Contributions of Studies on Alcohol Use Disorders to Understanding Cerebellar Function (original) (raw)

2010, Neuropsychology Review

https://doi.org/10.1007/S11065-010-9141-Y

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Abstract

Neuropathological, neuropsychological, and neuroimaging studies of human alcoholism provide evidence for degradation of frontal, pontine, thalamic, and cerebellar brain sites and disturbed associated functions. Current studies using neuroimaging combined with examination of executive functions, traditionally considered the sole purview of the frontal lobes, have identified a role for the cerebellum serving as a compensatory processing adjunct to enable normal performance

Increased frontocerebellar activation in alcoholics during verbal working memory: an fMRI study

NeuroImage, 2003

Although there is clear evidence of alcoholism-related damage to the frontal lobes and cerebellum from neuroimaging, neuropathological, and neuropsychological studies, the functional role of the cerebellum and cerebrocerebellar circuits related to verbal working memory deficits of alcoholics have not been well studied. Alcoholic and nonalcoholic subjects performed a Sternberg verbal working memory task while receiving an fMRI scan in a 3T magnet. This task has been found in previous studies to reliably activate the articulatory control and phonological storage components of the phonological loop (left frontal, left temporal/parietal structures, right superior cerebellar regions) in young healthy controls. We hypothesized that the alcoholics would show a different pattern of activation from the controls, based on the regions of interest (ROIs) identified from a previous study of healthy subjects. Behavioral results showed the alcoholics to be performing at a comparable level to the matched controls in terms of accuracy and median reaction time, with no statistically significant differences. However, analysis of the functional data revealed that the alcoholics exhibited greater activation in the left frontal (BA44/45) and right superior cerebellum (HVI) regions relative to the matched controls. These findings suggest that brain activation in left frontal and right cerebellar regions that support the articulatory control system of verbal working memory may require a compensatory increase in alcoholics in order to maintain the same level of performance as controls.

Dual Tasking and Working Memory in Alcoholism: Relation to Frontocerebellar Circuitry

Neuropsychopharmacology, 2010

Controversy exists regarding the role of cerebellar systems in cognition and whether working memory compromise commonly marking alcoholism can be explained by compromise of nodes of corticocerebellar circuitry. We tested 17 alcoholics and 31 age-matched controls with dual-task, working memory paradigms. Interference tasks competed with verbal and spatial working memory tasks using low (three item) or high (six item) memory loads. Participants also underwent structural MRI to obtain volumes of nodes of the frontocerebellar system. On the verbal working memory task, both groups performed equally. On the spatial working memory with the high-load task, the alcoholic group was disproportionately more affected by the arithmetic distractor than were controls. In alcoholics, volumes of the left thalamus and left cerebellar Crus I volumes were more robust predictors of performance in the spatial working memory task with the arithmetic distractor than the left frontal superior cortex. In controls, volumes of the right middle frontal gyrus and right cerebellar Crus I were independent predictors over the left cerebellar Crus I, left thalamus, right superior parietal cortex, or left middle frontal gyrus of spatial working memory performance with tracking interference. The brain-behavior correlations suggest that alcoholics and controls relied on the integrity of certain nodes of corticocerebellar systems to perform these verbal and spatial working memory tasks, but that the specific pattern of relationships differed by group. The resulting brain structure-function patterns provide correlational support that components of this corticocerebellar system not typically related to normal performance in dual-task conditions may be available to augment otherwise dampened performance by alcoholics.

