Alcohol-related Memory Research Articles

Psilocybin prevents reinstatement of alcohol seeking by disrupting the reconsolidation of alcohol-related memories.

For most psychiatric conditions, including alcohol use disorder (AUD), FDA-approved pharmacological treatments are limited and their efficacy is restricted to only certain subgroups of patients. Scientific interest in the potential of psychedelic drugs has dramatically increased because of clinical preliminary evidence of efficacy in treating various psychiatric disorders. One of the most promising compounds belonging to this class of molecules is psilocybin. Here, to elucidate the therapeutic potential and treatment modalities of this drug, we investigated the effect of psilocybin on alcohol drinking and seeking in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats, a well validated animal model of AUD characterized by excessive drinking and seeking. Using male and female msP rats, we tested the effect of psilocybin on home cage voluntary alcohol consumption. We also tested the effect of the drug on the alcohol deprivation effect (ADE) model of relapse and on cue-induced reinstatement of alcohol seeking after a period of abstinence. Finally, we evaluated if psilocybin may disrupt the reconsolidation process of alcohol-related memory. Psilocybin did not reduce alcohol consumption, nor it prevented increased alcohol drinking after a period of forced abstinence and cue-induced reinstatement of alcohol-seeking. Noteworthy, in a memory retrieval-reconsolidation paradigm, psilocybin markedly attenuated resumption of alcohol seeking. Altogether these data suggest that, despite psilocybin does not affect alcohol drinking and relapse, it may be highly effective if used to block the reconsolidation process of alcohol-related memories. This opens to the possibility of using this psychedelic drug in clinical settings in which AUD patients undergo procedures to recall the memory of alcohol and are then treated with psilocybin during the memory reconsolidation phase.

Predicting Alcohol-Related Memory Problems in Older Adults: A Machine Learning Study with Multi-Domain Features.

Memory problems are common among older adults with a history of alcohol use disorder (AUD). Employing a machine learning framework, the current study investigates the use of multi-domain features to classify individuals with and without alcohol-induced memory problems. A group of 94 individuals (ages 50-81 years) with alcohol-induced memory problems (the memory group) were compared with a matched control group who did not have memory problems. The random forests model identified specific features from each domain that contributed to the classification of the memory group vs. the control group (AUC = 88.29%). Specifically, individuals from the memory group manifested a predominant pattern of hyperconnectivity across the default mode network regions except for some connections involving the anterior cingulate cortex, which were predominantly hypoconnected. Other significant contributing features were: (i) polygenic risk scores for AUD, (ii) alcohol consumption and related health consequences during the past five years, such as health problems, past negative experiences, withdrawal symptoms, and the largest number of drinks in a day during the past twelve months, and (iii) elevated neuroticism and increased harm avoidance, and fewer positive "uplift" life events. At the neural systems level, hyperconnectivity across the default mode network regions, including the connections across the hippocampal hub regions, in individuals with memory problems may indicate dysregulation in neural information processing. Overall, the study outlines the importance of utilizing multidomain features, consisting of resting-state brain connectivity data collected ~18 years ago, together with personality, life experiences, polygenic risk, and alcohol consumption and related consequences, to predict the alcohol-related memory problems that arise in later life.

Distinct Sleep Alterations in Alcohol Use Disorder Patients with and without Korsakoff's Syndrome: Relationship with Episodic Memory.

Alcohol Use Disorder (AUD) results in sleep disturbances that may have deleterious impacts on cognition, especially on memory. However, little is known about the sleep architecture in patients with Korsakoff's syndrome (KS). This study aims at characterizing sleep disturbances in KS compared to AUD without KS and at specifying the relationships with cognitive impairments. Twenty-nine AUD patients (22 without KS and 7 with KS) and 15 healthy controls underwent a neuropsychological assessment and a polysomnography. The severity of sleep-disordered breathing and sleep fragmentation was similar in AUD and KS patients compared to controls. Sleep architecture differed between both patient groups: the proportion of slow-wave sleep was reduced in AUD patients only, while a lower proportion of rapid-eye movement (REM) sleep was specifically observed in KS patients. The proportion of REM sleep correlated with the severity of episodic memory deficits when AUD and KS were examined together. These data provide evidence for both similarities and specificities regarding sleep alterations in AUD patients with and without KS. They also indicate that altered sleep architecture may contribute to the pathophysiology of alcohol-related memory disorders.

