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PubMed2006

Enhancement of learning and memory by a medicinal formulation, Saenhyetang, in mice.

The effects on memory and learning ability of the Korean herbal medicine, Saenhyetang (SHT), which is consisted of nine herbs, were investigated. Hot water extracts (HWE-SHT) and ethanol extracts (EE-SHT) were used for the studies. It was shown that N-methyl-d-aspartate (NMDA) receptor 2B (NR2B) was increased in the forebrains of SHT-administrated mice (HWE-SHT), leading to enhanced activation of NMDA receptors, facilitating synaptic potentiation in response to stimulation at 10-100Hz. These HWE-SHT-treated mice exhibit superior ability in learning and memory in various behavioral tasks, showing that NR2B is enhanced by HWE-SHT treatment and also is critical in gating the age-dependent threshold for plasticity and memory formation. NMDA receptor-dependent modifications, which were mediated in part by HWE-SHT administration, of synaptic efficacy, therefore, represent a mechanism for associative learning and memory. Results suggest that oriental medical enhancement of NR2B attributes such as intelligence and memory in mammals is feasible. On the other hand, to examine the effects of EE-SHT on the learning and memory in experimental mice, the passive and active avoidance responses were studied. The EE-SHT ameliorated the memory retrieval deficit induced by ethanol, but not other memory impairment in mice. EE-SHT (10, 20mg/100g, p.o.) did not affect the passive avoidance responses of normal mice in the step through and step down tests, the conditioned and unconditioned avoidance responses of normal mice in the shuttle box and lever press performance tests, and the ambulatory activity of normal mice in normal condition. However, EE-SHT was shown to significantly decrease the spontaneous motor activity during the shuttle box test, and also to prolong the sleeping time induced by pentobarbital in mice at 20mg/kg. These results suggest that EE-SHT has an ameliorating effect on memory retrieval impairment and a weak tranquilizing action.

Animals↗

PubMed2004

Tracking human antigen-specific memory B cells: a sensitive and generalized ELISPOT system.

In the interest of better understanding the role of human memory B cells in protection against disease, we developed an assay to quantitate antigen-specific memory B cells in human blood. This assay utilizes a 6-day polyclonal stimulation of PBMC followed by an antigen-specific ELISPOT for the detection of memory B cells that have differentiated into antibody secreting cells (ASC) in vitro. We have used this assay to demonstrate that the anthrax vaccine (AVA; BioThrax) elicits a substantial population of protective-antigen (PA) specific memory B cells, and these B cells satisfy the canonical surface phenotype of human memory B cells: CD19(+)CD20(+)Ig(+)CD27(+). These anti-PA antigen-specific memory B cells are IgG(+) and represent up to 2% of circulating IgG(+) B cells. Furthermore, these results confirm that vaccine-elicited memory B cells reside in the CD27(+) B cell population. This ELISPOT-based system has been designed in a generalized manner, such that the assay can be rapidly adapted to detect human antigen-specific memory B cells of any given specificity. This method should be useful for quantitatively assessing the potency of vaccines and the longevity of B cell immunological memory to various vaccines or infectious diseases.

Anthrax Vaccines↗

PubMedDate not supplied

Verbal memory performance of patients with a first depressive episode and patients with unipolar and bipolar recurrent depression.

Depression is usually associated with episodic memory impairment. The main clinical features of depression associated with that memory impairment are not clearly defined. The main goal of that study was to assess the role of the diagnostic subtypes and the number of depressive episodes on the memory performance of acute unipolar (UP) and bipolar (BP) depressed patients.Twenty-three patients with a first major depressive episode (FE), 28 patients meeting DSM-IV criteria for UP recurrent depression (UR) and 18 BP patients with recurrent depression were compared with 88 healthy subjects on a verbal episodic memory task. Patients suffering from a first depressive episode did not show verbal memory impairment as compared to normal controls. Unlike FE patients, UR and BP patients exhibited verbal memory deficits with impaired free recall and normal cued recall and recognition. The memory deficits of the UR and BP patients was present in the first free recall trial. Depressed patients improved their memory performance across the three trials of the task at the same rate than normal controls. Our results suggest that the number of depressive episodes has a negative influence on verbal memory performance of acute depressed patients. The effects of the repetition of the depressive episodes are not modulated by the subtypes of depression and may reflect sensitization to the cognitive impact of depression associated with increasing prefrontal dysfunction.

