In vitro appetitive classical conditioning of the feeding response in the pond snail Lymnaea stagnalis

In vitro appetitive classical conditioning of the feeding response in the pond snail Lymnaea stagnalis. J. Neurophysiol. 78: 2351-2362, 1997. An in vitro preparation was developed that allowed electrophysiological analysis of appetitive conditioning of feeding in the model molluscan system, Lymnaea. The network generating the feeding motor program (fictive feeding) is well characterized at the cellular level and consists of identified central pattern generator (CPG) interneurons, motor neurons, and modulatory interneurons. Activation of a modulatory interneuron, the slow oscillator (SO), evokes the three-phase fictive feeding rhythm in the same semi-intact preparations where tactile stimuli can be applied to the lips. By pairing touch as a conditioned stimulus (CS) with stimulation of the SO as an unconditioned stimulus (US), we established an effective in vitro paradigm for appetitive conditioning. Before training, touch to the lips evoked only brief and weak activity in the feeding interneurons and motor neurons. After 6-10 conditioning trials, there was a significant enhancement in the fictive feeding response to CS alone. This was not seen in controls (CS only, US only, random CS and US) and in preparations where there was no initial brief response to touch before conditioning. Direct recordings from the protraction phase N1M interneurons during in vitro conditioning indicated that the enhancement of the fictive feeding is due to an increased activation of these CPG cells by mechanosensory inputs from the lips. We also found that the conditioned response was not due to a facilitated activation of modulatory neurons in the feeding network, such as the SO or the cerebral giant cells (CGCs), because the activity of these cells remained unchanged after conditioning.     

Verbal memory in drug-naive, newly diagnosed Parkinson's disease. The retrieval deficit hypothesis revisited.

Objective: The retrieval deficit hypothesis on memory impairment in patients with Parkinson's disease (PD) implies a selective impairment in recall of learned material with normal encoding, retention, and recognition. This hypothesis has been challenged by new data. We have therefore investigated verbal memory and learning in a large sample of newly diagnosed, drug na?ve, non-demented patients with PD. Method: From a sample of patients with PD from the Norwegian ParkWest study, 133 PD patients and 133 controls matched on sex, age, and education were included. The California Verbal Learning Test-2 (CVLT-2) was used to assess verbal memory. Results: Patients performed significantly worse than controls on free and cued recall as well as on recognition memory. Patients used the semantic clustering learning strategy significantly less extensively than the controls and the learning slope of the PD patients was significantly less steep. There was no difference in retention when controlling for encoding. Patients did not perform better on the recognition measure or on cued recall (d-prime), as compared to free recall. Executive functions explained a substantial part of the memory deficits. Conclusions: This study suggests that memory impairment in drug na?ve early PD to a large degree is a deficit of learning/ encoding and not of retention or retrieval. An implication is that the retrieval deficit hypothesis should be moderated in its general form. Executive deficits and less extensive use of the efficient semantic clustering learning strategy had a strong impact on learning and memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Larger nondeclarative than declarative deficits in learning and memory in human aging.

This study used classical conditioning as a measure of nondeclarative learning and compared it with verbal learning as a declarative measure. Eighty participants were tested using 1 of 2 paradigms (400-ms and 750-ms delay) for eyeblink classical conditioning (EBCC) and the California Verbal Learning Test (CVLT). Large age differences were observed in the nondeclarative EBCC task, even in the 750-ms paradigm, which is more optimal for older adults. Age differences in the nondeclarative EBCC task were larger in the 400-ms paradigm and equal in the 750-ms paradigm to the magnitude of age differences in the declarative CVLT task. Partial correlations (removing the variance that was due to age) showed no relation between performance on the nondeclarative and declarative tasks. The results contradict the common assumption that, in the same participants, nondeclarative learning and memory are more resistant to the effects of aging than are declarative learning and memory and suggest that nondeclarative learning and memory are not unitary. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time estimation abilities in mild cognitive impairment and Alzheimer's disease.

Accurate time estimation abilities are assumed to play an important role in efficient performance of many daily activities. The authors investigated the role of episodic memory impairment in temporal perception using a prospective verbal time estimation paradigm. Verbal time estimations were made for filled intervals both within (i.e., 30 s) intervals. The verbal time estimates of both older adult groups, however, deviated more significantly from true time when compared with younger adult controls. In Experiment 2, 17 individuals with Alzheimer's disease (AD) demonstrated greater error and variability in their time estimates, but no disproportionate differences emerged between short- and long-duration estimates when compared with age-matched controls. The findings did not support a noteworthy role for episodic memory impairment in temporal perception but rather elucidated a significant effect of normal aging, as well as a detrimental effect of AD on temporal perception. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Different storage and retrieval deficits in normal aging and mild cognitive impairment: A multinomial modeling analysis.

