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PubMed2004

Effects of nicotine and mecamylamine on cognition in rhesus monkeys.

RATIONALE: Nicotine and other agonists of nicotinic cholinergic receptors (nAChR) have been shown to improve performance in specific memory domains in rodents and monkeys. Such beneficial effects are observed in preclinical models of age-related cognitive decline, stimulating interest in nAChR ligands as possible therapeutics. Prior work has typically focused on assays of spatial working memory in rodent studies and visual recognition memory in monkey studies. OBJECTIVE: The current study was conducted to determine the role played by nAChRs in multiple types of memory in monkeys. METHODS: Rhesus monkeys (n=6) were trained to perform a battery of six behavioral tasks and then serially challenged with acute doses of nicotine (3.2-56 microg/kg, i.m.) and the nAChR antagonist mecamylamine (0.32-1.78 mg/kg, i.m.). RESULTS: Nicotine improved performance on tests designed to assay visual recognition memory, spatial working memory and visuo-spatial associative memory, while mecamylamine impaired visuo-spatial associative memory. Ballistic and fine motor performance was not significantly improved by nicotine but fine motor performance was impaired by mecamylamine. CONCLUSIONS: Although nicotine may improve performance in multiple domains, effects on visuo-spatial associative memory is the most specifically attributable to nAChR signaling.

Animals↗
PubMed2006

Signalling mechanisms mediated by the phosphoinositide 3-kinase/Akt cascade in synaptic plasticity and memory in the rat.

The phosphoinositide 3-kinase (PI3K)/Akt signalling cascade has classically been implicated in promoting cell survival but more recently has been shown to regulate a number of other cellular functions. In particular, studies have suggested that PI3K contributes to mechanisms associated with synaptic plasticity and memory processes but the function of this cascade in forms of synaptic plasticity, such as long-term potentiation, remains controversial and the PI3K substrates which mediate these effects are poorly understood. Here we report that the PI3K inhibitor LY294002 infused i.c.v. in vivo blocked maintenance of long-term potentiation induced in the dentate gyrus with a single tetanus to the perforant path but not with repeated tetani. This pattern of stimulation led to rapid and transient phosphorylation of the PI3K substrate Akt at Ser473 but not at Thr308. Functional readout of partial activation of Akt was demonstrated by an increase in phosphorylation of two downstream substrates, Forkhead (FKHR) and mammalian target of rapamycin (mTOR), in a delayed and prolonged manner at Akt-specific phosphorylation sites. LY294002 blocked phosphorylation of Akt and the prolonged phosphorylation of FKHR and mTOR but did not impair long-term potentiation-induced phosphorylation of extracellular receptor kinase. In addition, the same i.c.v. concentration of LY294002 impaired long-term consolidation of recognition memory but not short-term recognition memory or spatial learning and repeated training in the recognition memory task overcame the deficit in consolidation. These results suggest that activation of the PI3K/Akt pathway may contribute to the mechanisms of synaptic plasticity and memory consolidation by promoting cell survival via FKHR and protein synthesis via mTOR. Importantly, only partial activation of Akt at its Ser473 residue was necessary to mediate these effects.

Animals↗
PubMed1997

Effects of scopolamine on delayed-matching-to-sample and paired associates tests of visual memory and learning in human subjects: comparison with diazepam and implications for dementia.

