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Learning and memory in Holocaust survivors with posttraumatic stress disorder.

BACKGROUND: Impairments in explicit memory have been observed in Holocaust survivors with posttraumatic stress disorder. METHODS: To evaluate which memory components are preferentially affected, the California Verbal Learning Test was administered to Holocaust survivors with (n = 36) and without (n = 26) posttraumatic stress disorder, and subjects not exposed to the Holocaust (n = 40). RESULTS: Posttraumatic stress disorder subjects showed impairments in learning and short-term and delayed retention compared to nonexposed subjects; survivors without posttraumatic stress disorder did not. Impairments in learning, but not retention, were retained after controlling for intelligence quotient. Older age was associated with poorer learning and memory performance in the posttraumatic stress disorder group only. CONCLUSIONS: The most robust impairment observed in posttraumatic stress disorder was in verbal learning, which may be a risk factor for or consequence of chronic posttraumatic stress disorder. The negative association between performance and age may reflect accelerated cognitive decline in posttraumatic stress disorder.

Aged↗

The relationship of mismatch negativity to quantitative EEG and morphological findings in schizophrenia.

The goal of the present study is to investigate the relationships of mismatch negativity (MMN) to other markers in schizophrenics; Quantitative EEG (QEEG), CT and psychopathological ratings. Thirty unmedicated patients (28.4+/-9.8 y, 20 M) including twenty neuroleptic-naive cases were divided into two groups before treatment; Group A consisted of ten patients with greater MMN amplitudes, while twenty patients with smaller ones were assigned to Group B. In QEEG, Group A showed a closer profile to healthy controls, indicating their function is less distorted. Group B showed greater power in slow wave, slow alpha and fast beta bands. Their greater slow wave may be implicated in cognitive impairment reflected by attenuated MMN as well as greater dilation in lateral ventricles and Sylvian fissures on CT. After pharmacological treatment with conventional neuroleptics, Group A's MMN decreased, whereas that of Group B increased. Furthermore, neuroleptics' EEG-effects observed in Group A were close to the reported profiles of healthy subjects, while those in Group B were distinct from them. Conclusively, MMN might have crucial associations to other measures underlying the brain pathology of schizophrenia. The diagnostic value of MMN as a trait-marker was discussed.

Adolescent↗

Neuroimmune and neurovirological aspects of human immunodeficiency virus infection.

Like most lentiviruses, HIV-1 causes both immune suppression and neurological disease. Neurological disease may occur at any stage of HIV infection but is most apparent with severe immune suppression. Cognitive impairment, reflected strikingly by HIV-associated dementia, has attracted intense interest since the outset of the HIV epidemic, and understanding of its pathogenesis has been spurred on by the emergence of several hypotheses outlining potential pathogenic mechanisms. The release of inflammatory molecules by HIV-infected microglia and macrophages and the concurrent neuronal damage play central roles in the conceptualization of HIV neuropathogenesis. Many inflammatory molecules appear to contribute to the pathogenic cascade and their individual roles remain undefined. At the same time, the abundance of virus in the brain and the type or strain of virus found in the brain may also be important codeterminants of neurological disease, as shown for other neurotropic viruses. Coreceptor use by HIV found in the brain appears to closely mirror what has been reported in systemic macrophages. The impact of HAART on viral genotype and phenotype found in the brain, and its relationship to clinical disease, remain uncertain. Several interesting animal models have been developed, using other lentiviruses, transgenic animals, and HIV-infected SCID mice, that may prove useful in future pathogenesis and therapeutic studies. Despite the progress in the understanding of HIV neuropathogenesis, many questions remain unanswered.

Animals↗

Quantitative trait loci analysis of human event-related brain potentials: P3 voltage.

The P3 event-related brain potential (ERP) is a positive-going voltage change of scalp-recorded electroencephalographic activity that occurs between 300-500 ms after stimulus onset. It is elicited when a stimulus is perceived, memory operations are engaged, and attentional resources are allocated toward its processing. Because this ERP component reflects fundamental cognitive processing, it has found wide utility as an assessment of human mental function in basic and clinical studies. In particular, P3 attributes are heritable and have demonstrated considerable promise as a means to identify individuals at genetic risk for alcoholism. We have conducted a quantitative linkage analysis on a large sample from families with a high density of affected individuals. The analyses suggest that several regions of the human genome contain genetic loci related to the generation of the P3 component of the ERP, which are possible candidate loci underlying the functional organization of human neuroelectric activity.

Alcoholism↗

Who cares for a stressed brain? The mother, the kid or both?