Choline Metabolism Gene-Exposure Interactions in Fetal Alcohol-related Memory Deficits

ObjectivesAnimal and human studies have demonstrated the potential for the essential nutrient choline to ameliorate teratogenic effects of prenatal alcohol exposure (PAE), including growth and recognition memory deficits. We hypothesized that the presence of maternal SNPs in choline metabolism-related genes may modify fetal vulnerability to PAE.MethodsMothers from two prenatally recruited birth cohorts in Cape Town, South Africa (discovery cohort: n = 149; validation cohort: n = 153) were genotyped for 315 SNPs in choline metabolism-related genes. Primary outcomes were: height/length z-scores (disc. at age 9 yr; val. at 5 yr) and recognition memory (disc. = CVLT-C recognition discrimination score, age 9 yr; val. = Fagan Test of Infant Intelligence novelty preference score, 6.5 and 12 mo). Linear regression models were constructed using OLS: outcome ∼ PAE + gene dose (# effective alleles) + PAE x gene dose; significance of PAE-gene interaction was tested using a 2-sided Wald test on the PAE-gene dose interaction term with Benjamini-Hochberg (BH) multiple testing correction.ResultsPAE (drinking days/wk) was related to shorter height (disc. B(95% CI) = −.11(−.18, −.01); val. B = −.12(−.20, −.04) and poorer recognition memory (disc. B = −.11(−.26, −.02); val. B = −.11(−.19, −.03)). Gene-PAE interaction for recognition memory was seen in both cohorts for rs12262538 (discovery BH-adj. p = .0015; validation unadj. p = .004); for rs1043261, discovery BH-adj. p = .0235 and validation unadj. p = .0903. No gene-PAE interactions were seen for height. rs12262538 is in the 5’ flanking region near the Stearoyl-CoA Desaturase (SCD) gene. rs1043261 is in the 3’ flanking region near the choline dehydrogenase (CHDH) gene.ConclusionsWe identified two maternal SNPs that may confer higher fetal risk for teratogenic effects of PAE. These findings support the potential protective role of choline in fetal alcohol spectrum disorders prevention.Funding SourcesNational Institute on Alcohol Abuse and Alcoholism.

Use of akatinol memantine for the treatment of Korsakoff's syndrome: a clinical case

Approaches to treating cognitive-amnestic disorders of various origins, including Korsakoff's syndrome (KS), are currently being actively elaborated. KS is manifested by severe memory impairment, leading to disability. It is quite common in alcohol abusers. There is still no proven effective treatment for KS. In view of the fact that studies on the treatment of KS have been very few, there are no clear recommendations for its most effective treatment. There has been evidence that in addition to thiamine deficiency, the toxic effect of glutamate that is actively released through binding to NMDA receptors during the ethanol withdrawal period is the basis for KS development. Memantine, a noncompetitive NMDA receptor antagonist, has recently been used successfully to treat KS. The paper describes a clinical case of a 55-year-old patient with KS treated with akatinol memantine, in which the latter has demonstrated its high efficacy and good tolerance. Analysis of the data available in the literature and the presented clinical case suggest that it is advisable to prescribe memantine for patients with alcohol-related memory impairment.

Memory biases in alcohol use disorder: enhanced memory for contexts associated with alcohol prospectively predicts alcohol use outcomes.

