Personal semantic and episodic autobiographical memories in Korsakoff syndrome: A comparison of interview methods.

OBJECTIVE: The temporal gradient in patients with Korsakoff's syndrome has been of particular interest in the literature, as many studies have found evidence for a steep temporal gradient, but others have observed more uniform remote memory impairment across all past time periods. Inconsistencies might be the result of the nature of remote memory impairment under study (i.e., nonpersonal or autobiographical memory) and of methodological differences in the examination of remote memory loss. The aim of this study was to examine whether differences between autobiographical memory interview (AMI) and autobiographical interview (AI) procedures influence the presence of a temporal gradient in semantic and episodic autobiographical memory in Korsakoff patients. METHOD: The procedure used in the present study combined the AMI and AI into one study session. We compared the performance of 20 patients with Korsakoff's syndrome and 27 healthy controls. First, participants were asked to recall knowledge from different life periods. Second, participants were asked to recall memories from five life periods. Thirdly, participants were asked to rate their subjective experience of each event recalled on a 5-point scale. Finally, we analyzed the findings in terms of all the memories recalled versus the first memory from each life-period only. RESULTS: Both the AMI and the AI showed a temporally graded retrograde amnesia in the Korsakoff patients for personal semantic and episodic autobiographical memories. The pattern of amnesia in Korsakoff patients was not affected by examining only one event per life-period. Subjective ratings of recalled memories were largely comparable between the groups. CONCLUSIONS: The findings were generally consistent across the AMI and AI. Varying the number of events did not affect the pattern of the gradient. Hence, the temporal gradient in Korsakoff patients is not an artefact of either the AMI or the AI method.

Self-awareness of cognitive dysfunction: Self-reported complaints and cognitive performance in patients with alcohol-induced mild or major neurocognitive disorder.

Patients with Korsakoff's syndrome (KS) typically have difficulties in recognizing the impact of their alcohol-related cognitive deficits on daily-life functioning. In this study, mean scores on self-reported complaints (measured with Minnesota Multiphasic Personality Inventory-2-Restructured Form; MMPI-2-RF) and cognitive performance (measured with the Wechsler Adult Intelligence Scale-Third edition; WAIS-III; and the California Verbal Learning Test; CVLT) are compared between two matched patient groups with severe (KS) and mild alcohol-related cognitive disorders or non KS (NKS). KS patients demonstrate significantly lower scores on the WAIS-III indices and on the CVLT than the matched NKS group, and significantly higher scores on MMPI-2-RF validity scales that indicate denial of psychological complaints. Both groups are in the normal range on MMPI-2-RF Cognitive Complaints (COG) and Neurological Complaints (NUC) scales compared with the normative sample. Finally, self-reported complaints and cognitive performance are not correlated significantly in both groups. Despite their alcohol-related cognitive impairments, both groups report no cognitive complaints at all indicating self-awareness impairment. In addition to KS patients, also NKS patients are at risk that their apparently "without cognitive complaints" appearance on self-report questionnaires can be easily overlooked. These findings may have important clinical implications for diagnostic and treatment purposes.

Salient cues improve prospective remembering in Korsakoff's syndrome.

OBJECTIVE: Korsakoff's syndrome is characterized by deficits in episodic memory and executive functions. Both cognitive functions are needed to remember to execute delayed intentions (prospective memory, PM), an ability that is crucial for independent living in everyday life. So far, PM has only been targeted by one study in Korsakoff's syndrome. This study explored the effects of executive control demands on PM to shed further light on a possible interdependence of memory and executive functions in Korsakoff's syndrome, METHOD: Twenty-five individuals with Korsakoff's syndrome and 23 chronic alcoholics (without amnesia) performed a categorization task into which a PM task was embedded that put either high or low demands on executive control processes (using low vs. high salient cues). RESULTS: Overall, Korsakoff patients had fewer PM hits than alcoholic controls. Across groups, participants had fewer PM hits when cues were low salient as compared to high salient. Korsakoff patients performed better on PM when highly salient cues were presented than cues of low salience, while there were no differential effects for alcoholic controls. CONCLUSIONS: While overall Korsakoff patients' showed a global PM deficit, the extent of this deficit was moderated by the executive control demands of the task applied. This indicated further support for an interrelation of executive functions and memory performance in Korsakoff. PRACTITIONER POINTS: Positive clinical implications of the work Prospective memory (PM) performance in Korsakoff's syndrome is related to executive control load. Increasing cues' salience improves PM performance in Korsakoff's syndrome. Salient visual aids may be used in everyday life to improve Korsakoff individuals' planning and organization skills. Cautions or limitations of the study Results were obtained in a structured laboratory setting and need to be replicated in a more naturalistic setting to assess their transferability to everyday life. Given the relatively small sample size, individual predictors of PM performance should be determined in larger samples.

