Impairment of memory for spatial context in schizophrenia.

A group of 33 patients with schizophrenia were compared with control participants using a spatial memory task in which words were presented on locations of a grid. In the first part of the experiment, recognition of target information (words) was tested. In the second, 2 tasks of spatial location (contextual information) were given involving different sets of words placed in different locations: A location memory task (determining which word was in a particular spatial location) explored an associative form of spatial memory, and a relocation task (determining where a particular word was located) explored an associative and a nonassociative form of spatial memory. Patients were more impaired with regard to the location memory task than to the target recognition and relocation tasks. The impairment was negatively correlated with Stroop task performance. The results suggest that schizophrenia is associated with a spatial context memory deficit, which could be due to defective associations between target and spatial information. This deficit seemed to be related to frontal dysfunction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Changes in goal selection induced by cue conflicts are in register with predictions from changes in place cell field locations.

In the cognitive mapping theory of hippocampal function, currently active place cells represent a rat's spatial location (J. O'Keefe & L. Nadel, 1978). A systematic shift of firing field locations should therefore produce a similar shift in a rat's judgment of its location. A. A. Fenton, G. Csizmadia, and R. U. Muller (2000a) recorded place cells in cylinders with 2 cue cards separated by 135°. When the separation was changed, firing fields moved systematically, as described by a vector-field equation (A. A. Fenton, G. Csizmadia, & R. U. Muller, 2000b). Given this cohesive movement of firing fields, the mapping theory predicts that a rat's decisions about the location of an unmarked goal should move after card separation changes, as described by the vector-field equation. The authors tested this reasoning with a task in which the rat earned a food reward by pausing in a small, unmarked goal zone. When cues were shifted in the absence of reward, goal choice shifts were accurately predicted by the vector-field equation, providing strong support for the notion that a rat's judgment of its spatial location is intimately related to the across-cell discharge pattern of simultaneously active place cells. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Discrimination learning requiring different memory components in rats: Age and neurochemical comparisons.

Three experiments compared the performances of 19 young (8–9 mo old) and 23 aged (22–24 mo old) male ACI rats in a T-maze involving a spatial discrimination in the stem of the T-maze that required long-term reference memory, and discrete-trial, alternation discrimination in the arms of the T-maze that required working memory. Following acquisition training in 1 maze, Ss were trained in a 2nd maze in which the correct response in stem was opposite to that in the 1st maze. In Exps I and II, aged Ss made more errors in all phases of maze training than did young Ss, suggesting that all components of memory processing were affected equivalently. In Exp III, aged Ss were unimpaired in the ability to perform in a T-maze task involving a brightness discrimination with intramaze cues. This result suggests that the age-related impairment in the 2-component T-maze task was restricted to the cognitive demands of the task. Neurochemical analyses revealed a slight (8%) but significant age-related decline in the activity of glutamic acid decarboxylase but not of choline acetyltransferase. Although the correlation between maze performance and regional enzyme activities generally supported previous observations, the only significant correlation to emerge was between working memory performance and glutamic acid decarboxylase activity in the cingulate cortex. (45 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age differences in learning serial patterns: Direct versus indirect measures.

Adult age differences in learning and retention of a nonverbal sequence were examined using the serial reaction-time (RT) task of M. J. Nissen and P. Bullemer (see record 1987-13436-001), with 20 younger and 20 older Ss. An asterisk appeared in one of 4 spatial locations, and the Ss responded with a corresponding key press. The first 4 blocks each contained 10 repetitions of a 10- or 16-element spatial sequence, and the 5th block contained a random sequence. The difference between response time on Blocks 5 and 4 served as an indirect measure of pattern learning. The direct measure was accuracy in a final generation block in which the Ss predicted which location would appear next. Results were similar to those with verbal materials; the indirect measure revealed age similarity for patterns of both lengths, but the direct measure yielded age differences favoring the young. For both ages and types of measures, the long patterns led to poorer learning than did the short patterns. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The status of rapid response learning in aging.

