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Disturbed functional brain interactions underlying deficient tactile object discrimination in Parkinson's disease.

Somatosensory discrimination of cuboid objects was studied in a group of healthy volunteers and patients with Parkinson's disease using regional cerebral blood flow (rCBF) measurements obtained with positron emission tomography (PET) and 15O labeled water [H2 15O]. A 6-[18F]-fluoro-L-dopa (FDOPA) PET scan demonstrated that the patients may be grouped into those with normal and those with abnormally lowA FDOPA uptake in the caudate nucleus. The categorical group comparisons revealed that task-induced rCBF increases were deficient in bilateral motor and sensory cortical areas in the Parkinson patients. Moreover, deficient rCBF increases were evident in the mesial and right dorsolateral prefrontal cortex for patients in a more advanced disease state, who showed low FDOPA uptake in the caudate nucleus. A principal component analysis (PCA), performed on the rCBF data, identified three patterns (principal components, PCs) that differentiated patients from normals. The first PC represented a right-hemisphere dominant, bilateral group of brain areas known to be involved in tactile exploration. A second PC reflected a cortical-subcortical pattern of functional interactions, comprising cortical areas important for working memory processes. The third group-differentiating PC revealed a pattern of functional interactions involving bilateral temporo-parieto-occipital association cortices, which was consistent with a hypothesized supramodal network necessary for object discrimination. In an additional subgroup analysis, greater expression of the third PC pattern predicted greater caudate FDOPA uptake in patients. Our neuroimaging data revealed a disturbance of distinct patterns of brain functional interactions related to the sensorimotor deficit in Parkinson's disease and to deficits of cognitive information processing deficits in the more advanced stage of Parkinson's disease.

Adult↗

Role of membrane receptors in the induction of an in vitro secondary anti-hapten response. II. Antigen-immunoglobulin receptor interaction is not required for B memory cell proliferation.

In this study it has been investigated whether the interaction of antigen and B cell surface immunoglobulin (sIg) is required for full clonal expansion of memory B cells specific for the hapten, p-azophenyl-lactoside (lac). Cultures of lac-primed B cells and keyhole limpet hemocyanin (KLH)-specific T cells were activated in three ways: (a) by the antigen lac-KLH, (b) in the absence of lac epitopes by attaching KLH to the H-2 antigens of the B cells, and (c) in similar conditions where lac epitopes were supplied on carriers unrecognized by helper T cells. Dilution analyses showed that the yield of IgG anti-lac plaques per activated precursor was identical in all situations, and that the increased responses observed in the presence of lac epitopes were due to an increase in the frequency of activated precursors. Our results thus indicate that specific interacting T cells convey both the differentiative and proliferative signals to B memory cells, and are at variance with proposals advocating that an antigen-induced proliferative phase is succeeded by a T-cell-dependent differentiative event. We suggest that the effect of sIg-antigen interaction may be to cycle some precursors into a more easily activated state.

Animals↗

Innate inflammatory signals induced by various pathogens differentially dictate the IFN-I dependence of CD8 T cells for clonal expansion and memory formation.

Type-I IFNs (IFN-I) provide direct survival signals to T cells during Ag-driven proliferation. Because IFN-I production differs depending on the pathogen, we assessed CD8 T cell requirement for direct IFN-I signals during responses to vaccinia virus (VV), vesicular stomatitis virus (VSV), lymphocytic choriomeningitis virus (LCMV), and Listeria monocytogenes (LM) immunizations in vivo. IFN-I-receptor-deficient (IFN-IR(o)) CD8 T cells expanded 3- to 5-fold less and formed a diminished memory pool compared with wild-type (WT) CD8 T cells in response to VV, VSV, or LM. WT CD8 T cells expanded more robustly in response to LCMV-encoded Ags than to Ags encoded by the other three pathogens, and under these conditions the lack of direct IFN-I signals inhibited their expansion by approximately 100-fold. To test whether the high antigenic-load provided by LCMV caused greater expansion and greater IFN-I dependency, we primed WT and IFN-IR(o) OVA-specific OT-1 CD8 T cells with a fixed-number of OVA-peptide-pulsed dendritic cells along with adjuvant effect provided by LCMV, VV, VSV, or LM. Both WT and IFN-IR(o) OT-1 cells were recruited, proliferated, and differentiated into effectors in all the four cases. However, WT OT-1 cells expanded similarly in all four cases. IFN-IR(o) OT-1 cells expanded approximately 20-fold less than the WT OT-1 CD8 T cells when LCMV was used as adjuvant, whereas their expansion was affected only marginally when VV, VSV, or LM were used as adjuvants. Thus, innate/inflammatory signals induced by different pathogens contribute to CD8 T cell expansion and memory formation via distinct levels of IFN-I dependence.

