Accelerated long-term forgetting in patients with acquired brain injury.

OBJECTIVE: Recent research suggests that patients with neurological disorders without overt seizures may also experience accelerated long-term forgetting (ALF). This term describes unimpaired learning and memory performance after standard retention intervals, but an excessive rate of forgetting over delays of days or weeks. The objective of this retrospective study was to investigate ALF in patients with an acquired brain injury (ABI) and to associate memory performance with executive functions. METHODS: Verbal memory performance (short-term recall, 30-min recall, 1-week recall) was assessed in 34 adult patients with ABI and compared to a healthy control group (n = 54) using an auditory word learning and memory test. RESULTS: Repeated measure analysis showed significant effects of time and group as well as interaction effects between time and group regarding recall and recognition performance. Patients with ABI had a significantly impaired 1-week recall and recognition performance compared to the healthy control group. Correlations between recall performance and executive functions were nonsignificant. DISCUSSION: Our results demonstrate that non-epileptic patients with ABI, especially patients with frontal and fronto-temporal lesions, are prone to ALF. Additionally, our data support the assumption that ALF results from a consolidation impairment since verbal recall and recognition were impaired in patients with ABI.

How helpful are the European AIDS Clinical Society cognitive screening questions in predicting cognitive impairment in an aging, well-treated HIV-positive population?

OBJECTIVES: Diagnosing neurocognitive impairment (NCI) in HIV infection requires time-consuming neuropsychological assessment. Screening tools are needed to identify when neuropsychological referral is indicated. We examined the positive and negative predictive values (PPVs and NPVs, respectively) of the three European AIDS Clinical Society (EACS) screening questions in identifying NCI. METHODS: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study recruited patients aged ≥45 years enrolled in the Swiss HIV Cohort Study between 1 May 2013 and 30 November 2016. NAMACO participants (1) answered EACS screening questions, (2) underwent standardized neuropsychological assessment and (3) completed self-report forms [Center for Epidemiologic Studies Depression Scale (CES-D)] rating mood. NCI categories were defined using Frascati criteria. PPVs and NPVs of the EACS screening questions in identifying NCI categories were calculated. RESULTS: Of 974 NAMACO participants with complete EACS screening question data, 244 (25.1%) expressed cognitive complaints in answer to at least one EACS screening question, of whom 51.3% had NCI (26.1% HIV-associated and 25.2% related to confounding factors). The PPV and NPV of the EACS screening questions in identifying HIV-associated NCI were 0.35 and 0.7, respectively. Restricting analysis to NCI with functional impairment or related to confounding factors, notably depression, the NPV was 0.90. Expressing cognitive complaints for all three EACS screening questions was significantly associated with depression (P < 0.001). CONCLUSIONS: The EACS screening questions had an NPV of 0.7 for excluding patients with HIV-associated NCI as defined by Frascati criteria. The PPV and NPV may improve if NCI diagnoses are based on new criteria.

The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study: baseline participant profile.

OBJECTIVES: The aim of the study was to examine baseline neurocognitive impairment (NCI) prevalence and factors associated with NCI among patients enrolled in the Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study. METHODS: The NAMACO study is an ongoing, prospective, longitudinal, multicentre and multilingual (German, French and Italian) study within the Swiss HIV Cohort Study. Between 1 May 2013 and 30 November 2016, 981 patients ≥ 45 years old were enrolled in the study. All underwent standardized neuropsychological (NP) assessment by neuropsychologists. NCI was diagnosed using Frascati criteria and classified as HIV-associated or as related to other factors. Dichotomized analysis (NCI versus no NCI) and continuous analyses (based on NP test z-score means) were performed. RESULTS: Most patients (942; 96.2%) had viral loads < 50 HIV-1 RNA copies/mL. NCI was identified in 390 patients (39.8%): 263 patients (26.8%) had HIV-associated NCI [249 patients (25.4%) had asymptomatic neurocognitive impairment (ANI)] and 127 patients (13%) had NCI attributable to other factors, mainly psychiatric disorders. There was good correlation between dichotomized and continuous analyses, with NCI associated with older age, non-Caucasian ethnicity, shorter duration of education, unemployment and longer antiretroviral therapy duration. CONCLUSIONS: In this large sample of aging people living with HIV with well-controlled infection in Switzerland, baseline HIV-associated NCI prevalence, as diagnosed after formal NP assessment, was 26.8%, with most cases being ANI. The NAMACO study data will enable longitudinal analyses within this population to examine factors affecting NCI development and course.

