Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia.
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The specific neural substrate underlying the amnesia in alcoholic Korsakoff's psychosis is poorly defined because of the considerable brain damage found in many non-amnesic alcoholics, particularly those with Wernicke's encephalopathy. Using operational criteria to identify alcoholics with and without Korsakoff's psychosis, we have shown that many of the cortical and subcortical regions involved in the encoding and retrieval of episodic memory are either unaffected (hippocampus) or damaged to the same extent (prefrontal cortex and the cholinergic basal forebrain) in both amnesic and non-amnesic alcoholics. In the present study we analysed the diencephalic regions involved in episodic memory to determine the neural substrate for the amnesia observed in alcoholic Korsakoff's psychosis. The number of neurons in spaced serial sections containing the hypothalamic mamillary nuclei and the anterior and mediodorsal thalamic nuclei was estimated using unbiased stereological techniques. Neurodegeneration of the hypothalamic mamillary nuclei and the mediodorsal thalamic nuclei was substantial in both non-amnesic and amnesic alcoholics with Wernicke's encephalopathy. However, neuronal loss in the anterior thalamic nuclei was found consistently only in alcoholic Korsakoff's psychosis. This is the first demonstration of a differentiating lesion in alcoholic Korsakoff's psychosis and supports previous evidence that degeneration of thalamic relays are important in this memory disorder. (+info)
Lateralized memory deficits on the Wada test correlate with the side of lobectomy only for patients with unilateral medial temporal lobe epilepsy.
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The aim of this study was to determine whether the predictive value of the intracarotid amobarbital test (IAT) for the side to be resected is applicable only to medial temporal lobe epilepsy and to investigate whether there are different patterns of memory performances on the IAT between patients with unilateral mesial temporal sclerosis (UMT group) and those without (non-UMT group). We studied 30 patients in the UMT group and 10 in the non-UMT group, who underwent pre-surgical evaluation for intractable temporal lobe epilepsy. Memory performances on the IAT was defined as the percentage of memory items presented during unilateral hemispheric anesthesia that was recognized after recovery. More than a 20% decline of the memory performance on the IAT compared with the memory performance on the pre-test was regarded as a memory deficit. Age at onset of epilepsy was significantly younger in the UMT than in the non-UMT group. Surgical outcome was significantly better in the UMT than in the non-UMT group. The lateralizing value of unilateral memory deficits on the IAT was statistically confirmed. There was a significant association between falsely lateralizing memory performances and the non-UMT group. Excluding the exceptional cases with right-sided language dominance in spite of right-sided lesions, the high incidence of the unilateral right-sided memory deficits in the non-UMT group was statistically significant. This study suggested that the excellent lateralizing value of the memory performances on the IAT is limited to patients with mesial temporal lobe epilepsy. IAT memory performances in patients without such lesions can be misleading, even if lateralized, because their memory status presumably reflects a natural lateralization of the memory organization which is independent of the epileptogenic focus. (+info)
Plasma membrane ordering agent pluronic F-68 (PF-68) reduces neurotransmitter uptake and release and produces learning and memory deficits in rats.
(27/2556)
A substantial body of evidence indicates that aged-related changes in the fluidity and lipid composition of the plasma membrane contribute to cellular dysfunction in humans and other mammalian species. In the CNS, reductions in neuronal plasma membrane order (PMO) (i.e., increased plasma membrane fluidity) have been attributed to age as well as the presence of the beta-amyloid peptide-25-35, known to play an important role in the neuropathology of Alzheimer's disease (AD). These PMO increases may influence neurotransmitter synthesis, receptor binding, and second messenger systems as well as signal transduction pathways. The effects of neuronal PMO on learning and memory processes have not been adequately investigated, however. Based on the hypothesis that an increase in PMO may alter a number of aspects of synaptic transmission, we investigated several neurochemical and behavioral effects of the membrane ordering agent, PF-68. In cell culture, PF-68 (nmoles/mg SDS extractable protein) reduced [3H]norepinephrine (NE) uptake into differentiated PC-12 cells as well as reduced nicotine stimulated [3H]NE release. The compound (800-2400 microg/kg, i.p., resulting in nmoles/mg SDS extractable protein in the brain) decreased step-through latencies and increased the frequencies of crossing into the unsafe side of the chamber in inhibitory avoidance training. In the Morris water maze, PF-68 increased the latencies and swim distances required to locate a hidden platform and reduced the time spent and distance swam in the previous target quadrant during transfer (probe) trials. PF-68 did not impair performance of a well-learned working memory task, the rat delayed stimulus discrimination task (DSDT), however. Studies with 14C-labeled PF-68 indicated that significant (pmoles/mg wet tissue) levels of the compound entered the brain from peripheral (i.p.) injection. No PF-68 related changes were observed in swim speeds or in visual acuity tests in water maze experiments, rotorod performance, or in tests of general locomotor activity. Furthermore, latencies to select a lever in the DSDT were not affected. These results suggest that PF-68 induced deficits in learning and memory without confounding peripheral motor, sensory, or motivational effects at the tested doses. Furthermore, none of the doses induced a conditioned taste aversion to a novel 0.1% saccharin solution indicating a lack of nausea or gastrointestinal malaise induced by the compound. The data indicate that increases in neuronal plasma membrane order may have significant effects on neurotransmitter function as well as learning and memory processes. Furthermore, compounds such as PF-68 may also offer novel tools for studying the role of neuronal PMO in mnemonic processes and changes in PMO resulting from age-related disorders such as AD. (+info)
Chronic stress induces impairment of spatial working memory because of prefrontal dopaminergic dysfunction.
