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PubMed1998

Recognition memory in rats--III. Neurochemical substrates.

In the first part of three overviews on recognition memory in the rat, we discussed the tasks employed to study recognition memory. In the second part, we discussed the neuroanatomical systems thought to be of importance for the mediation of recognition memory in the rat. In particular, we delineated two parallel-distributed neuronal networks, one that is essential for the processing of non-spatial/item recognition memory processes and incorporates the cortical association areas such as TE1, TE2 and TE3, the rhinal cortices, the mediodorsal thalamic nucleus and prefrontal cortical areas (Network 1), the other comprising of the hippocampus, mamillary bodies, anterior thalamic nuclei and medial prefrontal areas (Network 2), suggested to be pivotal for the processing of spatial recognition memory. The next step will progress to the level of the neurotransmitters thought to be involved. Current data suggest that the majority of drugs have non-specific, i.e. delay-independent effects in tasks measuring recognition memory. This may be due to attentional, motivational or motoric changes. Alternatively, delay-independent effects may result from altered acquisition/encoding rather than from altered retention. Furthermore, the neurotransmitter systems affected by these drugs could be important as modulators rather than as mediators of recognition memory per se. It could, of course, also be the case that systemic treatment induces non-specific effects which overshadow any specific, delay-dependent, effect. This possibility receives support from lesion experiments (for example, of the septohippocampal cholinergic system) or studies employing local intracerebral infusion techniques. However, it is evident that those delay-dependent effects are relatively subtle and more readily seen in delayed response paradigms, which tax spatial recognition memory. One interpretation of these results could be that some neurotransmitter systems are more involved in spatial than in item recognition memory processes. However, performance in delayed response tasks can be aided by mediating strategies. Drugs or lesions can alter those strategies, which could equally explain some of the (delay-dependent) drug effects on delayed responding. Thus, it is evident that neither of the neurotransmitter systems reviewed (glutamate, GABA, acetylcholine, serotonin, dopamine and noradrenaline) can be viewed as being directly and exclusively concerned with storage/retention. Rather, our model of recognition memory suggests that information about previously encountered items is differentially processed by distinct neural networks and is not mediated by a single neurotransmitter type.

Animals↗

PubMed2000

Separate roles for beta2- and beta3-adrenoceptors in memory consolidation.

Consolidation of a labile memory which would not normally be stored can be achieved by intracerebral administration of noradrenaline. In a series of experiments using discriminated, one trial passive avoidance learning with the day-old chick, the effect of noradrenaline has been shown to be due to actions at different subtypes of adrenoceptors. The effect of noradrenaline is dose-dependent, with a moderate dose producing memory consolidation. However, higher doses of noradrenaline (0.3-10 nmol/hemisphere) prevent consolidation, an effect not seen with isoprenaline suggesting that these doses stimulate alpha-adrenoceptors. The promotion of memory consolidation by noradrenaline or isoprenaline at low doses was attributable to beta3-adrenoceptors and at medium doses to beta2-adrenoceptors. At higher doses of noradrenaline, there was alpha1-adrenoceptor-mediated inhibition of memory consolidation. Consolidation can also be achieved by administration of either beta2- or beta3-adrenoceptor agonists at specific times after training. Although these two adrenoceptors both promoted memory consolidation, there was a differential action on the stages of memory formation. The dose-response curve to the beta3- and the beta2-agonists was shifted by the appropriate antagonist but not by the antagonist at the other beta-adrenoceptor. Although beta1-adrenoceptors are present in chick brain, they do not seem to have a role in memory formation. These results explain why noradrenaline, acting at different adrenoceptors, can have different effects on memory formation with memory being either consolidated or inhibited depending on the dose. The findings also demonstrate a role in memory formation for beta3-adrenoceptors found in the brain. Agonists acting specifically at beta2- or beta3-adrenoceptors may be of value in diseases involving cognitive impairment.

Adrenergic beta-Agonists↗

PubMed1998

Defective inhibition of dream event memory formation: a hypothesized mechanism in the onset and progression of symptoms of schizophrenia.

