings show a pattern in recently abstinent alcoholic patients of specific deficits in functional connectivity and recruitment of additional brain regions for the performance of a simple finger‐tapping task. A small sample, differences in smoking, and a brief abstinence period preclude definitive conclusions, but this pattern of diminished fronto‐cerebellar functional connectivity is highly compatible with the characteristic neuropathological lesions documented in alcoholics and may reflect brain dysfunction associated with alcoholism.     

Mismatch negativity and auditory sensory memory in chronic alcoholics

BACKGROUND & METHODS: Preattentive auditory processing and sensory memory were investigated by means of mismatch negativity (MMN) in a sample of 22 middle-aged abstinent chronic alcoholics and 25 age-matched healthy controls. Stimuli were presented at two inter-stimulus intervals (ISIs, 0.75 sec and 2.0 sec) in separate blocks. RESULTS: No significant differences in amplitude or latency of MMN were found between alcoholic and control subjects in either of the two ISI conditions. However, when age was included as a factor in the analysis, MMN amplitude was attenuated in chronic alcoholics who were older than 40 years of age. CONCLUSIONS: These results indicate that the automatic stimulus-change detector mechanism associated with MMN generation is impaired in chronic alcoholics over the age of 40, suggesting that the neurotoxic effects of chronic consumption of alcohol are more prone to appear after a critical age.