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[Episodic autobiographical memory in depression: a review].

INTRODUCTION: Autobiographical memory and personal identity (self) are linked by a reciprocal relationship. Autobiographical memory is critical for both grounding and changing the self. Individuals' current self-views, beliefs, and goals influence their recollections of the past. According to Tulving, episodic memory is characterized by autonoetic consciousness, which is associated with a sense of the self in the past (emotions and goals) and mental reliving of an experience. Its close relationship with self and emotion strongly involves episodic autobiographical memory in the psychopathology of depression. However, due to methodological and conceptual issues, little attention has been paid to episodic autobiographical memory in depression. Since the seminal work of Williams et al. 15 years ago, there is now growing interest around this issue. LITERATURE FINDINGS: We reviewed the evidence for three major features of autobiographical memory functioning in depression: an increase in general memory retrieval (overgenerality), a mood-congruent memory effect and the high occurrence of intrusive memories of stressful events. Although it was first observed among suicidal patients, overgenerality is actually associated with both depression and post-traumatic stress disorder. Overgenerality is not associated with anxious disorders other than post-traumatic stress disorder, obsessive-compulsive disorder, or borderline personality disorder. Most of controlled studies carried out on autobiographical memory in depression rely on the Williams' Autobiographical Memory Test (AMT). When presented with positive and negative cue words and asked to retrieve specific personal events, depressed patients (unlike matched controls) are less specific in their memories. They tend to recall repeated events (categorical overgeneral memories) rather than single episodes (specific memories). Overgenerality in depression is: 1) more evident with positive than with negative events (mood-congruent memory effect); 2) related to avoidance of intrusive memories; 3) quite stable over time, ie, remaining after remission; and 4) related to short-term prognosis in depression. Although it is not clear whether overgenerality is a cause or an effect of depression, there is some evidence to suggest that overgenerality is a trait marker indicating vulnerability to persistent depression. Mood-congruent effect, a well-known effect in depression, has been addressed in both autobio-graphical and non-autobiographical memory. Depressed patients spontaneously recall more negative than positive memories. With the AMT, depressed patients take longer to respond to positive than to negative cues, whereas controls do the opposite. Depression is also associated with a high occurrence of spontaneous intrusive memories of stressful life events. Studies found intrusions and related avoidance, as measured by the Impact of Event Scale, to be positively correlated with overgenerality, whereas there was no direct link between performance on the Autobiographical Memory Test and stressful life events per se. Both Williams' mnemonic interlock model and Conway's self-memory system are useful models to address the complexity of findings regarding autobiographical memory and depression. DISCUSSION: According to Williams, repeated avoidance of stressful memories leads depressed patients to have an autobiographical memory functioning characterized by iterative retrievals of categorical overgeneral memories, producing an enduring overgeneral retrieval style. According to Conway, the recollection of autobiographical memories requires a retrieval process that provides access to sensory/perceptual event-specific knowledge (ie perceptions and feelings) via a personal semantic knowledge base (ie lifetime periods and generic events). This retrieval process (generative retrieval mode) relies on both executive functioning and current self-view, namely the working-self. Spontaneous memories, usually vivid, result from a direct retrieval mode in which event-specific knowledge is directly triggered. In line with this model, episodic autobiographical memory impairment in state depression may arise from the working self rather than from autobiographical knowledge. The mood-congruent effect may be explained by the current (depressed) self. The high occurrence of intrusive memories may be explained by lack of executive control during direct retrieval. Overgenerality may rely on the interaction of both executive dysfunction and current (depressed) self, within the working-self, during generative retrieval. Our review suggests that further evidence is needed to address the relationship between executive functioning, self and autobiographical memory in depression.

Attention↗

Fuzzy-trace theory: dual processes in memory, reasoning, and cognitive neuroscience.

