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Case report. Aphasia in thalamic stroke: CT stereotactic localization.

We present a patient in whom dysphasia followed suddenly upon an apparently discrete thalamic infarct proven by computed tomography (CT). Detailed psychometric data of the patient's speech and memory disorder obtained during the acute and chronic stages were correlated with the evaluation of a focal thalamic lesion as demonstrated by serial CT. The findings and deductions drawn from selective reports in the literature form the basis of this presentation.

Aphasia↗

Negative attitude towards medication is associated with working memory impairment in schizophrenia patients.

A lack of insight into illness and negative attitudes towards medication are common among individuals with schizophrenia and impact clinical outcomes. This study aimed to examine the relationships between attitudes towards medication and cognitive function in schizophrenia patients. Thirty-five male forensic inpatients who were suffering from chronic schizophrenia participated in the study. A drug attitude inventory was used to evaluate the attitudes of the patients towards medication. Neuropsychological function was assessed with a comprehensive battery of tests. Patients with positive attitudes towards medication performed significantly better than those with negative attitudes on tests of verbal working memory (digit span forwards and backwards), inhibition and set shifting (Penn Inhibition test), delayed object memory and overall mental status (Mini Mental State Examination). There were no differences in age, education, hospitalizations or clinical symptoms between the groups. Our findings support an association between negative attitudes towards medication and poor cognitive performance, particularly of working memory.

Adult↗

Electroconvulsive therapy and memory.

Recent research on the effects of electroconvulsive therapy (ECT) on memory is critically reviewed. Despite some inconsistent findings, unilateral nondominant ECT appears to affect verbal memory less than bilateral ECT. Adequate research on multiple monitored ECT is lacking. With few exceptions, the research methodologies for assessing memory have been inadequate. Many studies have confounded learning with retention, and only very recently has long term memory been adequately studied. Standardized assessment procedures for short term and long term memory are needed, in addition to more sophisticated assessment of memory processes, the duration of memory loss, and qualitative aspects of memories.

Amnesia↗

99Tcm-HMPAO SPECT in suspected dementia.

To evaluate the usefulness of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) in suspected dementia we studied 160 consecutively imaged elderly patients from our hospital's memory disorder clinic. The diagnosis was based on clinical data, laboratory tests, neuropsychological examination, computed tomography (CT) and EEG. The patients were divided into six diagnostic categories: Alzheimer's disease (AD), multi-infarct dementia (MID), frontal lobe-type dementia (FTD), vascular encephalopathy not fulfilling the criteria of dementia, specific organic conditions, and psychiatric disorders. SPECT images were assessed without knowing the clinical diagnosis, and divided into AD pattern, FTD pattern, MID pattern, abnormal but unclassifiable, and normal. Twenty-three of 36 patients with clinical AD, 25/33 patients with clinical MID, and 2/5 patients with clinical TFD had compatible SPECT patterns. SPECT distinguished AD from MID in the majority (80%) of cases. In patients with depression or anxiety SPECT was abnormal in 16/21 cases, suggesting that SPECT may give early clues to the presence of an underlying organic disease in such elderly patients. Thus, SPECT with 99Tcm-HMPAO seems to be useful in the diagnosis of suspected dementia.

Aged↗

Subtypes of memory dysfunction associated with ECT: characteristics and neurobiological bases.

Electroconvulsive therapy (ECT) is an effective treatment for a variety of psychiatric syndromes. However, one of its adverse secondary effects is neurocognitive dysfunction. The aim of this paper is to review different subtypes of memory dysfunction associated with ECT from a neuropsychological perspective. Declarative memory is clearly impaired after ECT. Immediate memory, however, is broadly preserved. Few studies have addressed procedural and incidental memory. Selective memory is impaired, probably due to the disruption of specific brain regions. Some of the possible neurobiological bases of ECT memory dysfunction are discussed in this paper. Synaptic plasticity, the cerebral neurotransmission system, and cerebral metabolism are examined in relation to the dysfunction and subsequent recovery of each memory subtype.

Brain Mapping↗

Effect of piracetam on ECT-induced cognitive disturbances: a randomized, placebo-controlled, double-blind study.

