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Biomedical subjects

N Raz

Publications and source records attributed to N Raz.

At least 19 recordsLinked to original sources
PubMed2006

Aging and the role of working memory resources in visuospatial attention.

Visuospatial attention has been shown to be robust to the effects of increasing age. Nonetheless, models linking individual differences in working memory capacity to attentional performance suggest that older adults may experience disruptions in visuospatial attention under conditions of resource load. Two experiments were conducted to investigate the effects of age and concurrent working memory load on two tasks that have been proposed to require posterior attentional processes. The findings suggest that loading working memory resources selectively disrupts performance on a nonintegrated Stroop task, whereas cue utilization remains intact. In addition, imposing a working memory load delays the deployment of visuospatial attention in both experiments. Regarding the effects of age, findings suggest that older adults can effectively perform both attentional tasks despite working memory load. Age differences did emerge in the time course of cue utilization. Findings point to the resilience of visuospatial attention in aging, even under conditions of significant cognitive load. We discuss these results and their implications for models postulating a role for working memory capacity in attentional behaviors.

Adolescent↗
PubMed2004

Differential aging of the medial temporal lobe: a study of a five-year change.

OBJECTIVE: To test the hypothesis that entorhinal cortex (EC) volume decreases at a slower rate than the hippocampal (HC) volume in healthy adults, and to examine whether the rate of shrinkage increases with age. METHODS: Volumes of the HC and EC were measured twice on MRI scans of 54 healthy adults (aged 26 to 82 years), with an average interval of 5 years. RESULTS: Markedly different age trends were noted in the examined regions. The EC showed no age-related differences on both occasions and only minimal age-related change (0.33%/y). By contrast, the HC exhibited significant age-related differences at baseline and at follow-up evaluation and decreased at a faster pace of 0.86%/y. Older participants (aged > or = 50 years) showed increased annual shrinkage of the HC (1.18%) and EC shrinkage (0.53%/y). The rate of HC volume loss significantly exceeded that of the EC. No EC shrinkage and modest HC volume reduction were observed in people aged <50 years. CONCLUSIONS: Age-related shrinkage occurs in the medial temporal lobes of healthy adults, with significant hippocampal decline and minimal entorhinal changes. In both regions, the rate of decline accelerates with age, although the role of pathologic factors in age-related increase of volume loss merits further investigation.

Adult↗
PubMed2004

Environmental enrichment in mice decreases anxiety, attenuates stress responses and enhances natural killer cell activity.

The importance of environment in the regulation of brain, behaviour and physiology has long been recognized in biological, social and medical sciences. Animals maintained under enriched conditions have clearly been shown to have better learning abilities than those maintained under standard conditions. However, the effects of environmental enrichment (EE) on immunity and emotionality have been less documented and remain questionable. Therefore, we investigated the effect of EE on natural killer (NK) cell activity, psychological stress responses and behavioural parameters. Male C3H mice were housed either in enriched or standard conditions for 6 weeks. Behaviour was then examined by the grip-strength test, staircase and elevated plus maze, and corticosterone levels and NK cell activity were measured. Furthermore, animals exposed to the stress paradigm, achieved by electric shock with reminders, were tested for freezing time in each reminder. Corticosterone levels were also measured. The EE mice showed decreased anxiety-like behaviour and higher activity compared to standard mice, as revealed by a greater percentage of time spent in the open arms of the elevated plus maze, and a higher rate of climbing the staircase. A shorter freezing time in the stress paradigm and no corticosterone level reactivity were measured in EE mice. In addition, NK cell activity in spleens of EE mice was higher than that demonstrated in those of standard mice. Thus, EE has a beneficial effect on anxiety-like behaviour, stress response and NK cell activity. The effect on NK cell activity is promising, due to the role of NK cells in host resistance.

Animals↗
PubMed2001

Expression of L-selectin and efficient binding to high endothelial venules do not modulate the dissemination potential of murine B-cell lymphoma.

