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PubMed2004

Working memory and aging: a cross-sectional and longitudinal analysis using a self-ordered pointing task.

Age-related declines in working memory performance have been associated with deficits in inhibition, strategy use, processing speed, and monitoring. In the current study, cross-sectional and longitudinal methodologies were used to investigate the relative contribution of these components to age-related changes in working memory. In Experiment 1, a sample of 140 younger and 140 older adults completed an abstract design version of the Self-Ordered Pointing Task modeled after Shimamura and Jurica (1994). Experiment 1 revealed that only processing speed and monitoring explained age differences in SOPT performance. Participants in Experiment 2 were 53 older adults who returned 4 years after the initial testing and 53 young adults. A task that assessed the ability to generate and monitor an internal series of responses as compared to an externally imposed series of responses was also administered. Experiment 2 replicated the key findings from Experiment 1 and provided some further evidence for age-related internal monitoring difficulties. Furthermore, the exploratory longitudinal analysis revealed that older age and lower intellectual abilities tended to be associated with poorer performance on the SOPT at Time 2.

Adolescent↗
PubMed2000

Antipsychoticlike effects of amoxapine, without catalepsy, using the prepulse inhibition of the acoustic startle reflex test in rats.

BACKGROUND: The dibenzoxazepine amoxapine was introduced as an antidepressant but has shown antipsychoticlike activity in a number of animal screening tests. A recent positron emission tomography study showed a 5-HT(2)/D(2) receptor occupancy profile of amoxapine that is very similar to that of established atypical antipsychotics. Schizophrenics display deficits in sensory gating mechanisms, such as prepulse inhibition (PPI) of the acoustic startle reflex. A similar deficit can be produced by dopamine (DA) and by 5-HT(2A/C) receptor agonists in rats. Antipsychotic compounds reverse this effect. METHODS: Effects of amoxapine on apomorphine- or 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced disruption of PPI were studied in adult male Sprague-Dawley rats. The extrapyramidal side effect (EPS) liability of amoxapine was assessed using the inclined grid catalepsy (CAT) test. Statistical analyses were performed by analysis of variance (ANOVA) for fully repeated measures (PPI) and by the Kruskal-Wallis one-way ANOVA by ranks (CAT). RESULTS: Apomorphine (0.5 mg/kg) produced a significant reduction in PPI compared with the case of rats in the saline control group. Pretreatment with amoxapine (10 mg/kg) significantly attenuated the apomorphine-induced disruption of PPI. DOI (0.5 mg/kg) significantly reduced PPI compared with saline controls. Pretreatment with amoxapine (5 or 10 mg/kg) produced a significant attenuation of the DOI-induced disruption of PPI. Amoxapine by itself did not alter PPI. Amoxapine (5 or 10 mg/kg) did not produce CAT. CONCLUSIONS: The DA D(2)/5-HT(2) receptor antagonist amoxapine produced an antipsychoticlike reversal of both apomorphine- and DOI-induced disruption of PPI. Furthermore, the same doses of amoxapine that reversed disruption of PPI did not produce CAT. The results confirm and lend further support to the results of previous studies on amoxapine, suggesting that amoxapine might possess antipsychotic activity with little propensity for producing EPS.

Acoustic Stimulation↗
PubMed2005

Reduced parahippocampal connectivity produces schizophrenia-like memory deficits in simulated neural circuits with reduced parahippocampal connectivity.