Electroconvulsive therapy (ECT) is still the fastest, most effective, and frequently life-saving therapeutic intervention in several forms of depression and some other psychiatric disorders. Transient memory disturbances are frequent after ECT. A randomized, double-blind, placebo-controlled study was conducted to investigate the effects of piracetam on ECT-induced confusion and memory disturbances. Thirty-eight consecutively admitted patients with depressive illness or schizophrenia requiring ECT were given either piracetam or an identical-looking placebo during the period of ECT treatment and for 2 weeks afterward. Daily dosage of piracetam was 7.2 g, given orally for the first 2 weeks while patients underwent ECT (loading phase), followed by 4.8 g for the rest of the study period. Participants were evaluated by standardized clinical rating scales and cognitive psychologic tests 1 to 2 days before ECT, 1 day after their third and sixth ECT treatments, and 2 weeks after they had completed their ECT courses. Piracetam had no significant effect in preventing ECT-induced memory disturbances. All clinical ratings were consistently, albeit not significantly, better in the piracetam group, suggesting that piracetam may have augmented the effects of ECT.

Adult↗

The neuroanatomical and neurophysiological basis of learning.

The physiological basis of learning is memory. The established facts about memory, the memory systems, and learning are presented along with relevant theories currently proposed. Additionally, current physiological theory about cognition is examined. Specifically, the functions of the memory systems in cognition and the function of the frontal lobes in goal orientation and elaboration of thought are addressed. Implications for neuroscience nursing practice are drawn.

Brain↗

Varying intertrial interval reveals temporally defined memory deficits and enhancements in NTAN1-deficient mice.

The N-end rule is one ubiquitin-proteolytic pathway that relates the in vivo half-life of a protein to the identity of its N-terminal residue. NTAN1 deamidates N-terminal asparagine to aspartate, which is conjugated to arginine by ATE1. An N-terminal arginine-bearing substrate protein is recognized, ubiquitylated by UBR1/E3alpha, and subsequently degraded by 26S proteasomes. Previous research showed that NTAN1-deficient mice exhibited impaired long-term memory in the Lashley III maze. Therefore, a series of studies, designed to assess the role of NTAN1 in short- and intermediate-term memory processes, was undertaken. Two hundred sixty mice (126 -/-; 134 +/ +) received Lashley III maze training with intertrial intervals ranging from 2-180 min. Results indicated that inactivation of NTAN1 amidase differentially affects short-, intermediate-, and long-term memory.

Amidohydrolases↗

Working memory deficits in retinoid X receptor gamma-deficient mice.

Retinoid signaling has been recently shown to be required for mnemonic functions in rodents. To dissect the behavioral and molecular mechanisms involved in this requirement, we have analyzed the spatial and recognition working memory in mice carrying null mutations of retinoid receptors RARbeta and RXRgamma. Double mutants appeared deficient in spatial working memory as tested in spontaneous alternation in the Y-maze and delayed nonmatch to place (DNMTP) test in the T-maze. These mutant mice did acquire, however, spatial place reference or right/left discrimination tasks in the T-maze set-up, indicating that basic sensorimotor functions, spatial orientation, and motivational factors are unlikely to account for deficits in working memory-sensitive tasks. Double-mutant mice were also deficient in novel object recognition at intermediate, but not short delays. RXRgamma appeared to be the functionally predominant receptor in modulation of the working memory, as RXRgamma, but not RARbeta single null mutant mice exhibited deficits similar to those observed in the double mutants. The mechanism of this modulation is potentially related to functions of RXRgamma in frontal and perirhinal cortex, structures in which we detected RXRgamma expression and which are functionally implicated in working memory processes.

Animals↗

Substrate- and pH-dependent contribution of oxyanion binding site to the catalysis of prolyl oligopeptidase, a paradigm of the serine oligopeptidase family.

