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Naive and memory T cell subsets are differentially mobilized during physical stress.

This study examined the naive and memory phenotypic profiles of CD4+ and CD8hi T cells that were mobilized to the peripheral circulation during a combination of aerobic exercise and heat stress, determining expression of the adhesion molecules CD62L and CD11a on the recruited cells. Twelve recreationally active males (age 27.1 +/- 5.3 yr, height 1.77 +/- 0.08 m, mass 76.9 +/- 12.0 kg, VO2peak 43.9 +/- 6.7 mL x kg(-1) x min(-1)) completed a 40 min bout of cycle ergometry at 65 % of VO2peak while immersed to mid-chest in a water bath at 39 degrees C. Venous blood samples were collected before (T0), during (T40) and 30 min after (T70) exposure to combined exercise and heat stress. Specimens were analyzed by three-colour flow cytometry for CD4+ and CD8hi T cell expression of CD45RO, CD11a and CD62L. Some 80 % of the CD4+ T cells that were mobilized were of the CD45RO memory phenotype, with the numbers of CD11alo and CD62L+ cells increasing more than those of CD11ahi and CD62L- cells. For the CD8hi cells, there was a more equal recruitment of CD45RO- naive (43 %) and CD45RO+ memory (57 %) cells. The majority (84 %) of recruited CD8+ cells were CD11ahi; there was a trend to predominance of CD62L- cells (57 %) for the memory subset, but with almost equal recruitment of CD62L+/- for the naive subset. We conclude that the exercise + heat stress induced trend to an increase in CD4+ T cells is linked in some way to memory phenotype; it cannot be explained simply by a high density expression of CD11a and lack of the lymph node homing receptor (CD62L). Furthermore, although mobilization of CD8hi T cells is not linked to memory phenotype, a high density expression of CD11a and a lack of the lymph node homing receptor are important determinants of CD8hi T cell mobilization.

Adult↗

Minimal model to document psychometric change after standard anterior temporal lobectomy for intractable seizure disorder.

Neuropsychological assessment of persons with epilepsy is recommended whenever neurosurgery is considered as an alternative therapy for seizure disorders refractory to ordinary medical management. Although psychological assessment is common in centers specialized in the care of epilepsy patients, standardized protocols are not common. This study addresses the question of the optimal minimal test battery necessary to differentiate groups of right-handed patients with refractory, complex partial seizure disorder who receive either right or left anterior temporal lobectomy or no surgery. No variable differentiated the groups before surgery. Only Logical Memory-Immediate of the Wechsler Memory Scale differentiated the groups following surgery. This finding is consistent with the literature.

Adolescent↗

Aging and its differential effects on consolidated memory forms in Drosophila.

Aging is known to be associated with a decrease of learning and memory. Little is known on the specificity of this process. In Drosophila, two forms of consolidated memory have been observed. Anesthesia-resistant memory (ARM) is formed after one or several consecutive training sessions whereas long-term memory (LTM) is formed only after multiple training sessions separated in time. Both memory forms last more than 24 h. In the present experiment I, address the question of the effect of aging on the formation of each memory form. Twenty four hours after being conditioned, old flies show similar ARM as young flies but LTM was completely abolished. Age memory impairment seems therefore to be specific to one consolidated memory form.

Aging↗

Differential components of prospective memory? Evidence from fMRI.

Two of the principal components of prospective memory (i.e., remembering to carry out delayed intentions) are recognizing the appropriate context to act ("cue identification") and remembering the action to be performed ("intention retrieval"). In this experiment, the demands on these components were manipulated while measuring brain activity using fMRI to explore whether the two components share a common neural basis. The results showed significant behavioral differences between the cue identification and intention retrieval conditions. However, a consistent pattern of hemodynamic changes was found in both prospective memory conditions in anterior prefrontal cortex (BA 10), with lateral BA 10 activation accompanied by medial BA 10 deactivation. These effects were more pronounced when demands on intention retrieval were high. This is consistent with the hypothesis that anterior prefrontal cortex (area 10) supports the biasing of attention between external events (e.g., identifying the cue amid distracting stimuli) and internal thought processes (i.e., maintaining the intention and remembering the intended actions). Together, the results suggest that whilst cue identification and intention retrieval may be behaviorally separable, they share at least some common neural basis in anterior prefrontal cortex.

Adolescent↗

The perfect time to be stressed: a differential modulation of human memory by stress applied in the morning or in the afternoon.

