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PubMed1999

Glutamatergic and dopaminergic afferents to the prefrontal cortex regulate spatial working memory in rats.

The integrity of the prefrontal cortex is critical for the expression of working memory. The prefrontal cortex is innervated by dopaminergic afferents from the ventral tegmental area and glutamatergic afferents from the mediodorsal thalamus. To determine the role of dopaminergic and glutamatergic afferents in the regulation of working memory, rats were trained to perform a spatial delayed alternation task in a T-maze. The microinjection of the ionotropic glutamate antagonists 6-cyano-7-nitroquinoxaline-2,3-dione or 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid into the prefrontal cortex impaired working memory. Consistent with a role for glutamate receptor activation, microinjecting the GABA(B) agonist baclofen into the mediodorsal thalamus produced a dose-dependent disruption of working memory. In contrast, inhibition of the mesocortical dopamine projection was without effect on working memory. The blockade of D1 and/or D2 dopamine receptors with SCH-23390 and sulpiride was without effect on working memory. Likewise, the microinjection of baclofen into the ventral tegmental area did not impair working memory. However, stimulating mu-opioid receptors in the ventral tegmental area with [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin produced a dose-dependent impairment of working memory that was reversed by blocking D1 dopamine receptors with SCH-23390 in the prefrontal cortex. These data demonstrate that increased dopamine tone or reduced glutamate tone in the prefrontal cortex disrupts working memory in a spatial delayed alternation task.

Animals↗

PubMed2000

1999 Curt P. Richter award. Glucocorticoids and the regulation of memory consolidation.

This paper summarizes recent findings on the amygdala's role in mediating acute effects of glucocorticoids on memory consolidation in rats. Posttraining activation of glucocorticoid-sensitive pathways involving glucocorticoid receptors (GRs or type II) enhances memory consolidation in a dose-dependent inverted-U fashion. Selective lesions of the basolateral nucleus of the amygdala (BLA) or infusions of beta-adrenoceptor antagonists into the BLA block the memory-modulatory effects of systemic injections of glucocorticoids. Additionally, posttraining infusions of a specific GR agonist administered directly into the BLA enhance memory consolidation, whereas those of a GR antagonist impair. These findings indicate that glucocorticoid effects on memory consolidation are mediated, in part, by an activation of GRs in the BLA and that the effects require beta-adrenergic activity in the BLA. Other findings indicate that the BLA interacts with the hippocampus in mediating glucocorticoid-induced modulatory influences on memory consolidation. Lesions of the BLA or inactivation of beta-adrenoceptors within the BLA also block the memory-modulatory effects of intrahippocampal administration of a GR agonist or antagonist. These findings are in agreement with the general hypothesis that the BLA integrates hormonal and neuromodulatory influences on memory consolidation. However, the BLA is not a permanent locus of storage for this information, but modulates consolidation processes for explicit/associative memories in other brain regions, including the hippocampus.

Amygdala↗

PubMed1999

The relationship between memory performance, perceived cognitive function, and mood in patients with epilepsy.

OBJECTIVE: The low correlations between memory performance and subjective memory may be attributable to disparities between tasks in neuropsychological tests and cognitive experiences of day-to-day living. This study evaluated the relationship between everyday memory performance, perceived cognitive functioning, and mood among patients with epilepsy. METHODS: From three epilepsy centers in the USA, 138 patients were recruited. Everyday memory performance was measured using the Rivermead Behavioural Memory Test (RBMT). Questionnaires assessed perceived cognitive function (cognitive domain, Quality of Life in Epilepsy Inventory, QOLIE-89) and mood (Profile of Mood States, POMS). RESULTS: Memory performance scores were weakly correlated with perceived cognitive functioning (r =0.22, P < 0.01). Perceived cognitive functioning was strongly correlated with mood (r = - 0.75, P < 0.0001). Multiple regression analysis indicated memory performance (RBMT) and mood (POMS) were independent predictors of perceived cognitive functioning (P < 0.02); however, the explained variance for RBMT and POMS combined (R2 = 0.58) is only slightly higher than the predictive value for the POMS score alone (R2 = 0.56). CONCLUSIONS: Memory performance tests provide qualitatively different information than patients' self-reported cognitive difficulties, thus it is important to assess memory performance, perceived cognitive function, and mood separately because the constructs are related but not redundant.

Adult↗

PubMed2003

Episodic memory in schizophrenic patients and their relatives.

