All Publications

  • Neurological, nutritional, and alcohol consumption factors underlie cognitive and motor deficits in chronic alcoholism Addiction Biology Fama, R., Le Berre, A., Hardcastle, C., Sassoon, S., Zahr, N., Pfefferbaum, A., Sullivan, E. 2017
  • Effects of Childhood Trauma and Alcoholism History on Neuropsychological Performance in Adults with HIV Infection: An Initial Study. Journal of HIV/AIDS & Infectious Diseases Sassoon, S. A., Le Berre, A., Fama, R., Asok, P., Hardcastle, C., Chu, W., Pfefferbaum, A., Sullivan V 2017
  • Deviant Functional Activation and Connectivity of the Right Insula are Associated with Lack of Awareness of Episodic Memory Impairment in Nonamnesic Alcoholism. Cortex Le Berre, A., Müller-Oehring, E. M., Schulte, T., Serventi, M. R., Adolf, A., Sullivan, E. V. 2017
  • Executive Functions, Memory, and Social Cognitive Deficits and Recovery in Chronic Alcoholism: A Critical Review to Inform Future Research. Alcoholism, clinical, and experimental research Le Berre, A., Fama, R., Sullivan, E. V. 2017

    View details for DOI 10.1111/acer.13431

  • Differential compromise of prospective and retrospective metamemory monitoring and their dissociable structural brain correlates CORTEX Le Berre, A., Mueller-Oehring, E. M., Kwon, D., Serventi, M. R., Pfefferbaum, A., Sullivan, E. V. 2016; 81: 192-202
  • Anosognosia for Memory Impairment in Addiction: Insights from Neuroimaging and Neuropsychological Assessment of Metamemory. Neuropsychology review Le Berre, A., Sullivan, E. V. 2016: -?


    In addiction, notably Alcohol Use Disorder (AUD), patients often have a tendency to fail to acknowledge the reality of the disease and to minimize the physical, psychological, and social difficulties attendant to chronic alcohol consumption. This lack of awareness can reduce the chances of initiating and maintaining sobriety. Presented here is a model focusing on compromised awareness in individuals with AUD of mild to moderate cognitive deficits, in particular, for episodic memory impairment-the ability to learn new information, such as recent personal experiences. Early in abstinence, alcoholics can be unaware of their memory deficits and overestimate their mnemonic capacities, which can be investigated with metamemory paradigms. Relevant neuropsychological and neuroimaging results considered suggest that the alcoholics' impairment of awareness of their attenuated memory function can be a clinical manifestation explained mechanistically by neurobiological factors, including compromise of brain systems that result in a mild form of mnemonic anosognosia. Specifically, unawareness of memory impairment in AUD may result from a lack of personal knowledge updating attributable to damage in brain regions or connections supporting conscious recollection in episodic memory. Likely candidates are posterior parietal and medial frontal regions known to be integral part of the Default Mode Network (DMN) and the insula leading to an impaired switching mechanism between the DMN and the Central-Executive Control (i.e., Lateral Prefronto-Parietal) Network. The cognitive concepts and neural substrates noted for addictive disorders may also be relevant for problems in self-identification of functional impairment resulting from injury following war-related blast, sport-related concussion, and insidiously occurring dementia.

    View details for PubMedID 27447979

  • Sensitive biomarkers of alcoholism's effect on brain macrostructure: similarities and differences between France and the United States. Frontiers in human neuroscience Le Berre, A., Pitel, A., Chanraud, S., Beaunieux, H., Eustache, F., Martinot, J., Reynaud, M., Martelli, C., Rohlfing, T., Pfefferbaum, A., Sullivan, E. V. 2015; 9: 354-?


    Alcohol consumption patterns and recognition of health outcomes related to hazardous drinking vary widely internationally, raising the question whether these national differences are reflected in brain damage observed in alcoholism. This retrospective analysis assessed variability of alcoholism's effects on brain cerebrospinal fluid (CSF) and white matter volumes between France and the United States (U.S.). MRI data from two French sites (Caen and Orsay) and a U.S. laboratory (SRI/Stanford University) were acquired on 1.5T imaging systems in 287 controls, 165 uncomplicated alcoholics (ALC), and 26 alcoholics with Korsakoff's Syndrome (KS). All data were analyzed at the U.S. site using atlas-based parcellation. Results revealed graded CSF volume enlargement from ALC to KS and white matter volume deficits in KS only. In ALC from France but not the U.S., CSF and white matter volumes correlated with lifetime alcohol consumption, alcoholism duration, and length of sobriety. MRI highlighted CSF volume enlargement in both ALC and KS, serving as a basis for an ex vacuo process to explain correlated gray matter shrinkage. By contrast, MRI provided a sensitive in vivo biomarker of white matter volume shrinkage in KS only, suggesting a specific process sensitive to mechanisms contributing to Wernicke's encephalopathy, the precursor of KS. Identified structural brain abnormalities may provide biomarkers underlying alcoholism's heterogeneity in and among nations and suggest a substrate of gray matter tissue shrinkage. Proposed are hypotheses for national differences in interpreting whether the severity of sequelae observe a graded phenomenon or a continuum from uncomplicated alcoholism to alcoholism complicated by KS.