Data are emerging that the altered development of adrenocortical and emotional reactivity in individuals exposed perinatally to adverse events is reflected in cognitive change and that maternal care is an important determinant. However, early trauma does not cause a generalized cognitive decline at older age, but rather drives cognitive performance to the extremes, at the expense of the average performance demonstrated by normally reared individuals.

Animals↗

Subjective social status: its determinants and its association with measures of ill-health in the Whitehall II study.

The purpose of this study was twofold-(1) investigate the role of subjective social status as a predictor of ill-health, with a further exploration of the extent to which this relationship could be accounted for by conventional measures of socioeconomic position; (2) examine the determinants of a relatively new measure of subjective social status used in this study. A 10 rung self-anchoring scale was used to measure subjective social status in the Whitehall II study, a prospective cohort study of London-based civil service employees. Results indicate that subjective status is a strong predictor of ill-health, and that education, occupation and income do not explain this relationship fully for all the health measures examined. The results provide further support for the multidimensional nature of both social inequality and health. Multiple regression shows subjective status to be determined by occupational position, education, household income, satisfaction with standard of living, and feeling of financial security regarding the future. The results suggest that subjective social status reflects the cognitive averaging of standard markers of socioeconomic situation and is free of psychological biases.

Adult↗

Nerve growth factor in never-medicated first-episode psychotic and medicated chronic schizophrenic patients: possible implications for treatment outcome.

Nerve growth factor (NGF) has been found to play a crucial role in the neuroplasticity of predominantly cholinergic neurons in brain development, and neuronal survival following brain injury, which reflect in cognitive performance. Wide ranges of neurodevelopmental abnormalities have been reported in schizophrenic patients, who also show poor cognitive performance. We report plasma NGF levels in never-medicated first-episode psychotic (FEP; N=24) and chronic medicated schizophrenic patients (N=24). NGF levels were determined in plasma by Enzyme-Linked ImmunoSorbent Assay (ELISA). Plasma NGF levels were significantly lower in both FEP and medicated chronic patients as compared to normal subjects (P<0.001). However, NGF levels were significantly higher in chronic schizophrenic patients, which were treated with antipsychotics as compared to FEP (P<0.05). Moreover, NGF levels in chronic patients treated with atypical antipsychotics were markedly higher as compared to patients treated with typical antipsychotics (P<0.05). Lower NGF levels in FEP patients at the onset of psychosis may have implications for the neurodevelopmental abnormalities. However, higher NGF levels in chronic patients treated with atypical antipsychotics may have implications for the treatment outcome.

Adult↗

Left-lateralized fMRI activation in the temporal lobe of high repressive women during the identification of sad prosodies.

We investigated with fMRI whether different lateralization types of cortical activation in prosodic tasks are caused by individually different stress-related coping strategies. After healthy women had been classified as high or low repressive they performed four different identification tasks with acoustically presented speech material while being in the MR scanner. The two materials presented in blocks were emotionally irrelevant CV syllables and adjectives with a mix of different prosodic intonations. Sad and happy intonations had to be targeted by two affective identification tasks in the same adjective mixtures. For testing stimulus-material effects the phoneme /a/ had to be identified both in the syllables and the adjectives. This design allowed us to test influences of coping strategies and affective tasks on cortical activation in both hemispheres. Results showed no differences in global cortical lateralization as a function of high or low repressiveness and no global support for either the valence hypothesis or the right-hemisphere hypothesis of emotional processing. However, we observed differences in auditory and speech cortex. In accordance to the construct of repression/sensitization, high repressive women showed larger left, low repressive women larger right hemisphere activation during the identification of sad intonations. Thus, differences in stress-related coping strategies may not lead to general differences in cortical lateralization, but may depend on specific elicitors and task-relevant brain areas. In contrast, the identification of happy intonations led to strong and right-lateralized global cortical activation independent of coping strategies which complies with the right-hemisphere hypothesis of emotional processing. In addition, this may reflect general cognitive and arousal effects of task difficulty as well as auditory cue-specific attentional effects.

Adaptation, Psychological↗

Latent inhibition is disrupted by acute and repeated administration of corticosterone.

Latent inhibition (LI), namely, a retardation in conditioning to a stimulus, as a consequence of its prior non- reinforced pre-exposure, is disrupted in amphetamine-treated rats and humans and in some subsets of schizophrenic patients. One factor that has been repeatedly implicated in precipitating and/or exacerbating psychotic episodes is stress. Since a principal biological response to stress is the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, leading, as its end product, to the secretion of corticosterone, the present experiments tested whether increase in corticosterone levels following exogenous corticosterone administration would disrupt LI. Both repeated (Experiment 1) and acute (Experiment 2) administration of corticosterone led to LI disruption, providing evidence for the involvement of the HPA axis alterations in LI and further supporting the viability of disrupted LI as an animal model of psychosis. Both regimens also increased amphetamine-induced activity. We suggest that disrupted LI may reflect a cognitive mechanism whereby prolonged periods of increased corticosterone levels can lead to 'sensory flooding' characteristic of psychosis.