Two experiments examined dose-related effects of 200, 400 and 600 micrograms scopolamine (n = 24, s.c.) and 5 and 10 mg diazepam (n = 6, PO) on parallel tests of visual memory and learning taken from the CANTAB battery. Scopolamine significantly impaired accuracy of performance on a delayed matching to sample test of visual recognition memory in a dose- and delay-dependent manner, but had only marginal decremental effects on a test of visuospatial paired associates learning. Scopolamine significantly lengthened decision times in a visual search matching to sample task at the 400 and 600 micrograms doses, without significantly affecting accuracy. The drug also impaired performance on tests of spatial (on accuracy and response time measures) and pattern (on response time only) memory. Most of the deleterious effects on scopolamine were removed by covariance analyses with indices of subjective sedation, but the effects of delayed matching accuracy and latency remained. By contrast, diazepam significantly impaired paired associates learning but affected delayed matching to sample in a delay-independent manner. These results suggest that scopolamine can produce selective deficits in tests of short-term visual recognition memory which do not depend on overall impairments in arousal and which contrast with deficits in visual associative learning produced by diazepam. They have implications for the pharmacological modelling of dementia and memory disorders in man and for the neurochemical substrates of the short-term recognition memory and associative learning for visual stimuli.

Adult↗
PubMed2001

Semantic memory is impaired in both dementia with Lewy bodies and dementia of Alzheimer's type: a comparative neuropsychological study and literature review.

OBJECTIVE: To test the hypothesis that semantic impairment is present in both patients with dementia with Lewy bodies (DLB) and those with dementia of Alzheimer's type (DAT). METHODS: A comprehensive battery of neuropsychological tasks designed to assess semantic memory, visuoperceptual function, verbal fluency, and recognition memory was given to groups of patients with DLB (n=10), DAT (n=10) matched pairwise for age and mini mental state examination (MMSE), and age matched normal controls (n=15). RESULTS: Both DLB and DAT groups exhibited impaired performance across the range of tasks designed to assess semantic memory. Whereas patients with DAT showed equivalent comprehension of written words and picture stimuli, patients with DLB demonstrated more severe semantic deficits for pictures than words. As in previous studies, patients with DLB but not those with DAT were found to have impaired visuoperceptual functioning. Letter and category fluency were equally reduced for the patients with DLB whereas performance on letter fluency was significantly better in the DAT group. Recognition memory for faces and words was impaired in both groups. CONCLUSIONS: Semantic impairment is not limited to patients with DAT. Patients with DLB exhibit particular problems when required to access meaning from pictures that is most likely to arise from a combination of semantic and visuoperceptual impairments.

Aged↗
PubMed2004

The effect of NMDA-NR2B receptor subunit over-expression on olfactory memory task performance in the mouse.

The N-methyl-D-aspartate (NMDA) receptor in the forebrain is thought to modulate some forms of memory formation, with the NR2B subunit being particularly relevant to this process. Relative to wild-type mice, transgenic animals in which the NR2B subunit was over-expressed demonstrate superior memory in a number of behavioral tasks, including object recognition [Nature 401 (1999) 63]. The purpose of the present study was to explore the generality of such phenomena, interpreted as the effect of increasing NR2B expression on the retention of other types of sensory-related information. To accomplish this, we focused our evaluation on the highly salient sensory modality of olfaction. In the first experiment, mice performed both a novel-object-recognition task identical to that performed by Tang et al. [Nature 401 (1999) 63] and a novel-odor-recognition task analogously constructed. Although the results of the object recognition task were consistent with the previous literature, there was no evidence of an effect of NR2B over-expression on the retention of odor recognition memory in the specific task performed. As it was possible that, unlike object recognition memory, novel odor recognition is not NMDA-receptor-dependent, a second task was designed using the social transmission of food preference paradigm. In contrast to the foregoing olfactory task, there is evidence that the latter procedure is, indeed, NMDA-dependent. The results of the second study demonstrated that transgenic mice with NR2B over-expression had a clear memory advantage in this alternative odor memory paradigm. Taken together, these results suggest the NR2B subunit is an important component in some but not all forms of olfactory memory organization. Moreover, for those functions that are NMDA-receptor-dependent, these data support the growing literature demonstrating the importance of the NR2B subunit.

Animals↗
PubMed2005

Verbal mediation and memory for novel figural designs: a dual interference study.