Memory for prior drinking experiences may powerfully drive later alcohol use in familiar drinking contexts, yet we know little about what patients with alcohol use disorder (AUD) remember of alcohol-related episodes. Although animal and theoretical models of addiction emphasize the importance of different memory systems for understanding maladaptive use, clinical research parsing what AUD patients remember from alcohol-related episodes is lacking. The current study applied a novel memory task in which moderate drinkers (N = 30) and treatment-seeking individuals with alcohol use disorder (AUD: N = 29) encoded associations between photographs of objects (alcoholic beverages and neutral items) and photographs of neutral scenes. At least 24 h later, two types of memory were assessed: item memory (object recognition) and associative memory (cued recognition of scenes associated with objects). To assess which memories predicted drinking, real-world behavior was assessed in patients with AUD at baseline and for 4 weeks following memory tests. Despite demographic differences, the results showed broadly impaired item memory in AUD compared with moderate drinkers (p < 0.001), but enhanced associative memory for scenes paired with alcohol (p = 0.015). These associative memory biases were especially pronounced for stimuli rated as more affectively salient. Furthermore, stronger but less detailed memory for alcohol-related associations (i.e., choosing the correct scene but the incorrect photograph) significantly predicted heavier baseline (p = 0.002) and higher subsequent (p = 0.01) drinking in patients with AUD. These findings reveal a novel alcohol-related memory bias in AUD, and uncover the importance of associative memory for understanding real-world heavy alcohol use.

Brain functional connectivity after cognitive-bias modification and behavioral changes in abstinent alcohol-use disorder patients

The use of the cognitive-bias modification (CBM) method has emerged as a therapeutic complement in the treatment of alcoholism, producing changes at behavioral and brain level. Nevertheless, the impact of the CBM procedure could be improved by the memory retrieval-extinction process (REP). Different studies have demonstrated that the retrieval of drug memories before extinction training later reduced the reinstatement of drug-seeking behavior. The main aim of this work was to study the effect of the CBM procedure itself, as well as in combination with the activation of alcohol-related memories, on the brain oscillatory activity of abstinent patients with alcohol-use disorder. The study sample comprised 33 patients divided into three groups: A-CBM (alcohol-related memory activation + CBM), N-CBM (neutral memory activation + CBM) and N-INT (no-intervention) groups. A resting-state EEG was obtained before and after each protocol, along with the assessment of the automatic action tendencies. A-CBM group showed a general alpha synchronization increase after the protocol, while the other groups did not show any significant change. Besides, A-CBM group showed significant intra and inter-group differences in the automatic action tendencies after the protocol, reflected in higher avoidance bias toward appetitive, aversive and without context alcohol-related stimuli. The alpha phase synchronization increase could be the neural manifestation of the conditioning produced between the alcohol-related stimuli and the automatic avoidance response. Moreover, the activation of the alcohol-related memories favors this conditioning with those alcohol-related stimuli associated with the activated memories, because it increases their threat level for the abstinence maintenance.

Prehabilitation in Alcohol Dependence as a Treatment Model for Sustainable Outcomes. A Narrative Review of Literature on the Risks Associated With Detoxification, From Animal Models to Human Translational Research.

In this review paper, we discuss how the overarching concept of prehabilitation is applicable to alcohol dependence. Central to prehabilitation are the concepts of expected harm, risks, and proactive planning to eliminate the harm or cope with the risks. We review the evidence from animal models, psychological experimental studies, as well as pharmacological studies, on the potential risks and harms associated with medically assisted alcohol detoxification and the current treatment paradigm for alcohol dependence. Animal models provide an approximation mostly of the physical aspect of alcohol withdrawal and detoxification process and make predictions about the development of the phenomena in humans. Despite their limitations, these models provide good evidence that withdrawal from chronic ethanol use induces cognitive impairment, which is worsened by repeated bouts of withdrawal and that these impairments are dependent on the duration of alcohol withdrawal. Initial clinical observations with alcohol-dependent patients confirmed increased incidence of seizures. In recent years, accumulating evidence suggests that patients who have had repeated episodes of withdrawal also show changes in their affect, increased craving, as well as significant deterioration of cognitive abilities, when compared to patients with fewer withdrawals. Alcohol dependence is associated with tolerance and withdrawal, with neuroadaptations in γ-Aminobutyric Acid-A Receptor (GABA-A) and glutamatergic N-methyl-D-aspartate (NMDA) receptors playing key roles. It is suggested that dysregulation of the NMDA receptor system underpins alcohol-related memory impairments. Finally, we discuss the Structured Preparation for Alcohol Detoxification (SPADe) as an example of how prehabilitation has been applied in clinical practice. We discuss the importance of partial control over drinking as an interim step toward abstinence and early introduction of lifestyle changes for both the patient and the immediate environment prior to detoxification and while the patient is still drinking.