    View details for DOI 10.3389/fnhum.2015.00354

    View details for PubMedID 26157376

  • 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 Le Berre, A., Pitel, A., Chanraud, S., Beaunieux, H., Eustache, F., Martinot, J., Reynaud, M., Martelli, C., Rohlfing, T., Sullivan, E. V., Pfefferbaum, A. 2014; 35 (9): 4635-4653


    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 T1-weighted, 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 fundamental differences in the consequences of alcoholism on brain structure between the two countries, possibly related to genetic or environmental differences. Hum Brain Mapp 35:4635-4653, 2014. © 2014 Wiley Periodicals, Inc.

    View details for DOI 10.1002/hbm.22500

    View details for PubMedID 24639416

  • Brain Structural Substrates of Cognitive Procedural Learning in Alcoholic Patients Early in Abstinence ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH Ritz, L., Segobin, S., Le Berre, A. P., Lannuzel, C., Boudehent, C., Vabret, F., Eustache, F., Pitel, A. L., Beaunieux, H. 2014; 38 (8): 2208-2216


    Procedural learning allows for the acquisition of new behavioral skills. Previous studies have shown that chronic alcoholism is characterized by impaired cognitive procedural learning and brain abnormalities affecting regions that are involved in the automation of new cognitive procedures in healthy individuals. The goal of the present study was to investigate the brain structural substrates of cognitive procedural learning in alcoholic patients (ALs) early in abstinence.Thirty-one ALs and 31 control participants (NCs) performed the Tower of Toronto task (4 daily learning sessions, each comprising 10 trials) to assess cognitive procedural learning. We also assessed episodic and working memory, executive functions, and visuospatial abilities. ALs underwent 1.5T structural magnetic resonance imaging.The initial cognitive phase was longer in the AL group than in the NC group, whereas the autonomous phase was shorter. In ALs, the longer cognitive phase was predicted by poorer planning and visuospatial working memory abilities, and by smaller gray matter (GM) volumes in the angular gyrus and caudate nucleus. ALs' planning abilities correlated with smaller GM volume in the angular gyrus.Cognitive procedural learning was impaired in ALs, with a delayed transition from the cognitive to the autonomous phase. This slowdown in the automation of the cognitive procedure was related to lower planning abilities, which may have hampered the initial generation of the procedure to be learned. In agreement with this neuropsychological finding, a persistent relationship was found between learning performance and the GM volumes of the angular gyrus and caudate nucleus, which are usually regarded as markers of planning and initial learning of the cognitive procedure.

    View details for DOI 10.1111/acer.12486

    View details for Web of Science ID 000341181900009

    View details for PubMedID 25156613

  • Impaired decision-making and brain shrinkage in alcoholism EUROPEAN PSYCHIATRY Le Berre, A., Rauchs, G., La Joie, R., Mezenge, F., Boudehent, C., Vabret, F., Segobin, S., Viader, F., Allain, P., Eustache, F., Pitel, A., Beaunieux, H. 2014; 29 (3): 125-133


    Alcohol-dependent individuals usually favor instant gratification of alcohol use and ignore its long-term negative consequences, reflecting impaired decision-making. According to the somatic marker hypothesis, decision-making abilities are subtended by an extended brain network. As chronic alcohol consumption is known to be associated with brain shrinkage in this network, the present study investigated relationships between brain shrinkage and decision-making impairments in alcohol-dependent individuals early in abstinence using voxel-based morphometry. Thirty patients performed the Iowa Gambling Task and underwent a magnetic resonance imaging investigation (1.5T). Decision-making performances and brain data were compared with those of age-matched healthy controls. In the alcoholic group, a multiple regression analysis was conducted with two predictors (gray matter [GM] volume and decision-making measure) and two covariates (number of withdrawals and duration of alcoholism). Compared with controls, alcoholics had impaired decision-making and widespread reduced gray matter volume, especially in regions involved in decision-making. The regression analysis revealed links between high GM volume in the ventromedial prefrontal cortex, dorsal anterior cingulate cortex and right hippocampal formation, and high decision-making scores (P<0.001, uncorrected). Decision-making deficits in alcoholism may result from impairment of both emotional and cognitive networks.