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Although the mechanism responsible for cognitive deficits in stress-related neuropsychiatric disorders has been obscure, prefrontal cortical (PFC) dopaminergic dysfunction is thought to be involved. In animals, the mesoprefrontal dopaminergic system is particularly vulnerable to stress, and chronic stress induces working memory impairment. However, the relation between the working memory impairment and altered dopaminergic activity in chronically stressed rats is unclear. Furthermore, the change of dopaminergic activity in the PFC induced by stress is thought to express as a stress response, not as a disorder of organic function. We have previously reported that chronic stress administered by water immersion and restraint for 4 weeks induces a organic disorder such as hippocampal neuronal degeneration. We therefore examined whether chronically stressed (4 weeks) and recovered (10 d) rats show a working memory impairment caused by reduced dopamine (DA) transmission in the PFC, as suspected in the neuropsychiatric disorders. The stress impaired the spatial working memory evaluated by T-maze task and induced a marked reduction of DA transmission concomitant with an increase in DA D1 receptor density in the PFC. This memory impairment was sufficiently ameliorated by intra-PFC infusion of 10 ng SKF 81297, a D1 receptor-specific agonist. Pretreatment with intraperitoneal injection of 20 microgram/kg SCH 23390, a D1 receptor antagonist, reversed the SKF 81297 response. These results indicate that chronic stress induces working memory impairment through a D1 receptor-mediated hypodopaminergic mechanism in the PFC. These findings provide important information for understanding of the mechanisms underlying PFC dysfunction in stress-related neuropsychiatric disorders. (+info)
Practice principles of cognitive enhancement therapy for schizophrenia.
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Cognitive Enhancement Therapy (CET) is a developmental approach to the rehabilitation of schizophrenia patients that attempts to facilitate an abstracting and "gistful" social cognition as a compensatory alternative to the more demanding and controlled cognitive strategies that often characterize schizophrenia as well as much of its treatment. Selected cognitive processes that developmentally underlie the capacity to acquire adult social cognition have been operationalized in the form of relevant interactive software and social group exercises. Treatment methods address the impairments, disabilities, and social handicaps associated with cognitive styles that appear to underlie the positive, negative, and disorganized symptom domains of schizophrenia. Style-related failures in secondary rather than primary socialization, particularly social cognitive deficits in context appraisal and perspective taking, are targeted goals. Illustrative examples of the techniques used to address social and nonsocial cognitive deficits are provided, together with encouraging preliminary observations regarding the efficacy of CET. (+info)
Panmodal processing imprecision as a basis for dysfunction of transient memory storage systems in schizophrenia.
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Schizophrenia is a severe mental disorder associated with cognitive disturbances that may reflect underlying deficits in the functioning of brain transient memory storage systems. This study investigates performance in three distinct tasks that require transient memory storage: (1) tone discrimination, (2) object weight discrimination, and (3) "AX"-type visual continuous performance task. The tests used were chosen to investigate the degree to which a similar pattern of performance deficit could be observed across multiple sensory and cognitive domains in schizophrenia. In each of the paradigms, a similar pattern emerged: subjects with schizophrenia showed severe performance deficits whenever performance depended on functioning of transient memory systems. The deficits were apparent at both short and long interstimulus intervals (ISI), however, and schizophrenia subjects were no more affected by increasing ISI than were controls. Moreover, when short ISI performance was matched across groups by manipulating task difficulty, subsequent decay in performance was equivalent across groups. Thus, although schizophrenia subjects show severe performance deficits in memory-dependent tasks, the deficits do not appear to reflect impaired transient memory per se. Rather, they appear to reflect impaired precision of operation of such systems, irrespective of the duration over which representations must be maintained. The severe deficits in processing precision, despite the relatively preserved maintenance of representation, may be relevant to pathophysiological models of schizophrenia. (+info)
Reduced brain edema after traumatic brain injury in mice deficient in P-selectin and intercellular adhesion molecule-1.
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Platelet (P-) selectin and intercellular adhesion molecule-1 (ICAM-1) mediate accumulation of neutrophils in brain. However, the mechanisms regulating neutrophil accumulation and damage after traumatic brain injury (TBI) are poorly defined. We hypothesized that mice deficient in both P-selectin and ICAM-1 (-/-) would have decreased brain neutrophil accumulation and edema, and improved functional and histopathological outcome after TBI compared with wild-type (+/+). In Protocol I, neutrophils and brain water content were quantified at 24 h after TBI. No difference in brain neutrophil accumulation was observed between groups; however, brain edema was decreased in dual P-selectin and ICAM-1 -/- (P < 0.05 vs. +/+ mice). In Protocol II, after TBI, tests of motor and memory function and histopathology were assessed over 21 days. No difference in motor or memory function or histopathological damage was observed between +/+ and -/- mice. A role for adhesion molecules in the pathogenesis of brain edema independent of leukocyte accumulation in brain is suggested. (+info)
Accelerated forgetting in patients with epilepsy: evidence for an impairment in memory consolidation.
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Patients with epilepsy frequently complain of memory difficulties yet perform normally on standard neuropsychological tests of memory. It has been suggested that this may be due to an impairment of very long-term memory consolidation processes, beyond those normally assessed in the neuropsychological clinic. We carried out a prospective study of verbal memory over a long-term retention interval of 8 weeks in patients with epilepsy and in controls. Results were compared with performance on conventional tests of memory. Despite normal learning and retention over 30 min, patients with epileptic foci in the left temporal lobe performed disproportionately poorly on the long-term test compared with both patients with epileptic foci in the right temporal lobe and controls. Our findings provide evidence for an extended period of memory consolidation and point to the critical region for this process, at least for verbal material, in the left temporal lobe. The implications of our findings for clinical assessment and therapeutic management of patients with epilepsy are discussed. (+info)