Fuzzy-trace theory has evolved in response to counterintuitive data on how memory development influences the development of reasoning. The two traditional perspectives on memory-reasoning relations--the necessity and constructivist hypotheses--stipulate that the accuracy of children's memory for problem information and the accuracy of their reasoning are closely intertwined, albeit for different reasons. However, contrary to necessity, correlational and experimental dissociations have been found between children's memory for problem information that is determinative in solving certain problems and their solutions of those problems. In these same tasks, age changes in memory for problem information appear to be dissociated from age changes in reasoning. Contrary to constructivism, correlational and experimental dissociations also have been found between children's performance on memory tests for actual experience and memory tests for the meaning of experience. As in memory-reasoning studies, age changes in one type of memory performance do not seem to be closely connected to age changes in the other type of performance. Subsequent experiments have led to dual-process accounts in both the memory and reasoning spheres. The account of memory development features four other principles: parallel verbatim-gist storage, dissociated verbatim-gist retrieval, memorial bases of conscious recollection, and identity/similarity processes. The account of the development of reasoning features three principles: gist extraction, fuzzy-to-verbatim continua, and fuzzy-processing preferences. The fuzzy-processing preference is a particularly important notion because it implies that gist-based intuitive reasoning often suffices to deliver "logical" solutions and that such reasoning confers multiple cognitive advantages that enhance accuracy. The explanation of memory-reasoning dissociations in cognitive development then falls out of fuzzy-trace theory's dual-process models of memory and reasoning. More explicitly, in childhood reasoning tasks, it is assumed that both verbatim and gist traces of problem information are stored. Responding accurately to memory tests for presented problem information depends primarily on verbatim memory abilities (preserving traces of that information and accessing them when the appropriate memory probes are administered). However, accurate solutions to reasoning problems depend primarily on gist-memory abilities (extracting the correct gist from problem information, focusing on that gist during reasoning, and accessing reasoning operations that process that gist). Because verbatim and gist memories exhibit considerable dissociation, both during storage and when they are subsequently accessed on memory tests, dissociations of verbatim-based memory performance from gist-based reasoning are predictable. Conversely, associations are predicted in situations in which memory and reasoning are based on the same verbatim traces (Brainerd & Reyna, 1988) and in situations in which memory and reasoning are based on the same gist traces (Reyna & Kiernan, 1994). Fuzzy-trace theory's memory and reasoning principles have been applied in other research domains. Four such domains are developmental cognitive neuroscience studies of false memory, studies of false memory in brain-damaged patients, studies of reasoning errors in judgment and decision making, and studies of retrieval mechanisms in recall. In the first domain, the principles of parallel verbatim-gist storage, dissociated verbatim-gist retrieval, and identity/similarity processes have been used to explain both spontaneous and implanted false reports in children and in the elderly. These explanations have produced some surprising predictions that have been verified: false reports do not merely decline with age during childhood but increase under theoretically specified conditions; reports of events that were not experienced can nevertheless be highly persistent over time; and false reports can be suppressed by retrieving verbatim traces of corresponding true events. In the second domain, the same principles have been invoked to explain why some forms of brain damage lead to elevated levels of false memory and other forms lead to reduced levels of false memory. In the third domain, the principles of gist extraction, fuzzy-to-verbatim continua, and fuzzy-processing preferences have been exploited to formulate a general theory of loci of processing failures in judgment and decision making, cluminating in a developmental account of degrees of rationality that distinguishes more and less advanced reasoning. This theory has in turn been used to formulate local models, such as the inclusion illusions model, that explain the characteristic reasoning errors that are observed on specific judgment and decision-making tasks. Finally, in the fourth domain, a dual-process conception of recall has been derived from the principles of parallel verbatim-gist storage and dissociated verbatim-gist retrieval. In this conception, which has been used to explain cognitive triage effects in recall and robust false recall, targets are recalled either by directly accessing their verbatim traces and reading the retrieved information out of consciousness or by reconstructively processing their gist traces.

Aging↗

Time-dependent processes in memory storage.