    View details for DOI 10.1016/j.eurpsy.2012.10.002

    View details for Web of Science ID 000332523800002

    View details for PubMedID 23182846

  • Relationship Between Brain Volumetric Changes and Interim Drinking at Six Months in Alcohol-Dependent Patients ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH Segobin, S. H., Chetelat, G., Le Berre, A., Lannuzel, C., Boudehent, C., Vabret, F., Eustache, F., Beaunieux, H., Pitel, A. 2014; 38 (3): 739-748


    Chronic alcohol consumption results in brain damage potentially reversible with abstinence. It is however difficult to gauge the degree of recovery of brain tissues with abstinence since changes are subtle and a significant portion of patients relapse. State-of-the-art morphometric methods are increasingly used in neuroimaging studies to detect subtle brain changes at a voxel level. Our aim was to use the most refined morphometric methods to observe in alcohol dependence the relationship between volumetric changes and interim drinking over a 6-month follow-up.Overall, 19 patients with alcohol dependence received volumetric T1-weighted magnetic resonance imaging (MRI) after detoxification. A 6-month follow-up study was then conducted, during which 11 of them received a second MRI scan. First, correlations were conducted between gray matter (GM) and white matter (WM) volumes of patients at alcohol treatment entry and the amount of alcohol consumed between treatment entry and follow-up. Second, longitudinal analyses were performed from pairs of MRI scans using tensor-based morphometry in the 11 patients, and correlations were computed between the resultant Jacobian maps of GM and WM and interim drinking.Our preliminary results showed that, among others, alcoholics with smaller thalamus at alcohol treatment entry tended to resume with heavy alcohol consumption (p < 0.005 uncorrected [unc.]). Our longitudinal study revealed an overall inverse relationship between recovery of brain structures like the cerebellum, striatum, and cingulate gyrus, and the amount of alcohol consumed over the 6-month follow-up (p < 0.005 unc.). The recovery could be observed not only with strict abstinence but also in cases of moderate resumption of alcohol consumption, when there had been no drastic relapse into alcohol dependence.Those preliminary findings indicate that the volume of the thalamus at treatment entry may have an influence on subsequent interim drinking. There is recovery of certain brain regions even when patients resume with moderate, but not drastic, alcohol consumption.

    View details for DOI 10.1111/acer.12300

    View details for Web of Science ID 000332758200018

    View details for PubMedID 24483366

  • Readiness to change and brain damage in patients with chronic alcoholism PSYCHIATRY RESEARCH-NEUROIMAGING Le Berre, A., Rauchs, G., La Joie, R., Segobin, S., Mezenge, F., Boudehent, C., Vabret, F., Viader, F., Eustache, F., Pitel, A., Beaunieux, H. 2013; 213 (3): 202-209


    High motivation to change is a crucial triggering factor to patients' engagement in clinical treatment. This study investigates whether the low readiness to change observed in some alcoholic inpatients at treatment entry could, at least partially, be linked with macrostructural gray matter abnormalities in critical brain regions. Participants comprised 31 alcoholic patients and 27 controls, who underwent 1.5-T magnetic resonance imaging. The Readiness to Change Questionnaire, designed to assess three stages of motivation to change (precontemplation, contemplation and action stages), was completed by all patients, who were then divided into "Action" (i.e., patients in action stage) and "PreAction" (i.e., patients in precontemplation or in contemplation stage) subgroups. The PreAction subgroup, but not the Action subgroup, had gray matter volume deficits compared with controls. Unlike the patients in the Action subgroup, the PreAction patients had gray matter abnormalities in the cerebellum (Crus I), fusiform gyri and frontal cortex. The low level of motivation to modify drinking behavior observed in some alcoholic patients at treatment entry may be related to macrostructural brain abnormalities in regions subtending cognitive, emotional and social abilities. These brain volume deficits may result in impairment of critical abilities such as decision making, executive functions and social cognition skills. Those abilities may be needed to resolve ambivalence toward alcohol addiction and to apply "processes of change", which are essential for activating the desire to change problematic behavior.

