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PubMed1996

Stress- and treatment-induced elevations of cortisol levels associated with impaired declarative memory in healthy adults.

Two studies investigated the association between cortisol levels and memory performance in healthy adults. In a first study, 13 subjects were exposed to a brief psychosocial laboratory stress ("Trier Social Stress Test") with a subsequent test of declarative memory performance. Results indicated a significant negative relationship between stress-induced cortisol levels and performance in the memory task, i.e. subjects with high cortisol response to the stressor showed poorer memory performance. In a second experiment it was investigated if cortisol, alone, i.e. independent of psychological stress, would also impair memory function. In this study, 40 healthy subjects received either 10 mg cortisol or placebo orally. One hour later they were tested for procedural and declarative memory and spatial thinking. Subjects who received cortisol showed impaired performance in the declarative memory and spatial thinking tasks but not in the procedural memory task. From these results we conclude that in healthy adults elevated free cortisol levels are associated with impaired memory function.

Adult↗

PubMed1991

Disproportionate incidental spatial-memory and recall deficits in amnesia.

Seventeen amnesics, including patients with Korsakoff's disease, post-encephalitic amnesia and amnesia caused by rupture of an anterior communicating artery aneurysm, were compared with 17 matched control subjects on a task in which 16 nameable shapes were placed on different squares of a 49-square grid. One version of the task tapped free recall and recognition of the shapes and a second version tapped three forms of spatial memory. The patients were tested after more learning opportunity and shorter delays than were the controls so as to match their recognition levels. Under these conditions, the amnesics performed worse than the controls on free recall, location-to-target memory, target-to-location memory and possibly on non-associative spatial memory although this was less impaired than target-to-location memory. Each of the main aetiological subgroups showed these disproportionate deficits to an apparently similar degree. The disproportionate free recall deficit was unrelated to the spatial memory deficits and overall severity of amnesia, and was associated with ageing and signs of frontal lobe dysfunction. The disproportionate spatial memory deficits were unrelated to frontal lobe dysfunction, but the target-to-location memory measure was associated with impairments of recognition and recall of target material. The results are broadly consistent with the context-memory deficit hypothesis of amnesia.

Adult↗

PubMed1995

Healthy aging, memory subsystems and regional cerebral oxygen consumption.

The present study was designed to search for concomitant age-related changes in memory subsystems, defined according to current structural theories, and resting oxygen consumption in selected brain regions. We have investigated a sample of subjects between 20 and 68 years of age and strictly screened for their good health. We applied in the same subjects a battery of neuropsychological tests selected to investigate several memory subsystems, and high-resolution positron imaging with stereotaxic localization to study a purposely limited number of cerebral structures, selected on a priori hypotheses to match the different memory subsystems. Our results showed significant age-related changes in performance on some tests, consistent with the literature, including an increase in semantic memory and a decrease in both working memory (central executive system) and verbal episodic and explicit memory. There was also an age-related linear decrease in global brain oxygen consumption which regionally reached statistical significance for the neocortical areas and the left thalamus. There was a limited number of significant, age-independent correlations between the raw psychometric test scores and resting regional oxidative metabolism. Consistent with our present understanding of the functional anatomy of memory, the Associate Learning scores (verbal episodic and explicit memory) were positively correlated with left hippocampal and thalamic metabolism. The positive relationships found between right hippocampal metabolism and performance in the Associate Learning and the Brown-Peterson tests were less expected but would be consistent with findings from recent PET activation studies. The results from this investigation are discussed in the light of current knowledge concerning the neuropsychology and the neurobiology of both aging and memory.

Adult↗

PubMed1995

Autobiographical memory and executive function in early dementia of Alzheimer type.

We studied executive function and autobiographical memory in a cohort of 33 DAT patients [divided into minimal (MMSE 24-30) and mild (MMSE 17-23) groups] and in 30 normal controls. Autobiographical memory, as assessed by autobiographical fluency and the Autobiographical Memory Interview (AMI), was impaired in DAT patients, even those with minimal disease. There was evidence of a gentle temporal gradient on the incident but not the personal semantic component of the AMI, suggesting that the two components are dissociable. Executive function was assessed by two separate dual performance tasks and letter fluency. Although there was a trend for minimal DAT patients to be impaired on executive tasks, this only reached significance for the mild group. Regression analysis suggested that the divided attention component of working memory was involved in the retrieval of personal semantic autobiographical memory, but verbal fluency was more important in the retrieval of autobiographical incidents. There was thus a dissociation in the type of executive function implicated in different subcomponents of autobiographical memory, arguing for subcomponents within executive function and autobiographical memory. The autobiographical memory deficit in DAT reflects, we argue, both impairment in retrieval processes, linked to executive function, and a loss of memory stores.