CONTEXT: Episodic memory impairments are well characterized in schizophrenia, but their neural origin is unclear. OBJECTIVE: To determine whether the episodic memory impairments in schizophrenia may originate from reduced parahippocampal connectivity. DESIGN: Experimental in silico model. SETTING: Department of Psychology, University of Amsterdam, Amsterdam, the Netherlands. INTERVENTIONS: A new, in silico medial temporal lobe model that simulates normal performance on a variety of episodic memory tasks was devised. The effects of reducing parahippocampal connectivity in the model (from perirhinal and parahippocampal cortex to entorhinal cortex and from entorhinal cortex to hippocampus) were evaluated and compared with findings in schizophrenic patients. Alternative in silico neuropathologies, increased noise and loss of hippocampal neurons, were also evaluated. RESULTS: In the model, parahippocampal processing subserves integration of different cortical inputs to the hippocampus and feature extraction during recall. Reduced connectivity in this area resulted in a pattern of deficits that closely mimicked the impairments in schizophrenia, including a mild recognition impairment and a more severe impairment in free recall. Furthermore, the schizophrenic model was not differentially sensitive to interference, also consistent with behavioral data. Notably, neither increased noise levels nor a reduction of hippocampal nodes in the model reproduced this characteristic memory profile. CONCLUSIONS: Taken together, these findings highlight the importance of parahippocampal neuropathology in schizophrenia, demonstrating that reduced connectivity in this region may underlie episodic memory problems associated with the disorder.

Entorhinal Cortex↗
PubMed2000

Use of the California Verbal Learning Test to detect proactive interference in the traumatically brain injured.

Recent studies using the California Verbal Learning Test (CVLT) to investigate the learning and memory capacities of traumatically-brain injured (TBI) individuals have suggested that this population does not show the expected buildup of proactive interference (PI). The purpose of this study was to investigate whether PI could be detected on the CVLT, in a TBI sample, if PI were calculated using alternative methods. CVLT data from 25 TBI individuals with varying degrees of brain injury and 21 healthy controls were compared. Results from the various analyses suggested that TBI individuals show buildup and release from PI when learning and attempting to recall competing forms of information if appropriate methods of analysis are used. Although the CVLT differs considerably from traditional PI paradigms (e.g., Wickens, 1970), our results suggest it can be used to detect PI in TBI individuals.

Adolescent↗
PubMed1998

Primacy and recency effects in rhesus monkeys (Macaca mulatta) using a serial probe recognition task. III. A developmental analysis.

In children, the recency effect emerges prior to the primacy effect. To determine whether this dissociation is also seen in nonhuman primates, we evaluated the development of the primacy and recency effect in 3 young adult (35 months) and 4 adolescent (21 months) male rhesus monkeys (Macaca mulatta) using a six-item serial probe recognition (SPR) task. As predicted, the young adult monkeys displayed both effects, while the adolescent monkeys only displayed the recency effect. Not until after 26 months of training on the SPR task did the adolescent monkeys exhibit both the primacy and recency effect. Interference and strategy differences are discussed in terms of the results along with an interpretation of Rudy's (1992) configural association theory of cognitive development. Additional possible explanations for this developmental dissociation include the delayed maturation of the neocortical, hippocampal, and/or cholinergic systems, the latter two having been shown to be important in the expression of the primacy but not the recency effect.

Age Factors↗
PubMed1995

Effects of postevent information on infants' memory for a central target.

In three experiments with 78 infants, we explored the effect of introducing novel information about a central target after a short delay on 6-month-olds' recognition of the original target, the novel exposure target, and a completely novel one. In all experiments, infants learned to move a particular crib mobile (the central target) by kicking and then were exposed to a novel mobile (the conflicting postevent information) immediately after training was over. In Experiment 1, memory for the original mobile was unimpaired, but infants treated both the exposure mobile and a completely novel one as if they had actually been present originally. In Experiment 2, only a completely novel mobile was an effective remainder in a reactivation paradigm, indicating that the impact of postevent information was relatively long-lasting and that the failure of the other mobiles to recover the training memory resulted from trace competition at the time of retrieval. In Experiment 3, identical novel information did not proactively affect recognition. Thus, 6-month-olds' memory of a central target is resistant to impairment by conflicting postevent information after a short delay, but they are highly prone to source misattribution. We propose that postevent information effects are cognitively efficient.

Association Learning↗
PubMedDate not supplied

Direct and continuous measurement of relational learning in human Pavlovian conditioning.