These observations indicate that the long-lasting trace of an experience is not completely fixed, consolidated, or coded at the time of the experience. Consolidation requires time, and under at least some circumstances the processes of consolidation appear to be susceptible to a variety of influences- both facilitating and impairing- several hours after the experience. There must be, it seems, more than one kind of memory trace process (31). If permanent memory traces consolidate slowly over time, then other processes must provide a temporary basis for memory while consolidation is occurring. The evidence clearly indicates that trial-to-trial improvement, or learning, in animals cannot be based completely on permanent memory storage. Amnesia can be produced by electroshock and drugs even if the animals are given the treatment long after they have demonstrated "learning" of the task. Of particular interest is the finding that retention of the inhibitory avoidance response increases with time. In a sense this should be expected, for it has long been known (and ignored) that, within limits, learning is facilitated by increasing the interval between repeated trials (7, 30). Our result may be the simplest case of such an effect. Since the improvement in retention with time seemed not to be due solely to consolidation (as indicated by electroshock effects), it would seem that the "distribution of practice" effect, as it is typically designated, may be due in part to a time-dependent temporary memory storage process. In our work with animals we have found no analog of human immediate memory such as that required for repeating digits (or finishing sentences). Animals tested immediately on the task described above after a trial typically showed no evidence of memory. It could be that the poor performance is due to excessive fright, but the "distribution of practice effect" is also typically observed in learning experiments in which food reward is used rather than shock avoidance. Since the retention tasks require the animals to change their behavior in some way, it could well be that the growth of retention over the first few minutes after a trial is due to time dependent processes involved in the organization of processes necessary for changing behavior, in addition to those involved in temporary storage and retrieval. It is worth pointing out that there is evidence of an analogous process in human memory (32). A complex picture of memory storage is emerging. There may be three memory trace systems: one for immediate memory (and not studied in our laboratory); one for short-term memory which develops within a few seconds or minutes and lasts for several hours; and one which consolidates slowly and is relatively permanent. The nature of the durability of the longterm memory trace (that is, the nature and basis of forgetting) is a separate but important issue. There is increasing evidence and speculation (20, 21, 33) that memory storage requires a "tritrace" system, and our findings are at least consistent with such a view. If there are, as seems possible, at least three kinds of traces involved in memory storage, how are they related? Is permanent memory produced by activity of temporary traces (31), or are the trace systems relatively independent? Although available findings do not provide an answer to this question, there does seem to be increasing evidence that the systems are independent. Acquisition can occur, as we have seen, without permanent consolidation, and both short-term and long-term memory increase with time. All this evidence suggests (but obviously does not prove) that each experience triggers activity in each memory system. Each repeated training trial may, according to this view, potentiate short-term processes underlying acquisition while simultaneously enhancing independent underlying long-term consolidation. Obviously, acceptance of these conclusions will require additional research. If this view is substantially correct, it seems clear that any search for the engram or the basis of memory is not going to be successful. Recognition of the possibility that several independent processes may be involved at different stages of memory may help to organize the search. A careful examination of the time course of retention and memory trace consolidation, as well as examination of the bases of the effects of memory-impairing and memory-facilitating treatments, may help to guide the search. It is clear that a complete theory of memory storage must eventually provide an understanding of time-dependent processes in memory. In 1930 Lashley wrote (2), "The facts of both psychology and neurology show a degree of plasticity, of organization, and of adaptation and behavior which is far beyond any present possibility of explanation." Although this conclusion is still valid, the current surge of interest in memory storage offers hope that this conclusion may soon need to be modified.

Animals↗

Material-specific memory changes after anterior temporal lobectomy as predicted by the intracarotid amobarbital test.

PURPOSE: The intracarotid amobarbital test (IAT) has been shown to predict verbal memory changes after anterior temporal lobectomy (ATL). Seeking to extend these findings, we examined two questions: (a) What is the relationship between material-specific aspects of IAT memory and material-specific memory changes after ATL? and (b) Which IAT memory score(s) optimally predict memory changes after surgery, the memory score after injection ipsilateral to the seizure focus, the memory score after injection contralateral to the seizure focus, or the IAT asymmetry score, comprising the ipsilateral minus contralateral injection scores? METHODS: Seventy left hemisphere language-dominant patients undergoing ATL for treatment of medically refractory seizures were administered a verbal and visuospatial recognition memory test before surgery and 3 weeks after surgery. IAT memory recognition scores for words and designs were used to predict verbal and visuospatial memory changes after surgery. RESULTS: After surgery, left ATL patients declined in verbal memory, whereas right ATL patients declined in visuospatial memory. IAT total recognition memory scores (collapsed across all types of materials) and IAT word memory scores were associated with postoperative verbal memory decline. This relationship was significant for the IAT ipsilateral injection memory scores and the IAT hemispheric asymmetry scores. IAT memory performances were not related to visuospatial memory changes. CONCLUSIONS: Results indicate IAT memory measures to be related to postoperative verbal, but not visuospatial, memory change. A specific relationship was found between postoperative verbal memory change and IAT verbal memory after injection ipsilateral to the seizure focus, when relying primarily on the contralateral hemisphere. This finding is consistent with the functional reserve model of memory change in ATL.

Adult↗

Memory B cells at successive stages of differentiation. Affinity maturation and the role of IgD receptors.