Journal Article↗

Working memory, attention, and communication disturbances in schizophrenia.

The authors hypothesized that schizophrenic communication disturbances reflect specific cognitive deficits in the areas of working memory and attention. They examined the cognitive correlates of communication disturbances, as measured by linguistic reference performance, in schizophrenic (n = 48), bipolar (n = 24), and nonpsychiatric control (n = 23) individuals. Reference performance ratings in the schizophrenic patients were associated with scores on tests of working memory and attention and were not related to performance on concept formation or verbal fluency tests. In contrast, in the bipolar and nonpsychiatric individuals, reference performance was associated with concept formation and verbal fluency test scores but was not related to performance on tests of working memory. Implications with respect to the processes underlying schizophrenic communication disturbances are discussed.

Adult↗

Natural choice in nonhuman primates.

In 5 experiments, 4 monkeys and 1 ape chose between 2 food sources, each held in 1 of the experimenter's hands while he stood in front of a cage. When choosing between 2 sources of the same food that differed in amount, preference for the larger amount decreased as the size of each good proportionately increased. A second finding was that subjects were indifferent between a 2-food mixture and a single food that was part of the mixture if the single food was the preferred food of the mixture, a result suggesting the less preferred food had no value. Experiment 6 replicated these effects in 4 additional monkeys. These effects may be incompatible with previous theorizing about animal choice and may reflect a cognitive difference between nonhuman primates and humans.

Animals↗

Memory and metamemory: a study of the feeling-of-knowing phenomenon in amnesic patients.

Accuracy of the feeling of knowing was tested in patients with Korsakoff's syndrome, patients prescribed electroconvulsive therapy, four other cases of amnesia, and control subjects. In Experiment 1, we tested feeling-of-knowing accuracy for the answers to general information questions that could not be recalled. Subjects were asked to rank nonrecalled questions in terms of how likely they thought they would be able to recognize the answers and were then given a recognition test for these items. Only patients with Korsakoff's syndrome were impaired in making feeling-of-knowing predictions. The other amnesic patients were as accurate as control subjects in their feeling-of-knowing predictions. In Experiment 2, we replicated these findings in a sentence memory paradigm that tested newly learned information. The results showed that impaired metamemory is not an obligatory feature of amnesia, because amnesia can occur without detectable metamemory deficits. The impaired metamemory exhibited by patients with Korsakoff's syndrome reflects a cognitive impairment that is not typically observed in other forms of amnesia.

Adult↗

The role of problem definitions in understanding age and context effects on strategies for solving everyday problems.

The participants (107 preadolescents, 124 college students, 118 middle-aged adults, and 131 older adults) described 2 everyday problems (1 unconstrained, the other constrained to 1 of 6 domains) that they experienced and their goals and strategies. Problem definitions reflected interpersonal or competence components or both; strategies reflected altering cognitions, actions, or regulating and including others. Age differences in problem definitions were found. For unconstrained-domain problems, age and problem definition were related to strategies; for unconstrained-domain problems age differences in strategies were not found. For constrained-domain problems, strategies related to problem domain and problem definition, with problem definition the better predictor of strategies. The results illustrate the value of individuals' problem definitions for addressing age and context effects on strategies used.

Activities of Daily Living↗

Age-based structural dynamics between perceptual speed and knowledge in the Berlin Aging Study: direct evidence for ability dedifferentiation in old age.

According to 2-component theories of intelligence, negative cross-sectional age gradients in mechanic (broad Gf) and pragmatic (broad Gc) cognitive components reflect the increasing constraining of the former in the expression and integrity of the latter component. The authors examined this widely held but untested assumption by applying a recently proposed dynamic structural modeling technique, the bivariate dual change score model, to longitudinal data from the Berlin Aging Study (N = 516, age range = 70-103 years). Mechanics and pragmatics were indexed by perceptual speed and knowledge, respectively. As hypothesized, results indicated that changes in knowledge are dominated by perceptual speed and offered strong support for the notion of "mechanization" of pragmatic abilities in old and very old age.

Aged↗

Rethinking schizophrenia: insights from genomics and implications for research.