Viral Escape in the Central Nervous System with Multidrug-Resistant Human Immunodeficiency Virus-1.

In this study, we report the case of a patient infected with human immunodeficiency virus (HIV)-1 who developed ataxia and neurocognitive impairment due to viral escape within the central nervous system (CNS) with a multidrug-resistant HIV-1 despite long-term viral suppression in plasma. Antiretroviral therapy optimization with drugs with high CNS penetration led to viral suppression in the CSF, regression of ataxia, and improvement of neurocognitive symptoms.

[Psychopathology of Ganser's syndrome. Literature review and case report]. / Psychopathologie des Ganser-Syndroms. Literaturübersicht und Falldiskussion.

The key feature of Ganser's syndrome includes approximate answers to simple questions. The cause of this rare syndrome remains uncertain. Current classification systems categorise it as a dissociative disorder, the symptoms of which are judged as psychogenic in origin. Our review of the literature (n=151) demonstrates however that Ganser's syndrome is frequently associated with brain injury, although detailed imaging, neuropsychological, and neurological data of this for the most part do not exist. We describe a right-handed patient with Ganser's syndrome after a large left-hemispheric middle cerebral artery infarction. Detailed neuropsychological examination showed atypical lateralisation of cognitive functions with so-called crossed nonaphasia and pronounced frontal-executive dysfunctions. Regarding both psychiatric and neuropsychological aspects, we discuss how the key feature of approximate answers may be associated with frontal-executive cerebral dysfunctions.

Probabilistic contingency learning with limbic or prefrontal damage.

A fundamental capacity of the human brain is to learn relations (contingencies) between environmental stimuli and the consequences of their occurrence. Some contingencies are probabilistic; that is, they predict an event in some situations but not in all. Animal studies suggest that damage to limbic structures or the prefrontal cortex may disturb probabilistic learning. The authors studied the learning of probabilistic contingencies in amnesic patients with limbic lesions, patients with prefrontal cortex damage, and healthy controls. Across 120 trials, participants learned contingent relations between spatial sequences and a button press. Amnesic patients had learning comparable to that of control subjects but failed to indicate what they had learned. Across the last 60 trials, amnesic patients and control subjects learned to avoid a noncontingent choice better than frontal patients. These results indicate that probabilistic learning does not depend on the brain structures supporting declarative memory.

[Aphasia research and speech localization in the brain]. / Zur Geschichte der Aphasiologie und Sprachlokalisation im Gehirn.

Aphasia research has become an acknowledged branch of modern cognitive neuropsychology research whose aim is to explore more fully the structures of knowledge and of cerebral processes which might both be affected in patients with aphasia. Up to the second half of this century, a model based on a specific cerebral localisation of language processes had emerged based on brain localisation research by Broca and Wernicke (among others). New modern neuroimaging techniques, however, such as computed tomography and magnetic resonance imaging (MRI), but also functional imaging modalities such as positron emission tomography or functional MRI, have modified these concepts. It emerges that in comprehension as well as in production of language, not only a few well defined centres are responsible for the activity, but there is a synchronised activity in large neuronal networks connecting various regions located both in the cortex and in the deep subcortical structures; today, this activity can be demonstrated best in a non-invasive and reproducible way with functional MRI.

Determination of language dominance: Wada test confirms functional transcranial Doppler sonography.