Commentary: Rewriting the Valuation and Salience of Alcohol-Related Stimuli via Memory Reconsolidation

Commentary: Rewriting the Valuation and Salience of Alcohol-Related Stimuli via Memory Reconsolidation

Assessment of Alcohol-related Memory Deficits: A Comparison between the Rivermead Behavioural Memory Test and the California Verbal Learning Test

Objectives: Neuropsychological assessment of memory disorders is an important prerequisite in the treatment of patients with alcohol-related cognitive disorders. Although many memory tests are available in clinical practice, a question remains regarding which test is most appropriate for this purpose. Our study's goal was to evaluate the discriminative power of indices of a standard memory test (the California Verbal Learning Test; CVLT) versus the subtests of an ecologically valid everyday memory test (the Rivermead Behavioural Memory Test; RBMT) in patients with alcohol-use disorder.Method: The patients included 136 with Korsakoff's syndrome (KS), 73 alcoholics with cognitive impairment (CI) not fulfilling the criteria for KS, and 24 cognitively unimpaired alcoholics (ALC).Results: KS patients performed significantly lower on all RBMT and CVLT variables than CI patients. ALC patients performed significantly better than CI patients on only one RBMT subtest, and had a significantly lower rate of forgetting and higher scores on free recall on CVLT. A combination of RBMT subtests and CVLT indices was able to discriminate KS patients from CI and ALC patients. The RBMT subtests could not significantly distinguish ALC from CI patients. Both rate of forgetting and a comparison between free and cued recall testing on the CVLT showed the largest between-group differences.Conclusion: Although the RBMT provides information about everyday memory performance, the CVLT indices are better able to distinguish between uncomplicated alcoholics and those with cognitive impairment or KS.

Alcohol-related memory associations in positive and negative affect situations: Drinking motives, working memory capacity, and prospective drinking.

Although studies on explicit alcohol cognitions have identified positive and negative reinforcing drinking motives that are differentially related to drinking indices, such a distinction has received less attention in studies on implicit cognitions. An alcohol-related Word-Sentence Association Task was used to assess implicit alcohol-related memory associations in positive and negative affect situations in 92 participants. Results revealed that enhancement motives were specifically associated with the endorsement of alcohol words in positive affect situations and coping motives were associated with the endorsement of alcohol words in negative affect situations. Furthermore, alcohol associations in positive affect situations predicted prospective alcohol use and number of binges, depending on levels of working memory capacity. The current findings shed more light on the underpinnings of alcohol use and suggest that implicit memory processes and working memory capacity might be important targets for intervention.

"Alcohol-related memory associations in positive and negative affect situations: Drinking motives, working memory capacity, and prospective drinking": Correction to Salemink and Wiers (2013).

"Alcohol-related memory associations in positive and negative affect situations: Drinking motives, working memory capacity, and prospective drinking": Correction to Salemink and Wiers (2013).

Alcohol‐Related Interpretation Bias in Alcohol‐Dependent Patients

Models of addictive behaviors postulate that implicit alcohol-related memory associations and biased interpretation processes contribute to the development and maintenance of alcohol misuse and abuse. The present study examined whether alcohol-dependent patients (AP) show an alcohol-related interpretation bias. Second, the relationship between the interpretation bias and levels of harmful drinking was investigated. The sample included 125 clinically diagnosed AP and 69 clinically diagnosed control patients (CP) who had either a mood or an anxiety disorder. Participants completed a booklet containing 12 open-ended ambiguous scenarios. Seven scenarios were alcohol-relevant, and 5 were emotionally relevant, that is, panic- or depression-relevant. Participants were asked to read each scenario and to generate a continuation. In addition, the Alcohol Use Disorder Identification Test (AUDIT) and Beck Depression Inventory were administered. Logistic multivariate multilevel analyses revealed that AP' probability of generating an alcohol-related continuation on all 3 scenario types was higher than that of CP. Moreover, alcohol-related interpretation biases were positively associated with levels of harmful drinking (i.e., AUDIT scores). These findings are the first to show that AP show an alcohol-related interpretation bias, which generalizes to other ambiguous emotionally relevant contexts, and therefore advance our understanding of the role of implicit biased alcohol-related memory associations and interpretation processes.