Three experiments were conducted employing a continuous measure of conditional stimulus/unconditional stimulus (CS/US) contingencies as perceived by the subject (i.e., subjective contingency or SC). It is argues that direct measurement of relational learning, as indexed by SC, can lead to a better understanding of Pavlovian conditioning processes. The first two experiments applied this approach to a methodologic controversy, raising the debate from a procedure-based argument to testing what the subject actually learns about CS/US relationships. While the issue was not resolved, testable hypotheses for future research were generated from the data. The third experiment contrasted the contingency stimulus-stimulus (S-S) account of Pavlovian conditioning with an earlier stimulus-response (S-R) contiguity-reinforcement account. In this experiment, both SC and skin resistance were measured. Evidence for the existence of both cognitive-propositional and response-learning processes in conditioning was obtained.

Adult↗
PubMed2004

Successive reversal of concurrent discriminations by macaques (Macaca mulatta): proactive interference effects.

Rhesus monkeys received concurrent within-session training on eight, two-choice object pairs and then underwent successive reversals of these problems. Initially, reversals required about six times more training than acquisition with no improvement over seven successive reversals. Surprisingly, performance on these eight problems was unimpaired if they were embedded in different eight-problem tasks, thereby indicating a release from proactive interference. When the original eight problems again underwent successive reversal, no improvement was seen over seven reversals, although there was significantly less error-per-reversal than in the initial test. Subsequently, monkeys appeared to be developing a learning set for successive reversal because performance on successive reversal of eight novel problems was not different from that seen with the old familiar task. Set acquisition was confirmed when proficient reversal was eventually achieved on both old and new concurrent tasks. Thus, "concurrent reversal set" did develop, but it required arduous training to overcome proactive interference effects on memory. The ubiquitous influence of measurement context on organization of monkey memory was noted.

Animals↗
PubMed1984

Amnesia in a patient with bilateral lesions to the thalamus.

A case of anterograde amnesia is described in a 38-yr-old man with bilateral thalamic lesions. The patient appeared to have suffered no general intellectual loss and performed normally on standard memory tasks involving immediate recall of new material. There was, however, consistent impairment in recalling material, verbal and non-verbal, over delays as brief as a few seconds. Impairment was especially marked on tests involving free recall and partial cueing procedures; recognition memory was also impaired. Premorbid memory tested normally and susceptibility to interference was less than in other organic amnesics. Various interpretations of the patient's amnesia were considered but a deficit at the initial stages of information processing appeared to be indicated.

Adult↗
PubMed1991

Normal release from proactive interference in untreated patients with Parkinson's disease.

The relationship of release from proactive interference (PI) to set-shifting, explicit free recall and language remains controversial. We tested 56 patients with Parkinson's disease (PD) who had never received medication and 37 matched normal control subjects on a test of PI release based on semantic category. The PD group showed normal PI release but impaired word recall. PI release was independent of impaired Wisconsin card-sorting test performance, language production, explicit memory, overall cognitive status and severity of depression. The results indicate dissociation between ability to benefit from semantic stimulus properties and processes of explicit memory, set-shifting and expressive language.

Attention↗
PubMed1994

A dissociation in the relation between memory tasks and frontal lobe tests in the normal elderly.

In this study a group of elderly subjects were examined on three tests of frontal lobe function. Two of these tests, FAS word fluency and the Alternate Uses Test, were considered tests of spontaneous flexibility, as defined by Eslinger and Grattan [Neuropsychologia 31, 17-28, 1993]. The third, the modified Wisconsin Card Sorting Test (WCST), is considered a test of reactive flexibility. Performance on two tests of memory, release from proactive interference (PI) and a matched recall and recognition test was also measured. The elderly were shown to be impaired on all tests when compared with young controls. Analysis revealed that release from proactive interference was significantly correlated with performance on alternative uses but not WCST while the size of subjects' discrepancy between recall and recognition correlated strongly with WCST but not with Alternate Uses. In addition there was a strong correlation between the two measures of spontaneous flexibility but these measures did not correlate with WCST. Performance on the two measures of memory was also uncorrelated. The data indicate that the pattern of frontal deterioration in the elderly does not comprise a single deficit and, furthermore, that the relationship between frontal dysfunction and normal age-related memory loss is not unidimensional.