    View details for DOI 10.1016/j.pscychresns.2013.03.009

    View details for Web of Science ID 000323934800004

    View details for PubMedID 23838052

  • Cognitive Barriers to Readiness to Change in Alcohol-Dependent Patients ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH Le Berre, A., Vabret, F., Cauvin, C., Pinon, K., Allain, P., Pitel, A., Eustache, F., Beaunieux, H. 2012; 36 (9): 1542-1549


    Patients' personal investment and readiness to change have proved to be a prerequisite for the successful treatment of alcohol addiction. The aim of this study was to determine the contribution of cognitive functions to the motivation process to abandon maladjusted behavior in favor of a healthier lifestyle.An adapted version of the "readiness to change" questionnaire was completed by 31 alcohol-dependent patients after detoxification and at alcohol treatment entry. This tool is designed to assess the 3 main stages of motivation to change regarding alcohol consumption: precontemplation (substance abuse and no intention to stop drinking), contemplation (strong intention to change habits but ambivalent behavior), and action (cessation of excessive alcohol consumption and behavioral changes for healthier habits) stages. Patients and 37 healthy controls also underwent an extensive neuropsychological battery including episodic memory, metamemory, executive functions, and decision-making assessment.When alcohol-dependent patients were considered as a group, the mean score on the action subscale was significantly higher than the precontemplation and contemplation ones. Nevertheless, when the stage of change reached by each patient was considered individually, we found that some alcohol-dependent patients were still in the earlier precontemplation and contemplation stages. Stepwise regression analysis revealed links between impaired memory and executive functions and low motivation, and between good decision-making skills and high motivation.Our results suggest that a set of complementary cognitive abilities is needed to achieve awareness and resolve ambivalence toward alcohol addiction, which is essential for activating the desire to change problematic behavior.

    View details for DOI 10.1111/j.1530-0277.2012.01760.x

    View details for Web of Science ID 000308435200010

    View details for PubMedID 22458335

  • Macrostructural abnormalities in Korsakoff syndrome compared with uncomplicated alcoholism NEUROLOGY Pitel, A., Chetelat, G., Le Berre, A. P., Desgranges, B., Eustache, F., Beaunieux, H. 2012; 78 (17): 1330-1333


    To distinguish, in patients with Korsakoff syndrome (KS), the structural brain abnormalities shared with alcoholic patients without KS (AL), from those specific to KS.MRI data were collected in 11 alcoholic patients with KS, 34 alcoholic patients without KS, and 25 healthy control subjects (CS). Gray and white matter volumes were compared in the 3 groups using a voxel-based approach.A conjunction analysis indicated a large pattern of shared gray and white matter volume deficits in AL and KS. There were graded effects of volume deficits (KS < AL < CS) in the medial portion of the thalami, hypothalamus (mammillary bodies), left insula, and genu of the corpus callosum. Abnormalities in the left thalamic radiation were observed only in KS.Our results indicate considerable similarities in the pattern of gray and white matter damage in AL and KS. This finding confirms the widespread neurotoxic effect of chronic alcohol consumption. Only a few cerebral regions, including the medial thalami, mammillary bodies, and corpus callosum, were more severely damaged in KS than in AL. The continuum of macrostructural damage from AL to KS is therefore restricted to key brain structures. Longitudinal investigations are required to determine whether alcoholic patients with medial thalamic volumes that are comparable to those of patients with KS are at increased risk of developing KS.

    View details for DOI 10.1212/WNL.0b013e318251834e

    View details for Web of Science ID 000303324100015

    View details for PubMedID 22496200

  • Study of Metamemory in Patients With Chronic Alcoholism Using a Feeling-of-Knowing Episodic Memory Task ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH Le Berre, A., Pinon, K., Vabret, F., Pitel, A., Allain, P., Eustache, F., Beaunieux, H. 2010; 34 (11): 1888-1898


    Alcoholism affects various cognitive processes, including components of memory. Metamemory, though of particular interest for patient treatment, has not yet been extensively investigated.?A feeling-of-knowing (FOK) measure of metamemory was administered to 28 alcoholic patients and 28 healthy controls during an episodic memory task including the learning of 20 pairs of items, followed by a 20-minute delayed recall and a recognition task. Prior to recognition, participants rated their ability to recognize each nonrecalled word among 4 items. This episodic FOK measure served to compare predictions of future recognition performance and actual recognition performance. Furthermore, a subjective measure of metamemory, the Metamemory In Adulthood (MIA) questionnaire, was completed by patients and controls. This assessment of alcoholic patients' metamemory profile was accompanied by an evaluation of episodic memory and executive functioning.FOK results revealed deficits in accuracy, with the alcoholic patients providing overestimations. There were also links between FOK inaccuracy, executive decline, and episodic memory impairment in patients. MIA results showed that although alcoholics did display memory difficulties, they did not differ from controls on questions about memory capacity.Chronic alcoholism affects both episodic memory and metamemory for novel information. Patients were relatively unaware of their memory deficits and believed that their memory was as good as that of the healthy controls. The monitoring measure (FOK) and the subjective measure of metamemory (MIA) showed that patients with chronic alcoholism overestimated their memory capacities. Episodic memory deficit and executive dysfunction would explain metamemory decline in this clinical population.

    View details for DOI 10.1111/j.1530-0277.2010.01277.x

    View details for Web of Science ID 000283594000008

    View details for PubMedID 20735374

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