Chapter 13 - Component processes of memory in alcoholism: pattern of compromise and neural substrates

Initially, alcohol-related memory deficits were considered only through the prism of Korsakoff's syndrome (KS). It is now clear, however, that chronic alcohol consumption results in memory disorders in alcoholics without ostensible neurologic complications, such as Wernicke's encephalopathy and KS. Most of the principal memory components are affected, including working memory, episodic memory, semantic memory, perceptual memory, and procedural memory. The extent of those cognitive impairments depends on several factors, such as age, gender, nutritional status, and psychiatric comorbidity. While memory disorders, especially episodic memory deficits, are largely definitive in patients with KS, recovery of memory abilities has been described with abstinence in uncomplicated alcoholics. Neuropsychologic impairments, and especially memory disorders, must be evaluated at alcohol treatment entry because they could impede patients from benefiting fully from cognitive and behavioral treatment approaches for alcohol dependence. Screening of memory deficits could also enable clinicians to detect, among alcoholics without ostensible neurologic complications, those at risk of developing permanent and debilitating amnesia that features KS.

Ceiling and floor effects on the Rivermead Behavioural Memory Test in patients with alcohol-related memory disorders and healthy participants

Objective. The Rivermead Behavioural Memory Test (RBMT) is a widely used measure of everyday memory performance. In the most recent revision of this test (RBMT-3) some important changes have been made compared with the RBMT. This study examines whether this revision has improved the quality of the clinical classifications using this test, as well as the frequency of floor and ceiling performances that were prominent on some subtests of the RBMT, using a heterogeneous study sample. Methods. Twenty-five healthy adults and 25 patients with alcohol-related memory impairment (including 15 Korsakoff patients) were examined using both the RBMT and the RBMT-3. The number of perfect scores and floor performances, as well as the percentage of individuals classified as impaired (< 5th percentile), were scored and compared. Results. Administration of the RBMT-3 results in less participants performing at or near individual subtest's ceiling, and resulted in less floor performances. Moreover, the RBMT-3 misclassifies less healthy participants as impaired than the RBMT. Conclusions. The RBMT-3 is a substantial improvement over the original RBMT, as it reduces the problem of ceiling and floor performances and the number of misclassifications. However, more research is needed on the ecological validity of the RBMT-3.

Does Negative Affect Prime Alcohol in Alcohol-Dependent Inpatients? A Large-Scale Clinical Investigation of the Moderating role of Depression and Executive Control

The present study tested to what extent alcohol-related concepts are automatically activated by negative affective words. Participants were alcohol-dependent inpatients (n = 847) and an inpatient control group (n = 130). An affective priming task was used to assess the automatic activation of alcohol-related memory associations. Executive control was assessed with an adapted Stroop task. We expected alcohol-dependent inpatients to show enhanced alcohol activation after negative primes. In addition, we predicted that this enhanced negative priming effect would be further qualified by participants' levels of depressive symptoms. Finally, we expected the interaction between executive control and priming effect as well as the interaction between executive control, priming effect and depressive symptoms to be predictive for group membership. Results showed that alcohol-dependent inpatients did not show an priming effect by negative words, and this effect was not moderated by levels of depressive symptoms. Moreover, group membership was not predicted by the interaction between priming effect and executive control, nor by the interaction between priming effect, executive control and depressive symptoms. We conclude that these results are most likely due to the particular population we studied (i.e., inpatients instead of at-risk populations) and to features of the priming task (i.e., low reliability, part of a test battery).

Disruption of alcohol-related memories by mTORC1 inhibition prevents relapse

Relapse to alcohol abuse is a critical clinical issue, frequently caused by cue-induced drug craving. Therefore, disruption of the memory for the cue-alcohol association is expected to prevent relapse. It is increasingly accepted that memories become labile and erasable soon after their reactivation through retrieval, during a memory reconsolidation process that depends on protein synthesis. Here, we show that reconsolidation of alcohol-related memories triggered by the sensory properties of alcohol itself (odor and taste) activates mammalian target of rapamycin complex 1 (mTORC1) in select amygdalar and cortical regions in rats, resulting in increased levels of several synaptic proteins. Furthermore, systemic or central amygdalar (CeA) inhibition of mTORC1 during reconsolidation disrupts alcohol-cue associated memories, leading to a long-lasting suppression of relapse. Our findings provide evidence that the mTORC1 pathway and its downstream substrates play a crucial role in alcohol-related memory reconsolidation, and highlight this pathway as a therapeutic target to prevent relapse.