To the extent that all types of visual stimuli can be verbalized to some degree, verbal mediation is intrinsic in so-called "visual" memory processing. This impurity complicates the interpretation of visual memory performance, particularly in certain neurologically impaired populations (e.g., aphasia). The purpose of this study was to investigate the relative contributions of verbal mediation to recognition memory for visual stimuli that vary with respect to their amenability to being verbalized. In Experiment 1, subjects attempted to verbally describe novel figural designs during presentation and then identify them in a subsequent recognition memory test. Verbalizing these designs facilitated memory. Stimuli that were found to be easiest or most difficult to verbalize at the group level were retained for the second study. In Experiment 2, subjects evidenced superior recognition memory for the relatively easy to verbalize items. This advantage was attenuated in subjects who performed a concurrent verbal interference task during encoding, but not in those who performed an analogous visual interference task. These findings provide evidence that impoverished verbal mediation disproportionately impedes memory for visual material that is relatively easy to verbalize. Implications for the clinical assessment of visual memory are discussed.

Association Learning↗
PubMedDate not supplied

Implicit and explicit measures of memory for perceptual information in young adults, healthy older adults, and patients with Alzheimer's disease.

In this study, we examined how implicit and explicit memory for perceptual information (modality and voice) and lexical information varied across three subject groups: healthy young adults, healthy older adults, and age-matched older adults with dementia of the Alzheimer's type (DAT). These groups exhibited cross-modality (abstract) priming of the same magnitude. However, young adults produced greater modality- and voice-specific priming than the other two groups, whose performance was equivalent, suggesting that aging, but not DAT, reduced form-specific priming. Young adults demonstrated better recognition memory than healthy older adults, who in turn exhibited better recognition memory than older adults with DAT. In young adults, recognition memory was also sensitive to perceptual information. These findings indicate that aging can affect implicit memory for perceptual information, whereas DAT magnifies the effect of aging on explicit memory.

Adult↗
PubMed2001

Histamine H(3)-receptor antagonism improves memory retention and reverses the cognitive deficit induced by scopolamine in a two-trial place recognition task.

Several reports have indicated that, under different experimental conditions, the administration of histamine H(3)-receptor antagonists exerts procognitive effects by activating central histaminergic transmission. In the present study the action of thioperamide, a H(3)-receptor blocker, is investigated on consolidation and recall mechanisms of the rat place recognition memory. The animals have been tested on a two-trial delayed comparison paradigm in a Y-maze. Thioperamide enhances the memory retention when administered intraperitoneally (i.p.) post-acquisition (0.7 and 5.0 mg/kg are ineffective, whereas the dose of 2.0 mg/kg improves memory) but does not affect the rat performance when injected 45 min prior to the testing trial. The post-acquisition effect of thioperamide is time-dependent since the administration of the drug 30 min after the end of the training trial has no effect on memory. In addition, thioperamide reverses the amnesia induced by the post-acquisition treatment with 0.02 mg/kg i.p. of scopolamine (SCOP). The procognitive effect of thioperamide is not modified by the contemporary administration of pyrilamine, an histamine H(1)-receptor antagonist. On the contrary, the blockade of H(2)-receptors by zolantidine 10 mg/kg reverses both the effect of thioperamide alone and the drug action on the scopolamine-induced memory deficit. The results indicate that the neuronal histamine released in consequence of the post-acquisition thioperamide treatment improves place recognition memory through the activation of postsynaptic H(2)-receptors.

Animals↗
PubMed1999

Fractionation of visual memory: evidence from a case with multiple neurodevelopmental impairments.

It is known that the adult visual memory system is fractionable into functionally independent cognitive subsystems, selectively susceptible to brain damage. However, it is unclear whether these cognitive subsystems can fractionate developmentally. The present study describes an investigation of visual memory of a patient (PE) with multiple developmental disorders. PE was congenitally deaf, had Gilles de la Tourette syndrome and autism, with non-verbal ability in the normal range. The patient presented with a recognition memory impairment for unknown human faces. This contrasted with his superior recognition memory for unknown buildings, landscapes and outdoor scenes. PE's memory impairment for faces could not be explained by a general deficit in face processing. Interestingly, PE also showed a recognition memory impairment for animals. These findings indicate that different domains of the visual memory system can be fractionated developmentally. In particular, it demonstrates that topographical memory can develop independently from other aspects of visual memory.