Adult↗
PubMed1994

Differing mechanisms for proactive effects of intermittent and single shock on gastric ulceration.

Rats exposed to either 80 5-s shocks on a VT 60-s or to a single 400-s shock plus 80-min rest in the shock apparatus show dramatically increased degree of ulceration induced 72 h later by exposure to 75-min restraint-in-water stress (at 19 degrees C). However, the proactive effect of the 80 shocks on later gastric ulceration was blocked by SC injection of 7 mg/kg naltrexone 20 min prior to the shock session; naltrexone treatment prior to the single shock session had no ameliorating effect. A second experiment confirmed opioid involvement in the proactive augmentation of vulnerability by showing that when a 20 mg/kg injection of morphine replaced the shocks, rats showed a comparable increase in vulnerability. A third experiment replicated the basic findings from the first experiments that 80 intermittent shocks increase vulnerability to the ulcerogenicity of restraint-in-water and that this effect can be mimicked by replacing the shock stress with a 20 mg/kg injection of morphine; however, other groups showed that injection of 40 mg/kg produced a similar effect whereas 10 mg/kg was ineffective as a mimic. This suggests that there are at least two types of proactive effects from shock experiences that can increase later vulnerability to shock-induced gastric ulceration; one is opioid mediated and the other is not. This finding parallels reports made about mediation of prior shock-induced hypoalgesias and expands the spectrum to psychosomatic phenomenon.

Animals↗
PubMed1991

Intraseptal administration of bicuculline produces working memory impairments in the rat.

Male Sprague-Dawley rats, trained to perform a delayed-non-match-to-sample eight-arm radial maze task, were implanted with a single cannula aimed at the medial septal nucleus. A within-subjects design was utilized to examine the effects of intraseptal administration of bicuculline (0.5 micrograms) on performance of this task with 1- and 4-h delay intervals imposed between choices four and five. Administration of bicuculline immediately following the first four choices produced an impairment in maze performance at both a 1- and a 4-h delay interval. This treatment also produced an increase in latency per choice. Bicuculline-induced impairments were not observed when administered 2 h following the predelay session (2 h prior to testing). These data support previous observations that pharmacological manipulation of GABAergic activity within the septum modifies working memory processes.

Animals↗
PubMed1986

Further analysis of encoding in patients with Huntington's disease.

Arguments favoring the view that derangement of normal encoding processes contributes to the memory defects of patients with Huntington's disease (HD) are supported by the finding that HD patients do not learn highly imageable words more rapidly than they learn words that are difficult to image. But other data indicating that HD patients can use verbal mediators as mnemonic aids for picture recognition question the existence of important and general encoding deficits in HD. In the first of two experiments the influence of imagery on the acquisition and recall of 14-word lists was studied using a free-recall paradigm. Both HD patients and controls learned highly imageable words more quickly and retained them better than low imagery words over a 30-min delay. The impact of imagery on learning was apparent by the first trial. In the second experiment, a modified Brown-Peterson distractor paradigm was used to assess release from proactive interference (PI). It was found that both HD patients and controls exhibited comparable release from PI following a shift in taxonomic categories. The results of both experiments question the importance of encoding deficits in the memorial dysfunctions associated with HD.

Adult↗
PubMed1981

Patterns of residual masking.

"Residual masking' was measured in a tonal forward masking paradigm. In one experiment, psychophysical tuning curves and masking patterns were obtained at several frequencies and levels for a fixed masker-probe time delay. In a second experiment, tuning curves and masking patterns were measured as masker-probe time delay was varied. Our results indicate that tuning curves and masking patterns are sharpest at low levels, high frequencies and brief masker-probe time delays. In addition, we observed that masked probe threshold returned to the level of unmasked probe threshold at approximately the same post-masker time regardless of masker level or the probe-to-masker frequency relationship. These findings suggest that frequency, level and time delay all affect the degree of frequency selectivity observed with these measures.

Adult↗