The authors compared patients with mild cognitive impairment with healthy older adults and young control participants in a free recall test in order to locate potential qualitative differences in normal and pathological memory decline. Analysis with an extended multitrial version of W. H. Batchelder and D. M. Riefer's (1980) pair-clustering model revealed globally decelerated learning and an additional retrieval deficit in patients with mild cognitive impairment but not in healthy older adults. Results thus suggest differences in memory decline between normal and pathological aging that may be useful for the detection of risk groups for dementia, and they illustrate the value of model-based disentangling of processes and of multitrial tests for early detection of dementia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential age effects for implicit and explicit conceptual associative memory.

Older adults show disproportionate declines in explicit memory for associative relative to item information. However, the source of these declines is still uncertain. One explanation is a generalized impairment in the processing of associative information. A second explanation is a more specialized impairment in the strategic, effortful recollection of associative information, leaving less effortful forms of associative retrieval preserved. Assessing implicit memory of new associations is a way to distinguish between these viewpoints. To date, mixed findings have emerged from studies of associative priming in aging. One factor that may account for the variability is whether the manipulations inadvertently involve strategic, explicit processes. In two experiments we present a novel paradigm of conceptual associative priming in which subjects make speeded associative judgments about unrelated objects. Using a size classification task, Experiment 1 showed equivalent associative priming between young and older adults. Experiment 2 generalized the results of Experiment 1 to an inside/outside classification task, while replicating the typical age-related impairment in associative but not item recognition. Taken together, the findings support the viewpoint that older adults can incidentally encode and retrieve new meaningful associations despite difficulty with the intentional recollection of the same information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evidence for preserved emotional memory in normal older persons.

Emotion has been shown to have a modulatory effect on declarative memory. Normal aging is associated with a decline in declarative memory, but whether aging might affect the influence of emotion on memory has not been established. To investigate this, we administered a task that provides a detailed assessment of emotional memory to 80 neurologically normal adults ranging in age from 35 to 85 years. Across ages, memory performance was found to be modulated by the emotional significance of stimuli in a comparable manner (improved memory for gist, compromised memory for visual detail), despite an overall decline in memory performance with increasing age. The results raise the interesting possibility that aging has a differential effect on hippocampal versus amygdala function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The semantic and episodic subcomponents of famous person knowledge: Dissociation in healthy subjects.

Fifty-two subjects between ages 40 and 79 years were administered a questionnaire assessing their ability to recall semantic information about famous people from 4 different decades and to recollect its episodic source of acquisition together with autonoetic consciousness via the remember-know paradigm. In addition, they underwent a battery of standardized neuropsychological tests to assess episodic and semantic memory and executive functions. The analyses of age reveal differences for the episodic source score but no differences between age groups for the semantic scores within each decade. Regardless of the age of people, the analyses also show that semantic memory subcomponents of the famous person test are highly associated with each other as well as with the source component. The recall of semantic information on the famous person test relies on participants' semantic abilities, whereas the recall of its episodic source depends on their executive functions. The present findings confirm the existence of an episodic-semantic distinction in knowledge about famous people. They provide further evidence that personal source and semantic information are at once distinct and highly interactive within the framework of remote memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reliability, performance characteristics, construct validity, and an initial clinical application of a visual object learning test (VOLT)

Whereas verbal learning has received considerable attention by cognitive neuropsychology, spatial object learning has been more resistant to study. The paucity of visual learning data has hampered attempts to clarify if visual learning has unique features with specialized neural substrates. In schizophrenia, severe verbal learning impairment has been established, but lack of comparable visual learning measures has thwarted the dissociation of verbal and visual abilities. The Visual Object Learning Test (VOLT) was developed to examine aspects of visual-spatial learning and memory in a manner analogous to available verbal tests. Studies were performed to establish normative performance characteristics, convergent and divergent validity, and the sensitivity of the VOLT to detection of individual differences in normal (through sex and age) and pathologic variability (through persons with schizophrenia). The results indicated excellent internal consistency, convergent and divergent validity, and sensitivity to the effects of aging and pathology. Persons with schizophrenia were impaired in both learning and retention. The authors conclude that memory impairment in schizophrenia may not be specific to verbal learning.     

Implicit memory for spatial context in depression and schizophrenia.