An average person normally spends at least 90 min to 2 h per night dreaming. Nevertheless, memories of dream events are not retrieved while awake unless the person awoke shortly after a dream. It is hypothesized here that schizophrenic delusions initially arise because a system that normally inhibits the formation of memories of dream events is defective. Therefore, memories of dream events or fragments would be occasionally made and placed in the normal memory store. The only reason that we really know anything happened to us in the past is that we have a memory of it, and having a memory of an event is sufficient to really believe it. Therefore, the schizophrenic would believe that the dream events actually happened. It is proposed that this is the basis of primary delusions. Because memories are represented by strengthened neural connections there will be an accumulation of connections that do not correspond to reality. This accumulation may account for other symptoms of schizophrenia such as thought disorder, loosening of associations, and hallucinations. The brain trying to draw conclusions from several memories may be the basis of secondary delusions. Evidence is presented for the ideas that primary delusions are due to memories of dream events, that a substance, with vasotocin-like bioactivity, is released in the brain during dreaming and inhibits memory formation, that the lateral habenula is a brain area involved in vasotocin actions and is affected by neuroleptics, and that brain mechanisms involved in vasotocin actions show pathological alterations in schizophrenia.

Delusions↗

PubMedDate not supplied

Associative memory in networks of spiking neurons.

Here, we develop and investigate a computational model of a network of cortical neurons on the base of biophysically well constrained and tested two-compartmental neurons developed by Pinsky and Rinzel [Pinsky, P. F., & Rinzel, J. (1994). Intrinsic and network rhythmogenesis in a reduced Traub model for CA3 neurons. Journal of Computational Neuroscience, 1, 39-60]. To study associative memory, we connect a pool of cells by a structured connectivity matrix. The connection weights are shaped by simple Hebbian coincidence learning using a set of spatially sparse patterns. We study the neuronal activity processes following an external stimulation of a stored memory. In two series of simulation experiments, we explore the effect of different classes of external input, tonic and flashed stimulation. With tonic stimulation, the addressed memory is an attractor of the network dynamics. The memory is displayed rhythmically, coded by phase-locked bursts or regular spikes. The participating neurons have rhythmic activity in the gamma-frequency range (30-80 Hz). If the input is switched from one memory to another, the network activity can follow this change within one or two gamma cycles. Unlike similar models in the literature, we studied the range of high memory capacity (in the order of 0.1 bit/synapse), comparable to optimally tuned formal associative networks. We explored the robustness of efficient retrieval varying the memory load, the excitation/inhibition parameters, and background activity. A stimulation pulse applied to the identical simulation network can push away ongoing network activity and trigger a phase-locked association event within one gamma period. Unlike as under tonic stimulation, the memories are not attractors. After one association process, the network activity moves to other states. Applying in close succession pulses addressing different memories, one can switch through the space of memory patterns. The readout speed can be increased up to the point where in every gamma cycle another pattern is displayed. With pulsed stimulation. bursts become relevant for coding, their occurrence can be used to discriminate relevant processes from background activity.

Action Potentials↗

PubMed2000

Memory for temporal order in patients with schizophrenia.

There is some evidence that memory for temporal order is a process that may be impaired independently of other forms of memory. For example, patients with Korsakoff's syndrome have been shown to have poorer temporal-order memory than other amnesic patients, despite item memory being equivalent. Patients with schizophrenia have been reported to have a variety of memory problems, although memory for the order of events has not been examined very frequently. In this study, we tested memory for temporal order in patients with schizophrenia and in control subjects. Subjects were presented with two lists of 15 words (at two different times) and were later asked to reproduce the order of each list from a random array of the words. In both versions of the test, patients with schizophrenia were impaired in placing the items in the correct temporal order. Recall and recognition of the actual words used to comprise the lists were also impaired in the schizophrenic patients. However, when recall measures were covaried, and when patients were matched with controls for recall, post-hoc group differences in temporal memory were eliminated. In contrast, covarying recognition (indexed by d' or matching for recognition) did not eliminate group differences. Therefore, although memory for temporal order is compromised in patients with schizophrenia, this deficit is highly correlated with generally poorer item-specific memory retrieval (i.e., recall). It is possible that both impairments are due to some third process that underlies and aids in the reconstruction of episodes.