BACKGROUND: Memory dysfunction among healthy relatives of patients with schizophrenia suggests that genetic liability to the disorder can also be manifested as cognitive impairment. This study was designed to further elucidate the nature of the memory dysfunction being transmitted. METHOD: Memory function was assessed in 62 schizophrenic patients, 98 of their healthy relatives and 66 controls. Material-specific immediate/delayed recall and percentage retention were investigated using the Logical Memory and Visual Reproduction tests of the Wechsler Memory Scale (WMS). A third subtest of the WMS, the Associate Learning and a visual analogue of it, the Abstract Paired Associates, were used to measure verbal and visual learning. Current general intellectual function was assessed using a five-subtest short-form of the Wechsler Adult Intelligence scale-Revised (WAIS-R). RESULTS: Schizophrenic patients performed significantly worse than controls on nearly all measures. Their relatives also showed significant deficit on the immediate and delayed recall of the Logical Memory, immediate recall of the Visual Reproduction, and the Abstract Paired Associates tests. Logical memory was substantially more impaired than the other measures for both patients and relatives. The deficit in immediate recall of the Logical Memory remained significant even after excluding those relatives with an Axis I diagnosis and schizotypal personality disorder. These findings were despite the relatives having an equivalent level of general intellectual function to that of controls. CONCLUSION: Familial, presumed genetic, liability to schizophrenia may be expressed as dysfunction in verbal memory.

Adolescent↗

PubMed2001

Amygdala-hippocampal volume and verbal memory in first-degree relatives of schizophrenic patients.

Verbal memory deficits have been related to reduced volume of medial temporal structures in several neurological and psychiatric populations, including schizophrenic patients. Impairments in verbal memory have been proposed to be a marker of risk for schizophrenia. Recently, relatives of schizophrenic patients have been reported to have reduced volume of the amygdala-hippocampal complex. In this study, we evaluate the possibility that amygdala-hippocampal volume reductions may constitute one neural substrate of verbal memory deficits in first-degree relatives. Subjects were 20 healthy first-degree relatives of schizophrenic patients and 14 demographically similar controls. Verbal memory was assessed with the Logical Memory Test. Subjects were scanned with high-resolution MRI and the images were transformed into Talairach space. Volumes of interest were amygdala-anterior hippocampus and posterior hippocampus. Relatives of schizophrenic patients had intact immediate verbal memory but significantly poorer delayed verbal memory than controls. Relatives also had significantly reduced amygdala-anterior hippocampus volumes. Across all subjects, delayed verbal memory was significantly correlated with amygdala-anterior hippocampus volume. The magnitude of the correlation did not differ between the groups. These data provide an empirical link between memory performance and volumetric abnormalities in the amygdala-hippocampal complex in the relatives of schizophrenic patients.

Adolescent↗

PubMed2004

Dynamics of blood-borne CD8 memory T cell migration in vivo.

Memory T cells are distributed throughout the body following infection, but the migratory dynamics of the memory pool in vivo is unknown. The ability of circulating microbe-specific memory T cells to populate lymphoid and nonlymphoid tissues was examined using adoptive transfer and parabiosis systems. While migration of memory CD8 T cells to lymph nodes and peritoneal cavity required G(i)-coupled receptor signaling, migration to the spleen, bone marrow, lung, and liver was independent of this pathway. Following parabiosis, memory T cells rapidly equilibrated into the lymphoid tissues, lung, and liver of each parabiont, implying most memory cells were not obligately tissue resident. Equilibration of memory cell populations was delayed in the brain, peritoneal cavity, and intestinal lamina propria, indicating controlled gating for entry into these tissues. In addition, memory cell migration to the lamina propria required beta7 integrins. Thus, the blood-borne T cell pool serves to maintain the homeostasis of tissue-based memory populations.

Animals↗

PubMed2000

Working memory dysfunction in major depression: an event-related potential study.

OBJECTIVES: To study working memory function in untreated major depression using a digit probe identification and matching task. METHODS: We compared behavioural performance and event-related potentials during processing of the Sternberg working memory task in 14 depressed patients and 14 healthy matched control subjects. RESULTS: Patients made more mistakes than controls as the memory load was increased from one to 5 digits and had significantly slower reaction times at all levels of memory load. The patients' event-related potentials (ERPs) differed significantly from controls. Pathological changes were similar for auditory and visual presentation. Surface negative activity in the 157-210 ms section of the waveform was reduced for all levels of memory load, suggesting abnormal sensory/perceptual processing in the modality-specific association cortices, possibly due to a failure of selective attention mechanisms. In the 375-840 ms epoch, the patients' responses showed large amplitude sustained negative activity, maximal at Cz and a reduced late positive wave. The large prolonged negativity in the patients' ERPs suggests activation of additional neuronal assemblies than those normally participating in the task. This could reflect either compensatory mechanism or dysfunction of inhibitory systems. These changes were sensitive to memory load, suggesting that they reflect alterations of memory-related processes. CONCLUSIONS: This study provides objective evidence that major depression significantly affects working memory. The ERP changes in depression could be accounted for by dysfunction of the central executive control of working memory.