Recent genomic research, considered in the wider context of knowledge from outside genomics, provides significant conceptual insights into the aetiology and pathogenesis of schizophrenia. The evidence indicates that genetic risk is expressed across the lifespan, from foetal development through to adulthood, and involves multiple neuronal types and brain regions. Schizophrenia appears to be primarily a neuronal disorder, with synaptic dysfunction playing a central role in pathogenesis both during development and in mature adult brain function, alongside earlier non-synaptic neurodevelopmental mechanisms. Importantly, non-familial genetic and environmental factors substantially influence neurodevelopmental impairment, and this is often reflected in cognitive performance falling below familial expectations. Cognitive deficits and structural brain abnormalities are weakly correlated with familial genetic risk and are better understood as markers of neurodevelopmental vulnerability rather than causal mediators. Genomic findings also position schizophrenia within a neurodevelopmental continuum, spanning childhood-onset disorders to adult-onset psychiatric conditions, and suggest heterogeneity within schizophrenia, with some cases exhibiting stronger neurodevelopmental involvement. These findings challenge notions that schizophrenia can be ascribed to, or understood by studying, dysfunction in particular neuronal types, brain regions or circuits, or to defects at a particular stage of neurodevelopment. While schizophrenia appears to be predominantly a neuronal disorder, pathophysiology appears to be manifest widely across time and space, and in different neuronal types across the adult and foetal brain. Moreover, despite schizophrenia's high heritability, there is mounting evidence that non-familial genetic and environmental factors play important roles in the neurodevelopmental processes that impact on schizophrenia risk. Finally, variation in the impact of the neurodevelopmental factors appears to be key to understanding some of the heterogeneity within schizophrenia and the relationship between schizophrenia and other conditions. These observations have profound implications for future research, particularly in clarifying pathogenic mechanisms and refining diagnostic frameworks.

Humans↗

Rise and fall of modular orthodoxy.

The premise of cortical modularity is based on strong dissociations caused by focal lesions. These dissociations are rare, and their explanatory power and theoretical importance are vastly overrated. The effects of brain lesions must be considered in their totality, rather than in idiosyncratic selectivity. These effects are more consistent with a continuous, graded functional neocortical geometry, than with a modular neocortex. Distinction must be drawn between strong intrinsic modularity, and weak emergent modularity. Strong intrinsic modularity is more characteristic of the thalamus than of the cortex. The advent of neocortex may have represented an evolutionary escape from strong modularity as the dominant principle of neural organization, and a shift toward a more interactive principle of neural organization dominated by emergent properties. The latter may take the form of weak modularity, reflective of cognitive skill routinization. The extent of weak, emergent modularization may be asymmetric, more pronounced in the left hemisphere, while the right hemisphere is essentially amodular.

Agnosia↗

Does naming contribute to memory self-report in temporal lobe epilepsy?

The present study evaluated the hypothesis (Mayeux et al., 1980) that visual confrontation naming deficits may underlie the memory complaint in patients with temporal lobe epilepsy (TLE). Thirty-nine patients with medically refractory left (n = 23) and right (n = 16) TLE were compared with an epilepsy control group with idiopathic primary generalized epilepsy (n = 38). All subjects completed selected subtests of the Multilingual Aphasia Examination and Wechsler Memory Scale (Form 1) together with a measure specifically designed for quantification of the memory complaint in TLE. Objective verbal memory test performance, confrontation naming, repetition, and comprehension were unrelated to memory self-report. Controlled Oral Word Association was the only measure to exert an influence on memory self-ratings, and this relationship was specific to the TLE group. The hypothesis of Mayeux et al. (1980) was not specifically supported, but the present findings do suggest that cognitive processes reflected in orthographically based and internally generated word retrieval play a role in memory self-report.

Adult↗

Statistical methods for a three-period crossover design in which high dose cannot be used first.

Design and analysis methods for the three-period crossover trial defined by the sequences: (D0, D1, D2), (D1, D0, D2), and (D1, D2, D0), where D0 is a placebo, and D1 and D2 are a low dose and a high dose of a drug, respectively, are developed. This design may be used when investigators are unwilling to administer a higher dose of a new drug to a patient before administering a lower dose. In using this design, patients should be randomized to sequences in blocks that are integer multiples of 3. Both parametric and non-parametric analysis methods are based on contrasts that capture intrapatient variability only and provide unbiased estimates and hypothesis tests of pairwise differences between carryover, direct dose, and period effects. The design and methods are illustrated with data reflecting the cognitive component of the Alzheimer's disease assessment scale collected in a large clinical trial of Tacrine at doses of 0, 40, and 80 mg/day.

Alzheimer Disease↗