Neuropsychological functioning and alcohol dependence

Current Opinion in Psychiatry, 2005

Purpose of review Alcohol dependence is a significant challenge to society and health-care services. The associated cognitive deficits are thought to affect behavioral control, therapy and liability to relapse. The present review demonstrates important new findings. Recent findings Recent interest focused on compensatory functional circuits, components of executive functioning, externally induced attentional biases and the relevance of the cognitive deficits for therapy and rehabilitation. Summary Recent studies found widespread compromised frontocortico-cerebellar circuits to underlie cognitive deficits. The inclusion of cerebellar structures to support functions traditionally associated with cortical and even prefrontal structures is important. However, most importantly, alcoholdependent patients use additional and generally higherorder executive functions to compensate for deficient task performance. The compensatory mechanisms might help to explain close to normal functioning in basic cognitive domains enabled by support of executive components. But deficits in executive functions themselves might emerge more directly. New approaches concerning executive functioning, analyzing functional components of executive tasks, found response inhibition and decision-making to be impaired but normal performance in simple working memory tasks. Multiple withdrawals have been shown to lead to a higher degree of executive deficit. The causing mechanism underlying the attentional bias induced by alcohol-related words (stroop effect) is still under debate. Correlation of cognitive deficits with therapy outcome turned out to be weak. However, important interactions of cognitive deficits with personality, therapy-setting and successful coping, together with the finding that cognitive performance of alcohol-dependent patients could be enhanced by motivating instructions, might open new strategies in treatment planning and cognitive rehabilitation.

Altered fronto-cerebellar connectivity in alcohol-naïve youth with a family history of alcoholism

NeuroImage, 2011

Fronto-cerebellar connections are thought to be involved in higher-order cognitive functioning. It is suspected that damage to this network may contribute to cognitive deficits in chronic alcoholics. However, it remains to be elucidated if fronto-cerebellar circuitry is altered in high-risk individuals even prior to alcohol use onset. The current study used functional connectivity MRI (fcMRI) to examine fronto-cerebellar circuitry in 13 alcohol-naïve, at-risk youth with a family history of alcoholism (FH+) and 14 age-matched controls. In addition, we examined how white matter microstructure, as evidenced by fractional anisotropy (FA) related to fcMRI. FH+ youth showed significantly reduced functional connectivity between bilateral anterior prefrontal cortices and contralateral cerebellar seed regions compared to controls. We found that this reduction in connectivity significantly correlated with reduced FA in the anterior limb of the internal capsule and the superior longitudinal fasciculus. Taken together, our findings reflect associated aberrant functional and structural connectivity in substance-naïve FH+ adolescents, perhaps suggesting an identifiable neurophenotypic precursor to substance use. Given the role of frontal and cerebellar brain regions in subserving executive functioning, the presence of premorbid abnormalities in fronto-cerebellar circuitry may heighten the risk for developing an alcohol use disorder in FH+ youth through atypical control processing.

Neuronal loss in functional zones of the cerebellum of chronic alcoholics with and without Wernicke's encephalopathy

Neuroscience, 1999

This study examines the effect of chronic alcohol consumption on the human cerebellum using operational criteria for case selection [Caine D. et al. (1997) J. Neurol. Neurosurg. Psychiat. 62, 51-60] and unbiased stereological techniques. We describe, for the first time, structural changes in different functional zones of the cerebellum of chronic alcoholics and correlate these changes with specific clinical symptoms. No consistent changes in the number of neurons or the structural volume for any cerebellar region were observed in the chronic alcoholics without the clinical signs of Wernicke's encephalopathy. In all cerebellar measures, these chronic alcoholics did not differ significantly from the non-alcoholic controls, suggesting that chronic alcohol consumption per se does not necessarily damage human cerebellar tissue. However, several cerebellar changes were noted in the thiamine-deficient alcoholics studied. There was a significant decrease in Purkinje cell density (reduced on average by 43%) and molecular layer volume (reduced by 32%) in the cerebellar vermis in all thiamine-deficient chronic alcoholics. A decrease in cell density and atrophy of the molecular layer, where the dendritic trees of the Purkinje cells are found, without significant cell loss suggests loss of cellular dendritic structure and volume. These thiaminedeficient alcoholics also had a significant decrease (36% loss) in the estimated Purkinje cell number of the flocculi, disrupting vestibulocerebellar pathways.