The homing receptor L-selectin is essential for the migration of naive lymphocytes into peripheral lymph nodes. In contrast to naive lymphocytes, activated and memory cells down-regulate L-selectin and enter peripheral lymph nodes by an L-selectin-independent mechanism. In view of the concept that lymphomas present the malignant counterparts of normal lymphocytes at a defined stage of differentiation, it has been suggested that in contrast to lymphomas with a memory/activated cell phenotype, L-selectin is essential for dissemination of lymphomas that represent naive cells. 38C-13 is a murine B-cell lymphoma with an immature naive cell phenotype. 38C-13 cells express high levels of L-selectin and bind to lymph node high endothelial venules in an L-selectin-dependent manner. In this study we demonstrate that treatment of 38C-13 tumor-bearing mice with anti-L-selectin antibodies did not inhibit tumor dissemination to peripheral lymph nodes. Moreover, L-selectin-negative 38C-13 variant cells disseminated as efficiently as wild-type cells. Thus, in spite of its expression, L-selectin is not required and does not affect the metastatic potential of the tumor. L-selectin of the malignant cells and of normal lymphocytes appears to be functionally different. Thus, whereas antibody cross-linking of L-selectin resulted in down-modulation of the receptor in normal lymphocytes, cross-linking had no effect on L-selectin expression in 38C-13 cells, suggesting that, in spite of comparable levels of surface expression in normal and malignant cells, L-selectin may be functionally impaired in some malignant cells.

Animals↗
PubMed2000

Neuroanatomical and cognitive correlates of adult age differences in acquisition of a perceptual-motor skill.

The objective of this study was to examine age differences in procedural learning and performance in conjunction with differential aging of central nervous system (CNS) structures. Sixty-eight healthy volunteers (age 22-80) performed a pursuit rotor task (four blocks of 20 15-second trials each). Volumes of the cerebellar hemispheres, neostriatum, prefrontal cortex, and hippocampus were measured from Magnetic Resonance (MR) images. Improvement in pursuit rotor performance was indexed by increase in time on target (TOT). A general improvement trend was evident across the blocks of trials. Overall, younger participants showed significantly longer TOT. The rate of improvement was age-invariant during the initial stages of skill acquisition but became greater in middle-aged participants as the practice progressed. When the influences of regional brain volumes were taken into account, the direct age effect on mean TOT measured during the first day of practice disappeared. Instead, reduced volumes of the cerebellar hemispheres and the putamen and poorer performance on nonverbal working memory tasks predicted shorter TOT. In contrast, neither the volume of the caudate and the hippocampus, nor verbal working memory showed association with motor performance. Pursuit rotor performance at the later stages of practice was unrelated to the reduction in putamen volume and was affected directly by age, cerebellar volume, and nonverbal working memory proficiency. We conclude that in a healthy population showing no clinical signs of extrapyramidal disease, age-related declines in procedural learning are associated with reduced volume of the cerebellar hemispheres and lower nonverbal working memory scores. During initial stages of skill acquisition, reduced volume of the putamen is also predictive of poorer performance.

Adult↗
PubMed2000

The cognitive correlates of white matter abnormalities in normal aging: a quantitative review.

Cerebral white matter of asymptomatic people frequently exhibits circumscribed areas of hyperintensity on magnetic resonance (MR) images and hypodensity on computed tomography scans. However, behavioral implications of this phenomenon remain unclear. In this meta-analysis, the authors examine cumulative evidence regarding the cognitive sequelae of white matter abnormalities in adults without dementia. The influence of potential moderator variables, such as neuroimaging technique, location of the lesions, rating scale, and demographic characteristics of the sample on the association between the burden of white matter hyperintensities and cognitive performance was also examined. Results indicate that white matter abnormalities observed on MR images are associated with attenuated performance on tasks of processing speed, immediate and delayed memory, executive functions, and indices of global cognitive functioning. There was no significant link between the white matter hyperintensities and psychometric indices of intelligence or fine motor performance.

Adult↗
PubMed1999

Age-related deficits in generation and manipulation of mental images: I. The role of sensorimotor speed and working memory.

