Revealing the Unseen: Detecting Negative Symptoms in Students.

Background: The transnosographic nature of negative symptoms (NS) makes them fruitful for detecting psychiatric symptoms. The main objective of this study was to determine whether NS can be useful in screening for ultra-high risk of psychosis (UHR) or depressive symptoms in the no-help-seeking student population. The most prevalent NS and their relationship with cannabis use were also researched. Methods: From an online survey sent to students, 2128 filled out the Self-evaluation of Negative Symptoms (SNS), Prodromal Questionnaire 16 (PQ-16), Beck Depression Inventory (BDI), and Cannabis Abuse Screening Test (CAST). Results: 367 students (17.2%, 95% CI [15.6-18.9]) were considered to have UHR (PQ-16 distress score ≥ 9) and/or depression (BDI ≥ 16). The receiver operation characteristic curve showed that a threshold of 13 for the SNS score discriminated this subgroup of students with a sensitivity and specificity of 79.8% and 70.6%, respectively. The motivational dimension was overrepresented and linked to cannabis use. Conclusions: The early detection of NS in the no-help-seeking student population is relevant for detecting depressive and prodromal symptoms. This will enable early intervention to limit the progression to chronic mental disorders. The predominance of NS linked to the amotivational dimension was observed and related to cannabis use.

Structural brain substrates of the deficits observed on the BEARNI test in alcohol use disorder and Korsakoff's syndrome.

Chronic and excessive alcohol consumption can result in alcohol use disorder (AUD) without neurological complications and in Korsakoff's syndrome (KS) when combined with thiamine deficiency. These two clinical forms are accompanied by widespread structural brain damage in both the fronto-cerebellar (FCC) and Papez circuits (PC) as well as in the parietal cortex, resulting in cognitive and motor deficits. BEARNI is a screening tool especially designed to detect neuropsychological impairments in AUD. However, the sensitivity of this tool to the structural brain damage of AUD and KS patients remains unknown. Eighteen KS patients, 47 AUD patients and 27 healthy controls (HC) underwent the BEARNI test and a 3 T-MRI examination. Multiple regression analyses conducted between GM density and performance on each BEARNI subtest revealed correlations with regions included in the FCC, PC, thalamus and posterior cortex (precuneus and calcarine regions). All these brain regions were altered in KS compared to HC, in agreement with the cognitive deficits observed in the corresponding BEARNI subtests. The comparison between KS and AUD regarding the GM density in the several nodes of the FCC and calcarine regions revealed that they were atrophied to the same extent, suggesting that BEARNI is sensitive to the severity of alcohol-related GM abnormalities. Within the PC, the density of the cingulate cortex and thalamus, which correlated with the memory and fluency subscores, was smaller in KS than in AUD, suggesting that BEARNI is sensitive to specific brain abnormalities occurring in KS.

Early Improvement of Neuropsychological Impairments During Detoxification in Patients with Alcohol Use Disorder.

AIMS: To assess recovery of alcohol-related neuropsychological deficits in a group of patients with pure severe alcohol use disorder (AUD) during a detoxification program using the Brief Evaluation of Alcohol-Related Neuropsychological Impairment (BEARNI) test. METHODS: Thirty-two patients with severe AUD using DSM-IV criteria (24 men, mean age = 45.5 ± 6.8 years old) were assessed using the BEARNI 8 ± 2 days after alcohol cessation (T1) and then were reassessed within 18 ± 2 days after alcohol cessation (T2). The primary study endpoint was the number of patients initially impaired at T1 who recovered cognitive functions at T2 assessment. RESULTS: At T1, 59% (n = 19) patients with pure severe AUD had at least one impaired cognitive function assessed by the BEARNI. At T2, 63% of the patients with AUD with deficits at T1 had normal BEARNI cognitive scores (χ2 = 7.7, P = 0.005); specifically, the percentages of participants with normal subtest scores were 63% on memory (χ2 = 12.4, P = 0.0004), 100% on verbal fluency (χ2 = 16; P = <0.0001), 60% on alphabetical span (χ2 = 12.8; P = 0.0003) and 67% on visuospatial (χ2 = 15, P = 0.0001). CONCLUSIONS: The cognitive impairments of two-thirds of patients with pure AUD included in the present study recovered within 18 days of abstinence, earlier than reported in previous studies.