Cerebellar Lingula Size and Experiential Risk Factors Associated with High Levels of Alcohol and Drug Use in Young Adults

The Cerebellum, 2009

Previous studies have reported cerebellar abnormalities or static ataxia associated with risk for chronic use of alcohol and drugs. Adverse childhood experience (ACE) is another strong risk factor for later substance abuse. We therefore, sought to ascertain the relationship between morphological phenotypes of the lingula (Lobule I) of the anterior cerebellar vermis (ACV), and exposure to emotional (EM) versus physical (PM) maltreatment,on the degree of ongoing alcohol or drug use. The study design consisted of a cross-sectional in vivo neuroimaging study, utilizing retrospective assessment of maltreatment history and self-reports of alcohol and substance use. Study participants were 153 subjects (54M/99F, 21.9±2.2 years) selected for imaging from a database of 1,402 community participants 18-25 years of age, who completed a detailed online screening instrument, and met rigorous inclusion/exclusion criteria. Subjects were exposed to only physical abuse or harsh corporal punishment (PM group, n=37); parental verbal abuse and/or witnessing domestic violence (EM group, n= 58); or had no history of maltreatment or Axis I disorders (n=58). The main outcomes measures consisted of the grey matter volume of Lobule I as measured by manual tracing, number and type of alcoholic beverages consumed during a drinking session, number of sessions per month, and monthly drug use, along with family history of drug and alcohol abuse. Lingula thickness was not attenuated by alcohol use or maltreatment history. However, increased lingula thickness was associated with greater consumption of drugs and hard liquor, particularly in physically maltreated subjects who consumed 2.5-and 2.7-fold more alcohol, and used drugs 6.1-and 7.8-fold more frequently than controls or EM subjects, respectively. In conclusion, physical maltreatment was observed to interact with cerebellar morphology resulting in a strong association with alcohol and substance use. Lingula thickness may represent a novel, experientially-sensitive, phenotypic risk factor for enhanced alcohol and drug use, that perhaps modulates sensitivity to these agents.

Alcohol: Effects on Neurobehavioral Functions and the Brain

Neuropsychology Review, 2007

Alcoholism results from an interplay between genetic and environmental factors, and is linked to brain defects and associated cognitive, emotional, and behavioral impairments. A confluence of findings from neuroimaging, physiological, neuropathological, and neuropsychological studies of alcoholics indicate that the frontal lobes, limbic system, and cerebellum are particularly vulnerable to damage and dysfunction. An integrative approach employing a variety of neuroscientific technologies is essential for recognizing the interconnectivity of the different functional systems affected by alcoholism. In that way, relevant experimental techniques can be applied to assist in determining the degree to which abstinence and treatment contribute to the reversal of atrophy and dysfunction.

The cerebellum and addiction: insights gained from neuroimaging research

Addiction Biology, 2014

Although cerebellar alterations have been consistently noted in the addiction literature, the pathophysiology of this link remains unclear. The cerebellum is commonly classified as a motor structure, but human functional neuroimaging along with clinical observations in cerebellar stroke patients and anatomical tract tracing in non--human primates suggest its involvement in cognitive and affective processing. A comprehensive literature search on the role of the cerebellum in addiction was performed. This review article (1) considers the potential role of the cerebellum in addiction, (2) summarizes the cerebellar structural alterations linked to addiction, presents the functional neuroimaging evidence linking the cerebellum with addiction, and (4) proposes a model for addiction that underscores the role of the cerebellum. The data implicate the cerebellum as an intermediary between motor and reward, motivation and cognitive control systems, as all are relevant etiologic factors in addiction. Furthermore, consideration of these findings could contribute to deeper and more sophisticated insights into normal reward and motivational function. The goal of this review is to spread awareness of cerebellar involvement in addictive processes, and to suggest a preliminary model for its potential role.

Effects of Lifelong Ethanol Consumption on Cerebellar Layer Volumes in AA and ANA Rats

