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PubMed2000

Cognitive factors and cochlear implants: some thoughts on perception, learning, and memory in speech perception.

Over the past few years, there has been increased interest in studying some of the cognitive factors that affect speech perception performance of cochlear implant patients. In this paper, I provide a brief theoretical overview of the fundamental assumptions of the information-processing approach to cognition and discuss the role of perception, learning, and memory in speech perception and spoken language processing. The information-processing framework provides researchers and clinicians with a new way to understand the time-course of perceptual and cognitive development and the relations between perception and production of spoken language. Directions for future research using this approach are discussed including the study of individual differences, predicting success with a cochlear implant from a set of cognitive measures of performance and developing new intervention strategies.

Child↗
PubMed2000

GABA and muscimol as reversible inactivation tools in learning and memory.

Reversible inactivation of brain areas is a useful method for inferring brain-behavior relationships. Infusion of GABA or of the GABA receptor agonist muscimol is considered one interesting reversible inactivation method because it may not affect fibers of passage and may therefore be compared to axon-sparing types of lesions. This article reviews the data obtained with this method in learning and memory experiments. A critical analysis of data, collected in collaboration with Simon Brailowsky, with chronic GABA infusion is presented, together with an illustration of data obtained with muscimol-induced inactivation.

Animals↗
PubMed1984

Dose-response analysis of the behavioral effects of diazepam: I. Learning and memory.

A total of 120 healthy volunteers were randomly assigned to four treatments (placebo, 0.1, 0.2, and 0.3 mg/kg) and three testing times (7 AM, 1 PM and 7 PM). Immediate and delayed free recall of word lists revealed consistent decreases in performance as oral diazepam dose increased from 0.1, 0.2, to 0.3 mg/kg. Paradoxically, as the dose increased, the number of predrug list words recalled also increased. A serial number-learning task displayed a pattern of delayed improvement of acquisition as the dose increased. Response times in a semantic-categories task were prolonged as the dose increased. Parallel recovery functions were observed for all doses and tasks. Full recovery after a single administration of 0.1, 0.2, and 0.3 mg/kg doses was estimated to occur after 3.5, 4.5, and 5.5 h, respectively. Several analyses were consistent with the view that acquisition and not retrieval was impaired by diazepam. There were no circadian interactions with the effects of the drug.

Adolescent↗
PubMed1993

Prevention of soman-induced cognitive deficits by pretreatment with human butyrylcholinesterase in rats.

This study examined the ability of pretreatment with human serum butyrylcholinesterase (HuBChE) to prevent soman-induced cognitive impairments. Behavioral testing was carried out using the Morris water maze task evaluating learning, memory, and reversal learning processes. Pretreatment with HuBChE significantly prevented the memory and reversal learning impairments induced by soman. A small deficiency in performance was observed only during part of the learning period in HuBChE-treated rats after administration of soman. Results support the contention that pretreatment alone with HuBChE is sufficient to increase survival and to prevent impairment in cognitive functioning following exposure to soman.

Animals↗
PubMed1991

Effects of MK-801 on learning and memory as assessed using a novel water maze.

The effects of the NMDA receptor antagonist MK-801 [(+)-10,11-dihydro-5-methyl-5H-dibenzo [a,d]-cyclohepten-5,10 imine hydrogen maleate] on learning and memory were assessed using a water maze. The maze was a traditional type of maze with alleys and choices between various paths, but set inside a pool of water to a height of 25 cm. Different mazes could be configured by altering the arrangement of open vs. closed doors. Both the time required to reach an out-of-the-water exit platform and the errors made during the swim from start to finish were recorded. Learning was assessed during the first 10 to 20 trials in a new maze configuration, while memory was tested after the maze was well learned. Three experiments, some with several phases, were performed. These experiments compared the effects of 0.1 mg/kg of either (+)-MK-801, or (-)-MK-801 vs. saline on learning new maze configurations as well as swimming well-learned mazes. Neither of the MK-801 isomers impaired performance of a previously learned maze. (+)-MK-801 clearly slowed learning of new mazes as measured by both maze completion time and errors committed, while (-)-MK-801 had a significant but smaller effect on learning. Rats given (+)- or (-)-MK-801 (0.1 mg/kg) for 16 days while learning one maze and then challenged to learn a new maze without drug administration performed no differently on the new maze than controls, suggesting that the acute effect of MK-801 on learning is not long lasting.