Adolescent↗

PubMed2000

Schizophrenia patients demonstrate a dissociation on declarative and non-declarative memory tests.

Declarative memory refers to the recall and recognition of factual information. In contrast, non-declarative memory entails a facilitation of memory based on prior exposure and is typically assessed with priming and perceptual-motor sequencing tasks. In this study, schizophrenia patients were compared to normal comparison subjects on two computerized memory tasks: the Word-stem Priming Test (n=30) and the Pattern Sequence Learning Test (n=20). Word-stem Priming includes recall, recognition (declarative) and priming (non-declarative) components of memory. The schizophrenia patients demonstrated an impaired performance on recall of words with relative improvement during the recognition portion of the test. Furthermore, they performed normally on the priming portion of the test. Thus, on tests of declarative memory, the patients had retrieval deficits with intact performance on the non-declarative memory component. The Pattern Sequence Learning Test utilizes a serial reaction time paradigm to assess non-declarative memory. The schizophrenia patients' serial reaction time was significantly slower than that of comparison subjects. However, the patients' rate of acquisition was not different from the normal comparison group. The data suggest that patients with schizophrenia process more slowly than normal, but have an intact non-declarative memory. The schizophrenia patients' dissociation on declarative vs. non-declarative memory tests is discussed in terms of possible underlying structural impairment.

Adult↗

PubMed1999

Differential effects of chronic stress on memory processes in the tree shrew.

Unpredictable and uncontrollable stressful events have been shown to affect cognitive processes. Interestingly, only hippocampus-mediated memory processes are thought to be sensitive to the effects of chronic stress. In contrast, the hippocampus-independent memory processes have been shown to be resistant to chronic stressful experiences. A central feature of the stress response is the activation of the hypothalamus-pituitary-adrenocortical (HPA)-axis, resulting in increased plasma levels of glucocorticoids, and several studies suggested that the performance of hippocampus-mediated memory processes might be directly modulated by these adrenal steroids. We investigated the impact of chronic psychosocial stress on hippocampus-mediated and hippocampus-independent memory processes in male tree shrews. By using a modified holeboard we followed memory performance during 23 weeks of alternating stress-free and stressful conditions. This schedule was designed to mimic a more realistic situation with stress-free conditions being sequentially interrupted by challenging events. The results indicate that chronic stress differentially affects hippocampus-mediated and hippocampus-independent memory processes in tree shrews. While hippocampus-independent memory processes remained unimpaired throughout the study, hippocampus-mediated memory was persistently impaired, not only during stress periods but also during recovery periods. This persistent impairment seems not to be exclusively triggered by glucocorticoids because urinary free cortisol concentration returned to normal during recovery periods. The present study is the first to evaluate the consequences of sequential stress exposure on memory performance in animals. Apparently, the mechanisms modulating cognitive processes are far from being understood and need a very systematic analysis in animal models with a high face and predictive validity to human stress-related memory disorders.

Aggression↗

PubMed2003

The staufen/pumilio pathway is involved in Drosophila long-term memory.

BACKGROUND: Memory formation after olfactory learning in Drosophila displays behavioral and molecular properties similar to those of other species. Particularly, long-term memory requires CREB-dependent transcription, suggesting the regulation of "downstream" genes. At the cellular level, long-lasting synaptic plasticity in many species also appears to depend on CREB-mediated gene transcription and subsequent structural and functional modification of relevant synapses. To date, little is known about the molecular-genetic mechanisms that contribute to this process during memory formation. RESULTS: We used two complementary strategies to identify these genes. From DNA microarrays, we identified 42 candidate memory genes that appear to be transcriptionally regulated in normal flies during memory formation. Via mutagenesis, we have independently identified 60 mutants with defective long-term memory and have defined molecular lesions for 58 of these. The pumilio translational repressor was found from both approaches, along with six additional genes with established roles in local control of mRNA translation. In vivo disruptions of four genes--staufen, pumilio, oskar, and eIF-5C--yield defective memory. CONCLUSIONS: Convergent findings from our behavioral screen for memory mutants and DNA microarray analysis of transcriptional responses during memory formation in normal animals suggest the involvement of the pumilio/staufen pathway in memory. Behavioral experiments confirm a role for this pathway and suggest a molecular mechanism for synapse-specific modification.