The following evidence, mainly presented here, suggests that IgD receptors play a crucial role in determining the potential for affinity maturation in memory B cell populations. IgD receptors are present on the first memory B cells to appear after priming. These memory cells give rise to more-mature memory cells that have lost their IgD receptors. The proportions of early (IgD(+)) and mature (IgD(-)) memory cells found in individual donors vary with time, priming conditions, and the availability of T cell help, and both populations frequently coexist for long periods of time. IgD(+) and IgD(-) memory cells carry IgG receptors and give rise to IgG responses with identical isotype representation in adoptive recipients. IgD(+) memory cells, however, always give rise to predominantly low-affinity antibody responses, whereas IgD(-) memory cells consistently generate responses of substantially higher average affinity. This affinity differential is maintained between early and mature memory populations in the same donor and does not appear to be a result of selective differentiation of higher-affinity IgD(+) memory cells into the IgD(-) memory pool. Thus, the selective forces responsible for affinity maturation appear to operate mainly in mature memory cell populations that have already lost IgD receptors; or, stated conversely, little or no selection towards high-affinity memory appears to occur among memory cells that retain IgD receptors. In discussing these findings, we suggest that the IgD receptors themselves are responsible for maintaining early memory populations at a lower average affinity than IgD(-) populations in the same animal. The IgD receptors, we argue, serve to increase the antigen-binding capacity of lower-affinity memory cells so that these cells can survive, expand, and differentiate (to IgD(-)) at antigen concentrations that select against expansion of low- affinity memory cells no longer carrying IgD receptors. Thus, when antigen is limiting, IgD(-) memory populations will be selectively expanded to higher average affinities, whereas coexisting IgD(+) populations will retain their initial affinity profile. This hypothesis suggests that mechanisms that regulate expression and loss of IgD receptors are central to the adaptability of the immune system in its response to invading pathogens. Two related roles can be envisioned for the IgD receptors in this regard. First, they extend the lower boundary of the affinity range of early memory cell populations induced by a given antigenic stimulus and therefore broaden the diversity of responses obtainable from these populations. Secondly, they support the persistence of low-affinity memory populations under conditions where antigen becomes limiting and eventually disappears. These persisting populations then serve as a diversely reactive reservoir from which mature memory populations can be drawn with higher affinities either for the original antigen or, more importantly, for related antigens that the animal may subsequently encounter. Thus the existence of IgD receptors on early memory cells maintains the full range of response diversity despite ongoing selective expansion of (mature) memory populations to produce antibodies with high combining affinities for individual antigens. The flexibility inherent in such an organizational system, we believe, could be expected to account for the evolutionary development of IgD receptors and the regulatory capabilities that support operation of the system.

Animals↗

Nature of personal semantic memory: evidence from Alzheimer's disease.

Personal semantic memory is factual knowledge about a person's own past. Although personal semantic memory is assumed to have features of both semantic memory and episodic memory, the relationship to episodic memory and to semantic memory have not been well documented. In patients with Alzheimer's disease, episodic memory, semantic memory, and personal semantic memory are all defective. In this study, the hypothesis that defective personal semantic memory is related to both semantic and episodic memory dysfunction was tested in patients with Alzheimer's disease. Functions of episodic, semantic, and personal semantic memory were examined by using the Wechsler Memory Scale-Revised (WMS-R), subtests of the WAIS-R (Information, Vocabulary, Comprehension and Similarities), and the Family Line Test (FLT) in 62 patients who met the NINCDS/ADRDA criteria for probable Alzheimer's disease. Specific effects of episodic and semantic memory on personal semantic memory were examined by using multiple linear regression analysis with the total score of the FLT as the dependent variable and the WMS-R Delayed Recall weighted sum score and the WAIS-R Semantic Memory score (a composite of standardized scores of the four subtests) as the independent variables. Personal semantic memory function was significantly correlated with both the episodic and semantic memory functions, after controlling age, sex, educational attainment, and severity of dementia. This result supports the hypotheses that personal semantic memory has features of both episodic and semantic memory, and that semantic memory is transformed from episodic memory.

Aged↗

Psychopathology and autobiographical memory in stroke and non-stroke hospitalized patients.

BACKGROUND: Psychopathology and autobiographical memory were investigated in a cohort of stroke and non-stroke hospitalized patients. Both these cohorts have been identified as having high levels of psychopathology (Katon and Sullivan 1990; Burvill et al., 1995). Difficulties recalling specific autobiographical memories (overgeneral memory) have been identified as important psychological variables in depression and predictors of outcome (Williams and Scott 1988; Brittlebank et al., 1993). Intrusive autobiographical memories have also been found to be associated with depression and overgeneral memory in depressed women (Kuyken and Brewin, 1995) and depressed cancer patients (Brewin et al., 1998a). This study looked at levels of psychopathology and autobiographical memories in stroke and non-stroke hospital patients. METHOD: 417 patients were screened, of the 176 eligible 103 agreed to participate (54 stroke and 49 non-stroke). Participants were assessed for overgenerality using the Autobiographical Memory Test and intrusiveness of memories using the Impact of Events Scale. Also assessed were PTSD-like symptoms (PCL-S), mood (HADS, GHQ-28) and cognitive ability (MMSE, verbal fluency, digit span and estimated pre-morbid IQ). RESULTS: No significant differences were found between stroke and non-stroke patients on severity of depression, anxiety, severity of PTSD-like symptoms or autobiographical memories. Backward multivariate regression analyses for combined data (stroke and non-stroke) indicated that overgeneral memory recall, intrusive memories of past events and intrusive memories of illness were significant independent predictors of depression (HADS). Avoidance of intrusive memories and reported childhood distress were not predictors of overgeneral memory recall. Significant predictors of overgeneral memory recall were; Gender, antidepressant medication, and estimated IQ. CONCLUSION: Significant levels of psychopathology were identified in this cohort. However, there were no significant differences in the levels of depression, anxiety, PTSD symptoms and autobiographical memory between stroke and non-stroke hospitalized patients. Of particular interest was the finding that PTSD-like symptoms did not appear to be influenced by the nature of the person's illness. In combined data (stroke and non-stroke) autobiographical memories (intrusive images of their illness, intrusive memories of other events and overgeneral memory recall variables) were significant predictors of depression in this cohort. This suggests that psychological intervention of memory processes may be a worthwhile target in psychological intervention for depression in these cohorts. Gender, cognitive impairment, antidepressant medication, and estimated IQ were significant predictors of overgeneral memory recall and further investigation into the validity of these findings are warranted. Suggestions for further research and limitations of the study are also discussed.