Strong evidence exists for an age-related impairment in associative processing under intentional encoding and retrieval conditions, but the status of incidental associative processing has been less clear. In 2 experiments, we examined the effects of age on rapid response learning—the incidentally learned stimulus–response association that results in a reduction in priming when a learned response becomes inappropriate for a new task. Specifically, we tested whether priming was equivalently sensitive in both age groups to reversal of the task-specific decision cue. Experiment 1 showed that cue inversion reduced priming in both age groups with a speeded inside/outside classification task, and in Experiment 2, cue inversion eliminated priming on an associative version of this task. Thus, the ability to encode an association between a stimulus and its initial task-specific response appears to be preserved in aging. These findings provide an important example of a form of associative processing that is unimpaired in older adults. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain

The hypothesis that age-associated impairment of cognitive and motor functions is due to oxidative molecular damage was tested in the mouse. In a blind study, senescent mice (aged 22 months) were subjected to a battery of behavioral tests for motor and cognitive functions and subsequently assayed for oxidative molecular damage as assessed by protein carbonyl concentration in different regions of the brain. The degree of age-related impairment in each mouse was determined by comparison to a reference group of young mice (aged 4 months) tested concurrently on the behavioral battery. The age-related loss of ability to perform a spatial swim maze task was found to be positively correlated with oxidative molecular damage in the cerebral cortex, whereas age-related loss of motor coordination was correlated with oxidative molecular damage within the cerebellum. These results support the view that oxidative stress is a causal factor in brain senescence. Furthermore, the findings suggest that age-related declines of cognitive and motor performance progress independently, and involve oxidative molecular damage within different regions of the brain.     

Inaccurate prediction of retrieval in a face matrix learning task after right frontal lobe lesions.

This study partly supports the hypothesis that frontal lobe lesions cause impairment of metamemory. Fifty-nine patients with a focal brain lesion and 21 non-brain-damaged patients memorized a 4?×?4 matrix of 16 faces in 6 consecutive trials and predicted the number of locations of faces they would be able to remember before each retrieval. When age-related impairment of learning was adjusted, the patients with right posterior lesions were inferior to the controls and to the patients with right frontal lesions on the total number of correctly placed faces. The patients with right frontal lesions were less accurate than the patients with right posterior lesions or the controls in the prediction of retrieval. The inaccuracy of retrieval prediction in the face test was associated with that in a word-list learning task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differentiating among prefrontal substrates in psychopathy: Neuropsychological test findings.

Frontal lobe and consequent executive dysfunction have long been related to psychopathy. More recently, there have been suggestions that specific regions of frontal cortex, rather than all of frontal cortex, may be implicated in psychopathy. To examine this issue, the authors presented 25 individuals with psychopathy and 30 comparison individuals with measures preferentially indexing the orbitofrontal cortex (OFC; object alternation task), dorsolateral prefrontal cortex (DLPFC; spatial alternation task), and anterior cingulate cortex (ACC; number-Stroop reading and counting tasks). The individuals with psychopathy showed significant impairment on the measure preferentially sensitive to OFC functioning. In contrast, the 2 groups did not show impairment on the measures preferentially sensitive to the functioning of the DLPFC or ACC. These results are interpreted with reference to executive dysfunction accounts of the disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Implicit learning of a nonverbal sequence in younger and older adults.

Two experiments examined age-related differences in implicit serial learning using the M. J. Nissen and P. Bullemer (see record 1987-13436-001) task. Younger adults and 2 samples of older adults who differed in educational attainment, occupational status, and verbal ability were given a 10-trial repeating sequence embedded in 100-trial blocks. On each trial, participants pressed a key that matched a designated spatial location. Implicit learning was inferred from the difference in reaction time (RT) between a random sequence trial block and the immediately preceding block with the repeating sequence. Results indicated that negative transfer effects were comparable for the younger and higher ability older adults, but lower ability older adults showed less evidence of implicit learning. On an explicit task, younger and higher ability older adults were more accurate than the lower ability older adults. The implications of these findings for current views on implicit learning in adulthood are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial learning and memory at defined points of the estrous cycle: Effects on performance of a hippocampal-dependent task.