Deficits in explicit spatial memory, as well as abnormalities of the hippocampus and neighboring medial temporal structures, have been documented in schizophrenia and depression. Recent evidence relying on the contextual cueing paradigm has shown that integrity of these structures is crucial not only for explicit memory but also for implicit spatial memory. Using this paradigm, the authors show that implicit memory for spatial context is severely impaired in clinically depressed patients but reaches a normal level in schizophrenia patients, although in these patients, acquisition is slower than in controls. By contrast, implicit memory for isolated locations and colors is normal in both schizophrenia and depressed patients. These findings suggest an implicit memory impairment specific to spatial context in depression. The implications for research on the differences between schizophrenia and depression in abnormalities of the hippocampal system and for research on the neural correlates of contextual cueing are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Examining the nature of impairment in visual paired associate learning in amnestic mild cognitive impairment.

Objective: Visual spatial learning is impaired in mild cognitive impairment (MCI) although the nature of this impairment is not clear. This study investigated the nature and magnitude of errors made by adults with amnestic MCI (aMCI) when learning pattern-location paired associations in a continuous manner. Method: Visual associate learning was measured using the Continuous Paired Associate Learning (CPAL) task in which 30 adults who met clinical criteria for aMCI and 30 matched controls were required to learn a set of associations between patterns and locations across increasing memory loads (two, four, six, and eight). Results: As hypothesized, the aMCI group made more total errors than controls for all memory loads above two. However, the rate of increase in errors with memory load in the aMCI group was approximately twice that for controls. Conclusions: In controls, errors on the CPAL task reflected almost exclusively difficulty in memory. In the aMCI group, errors on the CPAL reflected limitations in associative learning but also in short-term memory and response monitoring. These results suggest that impairments in specific aspects of executive function and working memory might contribute to poor performance on visual paired associate learning in aMCI. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Age-related decrease of plasma testosterone in SAMP8 mice: replacement improves age-related impairment of learning and memory

Corticosterone increases with aging but pregnenolone, dehydroepiandrosterone, and testosterone decrease. The marked decrease in hormones that occurs with aging may contribute to the age-related deficit in learning and memory. Administration of these hormones after training was found to improve long-term memory processing in normal young mice. SAMP8 (P8) mice show an age-related loss of learning and memory for a variety of tasks whereas age-matched control mice of the closely related SAMR1 (R1) strain do not. In this study, we found an age-related decrease in serum testosterone levels of 71% between P8 mice 4 and 12 months of age, but only a 26% decrease between R1 mice of the same ages. The difference between the P8 mice was significant (p < 0.01) and the difference between the R1 mice was not. The decrease in testosterone in 12-month-old P8 mice was not accompanied by gross morphological change in the testes. A SC testosterone implant, sufficient to increase plasma testosterone levels to 414 +/- 25 ng/dl, alleviated impaired learning and memory of a foot shock avoidance task in P8 mice. Castration of 4-month-old P8 mice did not produce a deterioration in learning and memory, indicating that low levels of testosterone per se are not responsible for the impairment seen in 12-month-old P8 mice. This suggests that impaired cognitive functioning of the older P8 mice was due to an interaction of aging and reduced testosterone levels.     

Specific- and Partial-Source Memory: Effects of Aging.

Normal aging can be associated with impairments in source memory (recollecting an event's context). This study examined the effects of aging on specific-source memory (e.g., remembering which of 4 people spoke a word) and partial-source memory (e.g., remembering the gender of the person who spoke the word). When young and older adults were matched in terms of old-new recognition, age-related deficits were observed on both specific- and partial-source recollection. When the groups were matched on partial-source performance, no disproportionate specific-source impairment was seen. The results suggest that aging does not differentially affect specific- versus partial-source memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Metastatic pulmonary artery sarcoma. Report of a case with diagnosis by fine needle aspiration

Spontaneously hypertensive rats (SHR) of 3 to 12 months of age learned and retrieved less information than normotensive Wistar-Kyoto rats (WKY), although no difference was found with animals from 18 and 24 months of age. The combined influence of hypertension and aging had an additive detrimental effect on cognitive functions. Notwithstanding these deficiencies in learning and memory, SHR have seldom been used as a model in the screening of drugs with therapeutic potential for treatment of disorders of cognitive processes. Moreover, the calcium channel blocker nimodipine has beneficial effects on learning in both aged and hypertensive animals and humans. However, no attempt has been made to investigate whether nimodipine can reverse the additive deleterious effects of aging and hypertension in the same subject. We recently reported that deteriorated animals (middle-aged and/or hypertensive) chronically treated with nimodipine (via osmotic minipumps) exhibit higher learning scores. This information indicates that nimodipine can reverse the impairing effects of either aging or hypertension on learning; the presence of the two conditions, however, produces a severe impairment that can be partially reversed by this drug. Therefore, we propose that mature and middle-aged SHR represent a model for the screening of potentially useful drugs in the treatment of learning disorders, probably associated with hypertension and/or aging. Nevertheless, it must be remembered that the SHR is a genetic model and the appearance of neural disturbances could be a parallel genetic phenomenon and not necessarily or exclusively related to hypertension per se.     