OBJECTIVE: To determine the efficacy of the invasive Wada test in determining language dominance, and to validate the functional transcranial Doppler sonography (fTCD) examination in patients. BACKGROUND: Previous work shows that simultaneous bilateral fTDC may identify cognitive hemispheric dominance in healthy individuals. METHOD: fTDC and the Wada test were performed prospectively in 14 patients with various diseases (tumors, cerebrovascular events, head injury, intractable epilepsy). fTDC hemispheric dominance was determined based on the hemispheric blood flow velocity shift for language and visuospatial tasks. RESULTS: fTDC was performed easily in patients. One patient could not be examined by fTDC because of absent temporal bone window for ultrasonic transmission. Two Wada tests were inconclusive due to patient somnolence. One of these patients suffered from right frontal tumor and had aphasia remitted under steroids when examined. fTDC indicated a bilateral language dominance. In the remaining 11 patients the correlation between fTDC and Wada language lateralization indices was 0.75 (p = 0.008). If a post hoc cutoff score was taken for the fTDC language lateralization index, in eight patients, both fTDC and Wada testing determined the left hemisphere to be dominant for language; in the other three patients, language function was bilateral in both examinations. CONCLUSION: Although the current results are preliminary and require replication in a larger sample, fTDC seems to be able to assess hemispheric language dominance not only in healthy individuals, but also in patients. It might become an alternative noninvasive or complementary tool to the Wada test, particularly in patients in whom the Wada test is impractical or gives inconclusive results.

Association learning in the acute confusional state.

The usefulness of cognitive rehabilitative treatment in the acute stages after brain injury seems questionable because patients in severe acute confusional state early after coma clinically seem unable to learn and store new information. Therefore, the capability of patients in acute confusional state to learn and retain associative information was assessed. On two occasions pairs of simple nouns were presented to six patients in severe acute confusional state. Stimuli were presented repeatedly either in written form only or with additional pictorial representations. Immediate and 20 minutes delayed recall was measured. Patients in acute confusional state were able to learn progressively more word pairs across several presentations. They retained some information over an interval of 20 minutes. In addition, they learned and remembered pictorially supported associations better than pure verbal associations. Patients in severe acute confusional state may retain some explicit information and may profit from an imagery mnemonic aid. These results were not expected on the basis of clinical findings alone and they have potential implications for the care of patients in acute confusional state.

Disorientation in amnesia. A confusion of memory traces.

Disorientation is a common phenomenon in delirium and amnesia. It is thought to have an obvious explanation, i.e. disoriented patients fail to store the information crucial for the maintenance of orientation. In this study, we explored whether disorientation was indeed associated with a failure to learn new information or rather with a confusion of information within memory. Twenty-one patients with severe amnesia were examined. Orientation was tested with a 20-item questionnaire. Two runs of a continuous recognition task were used to test the ability to acquire information (first run of the task) and the tendency to confuse the temporal context of information acquisition (comparison of the second with the first run). We found that orientation was much better predicted by the measure of temporal context confusion (r = 0.90) than by the ability to simply acquire information (r = 0.54). Superimposition of neuroradiological scans demonstrated that increased temporal context confusion was associated with medial orbitofrontal or basal forebrain damage; patients with normal levels of temporal context confusion did not have damage to these areas. We conclude that disorientation more often indicates a confusion of memory traces from different events, i.e. increased temporal context confusion, than an inability to learn new information. Disorientation appears to reflect primarily a failure of the orbitofrontal contribution to memory.

The mechanisms of spontaneous and provoked confabulations.