Alcoholism: Clinical and Experimental Research, 1997

Aging and chronic alcohol consumption can cause degenerative changes in the cerebellar cortex. In this study, the effects of aging and lifelong alcohol consumption on cerebellar cortical layer volumes (molecular and granular) and also white matter layer volumes were studied in alcohol-preferring (AA) and nonpreferring (ANA) rats of both sexes. The ethanol-consuming animals (EtOH) had 12% (wlv) ethanol as the only available fluid from 4 to 22 months of age, whereas the young (3 month) and old controls (24 months) had only water to drink. The volumes of molecular, granular, and white matter layers of the cerebellar vermis in folia II, IV, VII, and X were measured by using systematic sampling and a point-counting method. The volumes of the granular and white matter layers showed consistent increase between 3 and 24 months of age, whereas the volume of the molecular layer remained unchanged with increasing age. Individual ethanol intake was measured over a 1-week period at the beginning and at the end of chronic ethanol exposure. Significant (ANOVA, p = 0.0oO) sex difference was found in the drinking behavior in both lines, with females consuming more alcohol than males (daily ethanol consumption at 22 months of age 3.2 f 0.3 vs. 7.1 f 0.3 glkg for AA males and females; 3.2 f 0.3 vs. 5.4 f 0.4 glkg for ANA males and females, respectively). The only ethanol-induced effect on the cerebellum was observed in ANA-EtOH females with a 15% reduction in the volumes of the molecular and granular layer in folium II compared with agematched controls and a significant ( p c 0.05, analysis of covariance with ethanol intake as a covariate) line difference in folium II (molecular and granular layers) was observed between ANA-EtOH females and AA-EtOH females. Furthermore, the volume of the molecular layer in folium II was significantly ( p c 0.05, analysis of covariance with ethanol intake and body weights as covariates) reduced for ANA-EtOH females, compared with ANA-EtOH males indicating a sex difference in the cerebellar degeneration due to chronic alcohol consumption. Of the three layers studied, the white matter layer was the most resistant layer to the effects caused by chronic alcohol consumption. In view of the fact that AA and ANA rats of both sexes differ regarding the drinking behavior and ethanol metabolism, they provide an important model for further research on ethanol-induced pathological changes in the central nervous system.

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Disruption of Frontocerebellar Circuitry and Function in Alcoholism

Alcoholism: Clinical & Experimental Research, 2003

This article represents a symposium of the 2002 joint meeting of RSA and ISBRA held in San Francisco. Presentations were Neuropathology of alcohol-related cerebellar damage in humans, by Antony J. Harding; Neuropathological evidence of cerebellar damage in an animal model of alcoholism, by Roberta Pentney and Cynthia Dlugos; Understanding cortical-cerebellar circuits through neuroimaging study of chronic alcoholics, by

Cerebellar Hypermetabolism in Alcohol Use Disorder: Compensatory Mechanism or Maladaptive Plasticity

Background: Despite severe structural brain abnormalities within the frontocerebellar circuit (FCC), cerebellar metabolism studied with 18 F-2-fluoro-deoxy-glucose-positron emission tomography (FDG-PET) is relatively preserved in patients with alcohol use disorder (AUD). The compensatory role of the cerebellum has been explored mainly through fMRI examination of AUD patients with the preserved level of performance. The present study aims at examining cerebellar metabolism and its relationship with regional brain metabolism and neuropsychological functioning in AUD patients. Methods: Thirty-two recently detoxified AUD patients and 23 controls underwent an FDG-PET examination at rest. Participants also performed a neuropsychological battery assessing executive functions , verbal memory, and ataxia. Results: Compared to controls, AUD patients had higher glucose uptake in the cerebellar lobule VIII, in association with hypometabolism, notably in several nodes of the FCC. Cerebellar hypermetabolism correlated negatively with regional hypometabolism in the premotor and frontal cortices. This pattern of regional hypermetabolism and hypometabolism related to ataxia and working memory deficits. Conclusions: These specific brain-behavior relationships do not fulfill the criteria for brain compensatory processes. Cerebellar hypermetabolism may rather reflect the involvement of different pathological mechanisms, leading to a maladaptive plasticity phenomenon within the FCC in AUD patients who are early in abstinence. Further studies are required to examine the contributions of structural and functional connectivity alterations in the cerebellar hypermetabolism and the changes in these pathological mechanisms with abstinence or relapse.

Developmental Differences in Childhood Motor Coordination Predict Adult Alcohol Dependence: Proposed Role for the Cerebellum in Alcoholism

Alcoholism: Clinical & Experimental Research, 2005

The Danish Longitudinal Study of Alcoholism has identified a number of early biological indicators that predicted alcohol dependence 30 years later. In light of recent evidence linking deficits of the cerebellum to certain neuropsychiatric disorders often comorbid with alcoholism, we hypothesized that developmental deficits in the cerebellar vermis may also play a role in the initiation of adult alcohol dependence. The present study evaluated whether measures of motor development in the first year of life predict alcohol dependence three decades later.