Age of Onset↗

PubMed1982

Thalamic mediodorsal nucleus and memory: a critical evaluation of studies in animals and man.

Following a general description of the anatomical organization of the thalamic mediodorsal nucleus (MD) of animals and man, the involvement of this nucleus in the processing of memory related information has been evaluated by reviewing stimulation, electrophysiological, and lesion studies in animals, and by reviewing research on induced lesions, degenerative changes and vascular damage of MD in humans. Neither the results from animal experiments nor those from studies on humans provide clear-cut evidence for a specific, memory related role of MD. However, the findings here presented do support the theory that MD is one of several, possible memory related relay stations. While therapeutically induced and circumscribed lesions of MD rarely result in long-lasting memory deficits, pathological processes in MD are more likely to be followed by severe memory disturbances if one or more particular structures in addition to MD are included in the lesioned regions. Consequently, it is emphasized that only the disruption of more than one site along memory related pathways will result in severe and enduring memory deficits. To account for apparent inter-species differences in the involvement of MD in memory related processes, it has been argued that MD and its principal cortical target region might basically be involved in arousal and emotional processes, but that for primates and especially for man the phylogenetically young parvocellular sector of MD and its cortical projection region, the dorsolateral prefrontal cortex, are furthermore involved in memory functions, which are modulated by emotional factors via the rest of MD and the prefrontal cortex.

Afferent Pathways↗

PubMed1991

Quisqualate lesions of rat NBM: selective effects on working memory in a double Y-maze.

Some authors have reported that quisqualic acid lesions of the nucleus basalis magnocellularis (NBM), although producing large cortical cholinergic losses, have little effect on memory. The purpose of the present study was to investigate the effects of quisqualic acid lesions of the NBM on working and reference memory in a double Y-maze. Each trial started with placement into one of the two end arms of the first Y-maze, and the correct response was to go down the stem (reference memory). Access was then given to the second Y-maze, the correct response being conditional upon the side of the first Y-maze from which that trial had begun (working memory). Rats were trained to an 88% correct criterion and were then given either bilateral quisqualic acid (60 nM, 0.5 microliters) or sham lesions (0.9% saline, 0.5 microliters) of the NBM. One week postsurgery, rats were tested on the double Y-maze task with delays of 0, 5 or 30 seconds being introduced prior to both the working and reference memory choice. NBM lesions produced a 63.2 +/- 6.2% decrease of cortical choline acetyltransferase (ChAT) compared to unoperated controls. Delays affected only the working memory of the sham group. Rats with lesions showed a significant impairment of working memory at all delays, but no change in reference memory. Results indicate that quisqualic acid lesions of the NBM that produce significant reductions in cortical ChAT selectively impair working memory.

Animals↗

PubMed1996

Prefrontal and posterior cortical activation during auditory working memory.

The present study investigated brain mechanisms underlying auditory memory. In a modified Sternberg memory scanning task, 11 subjects indicated whether a probe sound was part of a previously presented 4-item memory set by a button press. Behaviorally, subjects responded fastest and most accurately to probes that matched the last memory set items and slowest and least accurately to negative probes and to positive probes to the first two memory set items. Electrophysiologically, probes to the last memory set items elicited the largest amplitude and earliest latency P3 components while other probes elicited smaller amplitude, prolonged P3s as well as a negativity around 400 ms. These results suggest that subjects utilized a trace strength/self-terminating search model to perform the memory scanning task. Subjects only generated the P3 component during the matching phase of the auditory memory task while a sustained frontal negativity was elicited during both the encoding and matching phase. Taken together these findings provide evidence of differential activation of distributed neural activity during non-linguistic auditory memory.

Acoustic Stimulation↗

PubMed2006

Memory dysfunction in caudate infarction caused by Heubner's recurring artery occlusion.

We report five cases with caudate infarction due to Heubner's recurring artery occlusion, in which we conducted detailed memory examinations in terms of explicit memory and implicit memory. We performed the auditory verbal learning test as explicit memory tasks, and motor and cognitive procedural memory tasks, developed by Komori, as implicit memory tasks. Comparing normal control subjects with patients with left caudate infarction due to Heubner's recurring artery occlusion demonstrated lower scores on both declarative and motor procedural memory tasks. These results suggest that the left caudate nucleus may be related with both declarative memory and procedural memory.