Why should we ask binge drinkers if they smoke cannabis? Additive effect of alcohol and cannabis use on college students' neuropsychological performance.

INTRODUCTION: Binge drinking (BD) and cannabis use are prevalent in European adolescents and students. BD has been shown to have a negative impact on neuropsychological functioning, but little is known about the additive effect when it is combined with cannabis consumption. We therefore investigated the neuropsychological profiles of students who engage in combined BD and cannabis use, in order to explore the potentially harmful additive effects of cannabis use and BD on cognition. MATERIAL AND METHODS: A sample of college students (N = 298) completed questionnaires on alcohol and cannabis use, and were screened for neuropsychological impairments using the Brief Evaluation of Alcohol-Related Neuropsychological Impairments (BEARNI). First, after dividing students into three groups according to their alcohol and cannabis use (i.e., light drinkers, binge drinkers, and binge drinkers consuming cannabis), we ran a linear mixed model based on the BEARNI z scores to test the performances of the three groups. Information yielded by the mixed model was supplemented by individual analyses. Second, to explore the heterogeneity of binge drinkers' profiles, we ran a cluster analysis to characterize the alcohol users at higher risk of more severe neuropsychological impairment. RESULTS: Overall, poorer neuropsychological performances were observed among binge drinkers compared with light drinkers, whether they used cannabis or not. However, flexibility, episodic memory and working memory were particularly affected among binge drinkers who used cannabis. CONCLUSIONS: Results emphasize the importance of asking binge drinkers if they smoke cannabis, in order to adapt care and prevention strategies to their consumption and neuropsychological profile.

What really matters in binge drinking: A dominance analysis of binge drinking psychological determinants among University students.

INTRODUCTION: Binge drinking (BD) is a public health concern, especially in young people. Multiple individual factors referring to different level of analyses - positional, inter-individual and intra-individual - are associated to BD. As they have mainly been explored separately, little is known about the psychological variables most associated with BD. This study, based on an integrative model considering a large number of variables, aims to estimate these associations and possible dominance of some variables in BD. METHODS: A sample of university students (N = 2851) participated in an internet survey-based study. They provided information on alcohol related variables (AUDIT, BD score), positional factors (sex, age), inter-individual factors (subjective norm, social identity, external motivations), and intra-individual factors (internal motivations, meta-cognitions, impulsivity and personality traits). The data were processed via a backward regression analysis including all variables and completed with a dominance analysis on variables that are significantly associated with BD intensity. RESULTS: The strongest variables associated with BD intensity were enhancement motives and drinking identity (average ΔR 2 = 21.81%), followed by alcohol subjective norm and social motives (average ΔR 2 = 13.99%). Other associated variables (average ΔR 2 = 2,84%) were negative metacognition on uncontrollability, sex, coping motives, lack of premeditation, positive metacognition on cognitive self-regulation, positive urgency, lack of perseverance, age, conformity motives and loneliness. CONCLUSION: Results offer new avenues at the empirical level, by spotting particularly inter-individual psychological variables that should be more thoroughly explored, but also at the clinical level, to elaborate new prevention strategies focusing on these specific factors.

Early Identification of Alcohol Use Disorder Patients at Risk of Developing Korsakoff's Syndrome.