Adult↗
PubMed2001

Components of episodic memory: the contribution of recollection and familiarity.

The examination of recognition memory confidence judgements indicates that there are two separate components or processes underlying episodic memory. A model that accounts for these results is described in which a recollection process and a familiarity process are assumed to contribute to recognition memory performance. Recollection is assumed to reflect a threshold process whereby qualitative information about the study event is retrieved, whereas familiarity reflects a classical signal-detection process whereby items exceeding a familiarity response criterion are accepted as having been studied. Evidence from cognitive, neuropsychological and neuroimaging studies indicate that the model is in agreement with the existing recognition results, and indicate that recollection and familiarity are behaviourally, neurally and phenomenologically distinct memory retrieval processes.

Humans↗
PubMed1994

Effects of breakfast and caffeine on cognitive performance, mood and cardiovascular functioning.

Two experiments examined the effect of breakfast (1.89 MJ) and caffeine (4 mg/kg) on cognitive performance, mood and cardiovascular functioning. In the first experiment, breakfast had no effect on performance of sustained attention tasks, but it increased pulse rate and influenced mood. The mood effects after breakfast differed between a cooked breakfast and a cereal/toast breakfast. In contrast to the effects of breakfast, this relatively high dose of caffeine improved performance of the sustained attention tasks, increased blood pressure and increased mental alertness. In the second experiment, effects of a breakfast and caffeine on mood and cardiovascular functions confirmed the results of the first study. The breakfast improved performance on free recall and recognition memory tasks, had no effect on a semantic memory task and impaired the accuracy of performing a logical reasoning task. In contrast to this, caffeine improved performance on the semantic memory, logical reasoning, free recall and recognition memory tasks. Overall, these results show that breakfast can improve performance in some but not all cognitive tasks and that these changes are very different from those observed after lunch, and those produced by caffeine.

Affect↗
PubMedDate not supplied

Postictal courses of cognitive deficits in focal epilepsies.

Patients with epileptic seizures frequently complain of long-lasting cognitive impairment after a seizure. We evaluated this issue in 31 patients with epileptic seizures of a frontal (n = 8) or temporal lobe origin [right temporal lobe (RTL) n = 8/left temporal lobe (LTL) n = 15]. Seizures were secondarily generalized in 18 patients. Computerized testing of verbal and nonverbal recognition memory was performed before the seizure, directly after postictal reorientation, and 30 min and 1 h later. Repeated testing of 14 healthy persons served as control. The following results were obtained: Depending on seizure generalization, postictal reorientation times were 1-45 min. Frontal lobe seizures showed no effect on postictal memory performances, but verbal and visual recognition memory was significantly decreased after temporal lobe seizures. Decrease in either verbal or visual memory and time of recovery were related to lateralization of seizure onset. Functional recovery after reorientation lasted 30 min to 1 h. The decrease in performance was more severe after generalized seizures. Decision times during memory performance were not significantly affected by the seizures. Temporal lobe seizures lead to circumscribed and long-lasting memory deficits, which can be assumed to affect patients' capabilities seriously. Pre- and postictal testing is a useful tool for determining postictal cognitive impairment and in determining the site of seizure onset.

Adult↗
PubMed2006

Prefrontal-hippocampal coupling during memory processing is modulated by COMT val158met genotype.