Adult↗

PubMed2006

Unique abnormalities of CD4(+) and CD8(+) central memory cells associated with chronic graft-versus-host disease improve after extracorporeal photopheresis.

Chronic graft-versus-host disease (cGVHD) remains a problematic complication of allogeneic hematopoietic stem cell transplantation. Laboratory parameters correlated with cGVHD have not been fully defined, although changes in CD4/CD8 ratios occur and a decrease in CD4(+) central memory T cells has been noted. Extracorporeal photopheresis (ECP) is an effective therapy for steroid-refractory cGVHD. We have noted changes in lymphocyte subsets after ECP. CD4(+) and CD8(+) T-cell central and effector memory populations were enumerated by flow cytometry in a cohort of 37 patients postallogeneic transplantation with symptomatic cGVHD. Of the patients with symptomatic cGVHD, 7 were treated with ECP over 6 months and prospectively assessed for changes in lymphocyte subsets. There was a highly significant correlation of an increase in CD8(+) central memory cells and a concomitant decrease in CD4(+) central memory cells in patients with symptomatic cGVHD. These changes were not detected in patients without cGVHD posttransplantation. In all, 7 patients with cGVHD followed up prospectively during ECP treatment showed a statistically significant normalization of the pattern of CD4(+) and a trend toward normalization of CD8(+) central memory T cells coincident with improvement of cGVHD. These data indicate a high correlation between disturbances in the balance of central and effector memory populations and cGVHD suggesting use in following up responses to therapy. The normalization of central and effector memory populations in response to ECP coincident with clinical improvement of cGVHD support a correlation between these laboratory parameters and cGVHD. Further studies are needed to demonstrate whether laboratory measurements of the magnitude of changes in central and effector memory populations are useful prognostically or can be used to guide response to therapy. The contrasting change in central memory cells (CD8(+) increased versus CD4(+) decreased) in cGVHD provide support for recent reports suggesting unique differences in the differentiation pathways for CD8(+) versus CD4(+) T cells.

Adult↗

PubMed2004

Hippocampal volume, memory, and cortisol status in major depressive disorder: effects of treatment.

BACKGROUND: Depression has been linked to stress, memory deficits, and hypercortisolemia. However, the relationships between depression, hippocampal structure and function, and cortisol levels are unclear and the effects of antidepressant treatment on the measures are not well studied. METHODS: Whole hippocampal volume, performance on verbal and visual declarative memory function and cortisol status was evaluated in 38 subjects with major depressive disorder (MDD) and 33 healthy subjects. All measures were repeated in a subgroup (n = 22) of depressed patients after successful selective serotonin reuptake inhibitor (SSRI) treatment. RESULTS: Hippocampal volume was not significantly different between patients with untreated MMD and healthy subjects, after controlling for whole brain volume, age and gender. However, depressed subjects had significantly greater deficits in delayed memory and percent retention on the verbal portion of the Wechsler Memory Scale-Revised (WMS-R) compared with healthy subjects, without significant differences in visual memory, attention, vigilance, or distractibility. Baseline plasma or urinary free cortisol (UFC) was not related to either hippocampal volume or memory deficits. Successful treatment with antidepressants did not change hippocampal volume but did result in a significant improvement in memory function and a reduction in UFC excretion. CONCLUSIONS: Medication-free nonelderly depressed outpatients without alcohol dependence or adverse experiences in childhood had normal hippocampal volume. Focal declarative memory deficits in depression supported localized hippocampal dysfunction in depressed patients. Treatment with antidepressants significantly improved memory and depression but did not alter hippocampal volume, suggesting that antidepressants may improve hippocampal function in the absence of detectable structural changes.

Adult↗

PubMed2004

A unified theory for systems and cellular memory consolidation.