Animals↗
PubMed1998

Alleviation of x-irradiation-based deficit in memory-based learning by D-amphetamine: suggestions for attention deficit-hyperactivity disorder.

Selective exposure to x-irradiation during infancy, from postnatal days (PND) 2-11 in the rat, results in severe hippocampal granule cell hypoplasia. Preweanling (PND 17-18) rats, which suffer such hippocampal granule-cell agenesis, show deficits in patterned single alternation (PSA), a form of memory-based learning. Deficits in short-term memory along with increased arousal have been suggested as characteristic of children diagnosed with attention deficit-hyperactivity disorder (ADHD). We report here on the ameliorating effects of D-amphetamine, a drug commonly used in the treatment of ADHD, before Ritalin, on PSA, after infantile (PND 2-15) exposure to x-irradiation. After i.p. injections of 0.3 mg/kg D-amphetamine, the onset and magnitude of the PSA memory-based discrimination in the x-irradiated preweanling rats was restored to about the level of controls. These results, showing alleviation of x-irradiation-related deficits in short-term memory by D-amphetamine injections, along with our earlier and present results, showing substantial deficits after x-irradiation alone, encourage the hypothesis that hippocampal granule-cell hypoplasia, which would occur in humans prenatally and is Altman's model of "minimal brain dysfunction" [Altman, J. (1986) in Learning Disabilities and Prenatal Risk, ed. Lewis, M. (Univ. of Illinois Press, Urbana), pp. 241-304], may be a factor in at least some forms of ADHD and may provide a basis for an animal model of the disease.

Animals↗
PubMed1993

Effect of 20(S)-ginsenoside-Rg2 and cyproheptadine on two-way active avoidance learning and memory in rats.

The effects of 20(S)-ginsenoside-Rg2 (GRg2, CAS 52286-74-5) and cyproheptadine (CYP, CAS 129-03-3) on acquisition, retention and retrieval were examined in male Wistar rats using a two-way active avoidance method. Learning and memory were estimated by the avoidance rate (%) and/or latency (s). Acute administration of CYP 1.0 mg/kg i.p. 30 min prior to training produced a significant impairment in acquisition of 3 d learning and 48 h memory by decreasing the rate from 87.9 +/- 2.1, 75.8 +/- 4.9 in saline rats to 55.8 +/- 9.6, 53.4 +/- 8.4, respectively (F(1,14) = 10.7, 14.8, p < 0.01). The CYP administration immediately following the end of training and 30 min before testing produced the impairments in retention of 24 h memory and in retrieval of 48 h memory by decreasing the rate from 86.7 +/- 1.7, 93.3 +/- 2.7 to 55.0 +/- 5.5, 60.0 +/- 6.8, respectively (F(1,12) = 27.2, 10.5, p < 0.01). Repeated administration of GRg2 20 mg/kg i.p. significantly improved the CYP-induced recognitional deficits by increasing the CYP-decreased rate from 55.8 +/- 9.6 to 80.8 +/- 4.2 in d 3 learning acquisition (F(1,14) = 5.6, p < 0.05), from 53.4 +/- 8.4 to 60.0 +/- 8.2 in 48 h memory acquisition (F(1,14) = 7.5, p < 0.05) and from 55.0 +/- 5.5 to 88.3 +/- 2.5 in 24 h memory retention (F(1,12) 27.5, p < 0.01) as well as from 60.0 +/- 6.8 to 85.6 +/- 6.9 in 48 h memory retrieval (F(1,12) = 5.2, p < 0.05), respectively. The results also provide the suggestive evidence that central serotonin may play a positive modulatory role in the acquisition, retention and retrieval of two-way active avoidance responding in rats.

Animals↗
PubMed2005

Diffusion tensor imaging in chronic head injury survivors: correlations with learning and memory indices.