Confabulation is a mysterious adjunct of amnesia. It remains unexplained why some patients invent untrue stories in response to questions (provoked confabulations) or even spontaneously with no apparent motivation (spontaneous confabulations). Hypothesized mechanisms range from a desire to fill gaps in memory to a loss of the temporal context in memory. We examined the mechanisms of confabulations in 16 amnesic patients. Patients were classified as spontaneous confabulators if they ever acted according to their confabulations. Provoked confabulations were measured as the number of intrusions in a verbal learning test. We found a double dissociation between the two types of confabulations, indicating that they represent different disorders rather than different degrees of the same disorder. Confabulating patients did not show an increased tendency to fill gaps in memory as measured by the number of fake questions concerning nonexistent items that they answered. Neither type of confabulation correlated with a failure to store new information as gauged with recognition tasks; pure information storage was even found to be normal in some patients. However, we found a positive correlation between several measures of verbal learning and verbal fluency with provoked, but not spontaneous, confabulations. In contrast, spontaneous, but not provoked, confabulations were associated with an inability to recognize the temporal order of stored information as measured by the comparison of two runs of a continuous recognition task. We suggest that provoked confabulations depend on an amnesic subject's search in his deficient memory and are the trade-off for increased item recollection. Spontaneous confabulations appear to be based on a failure to recognize the temporal order of stored information, resulting in erroneous recollection of elements of memory that do not belong together.

Memory without context: amnesia with confabulations after infarction of the right capsular genu.

OBJECTIVE: To explore the mechanism of an amnesia marked by confabulations and lack of insight in a patient with an infarct of the right inferior capsular genu. The confabulations could mostly be traced back to earlier events, indicating that the memory disorder ensued from an inability to store the temporal and spatial context of information acquisition rather than a failure to store new information. METHODS: To test the patient's ability to store the context of information acquisition, two experiments were composed in which she was asked to decide when or where she had learned the words from two word lists presented at different points in time or in different rooms. To test her ability to store new information, two continuous recognition tests with novel non-words and nonsense designs were used. Recognition of these stimuli was assumed to be independent of the context of acquisition because the patient could not have an a priori sense of familiarity with them. RESULTS: The patient performed at chance in the experiments probing knowledge of the context of information acquisition, although she recognised the presented words almost as well as the controls. By contrast, her performance was normal in the recognition tests with non-words and nonsense designs. CONCLUSION: These findings indicate that the patient's amnesia was based on an inability to store the context of information acquisition rather than the information itself. Based on an analysis of her lesion, which disconnected the thalamus from the orbitofrontal cortex and the amygdala, and considering the similarities between her disorder, Wernicke-Korsakoff syndrome, and the amnesia after orbitofrontal lesions, it is proposed that contextual amnesia results from interruption of the loop connecting the amygdala, the dorsomedial nucleus, and the orbitofrontal cortex.

Motion imagery in Parkinson's disease.

Patients with Parkinson's disease fail to fully profit from advance information about a target's movement in tracking tasks, possibly indicating deficient anticipation of the target's movement. Time estimation has been claimed to be deficient in Parkinson's disease. On the background of these studies, we tested the hypothesis that motion imagery is impaired in Parkinson's disease. Eleven non-demented patients with Parkinson's disease and nine age-matched controls participated in experiments testing their ability to anticipate trajectories of moving points (prediction whether two moving points would crash or not) and to estimate the time needed for completion of an invisible target's movement (a point moving around a circle). In addition, mirror drawing, a task involving motor learning and adjustment of movement to incongruent visual feedback, was tested. The Parkinson's disease patients, who failed to improve on mirror drawing, were not impaired on the imagery tasks: they estimated movement time and predicted trajectories with equal precision as the controls. Motion imagery thus appears to be intact in Parkinson's disease. However, Parkinson's disease patients did not accelerate their predictions of trajectories with practice as fast as the controls, a deficit which may be interpreted in terms of the fronto-striatal dysfunction repeatedly demonstrated in Parkinson's disease.

Determination of cognitive hemispheric dominance by "stereo" transcranial Doppler sonography.