Prefrontal Cortex, Thalamus, and Cerebellar Volumes in Adolescents and Young Adults with Adolescent-Onset Alcohol Use Disorders and Comorbid Mental Disorders

Alcoholism-clinical and Experimental Research, 2005

In adults, prefrontal, thalamic, and cerebellar brain injury is associated with excessive ethanol intake. As these brain structures are actively maturing during adolescence, we hypothesized that subjects with adolescent-onset alcohol use disorders, compared with control subjects, would have smaller brain volumes in these areas. Thus, we compared prefrontal-thalamic-cerebellar measures of adolescents and young adults with adolescent-onset alcohol use disorders (AUD, defined as DSM-IV alcohol dependence or abuse) with those of sociodemographically similar control subjects.

Cerebellar Volume in Offspring From Multiplex Alcohol Dependence Families

Biological Psychiatry, 2007

Background: Increased susceptibility for developing alcohol dependence (AD) might be related to structural differences in brain circuits that influence the salience of rewards and/or modify the efficiency of information processing. The role of the cerebellum in regulating cognitive functions is being increasingly recognized along with its well-known influence on motor performance. Additionally, developmental changes in cerebellar volume during adolescence have been reported. Methods: Magnetic resonance imaging was used to measure the cerebellum in 17 high-risk adolescent and young adult offspring from multiplex alcohol dependence families and 16 control subjects matched for gender, age, and IQ. Results: High-risk (HR) adolescents/young adults showed increased total cerebellum volume and total grey in comparison with control subjects. Age-related decreases in total grey volume were seen with age, a pattern that was not seen in HR offspring. Conclusions: Offspring from multiplex families for AD manifest genetic susceptibility by having larger cerebellar volume, which seems to be related to lesser grey matter pruning for age. Larger cerebellar volumes in adult obsessive compulsive disorder (OCD) patients have been reported. This suggests a possible similarity in structural underpinnings for alcohol dependence and OCD.

Remapping the Brain to Compensate for Impairment in Recovering Alcoholics

2012

Abnormal brain activity may reflect compensation when observed in patients who perform normally on tests requiring functions usually observed as impaired. Operational criteria defining compensation have been described and aid in distinguishing compensatory from chance events. Here, we tested whether previously published functional magnetic resonance imaging data acquired in 15 recovering alcoholics and 15 controls at rest and while performing a spatial working memory task would fulfill criteria defining functional compensation. Multivariate analysis tested how well abnormal activation in the affected group predicted normal performance, despite low or no activation in brain regions invoked by controls to accomplish the same task. By identifying networks that uniquely and positively correlated with good performance, we provide evidence for compensatory recruitment of cerebellar-based functional networks by alcoholics. Whereas controls recruited prefrontal-cerebellar regions VI/Crus I known to subserve working memory, alcoholics recruited 2 other parallel frontocerebellar loops: dorsolateral prefrontal cortex (DLPFC)-cerebellar VIII system during rest and DLPFC-cerebellar VI system while task engaged. Greater synchronous activity between cerebellar lobule VIII and DLPFC at rest and greater activation within cerebellar lobule VI and DLPFC during task predicted better working memory performance. Thus, higher intrinsic cerebellar activity in alcoholics was an adequate condition for triggering task-relevant activity in the frontal cortex required for normal working memory performance.

High ethanol intake and malnutrition in alcoholic cerebellar shrinkage

QJM, 2000

To determine the influence of chronic ethanol intake lar shrinkage (n=33) were older ( p=0.05) and tended to report greater daily ethanol intake than and nutritional status on cerebellar shrinkage in alcoholism, we studied 12 undernourished patients alcoholics without cerebellar shrinkage (n=15), although not significantly so ( p=0.09). Cerebellar with acute Wernicke's encephalopathy (WE), 12 undernourished and 24 well-nourished asympto-volume correlated negatively with age in controls and asymptomatic alcoholics (rÁ0.52, p∏0.01, matic chronic alcoholics, and 24 age-matched wellnourished controls, using morphometric analysis both), with a significantly greater shrinkage for age in the latter ( p=0.003). Logistic regression anal-of MRI scans with volumetry of the cerebellum. Alcoholics reported a mean daily intake of ethanol ysis showed that malnutrition (OR 6.6 [95%CI 1.7-25.6], p=0.005) and a daily ethanol intake of of 177±8 g over a period of 27±1 years. Most undernourished alcoholics and half of the well-more than 140 g over ten years .5], p=0.003) were independently associated nourished alcoholics, compared to one-tenth of the controls, showed a significant reduction in cerebel-with the development of cerebellar shrinkage. lar volume ( p∏0.01, both). Alcoholics with cerebel-