Animals↗

Interpersonal perception in a social context.

Interpersonal perception among well-acquainted individuals in a social context was studied. High acquaintance was expected to provide perceivers with a large sample of target behaviors across situations. In turn, memory for acquaintances should be organized by social group and personality characteristics, as predicted by the social context-personality index theory. Differentiation of the target's traits in memory should produce a target effect on perception that is stronger than the perceiver effect. Furthermore, evidence for accuracy, meta-accuracy, independence of self- and other-perception, and reciprocity of affect were anticipated. A social relations analysis of data from a multiple-interaction, reciprocal design was used to study these phenomena. At the individual level, analyses indicated that perceptions of targets were determined primarily by target characteristics and secondarily by perceiver construction of the judgment. Also, perceivers judged targets as targets judged themselves, and targets knew in general how perceivers viewed them. Self- and other-perceptions were largely independent. Surprisingly, we did not observe dyadic meta-accuracy.

Adult↗

Differential effects of anxiogenic central and peripheral benzodiazepine receptor ligands in tests of learning and memory.

Previous research has demonstrated that low doses of anxiogenic central benzodiazepine receptor (CBR) ligands, the beta-carbolines, improve performance in various learning and memory tests in animals if administered prior to training. The present experiments compared the effect of a beta-carboline (FG 7142) with that of a pharmacologically distinct anxiogenic compound, a peripheral benzodiazepine receptor (PBR) ligand, 4'-chlorodiazepam (Ro5-4864), in two tests of learning and memory in rats. As expected, FG 7142 significantly improved performance in a passive avoidance test. Ro5-4864 was without effect. In a shuttlebox escape test, Ro5-4864 significantly impaired performance while FG 7142 had no effect. The effect of Ro5-4864 was antagonized by the specific peripheral benzodiazepine receptor antagonist, PK 11195. These results indicate that the differential impact of CBR and PBR anxiogenic ligands on performance in aversively-motivated learning tests may be a reflection of their distinct pharmacologies.

Animals↗

Differential diagnosis in dementia.

Dementia is characterised by progressive memory loss, associated with agnosia, aphasia, dyscalculia, apraxia, and deficits in executive functioning. Alzheimer disease is the most frequent cause of dementia, with vascular dementia, diffuse Lewy body disease, and other etiologies being important differential diagnoses. A strategy and diagnostic hierarchy for diagnosis in dementia is proposed. Diagnostic criteria for Alzheimer disease, diffuse Lewy body disease, and vascular dementia are discussed.

Alzheimer Disease↗

Loss of IL-7Ralpha is associated with CD4 T-cell depletion, high interleukin-7 levels and CD28 down-regulation in HIV infected patients.

OBJECTIVE: Elevated levels of interleukin (IL)-7 are present in the blood of HIV-positive patients and it is known that IL-7 receptor (IL-7R)alpha expression decreases on T cells during HIV infection. The subset(s) of T cells with low IL-7Ralpha and the consequence of low IL-7Ralpha expression for T-cell survival are poorly characterized. DESIGN: The frequency of IL-7Ralpha-negative T cells in HIV-positive patients was studied in relation to CD4 T-cell counts, IL-7 concentration and survival in culture. We analysed IL-7Ralpha expression in different T-cell populations and in relation to Bcl-2 expression. METHODS: Specimens from 38 HIV-1 patients and 17 controls were examined. IL-7Ralpha and Bcl-2 expression in different T-cell populations was studied by flow cytometry. The influence of IL-7Ralpha expression on T-cell survival was studied by culturing T cells in the presence of IL-7. RESULTS: Down-regulation of IL-7Ralpha on T cells correlated with depletion of CD4 T cells (P < 0.001) and also with increased concentration of serum IL-7 (P < 0.05). The decreased IL-7Ralpha expression was associated with low Bcl-2 expression and with the reduced survival capacity of T cells in the presence of IL-7 in vitro. Particularly, T cells with memory phenotype showed a decreased IL-7Ralpha expression in association with CD28 down-regulation. CONCLUSIONS: The positive effects of IL-7 on survival and homeostatic proliferation of T cells might be severely impaired in HIV-infected individuals due to IL-7Ralpha down-regulation. Differentiation towards a CD28-negative memory phenotype in response to chronic activation may lead to an overall decrease of IL-7 mediated survival within the peripheral T-cell pool.