Diffusion tensor imaging (DTI) provides a unique insight into the cellular integrity of the brain. While conventional magnetic resonance imaging underestimates the extent of pathology following closed head injury, diffusion-weighted imaging has been shown to more accurately delineate the extent of cerebral damage. There have only been a few case studies of DTI in chronic head injury survivors. This study used DTI to investigate changes in anisotropy and diffusivity in survivors of head injury at least 6 months after their injury. The relationship between cognition and diffusion abnormality was also investigated. The voxel-based analysis revealed significant bilateral decreases in anisotropy, in major white matter tracts and association fibers in the temporal, frontal, parietal and occipital lobes. Statistically significant increases in diffusivity were also found in widespread areas of the cortex. A significant positive correlation was found between diffusivity and impairment of learning and memory in the left posterior cingulate, left hippocampal formation and left temporal, frontal and occipital cortex. The common pattern of abnormality despite heterogeneous injury mechanism and lesion location in the group suggests that these cellular changes reflect secondary insults. The importance of diffusion abnormalities in head injury outcome is emphasized by the significant correlation between a learning and memory index and diffusivity in areas known to subserve this cognitive function.

Adolescent↗
PubMed1990

Effect of clonazepam on brain development of mice.

Twenty-seven Kun-Ming white mice were divided randomly into three groups of 9 animals. One of these groups served as a control group. Clonazepam (CZP), 0.1 or 0.5 mg/kg/day, was administered by oral gavage for 22 days. The water-maze test was performed before giving CZP and 10 and 22 days later. The step-down test was performed on the 1st and the 2nd day after discontinuing CZP treatment to determine toxic effects on brain development and learning-memory function. Body weights and brain weight were also recorded. Brain development and learning-memory function, evaluated by water-maze and step-down tests, were not impaired by CZP. Although there was a trend toward lower weights in the higher-dose group, CZP treatment did not significantly affect either body weight or total or regional brain weight. The results of this study indicate that 4 weeks of treatment with CZP does not impair brain development and learning-memory function in baby mice.

Administration, Oral↗
PubMed1998

[The effect of NC-1900: its ameliorating effects on impairments of learning and memory in the CA1 neurons and its intracellular signal transduction pathways].

Effects of arginine vasopressin (AVP(1-9)) and its analogues on the glycine (Gly)-induced Cl- currents (IGly) were examined in acutely dissociated rat hippocampal CA1 neurons using nystatin perforated and conventional whole-cell patch recording modes under voltage-clamp conditions. The results suggest that the activation of V1 receptor induces IP3 production which release Ca2+ from IP3-sensitive Ca2+ storage sites. The Ca2+ binds to CaM, resulting in the activation of Ca2+/CaM-sensitive adenylate cyclases. Consequently, the activation of PKA inhibits IGly. The inhibitory actions of NC-1900 and its analogues on IGly might be involved in their ameliorating effects on impairments of learning and memory in the CA1 neurons.

Animals↗
PubMed2000

Molecular overexpression of extracellular superoxide dismutase increases the dependency of learning and memory performance on motivational state.

Extracellular superoxide dismutase (EC-SOD) controls the availability of extracellular superoxide and appears to play a role in controlling intercellular signaling. In this role EC-SOD can have potent effects on neurobehavioral function. In previous studies, we have found that either over- or under-expression of EC-SOD in mice significantly impairs spatial learning on the radial-arm maze. In the current study, the neurobehavioral nature of the EC-SOD role in cognitive function was determined. EC-SOD overexpression altered the relationship between both learning and memory with motivational state. Mice were tested in the radial-arm maze under a high motivational state (22-24 hours of food restriction) or a low motivational state (4-6 hours of food restriction). Under a high motivational state, the EC-SOD overexpressing mice were able to learn in the radial-arm maze, albeit at a slightly lower rate than wild-type controls. This contrasts with the failure to learn by EC-SOD overexpressing mice in our previous study conducted with the low motivational state. The change in motivational state did not significantly alter the learning rate of controls. Similarly, during postacquisition memory phase of testing, the EC-SOD overexpressing mice were significantly worse than controls when tested in a low motivational state but not under a high motivation state. As with learning, motivational state did not significantly affect memory performance in controls. This study shows that mice with EC-SOD overexpression are not incapable of learning and memory in the radial-arm maze, but that the mechanisms which allow control animals to perform this task well under low motivational states are deficient in the mice with EC-SOD overexpression.

Animals↗
PubMed2005

Loss of forebrain cholinergic neurons and impairment in spatial learning and memory in LHX7-deficient mice.