BACKGROUND: The aim of the present study was to determine whether the Brief Evaluation of Alcohol-Related Neuropsychological Impairments (BEARNI), a screening tool developed to identify neuropsychological deficits in alcohol use disorder (AUD) patients, can also be used for the early identification of AUD patients at risk of developing Korsakoff's syndrome (KS). METHODS: Eighteen KS patients, 47 AUD patients and 27 healthy controls underwent BEARNI testing (including 5 subtests targeting episodic memory, working memory, executive function, visuospatial abilities, and ataxia) and a comprehensive neuropsychological examination. RESULTS: Performance of AUD and KS patients on BEARNI subtests was consistent with the results on the standardized neuropsychological assessment. On BEARNI, ataxia and working memory deficits observed in AUD were as severe as those exhibited by KS patients, whereas for visuospatial abilities, a graded effect of performance was found. In contrast, the subtests involving long-term memory abilities (episodic memory and fluency) were impaired in KS patients only. AUD patients with a score lower than 1.5 points (out of 6) on the episodic memory subtest of BEARNI exhibited the lowest episodic memory performance on the neuropsychological battery and could be considered at risk of developing KS. CONCLUSIONS: These findings suggest that BEARNI is a useful tool for detecting severe memory impairments, suggesting that it could be used for the early identification of AUD patients at high risk of developing KS.

Thiamine and phosphate esters concentrations in whole blood and serum of patients with alcohol use disorder: a relation with cognitive deficits.

Background: In this study, we investigated (1) the effect of chronic and excessive alcohol consumption on whole blood (WB) and serum concentrations of thiamine and its metabolites after supplementation, and (2) the relationship between the perturbations of thiamine metabolism and neuropsychological abilities.Methods: WB and serum samples were collected in patients with Alcohol Use Disorder (AUD) and in healthy control subjects (after oral thiamine supplementation, or without supplementation). Thiamine (Th), thiamine monophosphate (TMP) and thiamine diphosphate (TDP) were quantified. The Brief Evaluation of Alcohol-Related Neuropsychological Impairments (BEARNI) and the Montreal Cognitive Assessment (MoCA) were performed by each AUD participant. Based on the BEARNI score, two groups of AUD patients were studied: AUD patients with no or mild cognitive impairment (AUD COG+), and AUD patients with moderate-to-severe cognitive impairment (AUD COG-).Results: In WB, Th concentrations were significantly higher, and percentages of phosphate esters of thiamine were significantly lower in AUD COG- patients compared to controls. In serum, Th concentrations were significantly higher in AUD COG- patients compared to controls. The percentage of Th in serum was significantly higher in AUD COG- patients compared to AUD COG+ patients, and to the groups of controls. When adjusted on education level, the percentage of Th in serum in AUD patients negatively correlated with the scores at BEARNI and MoCA, and Th concentration in serum negatively correlated with MoCA.Conclusions: These data support an impairment of metabolism and/or distribution of thiamine in AUD patients, and a relationship with the development of alcohol-related cognitive deficits.

What We Talk About When We Talk About Binge Drinking: Towards an Integrated Conceptualization and Evaluation.

RATIONALE: Binge drinking (BD), characterized by recurring alternations between intense intoxication episodes and abstinence periods, is the most frequent alcohol consumption pattern in youth and is growing in prevalence among older adults. Many studies have underlined the specific harmful impact of this habit by showing impaired abilities in a wide range of cognitive functions among binge drinkers, as well as modifications of brain structure and function. AIMS: Several controversies and inconsistencies currently hamper the harmonious development of the field and the recognition of BD as a specific alcohol consumption pattern. The main concern is the absence of consensual BD conceptualization, leading to variability in experimental group selection and alcohol consumption evaluation. The present paper aims at overcoming this key issue through a two-step approach. METHODS AND CONCLUSIONS: First, a literature review allows proposing an integrated BD conceptualization, distinguishing it from other subclinical alcohol consumption patterns. Six specific characteristics of BD are identified, namely, (1) the presence of physiological symptoms related to BD episodes, (2) the presence of psychological symptoms related to BD episodes, (3) the ratio of BD episodes compared to all alcohol drinking occasions, (4) the frequency of BD episodes, (5) the consumption speed and (6) the alternation between BD episodes and soberness periods. Second, capitalizing on this conceptual clarification, we propose an evaluation protocol jointly measuring these six BD characteristics. Finally, several research perspectives are presented to refine the proposed conceptualization.