Contributions of age and alcohol consumption to cerebellar integrity, gait and cognition in non-demented very old individuals

European Archives of Psychiatry and Clinical Neuroscience, 2006

j Abstract Gait disturbance and cognitive changes are common with ageing. The cerebellum contributes to motor coordination and participates in various aspects of cognition. However, no research has investigated the possible cerebellar contribution to gait and cognition in non-demented very old individuals. The current study aimed to determine the associations between indices of cerebellar size (vermal area and total volume) and measures of motor and cognitive integrity, as well as the role of variables known to impact on cerebellar size (alcohol consumption and chronological age) in a sample of 111 community dwellers (mean age: 85 years; range: 81-97 years). A marginally significant association was present between age and total vermal area. Significant correlations between current daily alcohol intake and some vermal areas were observed. These associations were more pronounced in men, particularly after controlling for cerebrum size. Multiple linear regression models revealed limited unique contributions of cerebellar predictors to neurological and cognitive measures. In summary, the results indicate that the cerebellum may be susceptible to alcohol-related shrinkage in non-demented very old individuals, more so in men, even at low dose. It also appears that the observed changes in cerebellum size in this population contribute little to neurological and cognitive changes. j

A comparison of ethanol concentrations in the occipital lobe and cerebellum

Forensic Science International, 1997

While many publications have addressed the issue of ethanol concentration in brain tissue as a better indicator of impairment than blood alcohol concentration (BAC), very few have looked at the regional distribution of ethanol in the brain and its possible significance in postmortem sampling. This paper reports on the analysis of occipital pole and cerebellar hemisphere for ethanol in 25 / brain samples obtained at autopsy from the brain collection of the National Institutes of Mental Health / Stanley Foundation. When available, these concentrations were compared to BAC. The average ratio of occipital lobe alcohol concentration (OAC) to BAC for cases which also had blood samples (18 / 24) was 0.9, SD50.5, with a range of 0-1.8; the average ratio of cerebellar alcohol concentration (CAC) to BAC for these cases was 0.6, SD50.4, range50-1.2. When only those cases with a BAC $0.04 g / dl (14 / 18 cases) were considered, the average OAC / BAC and CAC / BAC ratios were 0.8 (SD50.4) and 0.7 (SD50.4), respectively. These distribution ratios are well within the ranges reported by other authors and do not significantly differ from each other. The cortical brain region available or selected for postmortem ethanol analysis is probably not critical.

Relations between cognitive and motor deficits and regional brain volumes in individuals with alcoholism

Brain Structure and Function, 2019

Despite the common co-occurrence of cognitive impairment and brain structural deficits in alcoholism, demonstration of relations between regional gray matter volumes and cognitive and motor processes have been relatively elusive. In pursuit of identifying brain structural substrates of impairment in alcoholism, we assessed executive functions (EF), episodic memory (MEM), and static postural balance (BAL) and measured regional brain gray matter volumes of cortical, subcortical, and cerebellar structures commonly affected in individuals with alcohol dependence (ALC) compared with healthy controls (CTRL). ALC scored lower than CTRL on all composite scores (EF, MEM, and BAL) and had smaller frontal, cingulate, insular, parietal, and hippocampal volumes. Within the ALC group, poorer EF scores correlated with smaller frontal and temporal volumes; MEM scores correlated with frontal volume; and BAL scores correlated with frontal, caudate, and pontine volumes. Exploratory analyses investigating relations between subregional frontal volumes and composite scores in ALC yielded different patterns of associations, suggesting that different neural substrates underlie these functional deficits. Of note, orbitofrontal volume was a significant predictor of memory scores, accounting for almost 15% of the variance; however, this relation was evident only in ALC with a history of a non-alcohol substance diagnosis and not in ALC without a non-alcohol substance diagnosis. The brain-behavior relations observed provide evidence that the cognitive and motor deficits in alcoholism are likely a result of different neural systems and support the hypotheses that a number of identifiable neural systems rather than a common or diffuse neural pathway underlies cognitive and motor deficits observed in chronic alcoholism.