We measured the effects of a stressful experience on memory for emotionally arousing and neutral material learned after exposure to a stressor which induces a significant increase in corticosteroid stress hormones. Because memory performance can be influenced by circadian changes in corticosteroid levels, subjects were tested either in the morning or in the afternoon. Nineteen healthy men (9 in the morning group and 10 in the afternoon group) were submitted to a psychological stress task before viewing a story composed of emotionally negative and neutral segments, while another 20 healthy males (10 in the morning group and 10 in the afternoon group) viewed the story without being exposed to the psychological stressor. Salivary cortisol levels were measured before and after the stressor. Memory performance was assessed by a one week post learning delayed recall. Results show that stress-induced increases in salivary cortisol levels impaired delayed free recall of emotionally arousing material in the morning group, but not in the afternoon group. There was no effect of stress on memory for neutral material. Altogether, these findings suggest that stressing participants in the morning, at a time of high circulating levels of corticosteroids, over stimulated the corticosteroid receptors in the brain, impairing declarative memory for emotionally arousing material unrelated to the stressor. These findings suggest that the experimental context, i.e., time of day at which the experiment occurs, the nature of the to-be-remembered material (remembering the stressful event itself or material unrelated to the stressor) and the valence of the to-be-remembered material (emotionally arousing vs. neutral), modulates the effects of stress on human declarative memory.

Adolescent↗

Differential disruptions of working memory components in schizophrenia in an object-location binding task using the suppression paradigm.

Patients with schizophrenia exhibit normal memory for separate objects or locations but are disproportionately impaired when the items must be bound for later recognition in a working memory (WM) setting (Burglen et al., 2004). This study aimed at further evaluating the contribution of each WM component to the patients' binding deficit, using selective articulatory, visuospatial, and executive suppression tasks. In the object-location binding task used, a trial comprised the successive presentation of three drawings of familiar objects and of three spatial locations in a grid, either separately (i.e., objects alone or locations alone) or bound (i.e., object+location), and required a recognition test following an 8-s delay. In the suppression modalities, suppression was continuous from presentation to test. A total of 22 patients with schizophrenia and 24 healthy controls participated. The results confirmed the binding deficit in patients' performance in the baseline modality where no suppression was required. They also showed that patients were particularly disrupted when suppression was visuospatial. This last finding extends the specific visuospatial vulnerability in schizophrenia to the operations of binding.

Adult↗

Differential ontogeny of working memory and reference memory in the rat.

In two experiments we examined the ability of 15-, 21-, and 27-day-old rats to perform two spatial working memory problems (delayed alternation and discrete-trials delayed alternation) and a reference memory problem (position habit) in a T-maze. In the delayed alternation problem, each animal was presented with a series of free-choice trials and was rewarded for regularly alternating responses to the left and right arms of the T-maze. In the discrete-trials delayed alternation problem, each animal was forced to one maze arm and rewarded (forced run) and was then placed back into the start box and given a choice of arms (choice run). The direction of forced runs followed an irregular, counterbalanced series, and animals were rewarded for choosing the alternate maze arm on choice runs. In the position habit problem, animals were rewarded for consistently choosing one of the two arms of the T-maze. Performance on these problems was assessed relative to control conditions in which reward was not contingent on choice behavior. At all ages, rat pups learned to perform the delayed alternation and position habit problems (Experiment 1). However, only 21- and 27-day-old rats were able to learn the discrete-trials delayed alternation problem. The 15-day-olds were unable to learn this task (Experiment 2). The results of these experiments show that reference memory capacity is present by at least 15 days of age in the rat and does not develop further at later ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Expression of L-selectin (CD62L) discriminates Th1- and Th2-like cytokine-producing memory CD4+ T cells.

Human memory (CD45RO+) CD4+ T cells can be distinguished into two subpopulations on the basis of expression of the lymph node homing receptor, L-selectin (CD62L). In a prior study we showed that human L-selectin-positive memory T-helper (Th) cells promote the maturation of IgG- and IgA-producing cells by naive B cells. To further elucidate the contribution of memory CD4+ T cells to B-cell differentiation, human memory CD4+ T cells with or without L-selectin expression were evaluated for production of cytokines that participate in regulation of immunoglobulin production. It was found that L-selectin-positive human memory CD4+ T cells produce mainly interleukin (IL)-4 and IL-5, whereas L-selectin-negative CD4+ T cells produce mainly interferon-gamma (IFN-gamma). This profile of cytokine expression coincides with the profile that distinguishes Th1 and Th2 subsets. In contrast to the murine system, IL-10 production was similarly contributed by human L-selectin-positive and -negative memory CD4+ T-cell subpopulations. These results suggest that the human L-selectin-negative and -positive subpopulations of human memory CD4+ T cells contain Th1-like and Th2-like cytokine-producing cells, respectively.

Adult↗

Excitotoxic lesions of the rhinal cortex in the baboon differentially affect visual recognition memory, habit memory and spatial executive functions.