Animals↗

PubMed2003

Sex-related impairment of memory for emotional events with beta-adrenergic blockade.

On the basis of recent evidence indicating a sex-related lateralization of amygdala function in memory for emotional events, together with substantial evidence suggesting hemispheric specialization in processing global (central) versus local (detail) aspects of a situation, and the established dependence of the amygdala's memory modulating function on beta-adrenergic receptor activation, we predicted differential effects of a beta-adrenergic receptor antagonist (propranolol) on long-term memory for an emotionally arousing story in men and women. Specifically, we predicted that, relative to placebo, propranolol would impair memory for information central to the story line, but not memory for peripheral story details in men. Conversely, propranolol would impair memory for peripheral details, but not for central information in women. Here we confirm this prediction with a novel analysis of data from our two published studies of propranolol's effect on memory for an emotionally arousing story. These findings demonstrate a sex-related impairment of memory for emotional information by beta-adrenergic blockade. Additionally, they provide support for the hypothesis that, in this paradigm, emotional arousal enhances long-term memory for central information in men via activation of right amygdala/hemisphere function, and enhances long-term memory for peripheral details in women via activation of left amygdala/hemisphere function.

Adrenergic beta-Antagonists↗

PubMed1999

The N100 auditory cortical evoked potential indexes scanning of auditory short-term memory.

OBJECTIVE: To study activity of auditory cortex reflected by the N100 and P200 components of the auditory evoked potentials during memorization and scanning of short-term memory stores. METHODS: In a MEMORY task subjects classified a probe digit either as a member or not a member of a previously presented list of digits that varied in size from one, 3, 5 and 7 items. For comparison, subjects in a NUMBER task listened to a list of digits as in the MEMORY task but determined only whether the probe digit as odd or even. Evoked potentials to the presentation list and to probes were recorded from scalp electrodes and separately averaged for both tasks. The components peaking at approximately 100 ms (N100) and 200 ms (P200) that reflect activity of primary auditory cortex were identified and peak amplitudes and latencies were measured. RESULTS: For presentation set items, the amplitude of N100 was affected by set size in the MEMORY but not in the NUMBER task; N100 was larger for the one item set than for the 3, 5, and 7 item sets. P200 increased in amplitude in a linear manner for both the MEMORY and NUMBER tasks. For probe items, N100 but not P200 amplitude decreased in a linear manner as the number of items in the presentation set increased in the MEMORY but not in the NUMBER task. The linear change of N100 amplitude during memory scanning was particular to inset but not to out-of-set probes. The amplitudes of both N100 and P200 were almost twice as large in probe digits than in the digits in the presentation set in both the MEMORY and NUMBER tasks. CONCLUSION: Auditory sensory cortical activity in humans during an auditory short-term memory task shows dynamic changes during both memorization and memory scanning.

Acoustic Stimulation↗

PubMed2005

A model of verbal memory impairments in schizophrenia: two systems and their associations with underlying cognitive processes and clinical symptoms.

BACKGROUND: In a broad cognitive study of schizophrenia we investigated the relationships of verbal memory impairments with cognitive underpinnings on the one hand, and clinical symptomatology on the other. The results have been reported in previous papers. In this paper we show how all these data could be integrated into a consistent pattern of associations. METHOD: Fifty schizophrenic patients underwent a cognitive battery including a verbal memory task with free recall and recognition, a source memory task, and tests of processing speed and selective attention. Ratings for positive, negative and depressive symptoms were available for 40 of the patients. RESULTS: A factorial analysis revealed a distinction between measures of memory efficiency and measures of memory errors. The system of memory efficiency was associated with processing speed and selective attention at the cognitive level, and with depression at the symptom level. The system of memory errors was assumed to be underlain by source-monitoring deficits. These memory errors were increased by positive symptoms and decreased by certain negative symptoms. CONCLUSIONS: All the measures drawn from various memory tasks could be integrated into a model describing their associations with cognitive underpinnings and clinical symptomatology. This model provides a heuristic for the cognitive and pharmacological treatments of verbal memory impairments in schizophrenia, as well as for the understanding of positive symptoms.