The authors investigated age-related slowing of information processing in mental imagery tasks. Eighty-five healthy adults (ages 18 to 77) performed a visual, sensorimotor, reaction-time task; a visual-perceptual choice reaction task; and 3 mental imagery tasks that varied in apparent difficulty and involved stimuli at 2 levels of graphic complexity. Age was associated with prolongation of response time across all tasks and both levels of stimulus complexity. Accuracy of response was adversely affected by increase in stimulus complexity in all tasks, whereas it was negatively related to age only on the tasks with substantial mental imagery requirements. Slowing of information processing and reduction in accuracy were mediated by declines in working memory but not by decrease of sensorimotor speed.

Adult↗
PubMed1998

The glycosylphosphatidylinositol-anchored form and the transmembrane form of CD58 are released from the cell surface upon antibody binding.

The adhesion molecule CD58 is expressed on the cell surface in both a transmembrane form and a glycosylphosphatidylinositol (GPI)-anchored form. Here we report that CD58 is released from JY cells following cross-linking by immobilized anti-CD58 monoclonal antibodies. Antibodies to other cell surface proteins, as well as PMA and LPS, did not trigger CD58 release. The release resulted from membrane cleavage, since biotin-labeled CD58 was released from biotinylated cells, and down-modulation of CD58 surface expression accompanied accumulation of soluble CD58 IN culture media. We have previously reported the isolation of JY variant cells, which lack expression of GPI anchored proteins and thus express only the transmembrane form of CD58. Here we show that these variant cells release CD58 upon crosslinking, indicating that the transmembrane isoform is released, probably by proteolysis. Antibodies directed to the cytoplasmic domain of CD58, in contrast to antibodies against an extracellular epitope of CD58, did not react with released CD58, supporting a membrane cleavage mechanism. It is also shown that CD58, released from [3H]ethanolamine-labeled JY cells, contained ethanolamine. This result demonstrated that the GPI-anchored CD58 can be released in parallel to the transmembrane isoform and that this release does not result from proteolytic cleavage, since cleavage by a protease would have removed the ethanolamine. The present data suggest that the two isoforms of CD58 are released upon antibody binding and that their release is mediated by distinct mechanisms.

Antigen-Antibody Reactions↗
PubMed1998

The glycosylphosphatidylinositol-anchored form and the transmembrane form of CD58 associate with protein kinases.

The significance of the glycosylphosphatidylinositol (GPI) anchor is unknown. Since GPI-anchored proteins mediate signaling, it has been suggested that the GPI structure serves as a signal-transducing element. However, the division of signaling functions between transmembrane and GPI-anchored proteins is unclear. Studies of distinct membrane-anchored forms of the same protein may resolve this issue. The adhesion molecule CD58 is expressed on the cell surface in both a transmembrane and a GPI-anchored form and hence provides a useful model. We studied CD58 in the human B lymphoblastoid cell line JY. In addition to mediating adhesion, CD58 is involved in signal transduction. Incubation of JY cells with immobilized anti-CD58 Abs results in extensive tyrosine phosphorylation and in secretion of TNF-alpha. We demonstrate that CD58 is associated with protein kinase(s) and with several kinase substrates. We further demonstrate that both CD58 isoforms are involved. CD58 in JY variant cells, which express only the transmembrane form, as well as CD58 in JY variant cells, which express only the GPI-anchored form, are associated with kinase activity. This association results in a phosphorylation pattern that is common to the variant and to wild-type JY cells. Thus, these findings suggest that the capacity of GPI-anchored proteins to interact with kinases is not always dependent on the GPI anchor itself.

B-Lymphocytes↗
PubMed1998

Neuroanatomical correlates of cognitive aging: evidence from structural magnetic resonance imaging.

To examine putative brain substrates of cognitive functions differentially affected by age the authors measured the volume of cortical regions and performance on tests of executive functions, working memory, explicit memory, and priming in healthy adults (18-77 years old). The results indicate that shrinkage of the prefrontal cortex mediates age-related increases in perseveration. The volume of visual processing areas predicted performance on nonverbal working memory tasks. Contrary to the hypotheses, in the examined age range, the volume of limbic structures was unrelated to any of the cognitive functions; verbal working memory, verbal explicit memory, and verbal priming were independent of cortical volumes. Nevertheless, among the participants aged above 60, reduction in the volume of limbic structures predicted declines in explicit memory. Chronological age adversely influenced all cognitive indices, although its effects on priming were only indirect, mediated by declines in verbal working memory.