Adult↗

PubMed2005

Does widowhood affect memory performance of older persons?

BACKGROUND: The loss of a spouse has been found to have a negative effect on physical and mental health and leads to increased mortality. Whether conjugal bereavement also affects memory functioning has largely been unexamined. The present study investigates the effect of widowhood on memory functioning in older persons. METHOD: The sample consisted of 474 married women and 690 married men aged 60-85 years in 1992, followed up in 1995 and 1998. During the study 135 (28%) of the women and 69 (10%) of the men lost their spouse. Linear regression analysis was used to examine whether widowed men and women differed from those who had not been widowed in rate of memory change over 6 years. Cross-domain latent-change models were subsequently used to evaluate the extent to which changes in memory are related to changes in other domains of functioning that may be affected by widowhood. RESULTS: Older adults who lost a spouse during follow-up showed a greater decline in memory over 6 years than those who remained married. A higher level of depressive symptoms at baseline was related to lower levels of memory functioning and a greater decline. Memory decline was unrelated to changes in depressive symptoms and physical health. CONCLUSIONS: Loss of the spouse is related to a greater decline in memory in older adults. The absence of an association with physical functioning and the weak association with mental functioning suggest that losing a spouse has an independent effect on memory functioning.

Aged↗

PubMed2004

Memory complaints in a community sample aged 60-64 years: associations with cognitive functioning, psychiatric symptoms, medical conditions, APOE genotype, hippocampus and amygdala volumes, and white-matter hyperintensities.

BACKGROUND: Previous research has found that depression is a major cause of memory complaints. However, there is evidence that memory complaints also weakly predict cognitive decline and dementia. The present study examined a range of possible determinants of memory complaints, covering psychiatric and personality factors, medical history, cognitive test performance, and biological risk factors for dementia (APOE genotype, hippocampus and amygdala volumes, and white-matter hyperintensities). METHOD: A community survey was carried out with 2546 persons aged 60-64 years living in Canberra and Queanbeyan, Australia. Participants were asked about memory problems which interfered with daily life and whether medical help had been sought. A randomly selected subsample of 476 persons was given a brain MRI scan. RESULTS: Participants with memory complaints were found to have poorer memory test performance, more depression and anxiety symptoms, have higher scores on personality traits involving negative affect, and to have worse physical health. Multivariate analyses showed that measures of cognitive performance did not make a unique contribution to the prediction of memory complaints above that of the other categories of predictors. Those with memory complaints did not differ on any of the biological risk factors for dementia. CONCLUSION: In a community sample aged 60-64 years, memory complaints were most closely related to psychiatric symptoms, personality characteristics and poor physical health. There was no evidence of brain changes indicating early dementia.

Amygdala↗

PubMed2006

Autobiographical memory in non-amnesic alcohol-dependent patients.

BACKGROUND: Chronic alcohol abuse is associated with a wide range of cognitive deficits. However, little is known about memory for real-life events (autobiographical memory) in non-amnesic alcoholic patients. The purpose of this study was to investigate (a) non-amnesic alcoholics' ability to recall specific autobiographical memories and (b) their subjective experience when they access specific memories. METHOD: Twenty non-amnesic (without Korsakoff syndrome) recently detoxified alcoholics and 20 healthy controls completed the Autobiographical Memory Test (AMT), which assesses the frequency of specific (versus general) memories recalled in response to cue words, and the Memory Characteristics Questionnaire (MCQ), which assesses subjective experience (e.g. the amount of sensory and contextual details experienced) when remembering specific events. RESULTS: Alcoholic patients recalled specific memories less frequently and general memories more frequently than healthy controls. Nevertheless, when a specific past event was accessed, alcoholic patients subjectively experienced as many sensory and contextual details as controls. CONCLUSIONS: These findings suggest that non-amnesic alcoholics have difficulties strategically accessing event-specific autobiographical knowledge, which might result from changes in frontal lobe function that are associated with alcoholism.

Adult↗

PubMed2004

Use of medications to enhance memory in a large community sample of 60-64 year olds.