Assessment of Confabulation in Patients with Alcohol-Related Cognitive Disorders: The Nijmegen-Venray Confabulation List (NVCL-20).

OBJECTIVE: Even though the first awareness of confabulations is often based on observations, only questionnaires and structured interviews quantifying provoked confabulations are available. So far, no tools have been developed to measure spontaneous confabulation. This study describes and validates an observation scale for quantifying confabulation behavior, including spontaneous confabulations, in clinical practice. METHOD: An observation scale consisting of 20 items was developed, the Nijmegen-Venray Confabulation List-20 (NVCL-20). This scale covers spontaneous confabulation, provoked confabulation, and memory and orientation. Professional caregivers completed the NVCL-20 for 28 Korsakoff (KS) patients and 24 cognitively impaired chronic alcoholics (ALC). Their ratings were related to the Dalla Barba Confabulation Battery (DBCB), Provoked Confabulation Test (PCT), and standard neuropsychological tests. RESULTS: The categories of the NVCL-20 have "good" to "excellent" internal consistency and inter-rater agreement. The KS patients confabulated more (both spontaneously and provoked), and more memory and orientation problems were observed. Correlations with neuropsychological test scores showed that confabulations were associated with memory deficits, but not with intrusions or tests of executive dysfunction. CONCLUSIONS: The NVCL-20 is the first instrument that includes items addressing spontaneous confabulation. Administration is reliable, valid and feasible in clinical practice, making it a useful addition to existing confabulating measures.

A single-system model predicts recognition memory and repetition priming in amnesia.

We challenge the claim that there are distinct neural systems for explicit and implicit memory by demonstrating that a formal single-system model predicts the pattern of recognition memory (explicit) and repetition priming (implicit) in amnesia. In the current investigation, human participants with amnesia categorized pictures of objects at study and then, at test, identified fragmented versions of studied (old) and nonstudied (new) objects (providing a measure of priming), and made a recognition memory judgment (old vs new) for each object. Numerous results in the amnesic patients were predicted in advance by the single-system model, as follows: (1) deficits in recognition memory and priming were evident relative to a control group; (2) items judged as old were identified at greater levels of fragmentation than items judged new, regardless of whether the items were actually old or new; and (3) the magnitude of the priming effect (the identification advantage for old vs new items) overall was greater than that of items judged new. Model evidence measures also favored the single-system model over two formal multiple-systems models. The findings support the single-system model, which explains the pattern of recognition and priming in amnesia primarily as a reduction in the strength of a single dimension of memory strength, rather than a selective explicit memory system deficit.

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.

Applicability of the Rivermead Behavioural Memory Test - Third Edition (RBMT-3) in Korsakoff's syndrome and chronic alcoholics.

PURPOSE: To examine the applicability of the newly developed Rivermead Behavioural Memory Test - Third Edition (RBMT-3) as an ecologically-valid memory test in patients with alcohol-related cognitive disorders. PATIENTS AND METHODS: An authorized Dutch translation of the RBMT-3 was developed, equivalent to the UK version, and administered to a total of 151 participants - 49 patients with amnesia due to alcoholic Korsakoff's syndrome, 49 patients with cognitive impairment and a history of chronic alcoholism, not fulfilling the Korsakoff criteria, and 53 healthy controls. Between-group comparisons were made at subtest level, and the test's diagnostic accuracy was determined. RESULTS: Korsakoff patients performed worse than controls on all RBMT-3 subtests (all P-values < 0.0005). The alcoholism group performed worse than controls on most (all P-values < 0.02), but not all RBMT-3 subtests. Largest effects were found between the Korsakoff patients and the controls after delayed testing. The RBMT-3 had good sensitivity and adequate specificity. CONCLUSION: The RBMT-3 is a valid test battery to demonstrate everyday memory deficits in Korsakoff patients and non-Korsakoff patients with alcohol abuse disorder. Korsakoff patients showed an impaired performance on subtests relying on orientation, contextual memory and delayed testing. Our findings provide valuable information for treatment planning and adjustment in patients with alcohol-related cognitive impairments.