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Modulation of limbic-cerebellar functional connectivity enables alcoholics to recognize who is who

Brain Structure and Function, 2013

Chronic alcoholism is known to disrupt functions served by distributed brain systems, including limbic and frontocerebellar circuits involved in resting-state and task-activated networks subserving component processes of memory often affected in alcoholics. Using an fMRI paradigm, we investigated whether memory performance by alcoholics on a face-name association test previously observed to be problematic for alcoholics could be explained by desynchronous activity between nodes of these specific networks. While in the scanner, 18 alcoholics and 15 controls performed a face-name associative learning task with different levels of processing at encoding. This task was designed to activate the hippocampus, cerebellum, and frontal cortex. Alcoholics and controls were also scanned at rest. Twelve alcoholics and 12 controls were selected to be matched on face-name recognition performance. Task-related fMRI analysis indicated that alcoholics had preserved limbic activation but lower cerebellar activation (Crus II) than the controls in the facename learning task. Crus II was, therefore, chosen as a seed for functional connectivity MRI analysis. At rest, the left hippocampus and left Crus II had positively synchronized activity in controls, while hippocampal and cerebellar activities were negatively synchronized in alcoholics. Task engagement resulted in hippocampal-cerebellar desynchronization in both groups. We speculate that atypical cerebello-hippocampal activity synchronization during rest in alcoholics was reset to the normal pattern of asynchrony by task engagement. Aberrations from the normal pattern of resting-state default mode synchrony could be interpreted as enabling preserved face-name associative memory in alcoholism.

Function and Dysfunction of Prefrontal Brain Circuitry in Alcoholic Korsakoff’s Syndrome

Neuropsychology Review, 2012

The signature symptom of alcohol-induced persisting amnestic disorder, more commonly referred to as alcoholic Korsakoff's syndrome (KS), is anterograde amnesia, or memory loss for recent events, and until the mid 20th Century, the putative brain damage was considered to be in diencephalic and medial temporal lobe structures. Overall intelligence, as measured by standardized IQ tests, usually remains intact. Preservation of IQ occurs because memories formed before the onset of prolonged heavy drinking--the types of information and abilities tapped by intelligence tests--remain relatively well preserved compared with memories recently acquired. However, clinical and experimental evidence has shown that neurobehavioral dysfunction in alcoholic patients with KS does include nonmnemonic abilities, and further brain damage involves extensive frontal and limbic circuitries. Among the abnormalities are confabulation, disruption of elements of executive functioning and cognitive control, and emotional impairments. Here, we discuss the relationship between neurobehavioral impairments in KS and alcoholism-related brain damage. More specifically, we examine the role of damage to prefrontal brain systems in the neuropsychological profile of alcoholic KS.

Chronic alcohol consumption and its effect on nodes of frontocerebellar and limbic circuitry: Comparison of effects in France and the United States

Human Brain Mapping, 2014

Alcohol use disorders present a significant public health problem in France and the United States (U.S.), but whether the untoward effect of alcohol on the brain results in similar damage in both countries remains unknown. Accordingly, we conducted a retrospective collaborative investigation between two French sites (Caen and Orsay) and a U.S. laboratory (SRI/Stanford University) with T1weighted, structural MRI data collected on a common imaging platform (1.5T, General Electric) on 288 normal controls (NC), 165 uncomplicated alcoholics (ALC), and 26 patients with alcoholic Korsakoff's syndrome (KS) diagnosed at all sites with a common interview instrument. Data from the two countries were pooled, then preprocessed and analyzed together at the U.S. site using atlas-based parcellation. National differences indicated that thalamic volumes were smaller in ALC in France than the U.S. despite similar alcohol consumption levels in both countries. By contrast, volumes of the hippocampus, amygdala, and cerebellar vermis were smaller in KS in the U.S. than France. Estimated amount of alcohol consumed over a lifetime, duration of alcoholism, and length of sobriety were significant predictors of selective regional brain volumes in France and in the U.S. The common analysis of MRI data enabled identification of discrepancies in brain volume deficits in France and the U.S. that may reflect