Aged↗

Differential remoteness and emotional tone modulate the neural correlates of autobiographical memory.

Autobiographical memory relies on complex interactions between episodic memory contents, associated emotions and a sense of self-continuity along the time axis of one's life history. The neural correlates underlying autobiographical memory are known to primarily comprise areas of prefrontal cortex, medial and lateral temporal cortex, as well as posterior cingulate and retrosplenial cortex. By contrast, the effect of encoding and/or storage parameters such as the emotional tone of the memories retrieved or the length of the time-interval between the initial encoding of information and retrieval remains to be clarified. Using blocked design functional MRI and statistical parametric mapping, we investigated the impact of remoteness (factor 1: recent, remote) and emotional valence (factor 2: positive, negative) on the neural correlates of autobiographical memory retrieval. Changes in neural activity (P < 0.05, corrected) related to autobiographical memory retrieval (irrespective of remoteness and emotional tone) relative to baseline were observed bilaterally in medial and lateral temporal, temporal-occipital, posterior cingulate and frontal cortices. Recent (relative to remote) memories were associated with differentially increased neural activity bilaterally in the retrosplenial cortex and the hippocampal region, whereas remote (relative to recent) memories did not show any statistically significant differential neural activations. Positive (relative to negative) memories bilaterally activated the orbitofrontal cortex, the temporal pole, as well as medial temporal areas, with the activation peak being in the entorhinal region. By contrast, negative (relative to positive) memories differentially increased neural activity in the right middle temporal gyrus only. The data suggest differential functional roles for temporal, prefrontal and retrosplenial regions during autobiographical memory retrieval depending on the remoteness and the emotional valence of the memories retrieved. In particular, our findings support the 'classic' model of long-term memory processing, which suggests a time-limited differential involvement of the hippocampus in memory consolidation. Interestingly, the observation of such a time-dependent involvement of the hippocampal region in memory consolidation corresponds to the course of retrograde amnesia observed in demented patients, with the loss of recent memories appearing during early stages of the disease when conspicuous neurofibrillary changes are restricted mainly to the hippocampal and parahippocampal regions. Only during later stages, as the neurofibrillary changes spread out to neocortical association areas, do remote memories also become impaired. We conclude that the brain regions involved in autobiographical memory retrieval are influenced by the triggered memories' emotional significance and their relationship to the individual time axis.

Adult↗

"Brain-specific" nutrients: a memory cure?