Adult↗

PubMed2005

The influence of NMDA receptor agonist and antagonist on morphine state-dependent memory of passive avoidance in mice.

The measurement of step-down latency in passive avoidance has been used to study memory in laboratory animals. The pre-training injection of 5 mg/kg morphine impaired memory, which was restored when 24 h later the same dose of the drug was administered. To explore the possible involvement of NMDA modulators on morphine-induced memory impairment, we have investigated the effects of intracerebroventricular (i.c.v.) administration of NMDA and the competitive NMDA antagonist, DL-AP5, on morphine-induced memory impairment or recall, on the test day. Morphine (5 mg/kg, s.c.) was administered 30 min before training to induce impairment of memory and 24 h later, 30 min before test to improve it. Pre-test administration of NMDA (0.00001, 0.0001 and 0.001 microg/mouse, i.c.v.) did not alter the retention latency compared to the saline-treated animals. But restored the memory impairment induced by pre-training morphine (5 mg/kg, s.c.). Pre-test administration of DL-AP5 (1, 3.2 and 10 microg/mouse, i.c.v.) by itself decreased the retention latencies. The same doses of DL-AP5 increased pre-training morphine-induced memory impairment. Co-administration of NMDA (0.0001 and 0.001 microg/mouse, i.c.v.) and morphine (5 mg/kg, s.c.) on the test day increased morphine memory improvement. Conversely, DL-AP5 (1, 3.2 and 10 microg/mouse, i.c.v.) inhibited morphine-induced memory recall. It is concluded that NMDA receptors may be involved, at least in part, in morphine state-dependent learning in mice.

2-Amino-5-phosphonovalerate↗

PubMed2004

Episodic memory and the hippocampus: another view.

A popular view of the function of the hippocampus maintains that this structure temporarily encodes the neocortical representation of the experience of an episode. It uses the encoding to recreate repeatedly the neocortical representation. It is said that in time the episodic memory becomes consolidated in the neocortex and can be retrieved independent of the hippocampus. This paper is critical of that view and begins by raising four concerns. These include a question of how the hippocampus could encode the rich complexity of neocortical representations in sufficient detail to recreate them. And it observes that some data indicate episodic memories remain dependent on the hippocampus for life. Another view of hippocampal function is presented which addresses these concerns. Basically, this view hypothesizes that the ability to retrieve episodic memories involves the interplay between two modes of hippocampal function. Processes during the theta mode facilitate the development of context memory in the hippocampus and the registration of unique events in the neocortex, but block the influence of context memory upon the neocortex. By contrast, during the non-theta mode, context memory is projected onto the neocortex, creating a contextual framework. It is proposed that the ability to retrieve memory of episodes depends on the development, through contiguity, of associations between the representation of the episode (created during theta) and a contextual framework (evoked during non-theta). From this perspective, the episode does not need to be encoded in the hippocampus, but remains dependent indefinitely on associations formed between the episodic memory in the neocortex and a context memory maintained in hippocampal structures. However, for the associations that enable retrieval to form, the creation of the representation of an episode during theta must be followed quickly by the evocation of a contextual framework. During an extended period of the theta mode as occurs during REM sleep dreaming, these associations cannot usually be formed, resulting in amnesia for most dreams.

Animals↗

PubMed2005

REM sleep and the development of context memory.

The paper proposes that REM sleep exists to promote the development of a special form of memory. This memory is a composite of many specific experiences in a particular environment. When it is subsequently invoked, it creates a contextual framework, thus it may be called context memory. The development of this kind of memory during waking is limited by the need to focus on salient or relevant experiences and restrict the processing of others. These restrictions include mechanisms that support orienting responses and selective attention to what is relevant. It is argued that during REM sleep, the reduction of noradrenergic activity undermines the restrictive effects of orienting and reduction of frontal lobe activity undermines bias toward relevant events. When their reduction is combined with a high level of cholinergic activity, many recent and associated memories may be activated and merged together, giving rise to some of the bizarre events experienced in dreams. Patterns of their activation can be transmitted to the hippocampus where they become integrated to form context memory. From this perspective, the need for REM sleep is greatest when the individual is most lacking in context memory at the beginning of life, although innate structures in precocious infants may lessen their reliance on the acquisition of context memory. Later in life, the need for REM may increase temporarily if the subject encounters a novel environment and is unprepared to meet its demands. However, REM sleep may also become unadaptive when it begins to perpetuate a context memory that has become infused with negative emotions experienced during depression.