The identification of the genetic determinants specifying neuronal networks in the mammalian brain is crucial for the understanding of the molecular and cellular mechanisms that ultimately control cognitive functions. Here we have generated a targeted allele of the LIM-homeodomain-encoding gene Lhx7 by replacing exons 3-5 with a LacZ reporter. In heterozygous animals, which are healthy, fertile and have no apparent cellular deficit in the forebrain, b-galactosidase activity reproduces the pattern of expression of the wild-type Lhx7 locus. However, homozygous mutant mice show severe deficits in forebrain cholinergic neurons (FCNs), while other classes of forebrain neurons appear unaffected. Using the LacZ reporter as a marker, we show that in LHX7-deficient mice FCN progenitors survive but fail to generate cholinergic interneurons in the striatum and cholinergic projection neurons in the basal forebrain. Analysis of behaviour in a series of spatial and non-spatial learning and memory tasks revealed that FCN ablation in Lhx7 mutants is associated with severe deficits in spatial but only mild impairment of non-spatial learning and memory. In addition, we found no deficit in long-term potentiation in mutant animals, suggesting that FCNs modulate hippocampal function independently of its capacity to store information. Overall our experiments demonstrate that Lhx7 expression is required for the specification or differentiation of cholinergic forebrain neurons involved in the processing of spatial information.

Acetylcholine↗
PubMed1998

Verbal learning and memory in alcohol abusers and polysubstance abusers with concurrent alcohol abuse.

To define the combined effects of drug and alcohol abuse on verbal learning and memory, 70 alcoholic and 80 polysubstance abuse (PSA) individuals with concurrent alcohol abuse were compared on a list learning task, the California Verbal Learning Test (CVLT). Despite demonstrating similar learning strategies, response styles, and error patterns, the PSA group nontheless exhibited significantly greater recall deficits than the alcoholic group on the CVLT. These deficits were particularly evident in those who were heaviest abusers of cocaine. PSA participants did not, however, evidence greater recognition memory deficits. This pattern of greater deficits on recall than on recognition memory, as well as poor consolidation, is consistent with the initiation-retrieval difficulties of patient groups with subcortical dysfunction. It is concluded that the combined use of alcohol and drugs, cocaine in particular, may compound memory difficulties beyond what is typically observed in alcoholic individuals.

Adult↗
PubMed2006

Sleep-dependent consolidation of contextual learning.

Memory consolidation is facilitated by sleep. Specifying the functional domain of sleep-dependent consolidation (SDC) is important for identifying the neural mechanisms underlying this phenomenon. Previous work indicates that SDC may be limited to conditions in which learning is explicit. In the present study, we tested the hypothesis that SDC may also occur with implicit learning when learning benefits from the formation of contextual associations, a function associated with the hippocampus. Three versions of the serial-reaction-time task (SRTT) were examined, and SDC was assessed by comparing performance after 12 hr breaks that included or did not include sleep. SDC was observed in the Explicit condition. Two implicit conditions were compared. In the Implicit Noncontextual condition, participants performed a concurrent tone-counting task with the pitch of each tone selected at random, precluding cross-dimensional associations. In the Implicit Contextual condition, participants responded to the color of the cues while the spatial location of the cues followed a correlated sequence. Whereas learning was observed in both implicit conditions, SDC was restricted to the contextual condition. Given that the formation of contextual associations is dependent on the hippocampus, we suggest that SDC is a hippocampus-mediated process.

Awareness↗
PubMed2005

Centella asiatica treatment during postnatal period enhances learning and memory in mice.

Present investigation was planned to evaluate the nootropic effect of Centella asiatica. Three months old male Swiss albino mice were injected orally with graded doses (200, 500, 700, 1000 mg/kg body weight) of C. asiatica aqueous extract for 15 days to select an effective dose for nootropic studies. Animals were tested in radial arm maze to assess the learning and memory performance. Based on these results, mice were treated orally with 200 mg/kg of C. asiatica for 15 days from day 15 to day 30 post partum (p.p.) and the nootropic effect was evaluated on the 31st day and 6 months p.p. The behavioral (open field, dark/bright arena, hole board and radial arm maze tests), biochemical (acetylcholine esterase activity) and histological studies (dendritic arborization) were carried out. Performance of juvenile and young adult mice was significantly improved in radial arm maze and hole board tests, but locomotor activity did not show any change compared to control. Treatment resulted in increased acetylcholine esterase activity in the hippocampus. Dendritic arborization of hippocampal CA3 neurons was also increased in terms of intersections and branching points, both at one month and 6 months. Results of the present investigation show that treatment during postnatal developmental stage with C. asiatica extract can influence the neuronal morphology and promote the higher brain function of juvenile and young adult mice.