To specify the functional role of the rhinal cortex, baboons with bilateral excitotoxic lesions of the rhinal cortex (RH group) were tested on a series of computerized memory and learning tasks. Preoperatively, they were trained to and then tested on a delayed nonmatching-to-sample (DNMS) task with trial-unique stimuli. Postoperatively, this visual recognition memory task was given twice. As compared to a sham-operated group, the RH group showed good retention of rule learning and were unimpaired on the Delay memory subtest. Performance on the List Length memory subtest was, however, severely impaired at both postoperative evaluations, with a significant negative correlation between cognitive performance and neuronal loss in rhinal areas. Visual habit memory and spatial working memory were assessed postoperatively only, using a concurrent discrimination learning task and both a delayed-response task (with a two- and four-location choice) and a delayed alternation task, respectively. The RH group was unimpaired on the first two tasks and was even faster than the controls in learning the delayed-response task with four locations. Finally, most RH baboons failed to learn the delayed alternation task within the limits of testing. These results indicate that neuronal loss in the rhinal cortex is sufficient to impair visual recognition memory, and extend the implication of this area to spatial executive functions. Furthermore, the observation of impaired recognition memory and executive processes with preserved procedural memory and retrograde memory suggests that damage to the rhinal cortex probably participates in the cognitive deficits typical of the early stages of Alzheimer's disease.

Animals↗

Differential demands on working memory for guiding a simple action sequence: evidence from closed-head-injured subjects.

In the present study, a working memory paradigm was used to assess coordinative abilities required for the flexible control of a sequence of actions. Subjects had to maintain and recall a list of digits that functioned as an ensemble of activity cues used for guiding a sequence of forced-choice responses. In three task conditions, the demand on the selection of the activity cues was varied parametrically to manipulate the requirement of coordinating maintenance and processing operations of working memory for guiding the response sequences. A comparison between subjects suffering from severe closed head injury (CHI) and matched controls in a blocked presentation of task conditions revealed that patients, in contrast to controls, did not preplan the sequence by rearranging the ensemble of activity cues prior to execution of the action sequence. Patients' performance was more comparable to controls tested in a random presentation in which preplanning was not possible. Our results further suggest that patients are less efficient in selecting activity cues from working memory, especially in more demanding situations when activity cues have to be completely reordered for guiding a sequence of actions. These results point to an executive dysfunction in CHI subjects that may contribute to the deficits known as inflexible and rigid behavior.

Adolescent↗

What differentiates declarative and procedural memories: reply to Cohen, Poldrack, and Eichenbaum (1997)

CPE claim that procedural and declarative representations differ on two important dimensions: flexibility and compositionality. I have proposed that the apparent flexibility of a memory depends entirely on the transfer conditions. Any retest is, in some sense, a test of flexibility, because something has changed since the original encoding episodic. I have argued that if one changes something that does not provide support to memory performance, the memory will appear flexible, and resistant to changes in the environment. If one changes the very thing that the representation codes, the memory will appear inflexible and easily disrupted by changes in the environment. This principle is equally true for procedural and declarative memory. CPE contend that procedural representations lack compositionality. An ideal test of this claim would examine the representation of a task that is widely agreed to be procedural (e.g. that has been demonstrated to be learned normally by amnesic patients, and in the absence of awareness by neurologically intact subjects). Such experiments appear not to have been conducted, and the fact is that many tasks that are widely agreed to be procedural probably are not compositional. They appear to be, as CPE contend, biases in a processing system; it is hard to imagine how repetition priming could be compositional. Nevertheless, this is not true of all procedural memories. There is a good deal of evidence that motor behaviour is organised hierarchically and has compositionality. There is every reason to think that most if not all motor behaviour is procedural; motor behaviour might be driven by goals that are declarative, but the low-level operations that actually manipulate effectors are closed to consciousness, do not depend on the medial temporal lobe or diencephalon, and would therefore be classified as procedural. CPE framed their theory of differences between procedural and declarative memory systems as an account of the deficit in amnesic patients. They therefore predict that the learning of amnesic patients should not show flexibility or compositionality. There is already at least one study showing learning in amnesic patients that is as flexible as that of control participants (Knowlton & Squire, 1996). There are not, to my knowledge, data on whether the motor skill learning of amnesic patients shows compositionality, but one might expect that it would, given that it does in neurologically intact participants, and given that motor skill learning appears unimpaired in amnesic patients. Thus, the conception of declarative and procedural memory provided by CPE may not provide a complete account of amnesic performance. The anatomic distinction between procedural and declarative memory systems appears quite strong, and there is therefore reason to believe that there are accompanying computational differences. There does not, however, appear to be sufficient evidence to support those differences proposed by CPE.

Amnesia↗

Differential improvement in memory-related task performance with nicotine by aged male and female rhesus monkeys.