Learning based on hippocampal-dependent spatial navigation in female rats was assessed at identified points in the estrous cycle corresponding to low (estrus) and high (proestrus) circulating estrogen. With background training in water-maze procedures, rats learned the location of an escape platform in the maze in a single session of 8 training trials. A strong spatial bias for the escape platform was also evident in a probe trial used to assess retention of learning 30 min after the training session. This entire protocol was completed in less than an hour. The performance of the estrus and proestrus rats was indistinguishable on all behavioral measures, irrespective of the stage of estrous cycle during the task. These results indicate that rapid learning and retention for spatial information over a relatively short interval may be preserved despite morphological alterations in hippocampal dendritic spine density in the normally cycling female rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age-related deficits in context discrimination learning in Ts65Dn mice that model Down syndrome and Alzheimer's disease.

All individuals with Down syndrome (DS) eventually develop the neuropathology of Alzheimer's disease (AD), which is characterized by a premature loss of basal forebrain cholinergic neurons. Similarly, between 4 and 6 months of age, Ts65Dn mice, which model DS, lose cholinergic markers in their medial septal neurons. It is not known whether Ts65Dn mice have age-related learning deficits as well. Control and Ts65Dn mice were tested at several ages in context discrimination. Controls at all ages showed no deficits in learning this task. Ts65Dn mice younger than 3 months demonstrated impaired learning, suggesting a possible developmental delay in Ts65Dn mice. Four-month-old Ts65Dn mice showed no deficits, whereas Ts65Dn mice older than 5 months were impaired in learning the task. Therefore, Ts65Dn mice have an age-related learning impairment that coincides with their age-related neuroanatomical abnormalities and, consequently, may be a useful model of AD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Redistribution of spatial representation in the hippocampus of aged rats performing a spatial memory task.

Young and old rats performed on a maze according to a forced-choice and then a spatial memory procedure either in the same or a different environment. Aged rats were slower to learn the spatial memory task when tested in the same, but not in a different, room. One interpretation of this pattern of results is that although old rats learn new rules as quickly as young rats, they show less flexibility with old rules and familiar spatial information. Impaired choice accuracy during asymptote performance suggests poor processing of trial-unique information by old rats. Spatial correlates of hippocampal CA1 and hilar cells varied with task demand: CA1 cells of aged rats showed more spatially selective place fields, whereas hilar cells showed more diffuse location coding during spatial memory, and not forced-choice, tests. Such representational reorganization may reflect a compensatory response to age-related neurobiological changes in the hippocampus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial constraints on learning in visual search: Modeling contextual cuing.

Predictive visual context facilitates visual search, a benefit termed contextual cuing (M. M. Chun & Y. Jiang, 1998). In the original task, search arrays were repeated across blocks such that the spatial configuration (context) of all of the distractors in a display predicted an embedded target location. The authors modeled existing results using a connectionist architecture and then designed new behavioral experiments to test the model's assumptions. The modeling and behavioral results indicate that learning may be restricted to the local context even when the entire configuration is predictive of target location. Local learning constrains how much guidance is produced by contextual cuing. The modeling and new data also demonstrate that local learning requires that the local context maintain its location in the overall global context. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adaptation to visuomotor rotations in younger and older adults.

Adaptation to a visuomotor rotation is known to be impaired at older adult age. The authors examined whether the impairment is present already at preretirement age and whether it depends on the difficulty of the adaptation task. Moreover, the authors tested predictions of the hypothesis that the age-related impairment pertains primarily to strategic corrections and the explicit knowledge on which they are based but not to the acquisition of an (implicit) internal model of the novel visuomotor transformation. The authors found an age-related impairment of adaptation and explicit knowledge already at preretirement age but no age-related change of aftereffects. With an incremental simplification of the adaptation task, age-related changes were able to be eliminated. Individual differences of the quality of explicit knowledge were associated with differences of adaptation, but not of aftereffects. When age groups were matched by explicit knowledge, age-related impairments of adaptation largely disappeared. However, a reliable difference remained in one of the experiments, suggesting that other processes of adjustment to a visuomotor rotation might be affected by aging as well. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Parallel recovery of MK-801-induced spatial learning impairment and neuronal injury in male mice