Hippocampus↗

PubMed2005

Neurocognitive correlates of incidental verbal memory encoding: a magnetoencephalographic (MEG) study.

In our current study, we applied whole head magnetoencephalography (MEG) in a subsequent memory paradigm. Magnetic fields were recorded while 20 healthy subjects (10 females, 10 males) incidentally encoded words during semantic and structural verbal processing tasks. Physiological data were then sorted according to the performance in subsequent memory tests and according to levels of processing, respectively, and analyzed for gender effects. Behavioral results show a clear advantage of semantic processing over structural processing with respect to retrieval success for both females and males. Despite alikeness of behavioral data, MEG results show considerable differences between males and females concerning both subsequent memory effects and levels of processing effects. For male subjects, we identified more distinct magnetic fields in anterior regions for subsequently remembered than for subsequently forgotten words (latency range from 300-650 ms after word onset) and for semantic processing than for structural processing, respectively. For female subjects, corresponding magnetic field differences pointed to posterior regions (subsequent memory effects from 450 ms to 750 ms after word onset). No qualitative differences were observed between subsequent memory effects during semantic processing compared to subsequent memory effects during structural processing. We try to reconcile results from male data with previous findings concerning subsequent memory effects by proposing the concept of width of processing, which holds that incidental memory formation is mediated by frontal activity on a physiological level and brought forward on a cognitive level by enhanced associating imposed by the task demands of semantic processing. Female data cannot be fully incorporated in this framework, but all the more prompt further gender-specific analyses of subsequent memory effects.

Adult↗

PubMed2007

Sequential use of mushroom body neuron subsets during drosophila odor memory processing.

Drosophila mushroom bodies (MB) are bilaterally symmetric multilobed brain structures required for olfactory memory. Previous studies suggested that neurotransmission from MB neurons is only required for memory retrieval. Our unexpected observation that Dorsal Paired Medial (DPM) neurons, which project only to MB neurons, are required during memory storage but not during acquisition or retrieval, led us to revisit the role of MB neurons in memory processing. We show that neurotransmission from the alpha'beta' subset of MB neurons is required to acquire and stabilize aversive and appetitive odor memory, but is dispensable during memory retrieval. In contrast, neurotransmission from MB alphabeta neurons is only required for memory retrieval. These data suggest a dynamic requirement for the different subsets of MB neurons in memory and are consistent with the notion that recurrent activity in an MB alpha'beta' neuron-DPM neuron loop is required to stabilize memories formed in the MB alphabeta neurons.

Animals↗

PubMed2005

Working memory, psychiatric symptoms, and academic performance at school.

Previous studies of the relationship among working memory function, academic performance, and behavior in children have focused mainly on clinical populations. In the present study, the associations of the performance in audio- and visuospatial working memory tasks to teacher reported academic achievement and psychiatric symptoms were evaluated in a sample of fifty-five 6-13-year-old school children. Working memory function was measured by visual and auditory n-back tasks. Information on incorrect responses, reaction times, and multiple and missed responses were collected during the tasks. The children's academic performance and behavioral and emotional status were evaluated by the Teacher Report Form. The results showed that good spatial working memory performance was associated with academic success at school. Children with low working memory performance, especially audiospatial memory, were reported to have more academic and attentional/behavioral difficulties at school than children with good working memory performance. An increased number of multiple and missed responses in the auditory and visual tasks was associated with teacher reported attentional/behavioral problems and in visual tasks with teacher reported anxiety/depressive symptoms. The results suggest that working memory deficits may underlie some learning difficulties and behavioral problems related to impulsivity, difficulties in concentration, and hyperactivity. On the other hand, it is possible that anxiety/depressive symptoms affect working memory function, as well as the ability to concentrate, leading to a lower level of academic performance at school.

Adolescent↗

PubMed2006

Rapid induction of specific associative behavioral memory by stimulation of the nucleus basalis in the rat.