Cognitive functioning in older adults with early, late, and very late onset alcohol dependence

International Psychogeriatrics, 2014

ABSTRACTBackground:Alcohol dependence in older adults is associated with cognitive impairment. Age of onset of alcohol dependence is an important criterion to distinguish subgroups of alcohol-dependent people. Little is known about the influence of the age of onset of alcohol dependence on cognitive functioning. The primary aim of this study was to examine if older alcohol-dependent people with early, late or very late onset of alcohol dependence differ in terms of cognitive dysfunction.Methods:A total of eighty-five older alcohol-dependent people who were admitted to an inpatient detoxification program, were categorized into three age of onset groups: early onset (< 25 years: N = 27, mean age 57.7 ± 7.4), late onset (25–44 years: N = 28, mean age 61.1 ± 6.7) and very late onset (≥ 45 years: N = 30, mean age 65.6 ± 6.5). A neuropsychological test battery (Kaufman-Short Neuropsychological Assessment Procedure (K-SNAP), Trail Making Test (TMT) and Stroop Color Word Test) was admini...

Brain Responsivity to Emotional Faces Differs in Alcoholic Men and Women

2019

Inclusion of women in alcoholism research has shown that gender differences contribute to unique profiles of cognitive, emotional, and neuropsychological dysfunction. We employed functional magnetic resonance imaging (fMRI) of abstinent long-term alcoholics (21 women [ALCw] and 21 men [ALCm]) and demographically-similar nonalcoholic controls (21 women [NCw] and 21 men [NCm]) to explore how gender and alcoholism interact to influence emotional processing and memory. Participants completed a delayed match-to-sample emotional face memory fMRI task. While the results corroborated reports implicating amygdalar, superior temporal, and cerebellar involvement in emotional processing overall, the alcoholic participants showed hypoactivation of the left intraparietal sulcus to encoding the identity of the emotional face stimuli. The nonalcoholic participants demonstrated more reliable gender differences in neural responses to encoding the identity of the emotional faces than did the alcoholic...

Coordination and Cognition in Pure Nutritional Wernicke’s Encephalopathy with Cerebellar Degeneration after COVID-19 Infection: A Unique Case Report

Journal of Clinical Medicine

Background: Alcoholic cerebellar degeneration is a restricted form of cerebellar degeneration, clinically leading to an ataxia of stance and gait and occurring in the context of alcohol misuse in combination with malnutrition and thiamine depletion. However, a similar degeneration may also develop after non-alcoholic malnutrition, but evidence for a lasting ataxia of stance and gait and lasting abnormalities in the cerebellum is lacking in the few patients described with purely nutritional cerebellar degeneration (NCD). Methods: We present a case of a 46-year-old woman who developed NCD and Wernicke’s encephalopathy (WE) due to COVID-19 and protracted vomiting, resulting in thiamine depletion. We present her clinical course over the first 6 months after the diagnosis of NCD and WE, with thorough neuropsychological and neurological examinations, standardized clinical observations, laboratory investigations, and repeated MRIs. Results: We found a persistent ataxia of stance and gait a...

Alcohol and the Brain

Nutrients, 2021

Alcohol works on the brain to produce its desired effects, e.g., sociability and intoxication, and hence the brain is an important organ for exploring subsequent harms. These come in many different forms such as the consequences of damage during intoxication, e.g., from falls and fights, damage from withdrawal, damage from the toxicity of alcohol and its metabolites and altered brain structure and function with implications for behavioral processes such as craving and addiction. On top of that are peripheral factors that compound brain damage such as poor diet, vitamin deficiencies leading to Wernicke-Korsakoff syndrome. Prenatal alcohol exposure can also have a profound impact on brain development and lead to irremediable changes of fetal alcohol syndrome. This chapter briefly reviews aspects of these with a particular focus on recent brain imaging results. Cardiovascular effects of alcohol that lead to brain pathology are not covered as they are dealt with elsewhere in the volume.