The time-limited role of the hippocampus for explicit memory storage has been referred to as systems consolidation where learning-related changes occur first in the hippocampus followed by the gradual development of a more distributed memory trace in the neocortex. Recent experiments are beginning to show that learning induces plasticity-related molecular changes in the neocortex as well as in the hippocampus and with a similar time course. Present memory consolidation theories do not account for these findings. In this report, we present a theory (the C theory) that incorporates these new findings, provides an explanation for the length of time for hippocampal dependency, and that can account for the apparent longer consolidation periods in species with larger brains. This theory proposes that a process of cellular consolidation occurs in the hippocampus and in areas of the neocortex during and shortly after learning resulting in long-term memory storage in both areas. For a limited time, the hippocampus is necessary for memory retrieval, a process involving the coordinated reactivation of these areas. This reactivation is later mediated by longer extrahippocampal connectivity between areas. The delay in hippocampal-independent memory retrieval is the time it takes for gene products in these longer extrahippocampal projections to be transported from the soma to tagged synapses by slow axonal transport. This cellular transport event defines the period of hippocampal dependency and, thus, the duration of memory consolidation. The theoretical description for memory consolidation presented in this review provides alternative explanations for several experimental observations and presents a unification of the concepts of systems and cellular memory consolidation.

Animals↗

PubMed2006

Defective T cell receptor-mediated signal transduction in memory CD4 T lymphocytes exposed to superantigen or anti-T cell receptor antibodies.

Lymphocytes must promote protective immune responses while still maintaining self-tolerance. Stimulation through the T cell receptor (TCR) can lead to distinct responses in naive and memory CD4 T cells. Whereas peptide antigen stimulates both naive and memory T cells, soluble anti-CD3 antibodies and bacterial superantigens stimulate only naive T cells to proliferate and secrete cytokines. Further, superantigens, like staphylococcal enterotoxin B (SEB), cause memory T cells to become anergic while soluble anti-CD3 does not. In the present report, we show that signal transduction through the TCR is impaired in memory cells exposed to either anti-CD3 or SEB. A block in signaling leads to impaired activation of the kinase ZAP-70 so that downstream signals and cell proliferation do not occur. We further show that the signaling defect is unique to each agent. In anti-CD3-treated memory T cells, the src kinase Lck is only transiently activated and does not phosphorylate and activate ZAP-70. In SEB-treated memory T cells, ZAP-70 does not interact with the TCR/CD3 complex to become accessible to Lck. Finally, we provide evidence that alternative signaling pathways are initiated in SEB-treated memory cells. Altered signaling, indicated by an elevation in activity of the src kinase Fyn, may be responsible for memory cell anergy caused by SEB. Thus, differentiation of naive T cells into memory cells is accompanied by alterations in TCR-mediated signaling that can promote heightened recall immunity or specific tolerance.

Animals↗

PubMed2004

EEG synchronization likelihood in mild cognitive impairment and Alzheimer's disease during a working memory task.

OBJECTIVE: Synchronization likelihood analysis of resting state EEG has shown that cognitive dysfunction in Alzheimer's disease (AD) and its precursor mild cognitive impairment (MCI) are associated with a loss of functional connectivity in high (upper alpha and beta) frequency bands. Working memory tasks are known to change functional connectivity, but it is unknown whether this increases the differences between AD, MCI and healthy controls. Our objective was to investigate the behavior of synchronization likelihood of multichannel EEG in AD, MCI and cognitively healthy controls, both at rest and during a working memory task. METHODS: EEGs (200 Hz sample frequency, 21 channels, average reference) were recorded at rest as well as during a visual working memory task in 14 patients with AD according to the NINCDS-ADRDA criteria (mean age 76.4; SD 13.6), 11 patients with MCI according to the criteria of Petersen (mean age 78.4; SD 6.4) and 14 with subjective memory complaints but no demonstrable memory disturbance (mean age 61.6; SD 26.6). The synchronization likelihood was computed over 19 channels, comparing each channel with all the other channels for the 0.5-4, 4-8, 8-10, 10-12, 12-30, 30-50 Hz frequency bands. RESULTS: The synchronization likelihood was significantly decreased in the upper alpha (10-12) and beta (12-30) bands in AD compared to persons with subjective memory complaints. The working memory task scores strongly correlated with Mini-Mental State Examination scores. During the working memory task the synchronization likelihood was significantly higher in MCI compared to the control subjects in the lower alpha band (8-10 Hz). CONCLUSIONS: Decrease of beta band synchronization occurs in mild AD, both in a resting condition and during a working memory task. SIGNIFICANCE: Decrease of beta band synchronization in mild AD is a robust finding. The present study confirms our findings in a different cohort of patients, using alternative frequency bands. The diagnostic value of the synchronization likelihood in AD and MCI needs to be further established.