Hypothesized circuitry enabling behavioral memory formation can be tested by its direct activation in the absence of normal experience. Neuromodulation via the cortical release of acetylcholine by the nucleus basalis (NB) is hypothesized to be sufficient to induce specific, associative behavioral memory. Previously, we found that tone paired with stimulation of the nucleus basalis (NBs) for 3000 trials over 15 days induced such memory, supporting the hypothesis. However, as standard associative memory can be established much more rapidly, we asked whether NB-induced memory develops rapidly. Adult male Sprague-Dawley rats, trained and tested in the same calm, waking state, were divided into Paired (n=5) and control (n=4) groups, each of which received a single session of 200 trials of an 8.0 kHz conditioned stimulus (CS) either paired with NBs or with unpaired presentation of NBs. Respiration, cardiac activity, and evoked potentials in the primary auditory cortex (ACx) were recorded. Memory and its degree of specificity were assessed 24 h later by presenting tones of various frequencies (1-15 kHz) in the absence of NBs to yield behavioral frequency generalization gradients. Behavioral responses to test tones consisted of interruption of ongoing respiration and changes in heart rate. Post-training behavioral generalization gradients exhibited response peaks centered on the CS frequency for the Paired group alone. Tone evoked potentials from the ACx also developed CS-specific plasticity. The findings indicate that NB induction of specific behavioral associative memory, like normal memory, can develop rapidly and is accompanied by specific cortical plasticity, supporting the view that NB engagement during normal learning produces memory.

Acoustic Stimulation↗

PubMed2004

Effects of NMDA receptor antagonists on olfactory learning and memory in the honeybee (Apis mellifera).

In contrast to vertebrates the involvement of glutamate and N-methyl-D-aspartate (NMDA) receptors in brain functions in insects is both poorly understood and somewhat controversial. Here, we have examined the behavioural effects of two noncompetitive NMDA receptor antagonists, memantine (low affinity) and MK-801 (high affinity), on learning and memory in honeybees (Apis mellifera) using the olfactory conditioning of the proboscis extension reflex (PER). We induced memory deficit by injecting harnessed individuals with a glutamate transporter inhibitor, L-trans-2,4-PDC (L-trans-2,4-pyrrolidine dicarboxylate), that impairs long-term (24 h), but not short-term (1 h), memory in honeybees. We show that L-trans-2,4-PDC-induced amnesia is 'rescued' by memantine injected either before training, or before testing, suggesting that memantine restores memory recall rather than memory formation or storage. When injected alone memantine has a mild facilitating effect on memory. The effects of MK-801 are similar to those of L-trans-2,4-PDC. Both pretraining and pretesting injections lead to an impairment of long-term (24 h) memory, but have no effect on short-term (1 h) memory of an olfactory task. The implications of our results for memory processes in the honeybee are discussed.

Animals↗

PubMed2004

Early administration of nicotinamide prevents learning and memory impairment in mice induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine.

BACKGROUND AND PURPOSE: NAD has been reported to improve the dementia of the Alzheimer type or sensory register, short- and long-term memory loss in the aged. Although nicotinamide has been confirmed to decrease infarct volumes and neurological deficit findings in several animal stroke models, it is not clear whether its neuroprotective effects can prevent memory damage sequelae. METHODS: We have addressed this topic by designing two behavioral paradigms. A memory impairment and cognitive change model was used in mice following 1-methyl-4-phenyl-l, 2, 3, 6-tetrahydropyridine (MPTP) exposure. Step-down and step-through tests were performed to examine the effects of nicotinamide on learning and memory impairment. RESULTS: It was found that the early administration of nicotinamide (2 h after the injection of MPTP) could decrease error numbers, lessen stimulation time and prolong residence duration on the safety platform in the step-down test. Delayed administration of nicotinamide resulted in decreased effects. Similar results were found in the step-through test. Nicotinamide administrated 12 h after the induction of a memory-impairment model still exerted its effects on memory dysfunction. CONCLUSIONS: The injection of MPTP can cause a loss of brain functions including learning and memory. Learning and memory dysfunction probably occurs secondary to damage to arterioles and dopaminergic neurons by MPTP. By inhibiting oxidative stress, increasing NAD synthesis and ATP production and inhibiting poly (ADP-ribose) polymerase, nicotinamide is known to rescue the still viable, but injured, cells. This rescue process may partially restore learning and memory.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2005

Abnormal frontal and parietal activity during working memory updating in post-traumatic stress disorder.