Prolyl oligopeptidase, an enzyme implicated in memory disorders, is a member of a new serine peptidase family. Crystallographic studies (Fülöp et al., 1998) revealed a novel oxyanion binding site containing a tyrosine residue, Tyr473. To study the importance of Tyr473 OH, we have produced prolyl oligopeptidase and its Tyr473Phe variant in Escherichia coli. The specificity rate constant, k(cat)/Km, for the modified enzyme decreased by a factor of 8-40 with highly specific substrates, Z-Gly-Pro-Nap, and a fluorogenic octapeptide. With these compounds, the decline in k(cat) was partly compensated for by reduction in Km, a difference from the extensively studied subtilisin. With the less specific suc-Gly-Pro-Nap, the Km value, which approximates Ks, was not significantly changed, resulting in greater diminution (approximately 500-fold) in k(cat)/Km. The second-order rate constant for the reaction with Z-Pro-prolinal, a slow tight-binding transition-state analogue inhibitor, and the Ki values for a slow substrate and two product-like inhibitors were not significantly affected by the Tyr473 OH group. The mechanism of transition-state stabilization was markedly dependent upon the nature of substrate and varied with pH as the enzyme interconverted between its two catalytically competent forms.

Amino Acid Sequence↗

Severe cortical involvement in MV2 Creutzfeldt-Jakob disease: an autopsy case report.

MV2 type sporadic Creutzfeldt-Jakob disease (sCJD) is reported to have a long duration and marked involvement of the cerebral deep gray matter. We describe an autopsied long-surviving sCJD case of MV2. In the early stages, the patient exhibited memory impairment, attention deficit and semantic memory disorder. Diffusion-weighted MRI showed abnormal hyperintensity signals along the cerebral cortex, sparing the thalami and basal ganglia. Pathological observations included: severe spongiosis throughout the cerebral cortex, several kuru plaques and plaque-like PrP deposits in the cerebellum, with only minimal degeneration in the thalami and basal ganglia. Our case suggests that MV2 has a wide clinicopathological spectrum, which ranges from "VV2" to "MM2" type.

Aged↗

Spatial working memory deficit correlates with disorganization symptoms and social functioning in schizophrenia.

Both spatial working memory deficit and disorganization symptoms have been considered significant components of schizophrenic impairment involved with the dorsolateral prefrontal cortex. The purpose of the present study was to investigate the relationships among spatial working memory, psychiatric symptoms including disorganization symptoms, and social functioning in schizophrenia. Fifty clinically stable patients with schizophrenia and 34 healthy controls participated in the study. Patients were rated with the Brief Psychiatric Rating Scale and the Rehabilitation Evaluation Hall and Baker. The Advanced Trail Making Test was used to evaluate spatial working memory. Patients demonstrated significantly reduced spatial working memory compared to that of healthy controls. Spatial working memory in patients correlated significantly with social functioning such as self-care skills, community skills and speech disturbance, and with disorganization symptoms. Disorganization symptoms also correlated with these aspects of social functioning. In conclusion it is suggested that both spatial working memory deficit and disorganization symptoms, which are impairments involved with the dorsolateral prefrontal cortex dysfunction, can serve as effective predictors of social functioning.

Adult↗

Selective immunolesioning of the basal forebrain cholinergic system disrupts short-term memory in rats.

Selective depletion of nerve growth factor receptor-bearing neurons in the basal forebrain cholinergic system nuclei by the immunotoxin 192 IgG-saporin offers a new and highly useful tool for the study of the role of the forebrain cholinergic system in cognitive functions. In the present study, we have tested the effects of 192 IpG-saporin in an operant delayed matching-to-position task which has previously been used to discriminate between delay-dependent learning impairments and delay-independent disturbances of non-mnemonic processes. Rats were first trained to criterion performance and then received intraventricular injections of 5 microg of 192 IgG-saporin 4 weeks prior to a second testing session. Rats with 192 IgG-saporin lesions displayed a significant delay-dependent decline in performance compared to normal controls, indicating a deficit in short-term memory. Administration of the muscarinic blocker scopolamine (0.5 mg/kg, i.p.) produced more pronounced impairment in the performance of the normal control rats across all delays, and induced further impairment also in animals with 192 IgG-saporin lesions. These effects were not observed following control injections of methyl scopolamine, suggesting that the impairment induced by scopolamine was due to the blockade of central muscarinic receptors. No improvement in performance was observed in either group following systemic treatment with the muscarinic cholinergic agonist arecoline (1.00 mg/kg). Biochemical and morphological analyses confirmed the selective and severe (>90-95%) depletion of cholinergic neurons throughout the septal-diagonal band area and the nucleus basalis region by the intraventricular 192 IgG-saporin treatment. Although the immunotoxin was observed to produce additional damage to the cerebellar Purkinje cells, no gross motor abnormalities were observed that could contribute to the effects on accuracy in the task used here. In conclusion, the results show that selective combined lesions of the basal forebrain cholinergic neurons in the septal-diagonal band area and nucleus basalis produce long-lasting impairments in short-term memory, thus providing further support for a role of this system in cognitive functions.