Distinct psychological profiles among college students with substance use: A cluster analytic approach.

Substance use in youth is a central public health concern, related to deleterious consequences at psychological, social, and cognitive/cerebral levels. Previous research has identified impulsivity and consumption motives as key factors in the emergence of excessive substance use among college students. However, most studies have focused on a specific substance and have considered this population as a unitary group, ignoring the potential heterogeneity in psychological profiles. We used a cluster analytic approach to explore the heterogeneity in a large sample (N = 2741) of substance users (i.e., tobacco, alcohol, cannabis, ecstasy, cocaine, heroin) on impulsivity and consumption motives. We identified four clusters: The first two clusters, associated with good self-esteem, low anxiety, and moderate substance use, were respectively characterized by low impulsivity and consumption motives (Cluster 1) and by high social and enhancement motives without marked impulsivity (Cluster 2). The two other clusters were conversely related to low self-esteem and high anxiety, and characterized by high consumption motives (particularly conformity) together with elevated urgency (Cluster 3) and by globally increased impulsivity and consumption motives (Cluster 4). These two clusters were also associated with higher substance use. These results highlight the existence of distinct psychological profiles of substance users and underline the need to develop targeted prevention and intervention programs (e.g., focusing on the specific impulsivity facets and consumption motives presented by each subgroup). Based on these findings, we also suggest extending the exploration of distinct profiles of substance users by targeting other psychological variables (e.g., self-esteem).

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.

Neuropsychological and Neuroimaging Examinations of Self-Reported Sleep Quality in Alcohol Use Disorder With and Without Korsakoff's Syndrome.

BACKGROUND: Alcohol use disorder (AUD) patients without Korsakoff's syndrome (KS) report a variable self-rated sleep quality. Their ability to accurately judge their sleep quality may be related to their alcohol-related cognitive deficits and brain damage. KS patients, who present severe brain dysfunction, may be cognitively unable to judge their sleep quality. The aim of the present study is to examine, in AUD and KS patients, whether the absence of sleep complaint is associated with altered brain structure and impaired cognitive abilities within specific cerebral networks. METHODS: An assessment of subjective sleep quality was conducted in 20 healthy controls, 37 AUD patients, and 17 KS patients. Patients were first pooled together and then classified into 2 groups (no-complaintAUD + KS and complaintAUD + KS ) according to the total Pittsburg Sleep Quality Index score. Cognitive scores, gray matter (GM) volume, and white matter (WM) integrity were compared between these 2 groups, and then in AUD and KS patients separately. RESULTS: Poor sleep quality was reported by 70% of AUD and 18% of KS patients. Compared to controls, both no-complaintAUD + KS and complaintAUD + KS presented cortical and subcortical alterations as well as episodic memory deficits, which were more severe in patients without sleep complaint. Only no-complaintAUD + KS presented executive deficits. Then, considering the clinical diagnosis, GM volume in frontotemporal regions, WM integrity, and executive functions were affected to the same extent in AUD and KS patients without sleep complaint. CONCLUSIONS: Our results confirm the high prevalence of sleep complaint in AUD patients and the rare complaint in KS patients. In AUD and KS patients, the absence of sleep complaint may not indicate good sleep quality but rather reflect executive deficits and frontothalamic damage. Alcohol-related cognitive deficits may indeed alter the ability to self-evaluate sleep quality, suggesting that the use of sleep questionnaire should be considered with caution in patients with executive deficits.

Dissociating thalamic alterations in alcohol use disorder defines specificity of Korsakoff's syndrome.