BACKGROUND AND PURPOSE: Transcranial Doppler sonography (TCD) can assess blood flow velocity changes induced by focal brain activation. Therefore, TCD may have the potential to identify hemispheric dominance for cognitive tasks. METHODS: Using a system with two TCD probes ("stereo" TCD), we monitored simultaneously both middle cerebral arteries (MCAs) of 14 healthy right-handed volunteers while they performed cognitive tasks. The averaged blood flow velocity ratio of the two MCAs and the hemispheric blood flow velocity shift induced by the cognitive task were calculated. RESULTS: In every subject, language tasks resulted in blood flow velocity shift to the left compared with visuospatial tasks. Mean MCA blood flow velocity shift to the left was 1.67%, 2.01%, and 2.31% in three language tasks. Mean blood flow velocity shift to the right was 1.67% and 2.31% in two visuospatial tasks. CONCLUSIONS: Bilateral simultaneous MCA blood flow velocity monitoring and averaging during cognitive tasks can help to identify hemispheric dominance for cognitive tasks in individuals.

Coding and recall of categorized material in aphasics.

The aim of the present study was to examine whether the often reported impairments of aphasics in different short-term memory tasks could be the result of a failure to use the facilitating strategy of clustering. Aphasics (n = 60), right hemisphere brain-damaged (n = 36) and normal (n = 10) controls were tested with a modification of tasks developed by Petrides and Milner (1982). They were presented with sets of 16 cards with a random arrangement of the same 16 stimuli. On each card subjects had to point to one of the stimuli, trying not to point to the same stimulus in different cards. In some of the tasks pictures were selected to suggest a clustering into four equally sized subsets; in others the stimuli were highly heterogeneous with respect to perceptual and semantic characteristics. Prior to each task with items easy to categorize, half of the subjects were requested to sort the pictures into subsets, while the other half were given the pictures without any specific instruction, having been requested to do the sortings only after the main task. Aphasics (1) showed less clustering, i.e., sequential pointing according to the predefined categories, and (2) made significantly more errors than RH-controls especially in the tasks easy to categorize. While RH-controls benefited from the preceding sorting of the pictures aphasics made more errors when first introduced to the categorization task.

Memory for spatial and temporal order in aphasics and right hemisphere damaged patients.

Sets of five photographs per item were presented successively in five vertically arranged frames to 53 aphasics, 27 right hemisphere damaged (RHD) patients and 18 normal subjects. Following the presentation of the five slides subjects were given a spatial and a temporal recognition task. In the spatial task subjects had to indicate which of two pictures of a probe had been nearer to the top of the vertically arranged set of frames. In the temporal task they had to indicate which of the two pictures of the probe had been presented earlier. Aphasics made significantly more errors than RHD and normals in both the spatial and the temporal task, while RHD were significantly impaired in comparison to the normal controls only in the spatial task.

Recognition of random shapes in brain-damaged patients.

In two experiments the hypothesis was tested that left hemisphere-damaged patients and especially those with aphasia are impaired in the recognition of meaningless random shapes because they fail to attribute a meaning to the shapes. In a multiple choice recognition task, left hemisphere-damaged patients with aphasia and left and right hemisphere-damaged patients without aphasia were shown complex random shapes together with either a pictorial cue (experiment I and II) or a dotted drawing of its outline on which more or less outstanding parts were specially marked (experiment I). In experiment I no difference between conditions or groups emerged. In experiment II aphasics and left hemisphere-damaged patients without aphasia were generally inferior to right hemisphere-damaged controls and performed significantly better when a pictorial cue was given than when it was absent, however only when the conditions were given in a certain order.

Cognitive processing of tokens and their description in aphasia.

In a dual-reaction time task aphasics (N = 21) and right-hemisphere (RH) controls (N = 24) had to decide whether a list of features given verbally or pictorially correctly described the picture of a token. Although the error rates were extremely low, aphasics made significantly more errors than RH controls. There were no significant differences between the groups in latencies when pictures of tokens were presented; the groups differed drastically, however, when confronted with lists of features. The findings are interpreted as indicating a general deficit in the short-term storage of highly specific information.