Antisaccade performance in Korsakoff patients reveals deficits in oculomotor inhibition.

Oculomotor inhibition reflects the ability to suppress an unwanted eye movement. The goal of the present study was to assess oculomotor inhibition in patients with Korsakoff's syndrome (KS). To this end, an antisaccade task was employed in which an eye movement towards an onset stimulus has to be inhibited, and a voluntary saccade has to be executed in the opposite direction. Compared to the results of a matched control group, patients showed a higher percentage of intrusive saccades, made more antisaccade errors, and showed longer latencies on prosaccade trials. These results clearly show that oculomotor inhibition is impaired in KS. Part of these deficits in oculomotor inhibition may be explained by neuronal atrophy in the frontal areas, which is generally associated with KS.

Facilitation of memory by contextual cues in patients with diencephalic or medial temporal lobe dysfunction.

Item-context binding is crucial for successful episodic memory formation, and binding deficits have been suggested to underlie episodic-memory deficits. Here, our research investigated the facilitation of cued recall and recognition memory by contextual cues in 20 patients with Korsakoff's amnesia, 20 unilateral medial-temporal lobectomy (MTL) patients and 36 healthy controls. In a computerized task participants had to learn 40 nouns that were randomly combined with a photograph of an everyday scene. Korsakoff patients showed a general memory deficit in both the cued recall and the recognition condition. A less severe memory impairment was found in the patients with medial-temporal lobectomy. Contextual cues facilitated cued recall to an equal extent in unilateral temporal lobectomy patients and healthy controls. However, no facilitation was observed in Korsakoff patients, suggesting an impairment in item-context binding during cued recall tasks. In contrast to the presumed exclusive dependency of recognition memory on item information, all groups equally profited from the contextual cues in recognition tasks. Our findings show that unilateral lesions as with MTL result in normal binding of context and item information, while bilateral dysfunction of the hippocampal-diencephalic system results in impaired context and item binding.

The interaction of working memory performance and episodic memory formation in patients with Korsakoff's amnesia.

Both neuroimaging work and studies investigating amnesic patients have shown involvement of the medial temporal lobe during working memory tasks, especially when multiple items or features have to be associated. However, so far no study has examined the relationship between working memory and subsequent episodic memory in patients using similar tasks. In this study, we compared patients with amnesia due to Korsakoff's syndrome (n=19) with healthy controls (n=18) on an associative working memory task followed by an unexpected subsequent episodic memory task. The computerized working memory task required participants to maintain two pairs of faces and houses for either short (3s) or long (6s) delays. Approximately 5 minutes after completion of the working memory task, an unexpected subsequent recognition task with a two-alternative forced choice paradigm was administered. By directly comparing working memory and subsequent episodic memory, we were able to examine long-term encoding processes that may take place after longer delays. As expected, patients performed at chance level on the episodic memory task. Interestingly, patients also showed significantly impaired working memory performance (p<.01), even at short delays. Longer delays did not result in better subsequent memory, indicating that they do not facilitate long-term encoding processes. Our results are discussed in relation to Baddeley's working memory model as the episodic buffer is assumed to be a short-term store for maintaining bound representations. In light of these results, the long-standing view that working memory and long-term memory are strictly dissociated may need to be revisited.

Neurocognitive parameters should be incorporated in the Minnesota Multiphasic Personality Inventory-2 assessment of patients with alcohol use disorders.

INTRODUCTION AND AIMS: Treatment planning for alcohol use disorder (AUD) patients is often preceded by the assessment of psychopathology and personality with the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). However, during periods of abstinence, cognitive impairments (e.g. attention, memory and executive dysfunctions) related to neurological and somatic pathology may affect level and pattern of MMPI-2 scale scores, resulting in clinical misinterpretation. DESIGN AND METHODS: A re-analysis of the data of the Egger et al. study is conducted in order to examine the clinical significance of the MMPI-2 profiles of 222 AUD patients (mean age 42.2 ± 9.6 years; 76.6% men) by using neurologically relevant item correction procedures. Hierarchical cluster analyses of neurologically relevant item-corrected solutions were compared to the original MMPI-2 profile. RESULTS: Impulsiveness and psychopathic deviation were identified as a common denominator. DISCUSSION AND CONCLUSIONS: Uncorrected MMPI-2 assessment in AUD tends to overstress psychopathology and to overlook disinhibitory traits in early abstinence, caused by chronic alcoholism.