Central nicotinc acetylcholine receptors have been targeted for the development of novel treatments for memory deficits in Alzheimer's disease (AD) and other neurodegenerative disorders. Nicotine itself has been shown to improve memory-related task performance in aged animals and in AD patients. Administration of nicotinic receptor agonists to laboratory animals, and the effects of cigarette smoking in humans attributed to nicotine, have in many instances been shown to exert sexually dimorphic actions. Low doses (2.5-20 microg/kg, intramuscularly) of nicotine have been shown to improve the performance of an automated delayed matching-to-sample (DMTS) task in aged rhesus monkeys. The purpose of this study was to determine whether aged females receive the same level of benefit to the positive mnemonic action of nicotine as do males. In this study six male (21.7+/-1.2 years) and seven female (22.5+/-0.9 years) rhesus monkeys each received an ascending series of four doses of nicotine over 5 weeks. Most control parameters were similar between the two sexes, although task latencies were longer and more variable in the female subjects. The males maintained a significant improvement in task performance over the entire nicotine dose range. This level of improvement extended to 24 h after nicotine administration. Task accuracy by females appeared to improve only after they received the two higher doses of nicotine, and their responses exhibited considerable variability over the entire dose range. However, in calculating an individualized 'Best Dose', males and females exhibited a similar level of task improvement (15-30% above baseline). Therefore, aged female subjects may require a greater level of individualized treatment and perhaps higher doses of nicotinic agonists to achieve the maximal mnemonic benefit.

Aging↗

NMDA and muscarinic receptors of the nucleus accumbens have differential effects on taste memory formation.

Animals recognize a taste cue as aversive when it has been associated with post-ingestive malaise; this associative learning is known as conditioned taste aversion (CTA). When an animal consumes a new taste and no negative consequences follow, it becomes recognized as a safe signal, leading to an increase in its consumption in subsequent presentations (attenuation of neophobia, AN). It has been shown that the nucleus accumbens (NAcc) has an important role in taste learning. To elucidate the involvement of N-methyl-D-aspartate (NMDA) and muscarinic receptors in the NAcc during safe and aversive taste memory formation, we administrated bilateral infusions of DL-2-amino-5-phosphonopentanoic acid (APV) or scopolamine in the NAcc shell or core respectively. Our results showed that pre-training injections of APV in the NAcc core and shell disrupted aversive but not safe taste memory formation, whereas pre-training injections of scopolamine in the NAcc shell, but not core, disrupted both CTA and AN. These results suggest that muscarinic receptors seem to be necessary for processing taste stimuli for either safe or aversive taste memory, whereas NMDA receptors are only involved in the aversive taste memory trace formation.

2-Amino-5-phosphonovalerate↗

The phonological-similarity effect differentiates between two working memory tasks.

Working memory is a set of interactive cognitive processes that maintain information on-line and available for analysis. Part of the system is specialized for maintaining verbal information, a core component of which is thought to be a phonological store. On the basis of the study of patients with acquired brain lesions, this store has been localized to the supramarginal and angular gyri of the speech-dominant hemisphere, and some functional neuroimaging studies support this localization. However, other imaging studies localize the phonological store in a more dorsal region of the parietal lobe. To reconcile these findings, we examined the phonological-similarity effect in two different tasks. A phonological-similarity effect was observed only in the task that involved sequential presentation and explicit verbal rehearsal. We conclude that at least one possible source of the differences in brain activation between different working memory tasks may be differences in phonological processing.

Adult↗

Differential impairments of spatial memory and social behavior in two models of limbic epilepsy.

To explore memory impairments in temporal lobe epilepsy, we used two experimental models in the rats: (a) kainate-induced status epilepticus (SE) resulting in excitotoxic damage and in later spontaneous seizures; and (b) amygdala kindling, known to induce no lesions (or only minor) and neuronal reorganization. Long-term effects of these models on memory were investigated with a spatial learning task in a radial-arm maze, and a social interaction test that implies degree of short-term memory. An histological analysis was made to determine neuronal damage or loss caused by epileptic activity in brain regions that could be related to memory functions. Kainate-induced epilepsy produced large memory deficits in animals tested 5 months after the injection. The rats showed severe lesions in amygdala and hippocampus and piriform and entorhinal cortex. Spatial memory was strongly diminished. The social memory test was severely impaired, probably due to the extent of amygdala injury, which is known to disturb social behavior. On the contrary, kindled rats showed no evident lesion in any brain region and displayed performances as good as those of controls in both tests. These experiments demonstrated that memory deficits appear to be related to the severity of neuronal damage in limbic areas, and the ability to develop seizures (permanence) is not solely responsible for these memory disturbances.

Animals↗