BACKGROUND: There are no existing epidemiological data on use of medications to enhance memory. METHOD: A community survey was carried out in Canberra and Queanbeyan, Australia, of an electoral roll sample of 2551 adults aged 60-64 years. Data collected included self-reports of using medications to enhance memory, tests of memory and other cognitive functions, anxiety, depression, physical health and use of other medications. RESULTS: 2.8% of the sample reported using medications to enhance memory, the main ones being gingko biloba, vitamin E, bacopa (brahmi), and folic acid/B vitamins. Users were more likely to be female, to have subjective memory problems and to use other psychotropic medications. However, they did not differ in memory performance, anxiety, depression or physical health. DISCUSSION: Some older people are using complementary medications to improve their memory or prevent memory loss, despite the lack of strong evidence for their effectiveness. These people show no objective evidence of memory impairment.

Aged↗

PubMed2002

Verbal and spatial working memory performance among HIV-infected adults.

Subtypes of working memory performance were examined in a cohort of 50 HIV-infected adults and 23 uninfected controls using an n-back paradigm (2-back) in which alphabetic stimuli were quasi-randomly presented to a quadrant of a computer monitor. In the verbal working memory condition, participants determined whether each successive letter matched the letter that appeared two previously in the series, regardless of spatial location. In the spatial working memory condition, participants determined whether each letter matched the spatial location of the letter that had appeared two previously, regardless of letter identity. The dependent variable was percent accuracy in each condition. Results of mixed model ANOVA revealed that the HIV-infected participants performed significantly worse than controls on both the verbal and spatial working memory tasks. A significant main effect for working memory condition was also present with both participant groups performing better on the spatial working memory task. These results, the first study of HIV-infected adults to directly compare verbal versus spatial working memory performance using the identical test stimuli across task conditions, suggests that HIV infection is associated with a decrement in working memory efficiency that is equally apparent for both verbal and spatial processing. These findings implicate central executive dysfunction as a likely substrate and provide the basis for hypothesizing that decline in working memory may contribute to other HIV-associated neuropsychological deficits.

Adult↗

PubMed2004

Functional and anatomical memory indices in patients with or at risk for Alzheimer's disease.

We investigated the sensitivity of the P300 event-related brain potential (ERP) recorded during a memory-demanding task to memory function in subjects with dementia of the Alzheimer's type (DAT), those with mild cognitive impairment (MCI), and normal elderly controls. We also explored the ability of neuropsychological (delayed verbal memory), neuroanatomical (MRI-based hippocampal volume), and electrophysiological (memory search P300 amplitude) memory measures to distinguish between the three subject groups using discriminant function analyses. Fourteen patients with DAT, 16 with MCI, and 15 age- and education-matched controls were tested. P300 amplitude was reduced in DAT subjects at all levels of memory load; however, it did not differ between MCI and control subjects. Delayed verbal memory performance best discriminated DAT from MCI and control subjects, while delayed verbal memory and hippocampal volume best discriminated MCI subjects from controls. These results support the utility of neuropsychological and neuroanatomical measures in diagnosing dementia and do not support the notion that P300 amplitude is sensitive to mild memory dysfunction when measured using the current task.

Aged↗

PubMed2004

Procedural and declarative memory in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) has been associated with frontostriatal abnormality. This has led to the hypothesis that the disorder is characterized by abnormality of procedural memory. However, evidence for either procedural or declarative memory disturbance has been mixed, and few studies have directly assessed both of these forms of memory in the same patient group. In the present study, we assessed encoding and retrieval in declarative memory using the Rey Auditory Verbal Learning Test (RAVLT), and procedural memory using the Pursuit Rotor Task, in 27 adults with OCD and 29 matched healthy controls. Groups did not differ with respect to salient demographic characteristics or memory on the RAVLT. In contrast, patients with OCD performed significantly better than controls during the early, but not later trial blocks of the Pursuit Rotor Task. This pattern of results indicates intact encoding and retrieval in declarative memory, but abnormally enhanced procedural memory during the early course of learning in OCD. These findings may be consistent with striatal overactivation observed in neuroimaging studies of OCD, as well as the prominent role of the striatum during early stages of procedural memory.

Adolescent↗

PubMedDate not supplied

Memory impairment and deep brain structures.