Spatial and nonspatial implicit motor learning in Korsakoff's amnesia: evidence for selective deficits.

Patients with amnesia have deficits in declarative memory but intact memory for motor and perceptual skills, which suggests that explicit memory and implicit memory are distinct. However, the evidence that implicit motor learning is intact in amnesic patients is contradictory. This study investigated implicit sequence learning in amnesic patients with Korsakoff's syndrome (N = 20) and matched controls (N = 14), using the classical Serial Reaction Time Task and a newly developed Pattern Learning Task in which the planning and execution of the responses are more spatially demanding. Results showed that implicit motor learning occurred in both groups of participants; however, on the Pattern Learning Task, the percentage of errors did not increase in the Korsakoff group in the random test phase, which is indicative of less implicit learning. Thus, our findings show that the performance of patients with Korsakoff's syndrome is compromised on an implicit learning task with a strong spatial response component.

Intact memory for implicit contextual information in Korsakoff's amnesia.

Implicit contextual learning is the ability to acquire contextual information from our surroundings without conscious awareness. Such contextual information facilitates the localization of objects in space. In a typical implicit contextual learning paradigm, subjects need to find a target among a number of distractors during visual search. Some of the configurations of stimuli are repeated during the experiment resulting in faster responses than for novel configurations, without subjects being aware of their repetition. Patients with Korsakoff's syndrome (KS) have been found to show devastating explicit spatial amnesia. Less is know about their implicit spatial memory abilities. The aim of the present research was to examine whether implicit contextual learning is intact in KS. Therefore, eighteen KS patients and twenty-two age-IQ- and education-matched controls performed the Implicit Contextual Learning task and a paradigm intended to assess explicit, spatial working memory, i.e. the Box task. Intact implicit contextual learning was observed in both the control group and the KS patients. In turn KS patients did have markedly lower explicit spatial working memory scores. The implicit learning effect was not related to the spatial working memory scores. Together these results clearly suggest that implicit and explicit spatial memory have a different neurocognitive basis.

Spared unconscious influences of spatial memory in diencephalic amnesia.

Spatial memory is crucial to our daily lives and in part strongly depends on automatic, implicit memory processes. This study investigates the neurocognitive basis of conscious and unconscious influences of object-location memory in amnesic patients with Korsakoff's syndrome (N = 23) and healthy controls (N = 18) using a process-dissociation procedure in a computerized spatial memory task. As expected, the patients performed substantially worse on the conscious memory measures but showed even slightly stronger effects of unconscious influences than the controls. Moreover, a delayed test administered after 1 week revealed a strong decline in conscious influences in the patients, while unconscious influences were not affected. The presented results suggest that conscious and unconscious influences of spatial memory can be clearly dissociated in Korsakoff's syndrome.

Confabulation behavior and false memories in Korsakoff's syndrome: role of source memory and executive functioning.

AIMS: Confabulation behavior is common in patients with Korsakoff's syndrome. A distinction can be made between spontaneous and provoked confabulations, which may have different underlying cognitive mechanisms. Provoked confabulations may be related to intrusions on memory tests, whereas spontaneous confabulations may be due to executive dysfunction or a source memory deficit. METHODS: In 19 chronic Korsakoff patients, spontaneous confabulations were quantified by third-party rating (Likert scale). Provoked confabulations were assessed using the Dalla Barba Confabulation Battery. Furthermore, assessment of executive function was performed using an extensive neuropsychological battery. False memories (i.e. intrusions) and source memory were measured using twoparallelversions of a word-list learning paradigm (a modification of the Rey Auditory Verbal Learning Test). RESULTS: There were deficits in source memory, in which patients incorrectly assigned previously learned words to an incorrect word list. Also, Korsakoff patients had extensive executive deficits, but no relationship between the severity of these deficits and the severity of confabulation or intrusions on a memory task was found. CONCLUSION: The present findings provide evidence for a dissociation between spontaneous confabulation, provoked confabulation and false memories.