Influences of preclinical dementia and impending death on the magnitude of age-related cognitive deficits.

The authors examined the influence of preclinical dementia and impending death on the cross-sectional relationship between age and performance in tasks assessing episodic memory, visuospatial skill, and verbal fluency. Increasing age was associated with a general decrease in cognitive performance. In addition, those who were to be diagnosed with dementia had died by a 3-year follow-up, were older, and performed at a lower level than the remaining sample across all cognitive tasks at baseline. Nevertheless, removal of the preclinical dementia and impending death groups from the original sample affected the cross-sectional age-cognition relations relatively little. This pattern of findings suggests that the biological aging process exerts negative influences on cognitive functioning beyond those resulting from disease and mortality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contributions of source and inhibitory mechanisms to age-related retroactive interference in verbal working memory.

Determining contributions of source-monitoring and inhibitory function to age-related forgetting has been an elusive goal for cognitive theorists. Five studies used a verbal working memory paradigm to examine mechanisms accounting for disproportionate retroactive interference (RI) experienced with adult aging. Participants distinguished studied target-word pairs from interfering pairs that were read aloud. Source-monitoring and inhibitory task components varied through manipulations of response requirements. RI effects were primarily due to source-monitoring failures rather than to inhibitory failures. Removing both source and inhibitory components eliminated age differences in RI. When source monitoring was emphasized, RI continued to be observed in all age groups but disproportionately for older adults. Process dissociation analyses of memory found recollection decreases and familiarity increases consistent with source failures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A differential deficit in time- versus event-based prospective memory in Parkinson's disease.

Objective: The aim of the current study was to clarify the nature and extent of impairment in time- versus event-based prospective memory in Parkinson's disease (PD). Prospective memory is thought to involve cognitive processes that are mediated by prefrontal systems and are executive in nature. Given that individuals with PD frequently show executive dysfunction, it is important to determine whether these individuals may have deficits in prospective memory that could impact daily functions, such as taking medications. Although it has been reported that individuals with PD evidence impairment in prospective memory, it is still unclear whether they show a greater deficit for time- versus event-based cues. Method: Fifty-four individuals with PD and 34 demographically similar healthy adults were administered a standardized measure of prospective memory that allows for a direct comparison of time-based and event-based cues. In addition, participants were administered a series of standardized measures of retrospective memory and executive functions. Results: Individuals with PD demonstrated impaired prospective memory performance compared to the healthy adults, with a greater impairment demonstrated for the time-based tasks. Time-based prospective memory performance was moderately correlated with measures of executive functioning, but only the Stroop Neuropsychological Screening Test emerged as a unique predictor in a linear regression. Conclusions: Findings are interpreted within the context of McDaniel and Einstein's (2000) multiprocess theory to suggest that individuals with PD experience particular difficulty executing a future intention when the cue to execute the prescribed intention requires higher levels of executive control. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Selective adult age differences in an age-invariant multifactor model of declarative memory.

Confirmatory factor analysis was used to test competing models of declarative memory. Data from middle-aged participants provided support for a model comprised of 2 2nd-order (episodic and semantic memory) and 4 1st-order (recall, recognition, fluency, and knowledge) factors. Extending this model across young-old and old-old participants established support for age invariance. Tests of group differences showed an age deficit in episodic memory that was more pronounced for recall than for recognition. For semantic memory, there was an increase in knowledge from middle to young-old age and thereafter a decrease. Overall, the results support the view that episodic memory is more age sensitive than semantic memory, but they also indicate that aging has differential effects within these 2 forms of memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Different patterns of memory impairments accompany short- and longer-term maintenance on a high-energy diet.

Intake of diets high in saturated fat and simple carbohydrates is associated with cognitive impairments in both humans and rodents. Here we report that feeding rats this type of high-energy (HE) diet has different effects on different types of learning and memory processes. Rats were first trained to solve spatial and nonspatial reference (RM) and working (WM) memory problems in a radial maze paradigm. Memory retention was assessed following six durations of free access to an HE or standard chow control diet ranging from 72-hr to 90 days. The results showed that performance on spatial RM and WM was impaired following only 72-hr on the HE diet and that the magnitude of the spatial RM and WM retention deficits were stable across all tests. On the other hand, stable deficits in nonspatial RM and WM emerged only after 30 days on the HE diet. The results suggest that the processes underlying spatial memory may be especially sensitive to disruption following intake of HE diets. (PsycINFO Database Record (c) 2010 APA, all rights reserved)