Adult↗

Expression of the alpha1beta1 integrin, VLA-1, marks a distinct subset of human CD4+ memory T cells.

The alpha1beta1 integrin, very late antigen-1 (VLA-1), is a collagen receptor expressed in many CD4+ T cells localizing to inflamed tissues. Here we show that the expression of VLA-1 is a stable marker of a distinct subset of CD4+ memory T cells. Thus, in human peripheral blood lymphocytes (PBLs), approximately 1-4% of the CD4+ T cells express VLA-1, and following T cell receptor activation ex vivo, the percentage of VLA-1+ cells increases within the CD45RO+ population. Importantly, the activated VLA-1+ and VLA-1- cells can be isolated and maintained in culture as phenotypically stable subsets. Functionally, CD4+ memory T cells, operationally defined as the cells that divide rapidly following stimulation with a recall antigen, are highly enriched for VLA-1+ cells. Moreover, depletion of the small fraction of VLA-1+ cells present in CD4+ PBLs prior to stimulation significantly abrogated the proliferative response to recall antigens. Notably, the VLA-1+ cells in fresh CD4+ PBLs are composed of resting CD45RO+/RA-, CCR7-, CD62L+, CD25-, and VLA-4hi cells. Interestingly, this VLA-1+ subset is enriched for Th1-type cells, and Th1-polarizing conditions during T cell activation favor the emergence of VLA-1+ cells. Thus, VLA-1 expression is a stable marker of a unique subset of human memory CD4+ T cells that predominantly differentiates into Th1 cells.

Autoimmune Diseases↗

Anamnestic response to a thymus-independent antigen, TNP-LPS in C57BL/6 and DBA/2 mice: dominance of the IgG secondary response of the C57BL/6 mice in the F1 hybrids.

The primary and secondary immune responses to a thymus-independent antigen, TNP-LPS, were investigated in C57BL/6, DBA/2 and (C57BL/6 x DBA/2)F1 mice. While there is no evidence that TNP-LPS induces immunological memory in DBA/2 mice, a definite priming effect has been observed in C57BL/6 mice. Memory is revealed by the appearrance of antibody-forming cells of the IgG isotype. The differentiation of B micron precursors into B gamma memory cells is a dominant phenotype, since it is also found in the F1 C57BL/6 x DBA/2 hybrids.

Animals↗

Performance on the Wechsler Memory Scale-Revised for patients with mild traumatic brain injury and mild dementia.

The purpose of this study was to delineate significant differences among mild traumatic brain-injured and early onset mild dementia patients examined using the Wechsler Memory Scale-Revised subtests. In comparison to 12 mild traumatic brain-injured patients, 11 mild dementia patients scored significantly lower on Verbal Paired Associates I and II, Visual Reproduction I and II, and Visual Paired Associates I. Raw score summaries for the Wechsler Memory Scale-Revised indicated significantly lower scores on Verbal Memory, Visual Memory, and the over-all composite. General Memory for mild dementia patients in comparison to individuals who sustained a mild traumatic brain injury. Despite equivalent scores on Attention/Concentration, the dementia group did not show significantly lowered delay in memory recall by comparison with mild closed-head injured patients. The study recommends replication with much larger sample sizes to validate the results.

Adult↗

Spatial memory deficits in patients after unilateral selective amygdalohippocampectomy.

The present study investigated the differential involvement of the right and left hippocampus in various forms of spatial memory: spatial search, positional memory versus object-location binding, and coordinate versus categorical processing. Twenty-five epilepsy patients with selective amygdalohippocampectomy were examined using a sensitive computer paradigm to measure these spatial memory aspects. The patients' performance was compared to a group of thirty healthy controls. The results show that the left amygdalohippocampectomy group performed poorly on the ability to bind together object information to coordinate spatial locations. In turn, the right amygdalohippocampectomy group was impaired in coordinate positional memory. Both patient groups were unimpaired on the spatial search task. These findings are discussed focusing on the "binding device" hypothesis in combination with the cognitive map theory.