The mediating role of alcohol‐related memory associations on the relation between perceived parental drinking and the onset of adolescents' alcohol use

The aim of the current study was to examine the mediating role of alcohol-related memory associations in the relation between perceived parental drinking and the onset of adolescents' alcohol use. Gender and grade were also included in the analyses. We tested a mediation model within a structural path modelling framework using longitudinal data (two waves). The sample consisted of 608 Canadian adolescents (42.9% boys), who did not have any alcohol experiences at the first measurement. The adolescents were recruited from all grades 7-9 classes in a large school district in western Canada. Alcohol-related memory associations were tested with the Word Association Test. We used adolescent self-reports of alcohol use and parental drinking. Results clearly showed a mediation effect of alcohol-related memory associations [estimate = 0.023, 95% confidence interval (CI): 0.002-0.044). That is, parental drinking as perceived by the adolescent was related positively to alcohol-related memory associations, which in turn predicted adolescents' alcohol use a year later. Gender and grade were related to alcohol-related memory associations. That is, boys and adolescents of higher grades had more memory associations. Children appear to form memory associations related to alcohol before they ever drink alcohol themselves, and these associations appear to mediate the link between their perceptions of their parents' drinking and their own initial alcohol use.

Negative mood, implicit alcohol-related memory, and alcohol use in young adults: The moderating effect of alcohol expectancy

Objective Alcohol-related implicit (preconscious) cognitive processes are established and unique predictors of alcohol use, but most research in this area has focused on alcohol-related implicit cognition and anxiety. This study extends this work into the area of depressed mood by testing a cognitive model that combines traditional explicit (conscious and considered) beliefs, implicit alcohol-related memory associations (AMAs), and self-reported drinking behavior. Method Using a sample of 106 university students, depressed mood was manipulated using a musical mood induction procedure immediately prior to completion of implicit then explicit alcohol-related cognition measures. A bootstrapped two-group (weak/strong expectancies of negative affect and tension reduction) structural equation model was used to examine how mood changes and alcohol-related memory associations varied across groups. Results Expectancies of negative affect moderated the association of depressed mood and AMAs, but there was no such association for tension reduction expectancy. Conclusion Subtle mood changes may unconsciously trigger alcohol-related memories in vulnerable individuals. Results have implications for addressing subtle fluctuations in depressed mood among young adults at risk of alcohol problems.

Disruption of Long-Term Alcohol-Related Memory Reconsolidation: Role of β-Adrenoceptors and NMDA Receptors

Disrupting reconsolidation of drug-related memories may be effective in reducing the incidence of relapse. In the current study we examine whether alcohol-related memories are prone to disruption by the β-adrenergic receptor antagonist propranolol (10 mg/kg) and the NMDA receptor antagonist MK801 (0.1 mg/kg) following their reactivation. In operant chambers, male Wistar rats were trained to self-administer a 12% alcohol solution. After 3 weeks of abstinence, the animals were placed in the self-administration cages and were re-exposed to the alcohol-associated cues for a 20-min retrieval period, immediately followed by a systemic injection of either propranolol, MK801 or saline. Rats were tested for cue-induced alcohol seeking on the following day. Retrieval session, injection and test were repeated on two further occasions at weekly intervals. Both propranolol and MK801 administration upon reactivation did not reduce alcohol seeking after the first reactivation test. However, a significant reduction of alcohol seeking was observed over three post-training tests in propranolol treated animals, and MK801 treated animals showed a strong tendency toward reduced alcohol seeking (p = 0.06). Our data indicate that reconsolidation of alcohol-related memories can be disrupted after a long post-training interval and that particularly β-adrenergic receptors may represent novel targets for pharmacotherapy of alcoholism, in combination with cue-exposure therapies.