Adolescent↗
PubMed1998

Differential effects of age and sex on the cerebellar hemispheres and the vermis: a prospective MR study.

PURPOSE: The purpose of this study was to determine the effects of age and sex on the size of the cerebellar hemispheres, the cerebellar vermis, and the pons in healthy adults. METHODS: We estimated the volumes of the cerebellar hemispheres (excluding the vermis and the peduncles), the cross-sectional area of the vermis, and the cross-sectional area of the ventral pons from MR images obtained in 146 healthy volunteers, 18 to 77 years old. RESULTS: We found a mild but significant age-related reduction in the volume of the cerebellar hemispheres and in the total area of the cerebellar vermis; however, the analysis of age trends in the vermian lobules revealed differential age-related declines. The areas of lobules VI and VII and of the posterior vermian lobules (VIII-X) declined significantly with age, whereas the anterior vermis (I-V) showed no significant age-related shrinkage. The volume of the cerebellar hemispheres (especially the right) and the area of the anterior vermis were greater in men, even after adjustment for height. Neither age nor sex affected the area of the ventral pons. CONCLUSIONS: Normal aging of the cerebellum is associated with selective regional shrinkage. The cerebellar hemispheres and the area of the anterior vermis may be larger in men than in women regardless of differences in body size.

Adolescent↗
PubMed1998

Differential aging of the human striatum: a prospective MR imaging study.

BACKGROUND AND PURPOSE: Advancing age is associated with declines in motor function; understanding age-related changes in the basal ganglia, therefore, is imperative for comprehension of such functional changes. The purpose of this study was to examine the age, sex, and hemispheric differences in volume of the caudate nucleus, the putamen, and the globus pallidus. METHODS: In a sample of 148 healthy right-handed adults (18-77 years old) with no evidence of age-related motor disorders, we estimated the volume of the head of the caudate nucleus, the putamen, and the globus pallidus from MR images. RESULTS: The analyses revealed bilateral age-related shrinkage of the head of the caudate nucleus and the putamen in both sexes. In men, the age-related shrinkage of the caudate was stronger on the left, whereas, in women, the opposite trend was evident. In both sexes, age-related shrinkage of the right putamen was greater than of its left counterpart. The mild bilateral age-related shrinkage of the globus pallidus was observed only in men. In both sexes, we observed significant rightward asymmetry in the putamen, significant leftward asymmetry in the caudate, and no asymmetry in the globus pallidus. CONCLUSIONS: Bilateral age-related shrinkage of the neostriatum is found in healthy adults. The shrinkage of the globus pallidus is less pronounced and may be restricted to men only.

Adolescent↗
PubMed1997

Memory impairment in multiple sclerosis: a quantitative review.

To assess the nature and magnitude of memory impairment in multiple sclerosis (MS), the authors analyzed quantitatively 36 studies comparing the memory performance of MS participants to healthy controls. The authors studied (a) the pattern of impairment across short-term memory (STM), working memory (WM), and long-term memory (LTM); (b) the moderating influence of retrieval support on LTM impairment; (c) the covariation of WM and LTM impairment; and (d) the moderating influence of clinical characteristics of the MS sample on memory impairment. The analyses revealed significant impairment across all memory domains and failed to support a retrieval-based account of LTM dysfunction in MS patients. In addition, robust associations were found between clinical features of MS and memory impairment. The findings suggest a more global pattern of memory deficits in MS than has been previously believed, with deficits clearly associated with neurological disability and disease course.

Cognition Disorders↗
PubMed1997

Aging and olfactory recognition memory: effect of encoding strategies and cognitive abilities.

The effects of two encoding manipulations on recognition memory for odors were examined in 20 young and 20 elderly males. Subjects were instructed to use two different encoding strategies: (1) labeling-plus-definition (i.e., naming the odor and giving a short description) and, (2) life-episode association (i.e., associating a memory of a life-episode with each odor). Results revealed that elderly subjects performed significantly worse than young subjects in the labeling-plus-definition condition, but not in the life-episode task in which they achieved a level of performance not significantly different from the young. Encoding specificity or precision did not significantly impact recognition memory for the odors in either group. Analysis of response bias revealed that, in the label-plus-definition condition, young subjects were more conservative in responding style, while more liberal in their responding in the life-episode condition. In contrast, elderly subjects exhibited nearly identical response bias across both encoding conditions. The results suggest that age-related deficits in olfactory memory may be strategy dependent.