The relationship between spatial learning impairment and reversible neuronal injury in the posterior cingulate/retrosplenial (PC/RS) cortex induced by MK-801 in male mice was studied using a four-corner holeboard task. Mice were dosed with 1 mg/kg MK-801 and tested on acquisition of a new "baited" hole at 5 or 12 h posttreatment. Acquisition in drugged mice was impaired at 5 h, but not at 12 h posttreatment. Their retention performances were unaffected 24 h after either the 5 or 12 h posttreatment acquisition sessions. MK-801 (1 mg/kg) was found to induce locomotor hyperactivity and some sensorimotor impairment at 5 h posttreatment. which could have contributed to the acquisition deficit. However, nonassociative effects of the drug were not prominent because this same dose did not impair holeboard performance at 5 h posttreatment when the task was well learned. Histologic experiments showed that many injured neurons (containing cytoplasmic vacuoles) were present in the PC/RS cortex at 5 h posttreatment but the reaction was essentially reversed at 12 h posttreatment. The results suggest that the acquisition impairment and neuronal injury induced by MK-801 evolve and recover in parallel according to a similar time schedule.     

Serial pattern learning by event observation.

Serial pattern learning was investigated in a variation of the task introduced by M. J. Nissen and P. Bullemer (1987). The authors presented an asterisk at 1 of 4 spatial locations on each trial, and Ss either responded with a keypress or observed the event. The 1st 4 blocks contained 10 repetitions of a 10- or 16-element pattern, and the 5th block contained a random sequence. The difference in response time on the 5th random block and the previous patterned block served as an indirect measure of pattern learning. A direct measure was obtained in a final test block in which Ss predicted the next asterisk position. Equivalent learning occurred for responding and observing with indirect measures, but observation was superior with direct measures. These findings indicate that knowledge of serial order can develop through simple perceptual experience, and this is more available to deliberate recall than is knowledge acquired while responding. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Entorhinal-perirhinal lesions impair performance of rats on two versions of place learning in the Morris water maze.

The effects of entorhinal–perirhinal lesions in rats were studied with 2 versions of a place learning task in the Morris water maze. These lesions impaired performance on a multiple-trial task (3 days of 6 trials and a probe trial). This assessment was followed by a task in which rats were repeatedly trained to find novel locations with a variable delay (30 sec or 5 min) imposed between each sample trial and retention test. Entorhinal–perirhinal damage produced a delay-dependent deficit in spatial memory: Rats with lesions were impaired at the 5-min delay relative to the control group and to their own performance at 30 sec. These findings are discussed in relationship to memory impairment after entorhinal damage and spatial learning deficits observed after hippocampal damage. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Phencyclidine injections into the dorsal hippocampus disrupt long- but not short-term memory within a spatial learning task

Since the hippocampus is likely to be a major site of phencyclidine (PCP) action, the effects of various doses of PCP (1.8, 18 or 36 nM) as well as 3.6 nM MK-801 or saline injected directly into the dentate gyrus of the hippocampus was tested for acquisition of a spatial navigation task (dry land version of a water maze) using a paradigm that assesses short term memory based on learning within a day and long term memory based on learning between days. Results indicated that relative to saline or 1.8 nM PCP injected rats, rats with 18 or 36 nM PCP or 3.6 nM MK-801 injections were impaired in acquisition of the task as measured by increased distances traveled to find the food location between days but not within days. In additional experiments 36 nM PCP or 3.6 nM MK-801 did not produce any deficits in the acquisition of an object discrimination task. It is suggested that PCP through its blocking action of the NMDA receptor in the dentate gyrus or CA1 region of the dorsal hippocampus mediates the consolidation of new spatial location information.     

Effects of aging on conditional associative learning: Process analyses and comparison with focal frontal lesions.

Conditional associative learning (CAL), a measure validated in studies of frontal lesions, was used to evaluate the hypothesis that age-related cognitive decline is related to frontal dysfunction. Older adults and focal frontal participants showed impaired CAL performance, but the deficit was greater in the latter group, where it was specific to participants with dorsolateral prefrontal cortical (DLPFC) lesions. The deficits were attributable to strategic rather than basic associative processes. Error scores described ways in which past information failed to guide behavior, and they were related to lesion location. Congruence between older adults and DLPFC participants on a measure of defective inhibition suggests that age-related decline in inhibitory processes is due to DLPFC dysfunction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)