Clinical and neuropsychological investigations were performed using the Luriya method in 141 patients with arteriovenous malformations (AVM). These included 27 patients with AVM in different parts of the caudate nucleus, 34 with AVM in the thalamus, 39 with AVM in the hippocampal formation, and 41 with AVM in the cingulate gyrus. A total of 102 patients underwent surgery. Patients with AVM in various locations showed common memory impairments as well as individual features of memory disturbances depending on which structures were affected. The common feature was the development of an amnesiac symptom complex resembling Korsakov's syndrome. These lesions developed only in patients with combined damage to deep structures (preoperatively in patients with ventricular hemorrhages); with the exception of patients with AVM of the caudate nucleus, memory impairments were modality-non-specific; all patients showed impairment of auditory-speech memory at the late phase and of visual memory in terms of indirect recall. Memory impairments characteristic of lesions to individual structures were the presence of functional asymmetry of memory defects in available of the caudate nucleus and thalamus (if only speech problems were present) and constant inclusions and contaminations in patients with AVM of the cingulate gyrus. It is suggested that certain aspects of memory function may have been duplicated in different structures during evolution and that each structure makes its own contribution to overall memory function.

Adolescent↗

PubMed2002

The lesion of the rat substantia nigra pars compacta dopaminergic neurons as a model for Parkinson's disease memory disabilities.

1. In this article we review the studies of memory disabilities in a rat model of Parkinson's disease (PD). 2. Intranigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to rats causes a partial lesion in the substantia nigra, compact part (SNc) and a specific loss of dopamine and its metabolites in the striatum of rats. 3. These animals present learning and memory deficits but no sensorimotor impairments, thus modeling the early phase of PD when cognitive impairments are observed but the motor symptoms of the disease are barely present. 4. The cognitive deficits observed in these animals affect memory tasks proposed to model habit learning (the cued version of the water maze task and the two-way active avoidance task) and working memory (a working memory version of the water maze), but spare long-term spatial memory (the spatial reference version of the Morris water maze). 5. The treatment of these animals with levodopa in a dose that restores the striatal level of dopamine does not reverse these memory impairments, probably because this treatment promotes a high level of dopamine in extrastriatal brain regions, such as the prefrontal cortex and the hippocampus. 6. On the other hand, the adenosine receptor antagonist, caffeine, partly reverse the memory impairment effect of SNc lesion in these rats. This effect may be due to caffeine action on nigrostriatal neurons, since it induces dopamine release and modulates the interaction between adenosine and dopamine receptor activity. 7. These results suggest that the MPTP SNc-lesioned rats are a good model to study memory disabilities related to PD and that caffeine and other selective A(2A) adenosine receptor antagonists are promising drugs to treat this symptoms in PD patients.

Animals↗

PubMed2000

Quality of life and memory performance in patients with temporal lobe epilepsy.

OBJECTIVE: To explore the contribution of memory performance to quality of life (QOL) in patients with left or right temporal lobe epilepsy (TLE). SUBJECTS AND METHODS: Sixty-five patients with left or right TLE compiled the QOL in Epilepsy-89 Inventory (QOLIE-89), the State-Trait Anxiety Inventory (STAI) and the Hopelessness Scale (BDI) for self-evaluation of QOL and mood. Memory was assessed by tests of verbal and non-verbal memory and the Questionnaire of Memory Efficiency (QME). A neuropsychological battery was also administered to assess general intelligence, attention, visual perception, language, set shifting, word fluency and conceptual-motor tracking. RESULTS: On factor analysis, the neuropsychological battery and mood scales consisted of six factors (Memory, Mental Speed, Mood, Praxis, Sorting and Perception), while the QOLIE-89 consisted of five factors (Psychosocial Satisfaction, Epilepsy-Related Effects, Role, Physical Performance, Cognition). On regression analysis, overall QOLIE-89 score was predicted by the factor Mood and QME score. The QOLIE-89 factor Cognition was predicted by QME score and the Memory, Mental Speed, Perception and Praxis factors of the neuropsychological battery. CONCLUSION: In TLE patients self-reported memory, as assessed by QME, is an important predictor of QOL, and also correlates with performance on memory tests. This suggests that memory improvement by specific training may help to improve QOL in these patients.

Adolescent↗

PubMed1990

Aging increases the energetic demands of episodic memory: a cardiovascular analysis.

We hypothesized that older volunteers allocate more attentional resources to memory maintenance than do younger volunteers. Allocation of a resource supporting memory maintenance was inferred from performance and cardiovascular measures. Eighteen 18- to 26-year-old men and eighteen 60- to 79-year-old men performed a serial memory task both as a single task and as a dual task that added simple reaction time stimuli. Items presented early or later in the serial list created relatively low or high memory load. The results suggested that older men allocated greater attention to memory maintenance, particularly during high-memory-load items. They showed a slowing of dual-task reaction time and increased heart rate during high- vs. low-memory-load items. Cardiac and vascular reactions further suggested that memory maintenance is supported by phasic autonomic adjustments and that with age, more of this support is required for adequate maintenance of episodic memory.

Adolescent↗

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