Anne-Pascale Le Berre

Executive Functions, Memory, and Social Cognitive Deficits and Recovery in Chronic Alcoholism: A Critical Review to Inform Future Research

Alcoholism is a complex and dynamic disease, punctuated by periods of abstinence and relapse, and influenced by a multitude of vulnerability factors. Chronic excessive alcohol consumption is associated with cognitive deficits, ranging from mild to severe, in executive functions, memory, and metacognitive abilities, with associated impairment in emotional processes and social cognition. These deficits can compromise efforts in initiating and sustaining abstinence by hampering efficacy of clinical treatment and can obstruct efforts in enabling good decision making success in interpersonal/social interactions, and awareness of cognitive and behavioral dysfunctions. Despite evidence for differences in recovery levels of selective cognitive processes, certain deficits can persist even with prolonged sobriety. Herein is presented a review of alcohol-related cognitive impairments affecting component processes of executive functioning, memory, and the recently investigated cognitive domains of metamemory, social cognition, and emotional processing; also considered are trajectories of cognitive recovery with abstinence. Finally, in the spirit of critical review, limitations of current knowledge are noted and avenues for new research efforts are proposed that focus on (i) the interaction among emotion-cognition processes and identification of vulnerability factors contributing to the development of emotional and social processing deficits and (ii) the time line of cognitive recovery by tracking alcoholisms dynamic course of sobriety and relapse. Knowledge about the heterochronicity of cognitive recovery in alcoholism has the potential of indicating at which points during recovery intervention may be most beneficial.

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

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 Korsakoffs 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.

Anosognosia for Memory Impairment in Addiction: Insights from Neuroimaging and Neuropsychological Assessment of Metamemory

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.

Differential compromise of prospective and retrospective metamemory monitoring and their dissociable structural brain correlates

Metamemory refers to personal knowledge about ones own memory ability that invokes cognitive processes relevant to monitoring and controlling memory. An impaired monitoring system can potentially result in unawareness of symptoms as can occur in addiction denial. Monitoring processes can be assessed with prospective measures such as Feeling-Of-Knowing (FOK) judgments on prediction of future recognition performance, or retrospective confidence judgments (RCJ) made on previous memory performance. Alcoholic patients with amnesia showed poor FOK but intact RCJ. The neuropsychological continuum from mild to moderate deficits in nonamnesic to amnesic alcoholism raised the possibility that alcoholics uncomplicated by clinically-detectable amnesia may suffer anosognosia for their mild memory deficits. Herein 24 abstinent alcoholics and 26 age-matched controls completed an episodic memory paradigm including prospective FOK and retrospective RCJ monitoring measures and underwent 3T structural magnetic resonance imaging. Alcoholics were less accurate than controls in recognition and in assessing their future recognition performance, which was marked by overestimation, but were as accurate as controls on confidence ratings of actual recognition performance. Examination of brain structure-function relations revealed a double dissociation where FOK accuracy was selectively related to insular volume, and retrospective confidence accuracy was selectively related to frontolimbic structural volumes. Impaired FOK with intact RCJ was consistent with mild anosognosia and suggested evidence for neuropsychological and neural mechanisms of unawareness in addiction.

Sensitive biomarkers of alcoholism's effect on brain macrostructure: similarities and differences between France and the United States

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 alcoholisms 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 Korsakoffs 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 Wernickes encephalopathy, the precursor of KS. Identified structural brain abnormalities may provide biomarkers underlying alcoholisms 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.

Deviant functional activation and connectivity of the right insula are associated with lack of awareness of episodic memory impairment in nonamnesic alcoholism

A disorder of metamemory, expressed as unawareness of mnemonic ability, is typically associated with the profound amnesia of Korsakoffs Syndrome (KS). A similar but less severe type of limited awareness can also occur in non-KS alcoholism and is observed as an impairment in generating Feeling-of-Knowing (FOK) predictions about future recognition performance. We previously found that FOK accuracy was selectively related to volumes of the insula in alcoholics involved in the present study. Unknown, however, are the neural substrates of unawareness of memory impairment in alcoholism. A task-activated fMRI paradigm served to identify neural nodes and networks implicated in inaccurate self-estimation of mnemonic ability in sober alcoholics while they made prospective FOK judgments in an episodic memory paradigm. Lower activation in the right insula correlated with greater overestimations of future memory abilities in alcoholics. Weaker connectivity of the right insula with the left dorsal anterior cingulate cortex, a node of the salience network, and stronger connectivity of the right insula with the right ventromedial prefrontal cortex (vmPFC), a node of the default mode network (DMN), co-occurred in alcoholics relative to the controls. Specifically, alcoholics, who failed to desynchronize insula-vmPFC activity, had greater overestimation of their memory predictions and poorer recognition performance. This study provides novel support that deviant functional activation and connectivity involving the right insula, a hub of the salience network, appears to participate in disrupting metamemory functioning in alcoholics. Compromised FOK performance might result from disturbance of the switching mechanism between brain networks serving self-referential processes (i.e., DMN network) and networks serving externally-driven activities like memory monitoring (i.e., fronto-parietal network). Thus, compromise in insular network coupling could be a neural mechanism underlying anosognosia for subtle mnemonic impairment in nonamnesic alcoholism.

Neurological, nutritional and alcohol consumption factors underlie cognitive and motor deficits in chronic alcoholism: Factors underlying NP deficits

Variations in pattern and extent of cognitive and motor impairment occur in alcoholism (ALC). Causes of such heterogeneity are elusive and inconsistently accounted for by demographic or alcohol consumption differences. We examined neurological and nutritional factors as possible contributors to heterogeneity in impairment. Participants with ALC (n = 96) and a normal comparison group (n = 41) were examined on six cognitive and motor domains. Signs of historically determined subclinical Wernickes encephalopathy were detected using the Caine et al. criteria, which were based on postmortem examination and chart review of antemortem data of alcoholic cases with postmortem evidence for Wernickes encephalopathy. Herein, four Caine criteria provided quantification of dietary deficiency, cerebellar dysfunction, low general cognitive functioning and oculomotor abnormalities in 86 of the 96 ALC participants. Subgroups based on Caine criteria yielded a graded effect, where those meeting more criteria exhibited greater impairment than those meeting no to fewer criteria. These results could not be accounted for by history of drug dependence. Multiple regression indicated that compromised performance on ataxia, indicative of cerebellar dysfunction, predicted non‐mnemonic and upper motor deficits, whereas low whole blood thiamine level, consistent with limbic circuit dysfunction, predicted mnemonic deficits. This double dissociation indicates biological markers that contribute to heterogeneity in expression of functional impairment in ALC. That non‐mnemonic and mnemonic deficits are subserved by the dissociable neural systems of frontocerebellar and limbic circuitry, both commonly disrupted in ALC, suggests neural mechanisms that can differentially affect selective functions, thereby contributing to heterogeneity in pattern and extent of dysfunction in ALC.