Animals↗

Prolonged cannabinoid treatment results in spatial working memory deficits and impaired long-term potentiation in the CA1 region of the hippocampus in vivo.

Adult male Long-Evans rats were administered the potent cannabinoid 1 receptor agonist HU-210 (100 microg/kg, i.p.) for 15 days continuously and their performance on a matching-to-place version of the Morris water maze was subsequently evaluated. Overall, experimental animals performed significantly worse initially on the reference memory component of this task, but their performance improved over 5 days until it was indistinguishable from that of control animals. Animals given HU-210 did not exhibit working memory impairments at short intertrial delays (30 s); however, significant impairments were observed in learning performance with longer intertrial delays (300 s). In vivo electrophysiological analyses revealed that long-term potentiation in the CA1 region of the hippocampus was significantly impaired following the administration of HU-210 for 15 days. These results indicate that long-term cannabinoid exposure can produce marked deficits in reference and working memory performance, and also impair hippocampal synaptic plasticity in vivo.

Animals↗

Genetic ablation of the mammillary bodies in the Foxb1 mutant mouse leads to selective deficit of spatial working memory.

Mammillary bodies and the mammillothalamic tract are parts of a classic neural circuitry that has been implicated in severe memory disturbances accompanying Korsakoff's syndrome. However, the specific role of mammillary bodies in memory functions remains controversial, often being considered as just an extension of the hippocampal memory system. To study this issue we used mutant mice with a targeted mutation in the transcription factor gene Foxb1. These mice suffer perinatal degeneration of the medial and most of the lateral mammillary nuclei, as well as of the mammillothalamic bundle. Foxb1 mutant mice showed no deficits in such hippocampal-dependent tasks as contextual fear conditioning and social transmission of food preference. They were also not impaired in the spatial reference memory test in the radial arm maze. However, Foxb1 mutants showed deficits in the task for spatial navigation within the Barnes maze. Furthermore, they showed impairments in spatial working memory tasks such as the spontaneous alternation and the working memory test in the radial arm maze. Thus, our behavioural analysis of Foxb1 mutants suggests that the medial mammillary nuclei and mammillothalamic tract play a role in a specific subset of spatial tasks, which require combined use of both spatial and working memory functions. Therefore, the mammillary bodies and the mammillothalamic tract may form an important route through which the working memory circuitry receives spatial information from the hippocampus.

Animals↗

Dissociable memory effects after medial thalamus lesions in the rat.

Variable neuropathology in cases of diencephalic amnesia has led to uncertainty in identifying key thalamic nuclei and their potential role in learning and memory. Based on the principal neural connections of the medial thalamus, the current study tested the hypothesis that different aggregates of thalamic nuclei contribute to separate memory systems. Lesions of the anterior thalamic aggregate (AT), which comprises the anterodorsal, anteromedial and anteroventral nuclei produced substantial deficits in both working and reference spatial memory in a radial arm maze task in rats, supporting the view that the AT is an integral part of a hippocampal memory system. Lesions to the lateral thalamic aggregate (LT), which comprises the intralaminar nuclei (centrolateral, paracentral and rostral central medial nuclei) and lateral mediodorsal thalamic nuclei (lateral and paralamellar nuclei) produced a mild working memory impairment only, while lesions to the posteromedial thalamic aggregate (MT), which comprises the central and medial mediodorsal thalamic nuclei and the intermediodorsal nucleus had no effect on radial arm maze performance. In contrast, only MT lesions impaired learning associated with memory for reward value, consistent with the idea that the MT contributes to an amygdala memory system. Compared with chance discrimination, the control and AT groups, but not MT or LT groups, showed evidence for temporal order memory for two recently presented objects; all groups showed intact object recognition for novel vs. familiar objects. These new dissociations show that different medial thalamic aggregates participate in multiple memory systems and reinforce the idea that memory deficits in diencephalic amnesics may vary as a function of the relative involvement of different thalamic regions.

Animals↗