OBJECTIVE: We review the experimental evaluations of several widely marketed nonprescription compounds claimed to be memory enhancers and treatments for age-related memory decline. We generally limit our review to double-blind placebo-controlled studies. The compounds examined are phosphatidylserine (PS), phosphatidylcholine (PC), citicoline, piracetam, vinpocetine, acetyl-L-carnitine (ALC), and antioxidants (particularly vitamin E). RESULTS: In animals, PS has been shown to attenuate many neuronal effects of aging, and to restore normal memory on a variety of tasks. Preliminary findings with humans, though, are limited. For older adults with probable Alzheimer's disease, a single study failed to demonstrate positive effects of PS on memory performance. For older adults with moderate cognitive impairment, PS has produced consistently modest increases in recall of word lists. Positive effects have not been as consistently reported for other memory tests. There is one report of consistent benefits across a number of memory tests for a subset of normal adults who performed more poorly than their peers at baseline. The choline compounds PC and citicoline are thought to promote synthesis and transmission of neurotransmitters important to memory. PC has not proven effective for improving memory in patients with probable Alzheimer's disease. The issue remains open for older adults without serious degenerative neural disease. Research on citicoline is practically nonexistent, but one study reported a robust improvement in story recall for a small sample of normally aging older adults who scored lower than their peers in baseline testing. Animal studies suggest that piracetam may improve neuronal efficiency, facilitate activity in neurotransmitter systems, and combat the age-related decrease in receptors on the neuronal membrane. However, for patients with probable Alzheimer's disease, as well as for adults with age-associated memory impairment, there is no clear-cut support for a mnemonic benefit of piracetam. Vinpocetine increases blood circulation and metabolism in the brain. Animal studies have shown that vinpocetine can reduce the loss of neurons due to decreased blood flow. In three studies of older adults with memory problems associated with poor brain circulation or dementia-related disease, vinpocetine produced significantly more improvement than a placebo in performance on global cognitive tests reflecting attention, concentration, and memory. Effects on episodic memory per se have been tested minimally, if at all. ALC participates in cellular energy production, a process especially important in neurons, and in removal of toxic accumulation of fatty acids. Animal studies show that ALC reverses the age-related decline in the number of neuron membrane receptors. Studies of patients with probable Alzheimer's disease have reported nominal advantages over a range of memory tests for ALC-treated patients relative to placebo groups. Significant differences have been reported rarely, however. Whether ALC would have mnemonic benefits for aging adults without brain disease is untested as far as we know. Antioxidants help neutralize tissue-damaging free radicals, which become more prevalent as organisms age. It is hypothesized that increasing antioxidant levels in the organism might retard or reverse the damaging effects of free radicals on neurons. Thus far, however, studies have found that vitamin E does not significantly slow down memory decline for Alzheimer's patients and does not produce significant memory benefits among early Parkinson's patients. Neither did a combination of vitamins E and C significantly improve college students' performance on several cognitive tasks. CONCLUSIONS: In sum, for most of the "brain-specific" nutrients we review, some mildly suggestive effects have been found in preliminary controlled studies using standard psychometric memory assessments or more general tests designed to reveal cognitive impairment. We suggest that future evaluations of the possible memory benefits of these supplements might fruitfully focus on memory processes rather than on memory tests per se.

Acetylcarnitine↗

Two stages of B-cell memory development with different T-cell requirements.

We present evidence here for two stages in B-memory cell development, the first of which is T independent and the second T dependent. For these studies, we use a new type of T-deficient mouse (allotype suppressed) which specifically lacks T-helper activity (Th) for a subset of memory B cells responsible for approximately 10% of the overall IgG antibody response. We have shown elsewhere that these mice (SJL X BALB/c hybrids suppressed for Ig-1b) lack Th capable of helping Ig-1b memory cells, although they have normal Th activity for all other IgG memory B cells. This selective Th deficiency allows study of the effects of T depletion on memory development and avidity maturation of one population of B cells under conditions where the bulk of the immune response in the animal is proceeding normally, thus obviating environmental problems due to secondary effects of T depletion. With this sytem, we show that after a single priming dose of 2,4-dinitrophenyl-keyhole limpet hemocyanin, the memory B-cell pool in suppressed and nonsuppressed donors is indistinguishable with respect to magnitude and avidity of the response for all IgG antibodies produced, including Ig-1b antibody, despite the fact that expression of Ig-1b memory cells is prevented in intact Ig-1b-suppressed mice by the absence of Th capbale of cooperating with these memory cells. We have shown elsewhere that virtually all of the Ig-1b memory is carried by Ig-1b bearing cells. In contrast with the lack of suppressor T-cell effect on initial Ig-1b memory cell development, our data show that continued Ig-1b memory development is selectively impaired in suppressed mice. When primed mice are boosted repeatedly with the priming antigen, the average avidity of most of the IgG memory cells increases over 100-fold while there is no avidity increase in the Ig-1b component. To explain these data, we suggest that the development of high avidity memory occurs in two stages. The first stage, which occurs as a result of primary antigenic exposure, is the creation of a pool of IgG-bearing memory cells with a relatively low average avidity for the antigen. The appearance of these first stage memory cells does not require help from (post-thymic) Th, although Th are required for the expression of these memory cells (antibody production). The second stage of B-memory development requires both further antigenic stimulation and B-memory cell interaction with competent Th. This is a continuing process in which the number of memory cells in the pool remains relatively constant but the average avidity of these cells increases with continued antigenic exposure.