Aged↗

PubMed2005

Electrophysiological correlates of forming memories for faces, names, and face-name associations.

The ability to put a name to a face is a vital aspect of human interaction, but many people find this extremely difficult, especially after being introduced to someone for the first time. Creating enduring associations between arbitrary stimuli in this manner is also a prime example of what patients with amnesia find most difficult. To help develop a better understanding of this type of memory, we sought to obtain measures of the neural events responsible for successfully forming a new face-name association. We used event-related potentials (ERPs) extracted from high-density scalp EEG recordings in order to compare (1) memory for faces, (2) memory for names, and (3) memory for face-name associations. Each visual face appeared simultaneously with a unique spoken name. Signals observed 200-800 ms after the onset of face-name pairs predicted subsequent memory for faces, names, or face-name associations. Difference potentials observed as a function of subsequent memory performance were not identical for these three memory tests, nor were potentials predicting associative memory equivalent to the sum of potentials predicting item memory, suggesting that different neural events at the time of encoding are relevant for these distinct aspects of remembering people.

Adolescent↗

PubMed2003

Evolution of immunological memory and the regulation of competition between pathogens.

Memory is a central characteristic of immune responses. It is defined as an elevated number of specific immune cells that remain after resolution of infection and can protect the host against reinfection. The evolution of immunological memory is subject to debate. The advantages of memory discussed so far include protection from reinfection, control of chronic infection, and the transfer of immune function to the next generation. Mathematical models are used to identify a new force that can drive the evolution of immunological memory: the duration of memory can regulate the degree of competition between different pathogens. While a long duration of memory provides lasting protection against reinfection, it may also allow an inferior pathogen species to persist. This can be detrimental for the host if the inferior pathogen is more virulent. On the other hand, a shorter duration of memory ensures that an inferior pathogen species is excluded. This can be beneficial for the host if the inferior pathogen is more virulent. Thus, while in the absence of pathogen diversity memory is always expected to evolve to a long duration, under specific circumstances, memory can evolve toward shorter durations in the presence of pathogen diversity.

Biological Evolution↗

PubMed2004

Characterization of naïve, memory and effector CD8+ T cells: effect of age.

Aging is associated with progressive decline in T cell functions and increased frequency of infections, autoimmune phenomenon, and cancer. Memory T cells rapidly acquire effector functions to kill infected and malignant cells and/or inhibit their replication. Recently, memory T cells have been further classified into central and effector memory T cells (and early and intermediate T cells by some investigators). In aging, memory T cells are accumulated; however, these subpopulations of memory and effector T cells have not been fully characterized and changes in central memory and effector memory T cells in aged humans have not been described. In this article, we have further defined naïve, central memory, effector memory, and effector CD8+ T cells in humans and their changes in aged humans.

Aging↗

PubMed2006

Committed to memory: lineage choices for activated T cells.

The mechanisms for the generation of memory T cells and their delineation into heterogeneous subsets remain unknown. The linear model for memory T-cell generation from differentiated effector cells has been favored, although there is evidence that memory T cells can emerge directly from naive T cells undergoing homeostatic expansion and from activated T cells lacking effector functions. Here, we discuss the evidence from diverse studies of memory generation that support a new 'intersecting pathway' model for memory T-cell generation in which antigen-driven effector differentiation and homeostasis-driven memory differentiation follow distinct but analogous pathways. Antigen withdrawal during effector differentiation enables intersection with the memory pathway through a pre-memory intermediate, and memory heterogeneity is influenced by homeostasis, migration and persistence in vivo.

Animals↗

PubMed2005

Working memory in children with reading disabilities.

This study investigated associations between working memory (measured by complex memory tasks) and both reading and mathematics abilities, as well as the possible mediating factors of fluid intelligence, verbal abilities, short-term memory (STM), and phonological awareness, in a sample of 46 6- to 11-year-olds with reading disabilities. As a whole, the sample was characterized by deficits in complex memory and visuospatial STM and by low IQ scores; language, phonological STM, and phonological awareness abilities fell in the low average range. Severity of reading difficulties within the sample was significantly associated with complex memory, language, and phonological awareness abilities, whereas poor mathematics abilities were linked with complex memory, phonological STM, and phonological awareness scores. These findings suggest that working memory skills indexed by complex memory tasks represent an important constraint on the acquisition of skill and knowledge in reading and mathematics. Possible mechanisms for the contribution of working memory to learning, and the implications for educational practice, are considered.

Aptitude↗