Adult↗

PubMed2005

Memory and verbal learning functions in twins with bipolar-I disorder, and the role of information-processing speed.

BACKGROUND: Euthymic bipolar-I disorder (BP I) patients and their siblings have shown impairments in verbal learning and memory functions compared with controls, suggesting that these impairments may be genetic in origin. Reduced information-processing speed has been associated with impaired memory in the elderly, and recently in schizophrenia. The authors compared verbal learning and memory functioning in twins with BP I and co-twins to control twins, and examined whether the observed deficits are related to information-processing speed. METHOD: Finnish Medical and Population Registers and Twin Cohorts were used to identify the BP I and control twins. Neuropsychological tests assessing verbal learning and memory, working memory, facial recognition, visual memory, and information-processing speed were administered to 26 BP I twins, 19 non-bipolar co-twins, and 114 controls. Group differences were analyzed by generalized estimation equation modeling. RESULTS: BP I patients, but not co-twins, showed impairments in all memory tests compared with controls. Female co-twins showed impairment in verbal learning and memory. Information-processing speed had a significant effect on encoding and learning efficiency. CONCLUSIONS: This study showed for the first time that information-processing speed is related to memory functioning and verbal learning in BP I in a population-based, representative and euthymic sample. Furthermore, the data support the view that defects in verbal memory may be related to the genetic factors predisposing to BP I in females.

Adult↗

PubMed1999

Errorless learning and the cognitive rehabilitation of memory-impaired schizophrenic patients.

BACKGROUND: In recent years, evidence has accumulated that a significant proportion of schizophrenic patients have severe memory impairment, which cannot be attributed to the effects of medication, chronicity or institutionalization. Our group has demonstrated that memory impairment is associated with poor psychosocial outcome and treatment resistance. Work on the classical amnesic syndrome has suggested that memory training is facilitated by adopting an 'errorless learning' approach, where subjects do not experience failure during learning. This is based on the theory that the preserved implicit memory of amnesic patients results in implicitly remembered incorrect responses interfering with target items, in the absence of a functioning explicit memory system to allow differentiation. METHOD: We compared three groups of subjects, memory-impaired schizophrenic patients, memory unimpaired schizophrenic patients and healthy controls. RESULTS: An errorless learning approach conferred a significant advantage on the memory-impaired schizophrenic group, bringing their performance up to the level of both control groups. In contrast, adopting a traditional trial and error, or errorful approach resulted in markedly impaired performance in the memory-impaired schizophrenic group only. CONCLUSIONS: We conclude that errorless learning approaches may be worthy of further evaluation in the cognitive rehabilitation of memory-impaired schizophrenic patients.

Adult↗

PubMed2000

Decentring and distraction reduce overgeneral autobiographical memory in depression.

BACKGROUND: Increased recall of categorical autobiographical memories is a phenomenon unique to depression and post-traumatic stress disorder, and is associated with a poor prognosis for depression. Although the elevated recall of categorical memories does not change on remission from depression, recent findings suggest that overgeneral memory may be reduced by cognitive interventions and maintained by rumination. This study tested whether cognitive manipulations could influence the recall of categorical memories in dysphoric participants. METHODS: Forty-eight dysphoric and depressed participants were randomly allocated to rumination or distraction conditions. Before and after the manipulation, participants completed the Autobiographical Memory Test, a standard measure of overgeneral memory. Participants were then randomized to either a 'decentring' question (Socratic questions designed to facilitate viewing moods within a wider perspective) or a control question condition, before completing the Autobiographical Memory Test again. RESULTS: Distraction produced significantly greater decreases in the proportion of memories retrieved that were categorical than rumination. Decentring questions produced significantly greater decreases in the proportion of memories retrieved that were categorical than control questions, with this effect independent of the prior manipulation. CONCLUSIONS: Elevated categorical memory in depression is more modifiable than has been previously assumed; it may reflect the dynamic maintenance of a cognitive style that can be interrupted by brief cognitive interventions.

Adult↗

PubMed2006

Everyday memory functioning in obsessive- compulsive disorder.