Animals↗

Memory functioning among midlife women: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: As the number of midlife women increases, there is an increased interest in women's experiences of the perimenopause. Because of the evidence linking estrogen with cholinergic and serotonergic activity in the brain and with central nervous system development of dendritic arborization, and mixed evidence of estrogen use with incidence of Alzheimer's disease, the effects of the perimenopause on memory functioning are of interest. The purpose of these analyses, part of the Seattle Midlife Women's Health Study, was to describe changes in women's perceived memory functioning according to their perimenopausal group, age, perceived stress, health status, and mood. DESIGN: Memory functioning was assessed with the Memory Functioning Questionnaire as part of a questionnaire mailed to study participants annually. Perimenopausal group was assessed using Mitchell's rating schema. RESULTS: Age was unrelated to any of the Memory Functioning Questionnaire indicators except for retrospective memory; younger women reported more memory problems than older women. Perimenopausal groups were unrelated to most memory functioning ratings with few exceptions. Memory functioning ratings of current memory compared with the past were worse for women who were in early and middle transition and for those who were using hormone therapy than for those who were in late transition and postmenopause. Women reported more current memory problems compared with 10 and 20 years ago and at age 18. Health ratings were negatively correlated with memory functioning ratings, and depressed mood positively correlated with nearly every indicator of memory functioning (frequency of memory problems, ratings of current memory, past memory, and memory change). Greater perceived stress levels were associated with more memory problems. CONCLUSIONS: Perceived memory functioning seems more closely related to perceived health, depressed mood, and perceived stress than to perimenopausal stage or age. Further work is needed to determine whether these ratings provided by the Seattle cohort will change over time as women age and as they make the transition to menopause and beyond.

Adult↗

Cortical control of spatial memory in humans: the visuooculomotor model.

We review current knowledge of the cortical control of spatial memory, studied using visuooculomotor paradigms. Spatial memory is an essential cognitive process that can be involved in preparing motor responses. Our knowledge of spatial memory in humans recently has progressed thanks to the use of ocular saccades as a convenient model of motor behavior. Accuracy of memory-guided saccades, made to the remembered locations of visual targets, is a reflection of spatial memory. For the performance of memory-guided saccades with brief delays (up to 15-20 seconds), that is, involving short-term spatial memory, lesion studies have shown that the posterior parietal cortex, the dorsolateral prefrontal cortex, and the frontal eye field play significant roles. Studies of memory-guided saccades using transcranial magnetic stimulation have suggested that the right posterior parietal cortex is involved at the initial stage (<300 milliseconds) of visuospatial integration, whereas the dorsolateral prefrontal cortex in both hemispheres controls the following phase of short-term memorization, the frontal eye field mainly serving to trigger saccades. The new concept of a medium-term spatial memory has emerged from a behavioral study of memory-guided saccades in normal subjects, showing a paradoxical spontaneous improvement of spatial memory after delays of approximately 20 seconds. Lesion studies have shown that the parahippocampal cortex could specifically control this medium-term spatial memory. Last, different experimental and clinical arguments suggest that, after a few minutes, the hippocampal formation finally takes over the control of spatial memory for long-term spatial memorization. Therefore, spatial memory involved in the memorization of visual items could be successively controlled by the dorsolateral prefrontal cortex (short-term spatial memory), the parahippocampal cortex (medium-term spatial memory), and the hippocampal formation (long-term spatial memory), depending on specific periods of times. The applicability of this simple visuooculomotor model of spatial memory to other types of stimuli and general motoricity has yet to be confirmed.

Animals↗

Neuropsychological assessment in illiterates: visuospatial and memory abilities.

A basic neuropsychological battery of visuospatial and memory abilities was administered to extreme educational groups (illiterates and professionals). Subjects were matched according to sex and age. The following visuospatial tasks were included: figure copy (cube, house, and Rey-Osterrieth complex figure), telling time, recognition of superimposed figures, recognition of a map, and drawing of the plan of the room. The following memory tasks were used: basic information, digit retention (forward and backward), memory curve, delayed verbal recall, sentence repetition, logical memory, delayed logical memory, immediate recall of the Rey-Osterrieth complex figure, immediate reproduction of a cube, visuospatial memory, and sequential memory. In visuospatial tasks all differences between the two groups were statistically significant. Five of the seven visuospatial tasks (all but telling time and recognition of superimposed figures) showed differences between age groups with a better performance found in the younger groups and four of the tasks (cube, house, Rey-Osterrith complex figure copying, and telling time) were significant between sexes with a better performance in men. In memory tasks, with the exception of the immediate memory of sentences, all tasks showed statistically significant differences between educational groups. Eight of the 13 memory tasks (digits forward and backward, delayed memory of words, immediate and delayed logical memory, Rey-Osterrieth immediate memory, cube immediate memory, and sequential memory) showed significant differences for age while 4 of the tasks (digits backward, memory curve, Rey-Osterrieth immediate memory, and cube immediate memory) were significant for sex. Results are analyzed with regard to current theories in cognitive psychology and anthropology. Emphasis is placed on the finding that cognitive skills usually examined by neuropsychological tests represent learned and highly trained abilities.