The thalamus, a relay organ consisting of several nuclei, is shared between the frontocerebellar circuit and the Papez circuit, both particularly affected in alcohol use disorder. Shrinkage of the thalamus is known to be more severe in alcoholics with Korsakoff's syndrome than in those without neurological complications (uncomplicated alcoholics). While thalamic atrophy could thus be a key factor explaining amnesia in Korsakoff's syndrome, the loci and nature of alterations within the thalamic nuclei in uncomplicated alcoholics and alcoholics with Korsakoff's syndrome remains unclear. Indeed, the literature from animal and human models is disparate regarding whether the anterior thalamic nuclei, or the mediodorsal nuclei are particularly affected and would be responsible for amnesia. Sixty-two participants (20 healthy controls, 26 uncomplicated alcoholics and 16 patients with Korsakoff's syndrome) underwent a diffusion tensor imaging sequence and T1-weighted MRI. State-of-the-art probabilistic tractography was used to segment the thalamus according to its connections to the prefrontal cortex and cerebellar Cruses I and II for the frontocerebellar circuit's executive loop, the precentral gyrus and cerebellar lobes IV-VI for the frontocerebellar circuit's motor loop, and hippocampus for the Papez circuit. The connectivity and volumes of these parcellations were calculated. Tractography showed that the hippocampus was principally connected to the anterior thalamic nuclei while the prefrontal cortex was principally connected to the mediodorsal nuclei. The fibre pathways connecting these brain regions and their respective thalamic nuclei have also been validated. ANCOVA, with age and gender as covariates, on connectivity measures showed abnormalities in both patient groups for thalamic parcellations connected to the hippocampus only [F(2,57) = 12.1; P < 0.0001; η2 = 0.2964; with graded effects of the number of connections from controls to uncomplicated alcoholics to Korsakoff's syndrome]. Atrophy, on the other hand, was observed for the prefrontal parcellation in both patient groups and to the same extent compared to controls [F(2,56) = 18.7; P < 0.0001; η2 = 0.40]. For the hippocampus parcellation, atrophy was found in the Korsakoff's syndrome group only [F(2,56) = 5.5; P = 0.006; η2 = 0.170, corrected for multiple comparisons using Bonferroni, P < 0.01]. Post hoc Tukey's test for unequal sample sizes, healthy controls > patients with Korsakoff's syndrome (P = 0.0036). Two different mechanisms seem to affect the thalamus. In the frontocerebellar circuit, atrophy of the mediodorsal nuclei may lead to the alterations, whereas in the Papez circuit, disconnection between the anterior nuclei and hippocampus may be the leading factor. Shrinkage of the anterior nuclei could be specific to patients with Korsakoff's syndrome, hence a potential neuroimaging marker of its pathophysiology, or more generally of thalamic amnesia for which Korsakoff's syndrome has historically been used as a model.

Clinical and Biological Risk Factors for Neuropsychological Impairment in Alcohol Use Disorder.

The effects of alcoholism on cognitive and motor functioning are heterogeneous. While the role of some factors (patterns of alcohol consumption, eating habits or associated liver disease) has been hypothesized, the origins of this heterogeneity remain difficult to establish. The goals of the present study were thus to identify the clinical and biological risk factors for alcohol-related neuropsychological impairments and to determine the threshold beyond which these risk factors can be considered significant. Thirty alcoholic patients and 15 healthy controls had a blood test and underwent a neuropsychological examination. Alcohol severity measures, and liver, thiamine and malnutrition variables, were included in logistic regression models to determine the risk factors for cognitive and motor impairments (executive functions, visuospatial abilities, verbal episodic memory, ataxia), as well as those related to the severity of patients' overall neuropsychological profile (moderate or severe impairments). Liver fibrosis was found to be a risk factor for executive impairments and also for ataxia, when it was associated with long-term alcohol misuse and symptoms of withdrawal. Altered thiamine metabolism was solely predictive of verbal episodic memory impairments. This combination of biological abnormalities was associated with a profile of moderate neuropsychological impairments. Malnutrition was associated with a profile of more severe impairments. Malnutrition, altered liver function and thiamine metabolism explain, at least partially, the heterogeneity of alcohol-related neuropsychological impairments. Our findings could allow clinicians to identify patients at particular risk of severe neuropsychological impairments before the onset of irreversible and debilitating neurological complications.