Adult↗
PubMed1995

Age, gender, and hemispheric differences in human striatum: a quantitative review and new data from in vivo MRI morphometry.

We reviewed postmortem and neuroimaging studies of striatal neuroanatomy in humans. The quantitative review revealed evidence of moderate age-related shrinkage of the caudate nucleus and the putamen and consistent leftward asymmetry of the globus pallidus. The data on sex differences were very sparse. We examined neostriatal structures in two samples (healthy volunteers and patients with negative radiological findings) using in vivo magnetic resonance imaging. In both samples, bilateral age-related shrinkage of the caudate nucleus was found, although among the patients the effect was significant only for males. The putamen was measured only in the second sample, and age-related reduction in its volume was found also only among males. A trend for rightward asymmetry in the volume of caudate nucleus was observed in both samples, although it reached statistical significance only among the patients. Putative pathological and physiological mechanisms underlying the observed differences in teh neostriatum are discussed.

Adolescent↗
PubMed1995

Differential effects of aging on memory for content and context: a meta-analysis.

The authors reviewed the evidence of age differences in episodic memory for content of a message and the context associated with it. Specifically, the authors tested a hypothesis that memory for context is more vulnerable to aging than memory for content. In addition, the authors inquired whether effort at encoding and retrieval and type of stimulus material moderate the magnitude of age differences in both memory domains. The results of the meta-analysis of 46 studies confirmed the main hypothesis: Age differences in context memory are reliably greater than those in memory for content. Tasks that required greater effort during retrieval yielded larger age differences in content but not in context memory. The greatest magnitude of age differences in context memory was observed for those contextual features that were more likely to have been encoded independently from content. Possible mechanisms that may underlie age differences in context memory-attentional deficit, reduced working memory capacity, and failure of inhibitory processing are discussed.

Adult↗
PubMed1995

Selective neuroanatomic abnormalities in Down's syndrome and their cognitive correlates: evidence from MRI morphometry.

We examined the pattern of neuroanatomic abnormalities in adults with Down's syndrome (DS) and the cognitive correlates of these abnormalities. Specifically, we compared this pattern with what would be predicted by the hypotheses attributing DS pathology to either premature aging or Alzheimer's disease. We measured a number of brain regions on MRIs of 25 subjects: 13 persons with the DS phenotype and 12 age- and sex-matched healthy volunteers. Study participants had no history of cardiovascular disease, diabetes, thyroid dysfunction, or seizure disorder. After statistical adjustment for differences in body size, we found that, in comparison with controls, DS subjects had substantially smaller cerebral and cerebellar hemispheres, ventral pons, mammillary bodies, and hippocampal formations. In the cerebellar vermis of DS subjects, we observed smaller lobules VI to VIII without appreciable differences in other regions. In addition, we noted trends for shrinkage of the dorsolateral prefrontal cortex, anterior cingulate gyrus, inferior temporal and parietal cortices, parietal white matter, and pericalcarine cortex in DS subjects compared with normal controls. The parahippocampal gyrus was larger in DS subjects. We found no significant group differences in the volumes of the prefrontal white matter, the orbitofrontal cortex, the pre- and postcentral gyri, or the basal ganglia. We conclude that the pattern of selective cerebral damage in DS does not clearly fit the predictions of the premature aging or Alzheimer's disease hypotheses. To examine the relationship between brain abnormalities and cognitive deficits observed in DS, we correlated the size of brain regions that were significantly reduced in DS with performance on tests of intelligence and language. The correlation analysis suggested age-related decline in the DS subjects in general intelligence and basic linguistic skills. General intelligence and mastery of linguistic concepts correlated negatively with the volume of the parahippocampal gyrus. There was no relationship between total brain size and the cognitive variables.

Adult↗