Memory performance in obsessive-compulsive disorder (OCD) is discussed as a pathogenetic risk factor for the emergence of OCD, particularly checking compulsions. At present, however, findings are mixed and little is known about memory performance in tasks relevant to everyday functioning in patients with OCD. For the present study, memory performance was assessed in 31 patients diagnosed with OCD and 33 healthy controls with the Rivermead Behavioural Memory Test (RBMT), which covers a wide range of verbal and nonverbal memory components as well as prospective memory. OCD patients performed comparably to healthy controls on the memory task for verbal, nonverbal, and prospective memory (p > .1). According to norm values, memory performance was unimpaired in most OCD patients. The present findings further challenge a broad account of the "memory deficit" hypothesis of OCD and compulsive checking, respectively.

Activities of Daily Living↗

PubMed2007

Cognitive rehabilitation in the elderly: effects on memory.

This study reports the effects of a 12-week multimodular cognitive rehabilitation training program on memory performance in two groups of older adults. In the Memory Training module, participants were instructed on the nature of memory and how to improve memory performance; internal and external strategies were described and practiced over the training sessions. Memory performance was assessed by four tests: Alpha Span, Brown-Peterson, Hopkins Verbal Learning Test - Revised (HVLT-R), and Logical Stories. One group received training on entry into the study (Early Training Group, ETG), the other after a 3-month delay (Late Training Group, LTG). The results showed no training-related improvement in working memory (Alpha Span), primary memory (Brown-Peterson, HVLT-R), or recognition memory (HVLT-R). While the most direct analyses of a training effect (analyses of covariance) rarely demonstrated significant effects, exploratory analyses provided some evidence for a training benefit in several measures of secondary memory (Logical Stories; HVLT-R) and strategic processing (Brown-Peterson; Logical Stories; HVLT-R). Positive results were largely restricted to the ETG, possibly because the LTG lost motivation as a consequence of their delayed training. The results need to be treated with caution, but are promising for the rehabilitation of memory functioning in older adults.

Aged↗

PubMed1999

MRI extrahippocampal volumes and visual memory: correlations independent of MRI hippocampal volumes in temporal lobe epilepsy patients.

Limbic system atrophy and memory dysfunction are common in patients with temporal lobe epilepsy (TLE). However, the relationship between extrahippocampal limbic structures and memory functioning within TLE has received little attention. The present study examined associations of MRI volumetric measurements of the mammillary body, fornix, amygdala, and hippocampus to measures of episodic verbal and visual memory. The Logical Memory and Visual Reproduction subtests from the Wechsler Memory Scale were administered to 47 unilateral TLE patients (25 right, 22 left). Normalized right and left MRI volumes were determined for each patient by cursor tracing 1.5 mm slices from 3D-MRI. Significant associations were found between left hippocampal volume and the immediate, delayed, and percent retention scores of the Logical Memory Test; between the left mammillary body volume and the Logical Memory Test delayed and percent retention scores; immediate Visual Reproduction performance was significantly related to the right and left amygdala volumes, and right mammillary body volume; only the right amygdala and right mammillary body volume were associated with the delayed Visual Reproduction trial. However, neither right nor left hippocampal volumes were related to visual memory performance. Multiple limbic system structural volumes were independently associated with verbal and nonverbal memory performance. Results suggest that visual memory, as measured by the Visual Reproduction Test, may be uniquely associated with extrahippocampal volumes in patients with TLE.

Adult↗

PubMed1994

Depression and memory narrative type.

Research with autobiographical memories has distinguished between memory narratives of specific events and summaries of many events blended together. Depression has been associated with a reduced ability to retrieve and orally relate specific positive memories. This study explored the hedonic bias in memory through collection of written autobiographical memories from 90 nonclinical college students whose mood was assessed for depression. Participants with higher depression scores recalled significantly more summary memories in response to a request for a positive self-defining memory than did participants with lower depression scores. There were no significant differences in the number of single-event and summary memories when participants were asked for a negative memory. We used J. A. Singer and K. H. Moffitt's (1991-1992) scoring system to distinguish between summarized and specific memory narratives.

Adolescent↗