[Alcohol-related neuropsychological impairments: Nature, impact and detection]. / Troubles cognitifs liés à l'alcool : nature, impact et dépistage.

Alcohol-related neuropsychological deficits result from chronic and excessive alcohol consumption and are associated with structural and functional damage of Papez's circuit and frontocerebellar circuit. Alcohol-related cognitive deficits are heterogeneous but especially affect executive functions and memory abilities. They result in difficulties to change alcohol behavior combined with a tendency for patients to overestimate their capacity to succeed. Alcohol-related cognitive deficits could be a risk-factor for relapse since they hamper patients to benefit fully from treatment (especially when based on relapse prevention). Screening tools usable by non-psychologists are available and can be completed by an extensive neuropsychological examination conducted by a neuropsychologist when necessary. Alcohol treatment should be adjusted to take alcohol-related cognitive deficits into account, by promoting longer treatment in healthy environment for example. Improvements of alcohol treatment options, including specific neuropsychological rehabilitation, are required for patients with persistent alcohol-related cognitive deficits.

Direct voxel-based comparisons between grey matter shrinkage and glucose hypometabolism in chronic alcoholism.

Alcoholism is associated with widespread brain structural abnormalities affecting mainly the frontocerebellar and the Papez's circuits. Brain glucose metabolism has received limited attention, and few studies used regions of interest approach and showed reduced global brain metabolism predominantly in the frontal and parietal lobes. Even though these studies have examined the relationship between grey matter shrinkage and hypometabolism, none has performed a direct voxel-by-voxel comparison between the degrees of structural and metabolic abnormalities. Seventeen alcoholic patients and 16 control subjects underwent both structural magnetic resonance imaging and (18)F-2-fluoro-deoxy-glucose-positron emission tomography examinations. Structural abnormalities and hypometabolism were examined in alcoholic patients compared with control subjects using two-sample t-tests. Then, these two patterns of brain damage were directly compared with a paired t-test. Compared to controls, alcoholic patients had grey matter shrinkage and hypometabolism in the fronto-cerebellar circuit and several nodes of Papez's circuit. The direct comparison revealed greater shrinkage than hypometabolism in the cerebellum, cingulate cortex, thalamus and hippocampus and parahippocampal gyrus. Conversely, hypometabolism was more severe than shrinkage in the dorsolateral, premotor and parietal cortices. The distinct profiles of abnormalities found within the Papez's circuit, the fronto-cerebellar circuit and the parietal gyrus in chronic alcoholism suggest the involvement of different pathological mechanisms.

Validation of a brief screening tool for alcohol-related neuropsychological impairments.

BACKGROUND: Alcohol-related neuropsychological impairments mainly affect episodic memory, working memory, and visuospatial abilities, as well as executive and motor functioning. These impairments can prevent alcoholic patients (ALs) early in abstinence from benefiting fully from treatment and reduce their ability to remain abstinent. A neuropsychological assessment seems essential for making the relevant clinical decisions. However, very few alcohol treatment departments have the financial and human resources needed to conduct an extensive neuropsychological examination of each AL. The goal of this study was therefore to assess the validity and the psychometric properties of the Brief Evaluation of Alcohol-Related Neuropsychological Impairments (BEARNI), a new screening tool especially designed to assess alcohol-related neuropsychological impairments. METHODS: A total of 254 healthy controls (HCs) completed the BEARNI, and 58 of them also performed an extensive neuropsychological battery. Seventy-three ALs underwent both the BEARNI and the neuropsychological battery. This extensive neuropsychological battery of proven classification accuracy served as the reference (i.e., gold standard) for determining the ALs' cognitive status. RESULTS: An exploratory factor analysis validated the BEARNI's underlying structure, highlighting 5 factors that reflected visuospatial abilities, executive functions, ataxia, verbal episodic memory, and verbal working memory. The standardization of each BEARNI subtest and the 2 total scores revealed that this test has sufficient diagnostic accuracy for the detection of ALs with cognitive and motor impairments. CONCLUSIONS: This study indicates that the BEARNI is a useful screening tool in clinical settings for detecting ALs' motor and cognitive impairments.