BACKGROUND: Studies in humans and in animals have demonstrated that a network of brain regions is involved in performance of declarative and recognition memory tasks. This network includes the hippocampal formation (HF) as well as the ventrolateral prefrontal cortex (VLPFC). Studies in animals have suggested that the relationship between these brain regions is strongly modulated by dopamine. METHODS: Using fMRI in healthy humans matched for a series of demographic and genetic variables, we studied the effect of the COMT val158met polymorphism on function of HF and VLPFC as well as on their functional coupling during recognition memory. RESULTS: The COMT Val allele was associated with: relatively poorer performance at retrieval; reduced recruitment of neuronal resources in HF and increased recruitment in VLPFC during both encoding and retrieval; and unfavorable functional coupling between these two regions at retrieval. Moreover, functional coupling during retrieval was predictive of behavioral accuracy. CONCLUSIONS: These results shed new light on individual differences in responsivity and connectivity between HF and VLPFC related to genetic modulation of dopamine, a mechanism accounting at least in part for individual differences in recognition memory performance.

Adult↗
PubMed2005

A longitudinal investigation of visual event-related potentials in the first year of life.

The goal of the current study was to assess general maturational changes in the ERP in the same sample of infants from 4 to 12 months of age. All participants were tested in two experimental manipulations at each age: a test of facial recognition and one of object recognition. Two sets of analyses were undertaken. First, growth curve modeling with mixed models was used to examine trajectories of development and possible differences in trajectories based on recognition memory (novel versus familiar) and/or stimulus-specific memory (face versus object recognition). Our results suggest that the Pb, Nc and Slow Wave components change significantly in terms of amplitude and latency over the first year of life. Pb amplitude showed a significant non-linear increase over time, whereas Pb latency showed a significant linear decrease over time with a plateau beginning at 10 months. Nc amplitude showed a significant linear decrease over time (i.e. a stronger negative value), whereas Nc latency showed a significant linear decrease over time, with a plateau beginning at 8 months. Second, to relate our findings to those reported in the literature, we examined the effects of memory and stimulus and their combination. Differences between recognition memory and stimulus specific memory were found in the responses to familiar and novel faces and objects for all three components, although the pattern differed across the five ages. These results have implications for future studies that involve the recording of the visual ERP, and point to the advantages of growth curve modeling in examining longitudinal data to account for non-linear development.

Age Factors↗
PubMed2002

Spacing effects in cued-memory tasks for unfamiliar faces and nonwords.

Memory for repeated items improves as the interval between repetitions in a list increases (the spacing effect). This study investigated the spacing effect in recognition memory and in a frequency judgment task for unfamiliar target faces that were repeated in the same or in a different pose during incidental learning. Changing the pose between prime and probe trials reduced perceptual repetition priming in a structural discrimination task and also reduced the spacing effect in a subsequent unexpected recognition memory task. Three further experiments confirmed that the spacing effect inrecognition memory (Experiments 2 and 4) or frequency judgment (Experiment 3) was reduced when the pose was changed between repeated presentations at study. Similarly, with nonwords as targets (Experiment 5), changing the font between repeated occurrences of targets at study removed the spacing effect in a subsequent unexpected recognition memory test. These results are interpreted to support the view that short-term perceptual repetition priming underlies the spacing effect in explicit cued-memory tasks for unfamiliar nonsense material.

Adult↗
PubMed2000

The contribution of recollection and familiarity to yes-no and forced-choice recognition tests in healthy subjects and amnesics.

Recent reports suggest that some amnesic patients perform relatively normally on forced-choice recognition memory tests. Their preserved performance may reflect the fact that the test relies more heavily on assessments of familiarity, a process that is relatively preserved in these patients, than do other recognition tests such as yes-no tests, which may rely more on recollection. The current study examined recognition memory using yes-no and forced-choice procedures in control and amnesic patients in order to determine whether the two tasks differentially relied on recollection and familiarity, and whether the extent of the recognition memory deficit observed in amnesia was dependent upon the type of recognition test used to measure performance. Results using the remember-know procedure with healthy subjects showed that there were no substantial differences in recognition accuracy or in the contribution of recollection to these two tasks. Moreover, amnesic patients were not found to perform better on a forced-choice test than on a yes-no test, suggesting that familiarity contributed equally to these two types of recognition test.

Adolescent↗