This study used event-related potentials (ERPs) to investigate the timing and scalp topography of working memory in post-traumatic stress disorder (PTSD). This study was designed to investigate ERPs associated with a specific working memory updating process. ERPs were recorded from 10 patients and 10 controls during two visual tasks where (a) targets were a specific word or (b) targets were consecutive matching words. In the first task, nontarget words are not retained in working memory. In the second task, as in delay-match-to-sample tasks, a non-target word defines a new target identity, so these words are retained in working memory. This working memory updating process was related to large positive ERPs over frontal and parietal areas at 400-800 ms, which were smaller in PTSD. Estimation of cortical source activity indicated abnormal patterns of frontal and parietal activity in PTSD, which were also observed in regional cerebral blood flow [Clark, C.R., McFarlane, A.C., Morris, P., Weber, D.L., Sonkkilla, C., Shaw, M., Marcina, J., Tochon-Danguy, H., Egan, G., 2003. Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study. Biological Psychiatry 53, 474-481]. Frontal and parietal cortex are known to be involved in distributed networks for working memory processes, interacting with medial temporal areas during episodic memory processes. Abnormal function in these brain networks helps to explain everyday concentration and memory difficulties in PTSD.

Brain Mapping↗

PubMed2004

Long-term subjective memory function in ventricular fibrillation out-of-hospital cardiac arrest survivors resuscitated by early defibrillation.

BACKGROUND: Brain injury after a cardiac arrest remains a major cause of morbidity. Programs focusing on early defibrillation have yielded improved survival of patients after hospital discharge following ventricular fibrillation (VF) out-of-hospital cardiac arrest (OHCA). Early defibrillation that promptly restores a circulating rhythm should decrease the hypoxic period and subsequent organ injury. Therefore this study was designed to determine if long-term memory complaints persist in VF OHCA survivors resuscitated in an early defibrillation program when compared with a healthy control population not experiencing cardiac arrest. METHODS: All patients with an OHCA between November 1990 and January 2001 who received defibrillation by emergency medical services personnel in Olmsted County, MN, USA, were included. The memory function questionnaire (MFQ), a 64-item, 7-point Likert-scaled instrument to evaluate the perception of everyday memory functioning was sent to all survivors. The MFQ comprises four scales: general frequency of forgetting (rates general forgetting), retrospective functioning (compares current memory with past ability), seriousness of forgetting (rates how memory impairment impacts daily life), and mnemonics usage (measures adaptation). The MFQ is scaled so that high scores reflect less severe memory complaints. The comparison population comprised members of the Mayo Older Americans Normative Studies (MOANS) cohort. Quality of life was ascertained with a short form (SF)-36 survey. RESULTS: Seventy-nine of the 200 VF OHCA patients (40%) were discharged. Twenty-two patients have died since dismissal, with an overall average length of follow-up of 4.9+/-3.0 years. Thirty-eight (67%) of the survivors completed the MFQ. Compared with the normal, there was a significant decrease in the general frequency of forgetting score of 144.2+/-37.4 versus 168.1+/-27.3 ( P<0.001) and the seriousness of forgetting score of 84.8 +/-26.7 versus 95.2+/-19.7 (P=0.004). The retrospective function-scale scores were not significantly different ( 18.4+/-6.8 versus 18.7+/- 5.0 (P=0.74). Younger patients (lesser than 65 years of age) reported an increase in general forgetting and the seriousness of forgetting compared with older survivors. A comparison with SF-36 scores suggested an association between general forgetting and decreased vitality (P=0.03) and the seriousness of forgetting with a decreased general health (P=0.005), mental health (P=0.009), physical functioning ( P=0.02 ), and vitality ( P=0.05). CONCLUSION: In a cohort of VF OHCA patients, survivors report more memory complaints in comparison with a general healthy older population. There were more long-term-memory complaints in younger patients. Patients with higher long-term quality-of-life score have fewer memory complaints.

Adult↗

PubMed2006

Transient and executive function working memory in schizophrenia.