Route learning in amnesia: a comparison of trial-and-error and errorless learning in patients with the Korsakoff syndrome.

OBJECTIVE: To examine the errorless learning approach using a procedural memory task (i.e. learning of actual routes) in patients with amnesia, as compared to trial-and-error learning. DESIGN: Counterbalanced self-controlled cases series. SETTING: Psychiatric hospital (Korsakoff clinic). SUBJECTS: A convenience sample of 10 patients with the Korsakoff amnestic syndrome. INTERVENTION: All patients learned a route in four sessions on separate days using an errorless approach and a different route using trial-and-error. MAIN MEASURES: Error rate was scored during route learning and standard neuro-psychological tests were administered (i.e. subtest route recall of the Rivermead Behavioural Memory Test (RBMT) and the Dutch version of the California Verbal Learning Test (VLGT)). RESULTS: A significant learning effect was found in the trial-and-error condition over consecutive sessions (P = 0.006), but no performance difference was found between errorless and trial-and-error learning of the routes. VLGT performance was significantly correlated with a trial-and-error advantage (P < 0.05); no significant correlation was found between the RBMT subtest and the learning conditions. CONCLUSION: Errorless learning was no more successful than trial-and-error learning of a procedural spatial task in patients with the Korsakoff syndrome (severe amnesia).

Spatial and non-spatial contextual working memory in patients with diencephalic or hippocampal dysfunction.

Damage to the medial temporal lobe (MTL) and diencephalon results in impaired long-term memory, which relies on the binding of multiple, mostly contextual, features. Recent neuroimaging and patient studies have suggested that impairments may also be present in working memory after MTL or diencephalic damage. To examine whether patients with damage to these brain structures have impairments in working memory for contextual information, 15 patients with damage to the diencephalon due to Korsakoff's syndrome and 12 patients with unilateral MTL lesions, and 30 age-matched healthy controls performed a delayed match-to-sample (DMS) task in which they had to maintain either object-location associations, color-number associations, single colors or single locations. Compared to their age-matched controls, performance on the DMS task was generally impaired in both patient groups, whereas no deficits were found on standard neuropsychological span tasks that do not rely on maintenance aspects of working memory. The patients did not show disproportionate impairments on the binding condition. In all, the results clearly show that impairments in working memory maintenance are present in patients with MTL or diencephalic lesions. However, we did not find a disproportionate inability in maintaining spatial or non-spatial associations within working memory as previously demonstrated in long-term memory.

Spatial and temporal order memory in Korsakoff patients.

This study directly compared how well Korsakoff patients can process spatial and temporal order information in memory under conditions that included presentation of only a single feature (i.e., temporal or spatial information), combined spatiotemporal presentation, and combined spatiotemporal order recall. Korsakoff patients were found to suffer comparable spatial and temporal order recall deficits. Of interest, recall of a single feature was the same when only spatial or temporal information was presented compared to conditions that included combined spatiotemporal, presentation and recall. In contrast, control participants performed worse when they have to recall both spatial and temporal order compared to when they have to recall only one of these features. These findings together indicate that spatial and temporal information are not automatically integrated. Korsakoff patients have profound problems in coding the feature at hand. Moreover, their lower recall of both features at the same time suggests that Korsakoff patients are impaired in binding different contextual attributes together in memory.

Processing of emotional facial expressions in Korsakoff's syndrome.

Interpersonal contacts depend to a large extent on understanding emotional facial expressions of others. Several neurological conditions may affect proficiency in emotional expression recognition. It has been shown that chronic alcoholics are impaired in labelling emotional expressions. More specifically, they mislabel sad expressions, regarding them as more hostile. Surprisingly, there has been relatively little research on patients with Korsakoff's syndrome as a result of chronic alcohol abuse. The current study investigated 23 patients diagnosed with Korsakoff's syndrome compared to 23 matched control participants. This study is the first to make use of a newly developed sensitive paradigm to measure emotion recognition for several emotions (anger, disgust, fear, happiness, sadness and surprise). The results show that patients with Korsakoff's syndrome are impaired at recognizing angry, fearful and surprised facial emotional expressions. These deficits might be due to the reported sub-cortical brain dysfunction in Korsakoff's syndrome.