Adolescent↗

Behavioral markers for self- and other-attribution of memory: a study in patients with temporal lobe epilepsy and healthy volunteers.

OBJECTIVES: The correlation between clinical measures of memory and subjectively reported memory is often poor. Regarding this we investigated in patients with temporal lobe epilepsy (TLE) whether there is evidence that persons mistake other cognitive performances for memory due to subjective memory theories. METHODS: a neuropsychological test battery comprising measures of attention, verbal/figural memory and other visual or language related functions was applied in patients with left (L-TLE, n=24) or right temporal lobe epilepsy (R-TLE, n=21) and healthy volunteers (n=20). In addition, subjective self- and other-reported memories were assessed by the subjective memory questionnaire (SMQ). RESULTS: subjective measures as well as objective measures indicate significant cognitive impairment in TLE and in L-TLE in particular. Self-reports and other-reports are interrelated but only self-reported memory correlates significantly with objective memory performance. Regression analysis indicates that self-reported memory is best predicted by word fluency followed by verbal memory and vocabulary, and other-reported memory is best predicted by word fluency, vocabulary, confrontation naming, and verbal recognition memory. DISCUSSION: The results suggest that attribution of memory refers to a subjective view of memory which is wider than its neuropsychological definition. It furthermore differs dependent on the observer's point of view. Memory is preferentially concluded from verbal behaviors. These reflect language skills and access to vocabulary rather than declarative memory. Consideration of subjective memory theories and associated attribution processes can significantly contribute to our understanding of the often-poor relationship between objective test results and subjective impairment in TLE.

Adolescent↗

Dependence of explicit and implicit memory on hypnotic state in trauma patients.

BACKGROUND: It is still unclear whether memory of intraoperative events results entirely from moments of inadequate anesthesia. The current study was designed to determine whether the probability of memory declines with increasing depth of the hypnotic state. METHOD: A list of words was played via headphones during surgery to patients who had suffered acute trauma. Several commonly used indicators of anesthetic effect, including the bispectral index, were recorded during word presentation. First, these indicators served as predictors of the memory performance in a postoperative word stem completion test. Second, general memory performance observed in the first part was separated into explicit and implicit memory using the process dissociation procedure, and then two models of memory were compared: One model assumed that the probability of explicit and implicit memory decreases with increasing depth of hypnotic state (individual differences model), whereas the other assumed equal memory performance for all patients regardless of their level of hypnotic state. RESULTS: General memory performance declined with decreasing bispectral index values. None of the other indicators of hypnotic state were related to general memory performance. Memory was still significant at bispectral index levels between 60 and 40. A comparison of the two models of memory resulted in a better fit of the individual differences model, thus providing evidence of a dependence of explicit and implicit memory on the hypnotic state. Quantification of explicit and implicit memory revealed a significant implicit but no reliable explicit memory performance. CONCLUSIONS: This study clearly indicates that memory is related to the depth of hypnosis. The observed memory performance should be interpreted in terms of implicit memory. Auditory information processing occurred at bispectral index levels between 60 and 40.

Adolescent↗

Patients' perceptions of memory functioning before and after surgical intervention to treat medically refractory epilepsy.

PURPOSE: One risk associated with epilepsy surgery is memory loss, but perhaps more important is how patients perceive changes in their memories. This longitudinal study evaluated changes in memory self-reports and investigated how self-reports relate to changes on objective memory measures in temporal or extratemporal epilepsy patients who underwent surgery. METHODS: Objective memory (Wechsler Memory Scale-Revised) and subjective memory self-reports (Memory Assessment Clinics Self-Rating Scale) were individually assessed for 136 patients approximately 6 months before and 6 months after surgery. A measure of depressive affect (Beck Depression Inventory-2nd Edition) was used to control variance attributable to emotional distress. RESULTS: Despite a lack of significant correlational relationships between objective and subjective memory for the entire sample, significant correlations between objective memory scores and self-reports did emerge for a subset of patients who evidenced memory decline. Differences also were found in the subjective memory ratings of temporal lobe versus extratemporal patients. Temporal lobe patients rated their memories more negatively than did extratemporal patients and were more likely to report significant improvements in their memory after surgery. CONCLUSIONS: In general, patients were not accurate when rating their memories compared to other adults. However, patients with significant declines in their memories were sensitive to actual changes in their memories over time relative to their own personal baselines.

Adolescent↗