FDG-PET Contributions to the Pathophysiology of Memory Impairment.

Measurement of synaptic activity by Positron Emission Tomography (PET) and its relation to cognitive functions such as episodic memory, working memory and executive functions in healthy humans and patients with neurocognitive disorders have been well documented. In this review, we introduce the concept of PET imaging that allows the observation of a particular biological process in vivo through the use of radio-labelled compounds, its general use to the medical world and its contributions to the understanding of memory systems. We then focus on [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG-PET), the radiotracer that is used to measure local cerebral metabolic rate of glucose that is indicative of synaptic activity in the brain. FDG-PET at rest has been at the forefront of functional neuroimaging over the past 3 decades, contributing to the understanding of cognitive functions in healthy humans and how these functional patterns change with cognitive alterations. We discuss methodological considerations that are important for optimizing FDG-PET imaging data prior to analysis. We then highlight the contribution of FDG-PET to the understanding of the patterns of functional differences in non-degenerative pathologies, normal ageing, and age-related neurodegenerative disorders. Through reasonable temporal and spatial resolution, its ability to measure synaptic activity in the whole brain, independently of any specific network and disease, makes it ideal to observe regional functional changes associated with memory impairment.

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 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.

Integrity of white matter microstructure in alcoholics with and without Korsakoff's syndrome.

Alcohol dependence results in two different clinical forms: "uncomplicated" alcoholism (UA) and Korsakoff's syndrome (KS). Certain brain networks are especially affected in UA and KS: the frontocerebellar circuit (FCC) and the Papez circuit (PC). Our aims were (1) to describe the profile of white matter (WM) microstructure in FCC and PC in the two clinical forms, (2) to identify those UA patients at risk of developing KS using their WM microstructural integrity as a biomarker. Tract-based spatial statistics and nonparametric voxel-based permutation tests were used to compare diffusion tensor imaging (DTI) data in 7 KS, 20 UA, and 14 healthy controls. The two patient groups were also pooled together and compared to controls. k-means classifications were then performed on mean fractional anisotropy values of significant clusters across all subjects for two fiber tracts from the FCC (the middle cerebellar peduncle and superior cerebellar peduncle) and two tracts from the PC (fornix and cingulum). We found graded effects of WM microstructural abnormalities in the PC of UA and KS. UA patients classified at risk of developing KS using fiber tracts of the PC from DTI data also had the lowest scores of episodic memory. That finding suggests that WM microstructure could be used as a biomarker for early detection of UA patients at risk of developing KS.

Thalamic abnormalities are a cardinal feature of alcohol-related brain dysfunction.

Two brain networks are particularly affected by the harmful effect of chronic and excessive alcohol consumption: the circuit of Papez and the frontocerebellar circuit, in both of which the thalamus plays a key role. Shrinkage of the thalamus is more severe in alcoholics with Korsakoff's syndrome (KS) than in those without neurological complication (AL). In accordance with the gradient effect of thalamic abnormalities between AL and KS, the pattern of brain dysfunction in the Papez's circuit results in anterograde amnesia in KS and only mild-to-moderate episodic memory disorders in AL. On the opposite, dysfunction of the frontocerebellar circuit results in a similar pattern of working memory and executive deficits in the AL and KS. Several hypotheses, mutually compatible, can be drawn to explain that the severe thalamic shrinkage observed in KS has different consequences in the neuropsychological profile associated with the two brain networks.