Adult↗

Basal ganglia involvement in memory-guided movement sequencing.

The basal ganglia (BG) are thought to play a critical role in motor planning and movement sequencing. While electrophysiological and imaging studies have shown that the dorso-lateral prefrontal cortex (DLPFC) is involved in working memory (WM), the involvement of the BG in this process is not well understood. We used a motor sequencing task to investigate the differential role of BG nuclei in memory-guided movement. Significant activation was observed in the DLPFC and posterior putamen and globus pallidus (GP), with a trend in the caudate and no differences in the anterior putamen. We then investigated the effect of BG outflow on thalamic activation using functional connectivity analysis. Activation in the posterior putamen + GP was found to be correlated with thalamic activation only in the hemisphere contralateral to movement. These results provide the first fMRI evidence that the BG may modulate activity in the thalamus during working memory-guided movement sequencing. Our findings suggest that the BG activation may reflect increased motor sequencing demands during the memory-guided movement condition and, specifically, that the posterior putamen and GP may play a role in maintenance of representations in WM in a manner that contributes to planning and temporal organization of motor sequencing.

Adult↗

Learning to remember: generation and maintenance of T-cell memory.

Immunologic memory results from a carefully coordinated interplay between cells of the immune system. In this review, we explore various aspects of the nature, generation, and maintenance of T lymphocyte-mediated immunologic memory. In light of the demonstrated heterogeneity of the memory T-cell pool, we hypothesize that subsets of memory T cells instructed to mature to distinct differentiation stages may differ, not only in functional and homing properties, but also in the conditions they require for survival, including antigen persistence and cytokine environment. Hence, according to this hypothesis, distinct memory T-cell subsets result from the nature and timing of the signals provided by the immune environment and occupy distinct niches. Intracellular and extracellular molecular mechanisms that underlie and modulate T-cell memory are discussed.

Animals↗

Effects of simultaneous vs sequential stimulus presentation on memory performance following temporal lobe resection in humans.

This study examines the differential effects of simultaneous vs sequential stimulus presentation on performance of a visuo-spatial memory task in patients following unilateral temporal lobectomy for relief of complex-partial seizures. Eleven subjects with surgical resection of the left temporal lobe, 13 subjects with surgical resection of the right temporal lobe, and 12 normal controls were examined. Results indicate that both the Right and the Left surgical groups were impaired on the visuo-spatial memory task employed. Further, the Right resection group was significantly more impaired for the recall of stimuli presented in the sequential condition as compared to the simultaneous condition.

Adult↗

Concurrent validity of the Luria-Nebraska Memory Scale.

Investigated the concurrent validity of the Luria-Nebraska Neuropsychological Battery (LNNB) Memory Scale using the Wechsler Memory Scale (WMS) as the criterion. For 32 psychiatric patients, the LNNB Memory Scale yielded a significant correlation with the WMS MQ, r (30) = -.65, p less than .001. Moreover, there was a 72% agreement between the two scales with respect to the identification of memory impairment. Memory-impaired Ss earned a significantly higher (p less than .01) mean T-score on the LNNB Memory Scale than did Ss without memory problems. It was concluded that the LNNB Memory Scale is an adequate measure of short-term memory.

Adult↗

Differential expression of glycans in the hippocampus of rats trained on an inhibitory learning paradigm.