Age Factors↗
PubMed2006

Over-expression of two different forms of the alpha-secretase ADAM10 affects learning and memory in mice.

Members of the ADAM family (adisintegrin and metalloprotease) are the main candidates for physiologically relevant alpha-secretases. The alpha-secretase cleaves in the non-amyloidogenic pathway the amyloid precursor protein within the region of the Abeta peptides preventing their aggregation in the brain. The increase of alpha-secretase activity in the brain provides a plausible strategy to prevent Abeta formation. Concerning this possibility two transgenic mouse lines (FVB/N) have been created: mice over-expressing the bovine form of the alpha-secretase (ADAM10) and mice over-expressing an inactive form of the alpha-secretase (ADAM10-E348A-HA; ADAM10-dn). For behavioral examination a F1 generation of transgenic mice (C57Bl/6 x FVB/N (tg)) was generated and compared to wild type F1 generation (C57Bl/6 x FVB/N). Behavior was characterized in the following tasks: standard open field, enriched open field, elevated plus-maze, and the Morris water maze hidden platform task. Concerning basal activity, exploration, and anxiety, transgenic mice behaved similar to controls. With respect to learning and memory both transgenic lines showed a significant deficit compared to controls. ADAM10 mice however, showed thigmotaxis with passive floating behavior in the Morris water maze indicating differences in motivation, whereas, ADAM10-dn mice displayed an inconspicuous but limited goal-directed search pattern. Thus variation of the enzymatic activity of alpha-secretase ADAM10 alters learning and memory differentially. Nevertheless, it could be concluded that both, ADAM10 and ADAM10-dn mice are suitable control mice for the assessment of alpha-secretase-related effects in animal models of Alzheimer's disease.

ADAM Proteins↗
PubMed2000

Effects of ACE-inhibitors on learning and memory processes in rats.

INTRODUCTION: Besides their well known effect on systemic blood vessels and heart, ACE inhibitors are supposed to have an effect on CNS by changing the local peptide-protein system. AIM: To study the effect of ACE-inhibitors on learning and memory processes using active and passive avoidance. MATERIAL AND METHODS: Male Wistar rats were used; the animals were divided into 4 groups of 20 animals each. Distilled water (group C), captopril 1.5 mg/kg (group E1), trandolapril 2 mg/daily (group E2), and oxiracetam 0.1 mg/kg (group E3), respectively, were given orally 60 minutes before the test. Active (shuttle box) and passive (step-through) avoidance tests with standard configuration were used. RESULTS: The experimental and control animals increased the number of avoidances during the learning session of the active avoidance test; groups C, E1 and E2 showed no change in the number of escapes and intertrial crossings; in group E3 animals both variables were decreased. In memory retention test the experimental animals increased the number of avoidances in comparison to the controls. No difference was found in the number of escapes and intertrial crossings. In passive avoidance test all animals showed prolonged latencies during the learning session. In the early and late retention test prolonged latencies were found only in the experimental animals. CONCLUSION: The ACE inhibitors captopril and trandolapril improve learning and memory in active and passive avoidance tests comparable to the effect of the nootropic drug oxiracetam.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Effects of vinburnine on experimental models of learning and memory impairments.

Retrograde amnesia can be induced experimentally in mice by injecting them with scopolamine (3 mg/kg, IP) or by inducing seizures with pentylenetetrazol (50 mg/kg, IP), and in rats by subjecting them to hypobaric hypoxia (at a barometric pressure of 300 mmHg for 3 min). We have studied the effects of vinburnine (VNB) in these amnesic states compared to vincamine (VNC) and nicergoline (NCG), in order to assess its activity on drug-induced learning and memory impairments. Vinburnine reduced the disrupting effect of both scopolamine and pentylenetetrazol-induced seizures on the retention of a step-through passive avoidance behavior in mice and on the acquisition of shuttle-box active avoidance behavior in rats. This effect was dose-related up to 20 mg/kg, the peak effect dose after IP administration, and more pronounced than that of VNC and NCG in some tests. These results indicate that VNB influences learning and memory processes disrupted by a pharmacological manipulation. In particular, as scopolamine acts as anticholinergic drug, it is possible that VNB mechanism of action includes also a stimulation of acetylcholine neurotransmission.

Amnesia, Retrograde↗