Transient working memory requires attention and temporary storage of information, whereas executive function working memory requires additional mental manipulation of that information. Working memory impairment is common in schizophrenia patients, but only some studies have found differential impairment in executive function working memory compared to transient working memory. We measured both types of working memory using the Digit Span forward (DF) and backward (DB) tasks in a large sample of schizophrenia patients (n=267) and normal comparison subjects (n=82); in the patients, we also examined associations between performance on the Digit Span tasks and Letter-Number Sequencing (LNS), a putative executive function working memory test. Compared to healthy subjects, the schizophrenia patients showed impairment in the medium effect size range on both DF (d=-0.55) and DB (d=-0.68). DB scores predicted LNS performance, whereas DF scores did not. Worse negative symptoms were associated with worse performance on DF, DB and LNS. These results do not reflect differential executive function working memory dysfunction in schizophrenia, but appear to support transient and executive function working memory as separable constructs.

Adult↗

PubMed2006

Hippocampal memory function as reflected by the intracarotid sodium methohexital Wada test.

The intracarotid amobarbital procedure (IAP) determines lateralization of memory function for predicting the risk of amnesia after epilepsy surgery. Shortages of amobarbital led to its substitution with sodium methohexital in the intracarotid methohexital procedure (IMP). We compared IAP scores (32 patients) with IMP scores (20 patients). Wada ipsilateral and contralateral memory scores were analyzed and compared, as was the relationship of these scores to the results of standard neuropsychological memory tests. There was no significant difference in Wada contralateral memory scores (first injection) between the IAP and IMP. Differences between the IAP and IMP in memory scores for the hemisphere ipsilateral to the epileptogenic focus (second injection) were significant (P=0.01), patients who underwent the IMP manifesting a higher ipsilateral memory reserve. IAP scores related better to standard neuropsychological memory test scores than did IMP scores. The anesthetic drug used in Wada testing may affect lateralized memory assessment and prediction of postsurgical memory changes.

Adolescent↗

PubMed1999

Memory bias in obsessive-compulsive disorder (OCD).

There is a memory bias associated with depression, and good reason to expect a memory bias associated with anxiety. However, the results of studies reported to date have been ambiguous. Accordingly, an experiment was conducted to assess memory for contamination in people with different types of anxiety. Memory for contaminated stimuli among participants who met DSM-IV criteria for obsessive-compulsive disorder (OCD) and indicated a fear of contamination (n = 10) was compared to memory in a group of anxious controls (n = 10), and in undergraduate students (n = 20). Participants were shown 50 objects, 25 of which were contaminated by the experimenter and 25 which were touched but not contaminated. They then completed a neuropsychological memory assessment, after which the participants were asked to recall all of the objects touched by the experimenter. They were then asked to approach each object and to rate their anxiety about touching it. Finally, participants were asked about their perceptions of the cleanliness of each object. The OCD group had better memory for contaminated objects than for clean ones. Neither control group showed such a bias. Neuropsychological test scores indicated that this bias is not the result of differences in general memory ability. The results are discussed in terms of the memory-deficit theory of OCD and of behavioural and cognitive approaches to understanding the role of information processing in fear and anxiety.

Adult↗

PubMed2001

Influence of benzodiazepine binding site ligands on fear-conditioned contextual memory.

Eight compounds that bind to the benzodiazepine binding site on the gamma-amino butyric acid(A) (GABA(A)) receptor were assessed for their influence on contextual memory, an aspect of memory affected in various cognitive disorders including Alzheimer's disease. Using a Pavlovian fear-conditioning paradigm, each ligand was evaluated in C57Bl/6 mice in regards to its direct affect on contextual memory and whether the ligand could attenuate scopolamine-induced contextual memory impairment. Of the eight ligands tested, one impaired contextual memory (agonist), six attenuated scopolamine-induced contextual memory impairment (inverse agonists), and one antagonized the ability of an inverse agonist to attenuate scopolamine-induced contextual memory impairment. Hence, further demonstrating the bi-directional influence benzodiazepine binding site ligands are able to exert on memory modulation. This study serves as an initial starting point in the development of pharmacological tools to be used in deciphering how GABA(A) receptors influence contextual memory.

Animals↗