The glycan chains of glycoconjugates play important roles in cell-cell and cell-matrix interactions. In the CNS, previous studies on learning and memory suggest the importance of oligosaccharides attached to glycoconjugates in the modulation of synaptic connections. We studied the hippocampal glycan distribution of rats subject to an inhibitory avoidance task. The expression of glycans was examined by lectin-histochemistry using Vicia villosa lectin (VVL) for terminal alpha/beta N-acetylgalactosamine (alpha/beta GalNAc); Galanthus nivalus lectin (GNL) for terminal mannose alpha-1,3 (Man alpha-1,3); Peanut agglutinin (PNA) for galactose beta-1,3N-acetylgalactosamine (Gal beta-1,3 GalNAc); Erythrina cristagalli lectin (ECL) for galactose beta-1,4 N-acetylglucosamine (Gal beta-1,4 GlcNAc); Sambucus nigra lectin (SNA) for sialic acid alpha-2.6 galactose (SA alpha-2,6 Gal); Maackia amurensis lectin II (MAL II) for sialic acid alpha-2,3 (SA alpha-2,3); Wheat germ agglutinin (WGA) for terminal N-acetylglucosamine with/ without sialic acid (GlcNAc wo SA); succynilated WGA (sWGA) for terminal N-acetylglucosamine without sialic acid (terminal GlcNAc without SA); Griffonia simplicifolia lectin II (GSL II) for terminal alpha/beta N-acetylglucosamine (alpha/beta GlcNAc terminal); and Lotus tetragonolobus lectin (LTL) alpha-fucose. Two groups of 10 animals were examined: non-trained (Control) and Trained rats. ECL, sWGA and GSL II were negative for both groups in all the hippocampal subfields studied. For both groups, VVL was negative in CA4 and granular cells of the Dentate Gyrus (DG) and LTL was negative in the CA4 subfield. Expression of alpha/beta GalNAc, alpha-fucose and GlcNAc in other hippocampal subflields was positive, with no differences between groups. However, expression of Man alpha-1,3 was significantly higher in the CA1, CA2, CA3, and CA4 subfields in the Trained group. On the other hand, expression of Gal beta-1,3 GalNAc was significantly low in CA4 and DG in the Trained group. In conclusion, the results here presented indicate that the exposure of rats to an associative behavioral paradigm related to declarative memory, involves some regulatory mechanism/s for the differential patterns of glycan expression.

Animals↗

Flow cytometric differentiation of Asian and Western types of multiple sclerosis, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and hyperIgEaemic myelitis by analyses of memory CD4 positive T cell subsets and NK cell subsets.

We examined the alterations of memory CD4(+) T cell subsets bearing surface receptors linked to either Th1 or Th2 cytokine production as well as natural killer (NK) cell subsets by three color flow cytometry in the peripheral blood from 36 patients with clinically definite multiple sclerosis (MS), 27 patients with HAM/TSP, 13 patients with hyperIgEaemic myelitis who had mite antigen-specific IgE and 25 healthy controls (HC). The patients with MS were clinically classified into an optico-spinal form of MS (Asian type, MS-A) and the conventional form of MS (Western type, MS-W). MS-A showed a significant increase of CD4(+)CD45RA(-)CCR5(+) cells (Th1 cells) through the relapse and remission phases in comparison to HC, while MS-W showed a significant increase of CD4(+)CD45RO(+)CD62L(-) cells (Th1 cells) only at the relapse phase. HAM/TSP showed a significant increase of CCR5(+) and CD62L(-) memory CD4(+) T cells as well as CD30(+) memory CD4(+) T cells (Th2 cells) in comparison to HC. On the other hand, a selective increase of CD4(+)CD45RO(+)CD30(+) cells was found in hyperIgEaemic myelitis. The percentage of mature NK cells (CD3(-)CD16(+)CD56(+) cells) as well as double negative T cells (CD3(+)CD4(-)CD8(-) cells) decreased significantly in HAM/TSP in comparison to HC. Our findings therefore suggest a flow cytometric analysis of Th1/Th2-associated markers on memory CD4(+) T cells as well as NK cell subsets to be useful for differentiating various inflammatory neurologic conditions.

Adult↗

Surviving roots of trauma: prevalence of silent signs of sex abuse in patients who recover memories of childhood sex abuse as adults.

Recent research suggests that victimization imagery is chronically accessible in sex-abused populations, which is helpful in distinguishing them from nonabused populations. Eight categories of victimization imagery were selectively activated by Rorschach stimuli. These 8 sex-abuse signs were replicated in a new sample of 36 patients with continuous memory of sex abuse. Classification accuracy was 83%. By contrast, these signs were present in only 4% (5 of 115) of the protocols of nonabused patients. Taken together, the 2 studies confirm reasonably high sensitivity of the 8 signs for sex-abused populations and high specificity for nonabused populations. The 8 signs were also differentially salient for patients who recovered memory of childhood sexual trauma as adults. The Rorschach protocols of 59 of 114 patients with delayed recall of sexual abuse possessed signs of sex abuse. There was no linkage between therapy and recovered-memory cases with and without sex-abuse signs. Emergence of trauma memories was not uniquely traceable to treatment. Memories arose outside of the context of therapy in over 56% of the cases. Implications for the false-memory debate are discussed.

Adult↗