Neuroanatomical correlates of episodic encoding and retrieval in young and elderly subjects.

Lesion studies have shown convincingly that the medial temporal lobes (MTL) and frontal lobes are critical to episodic memory. Ageing generally has been found to have a generally negative effect on episodic memory performance, which might relate to neurofunctional changes in the frontal and medial temporal brain regions. In the present study, we used functional MRI (fMRI) to investigate separately the contributions of encoding and retrieval to the age-related decline in memory. To this end, we compared brain activity patterns obtained during incidental encoding (pleasant/unpleasant judgements about nouns) and subsequent retrieval (recognition) in three groups: a group of young subjects, a group of elderly subjects showing reduced memory performance (ELD-RED), and a group of elderly subjects who still performed in the normal range (ELD-NORM). This allowed us to differentiate between age-related changes in brain activity that affect memory function and those that do not have an apparent effect on memory function, because they are found in both elderly groups. Contrary to previous imaging studies on this topic, we used (self-paced) event-related fMRI to control for differences in performance level across groups by including correct responses only. Comparing the encoding of successfully remembered items with baseline (press left/press right), the young subjects showed a significant increase in brain activation in the left anterior MTL compared with the ELD-RED but not the ELD-NORM subjects. Comparing correctly rejected items (retrieval attempt) with baseline, the ELD-RED group showed much increased overall activity throughout the brain compared with the other groups. However, when correctly recognized items (retrieval attempt + success) were compared directly with correctly rejected items (retrieval attempt), these differences were greatly reduced, revealing common activity in the left parietal, retrosplenial and left anterior prefrontal regions. Therefore, we conclude that the reduced performance in the ELD-RED group is likely to be due to MTL dysfunction during encoding. The differences observed during retrieval attempts may reflect strategic differences. The lack of differences observed in relation to retrieval success suggests that ageing does not affect the processes that support the actual recovery of information.

Parahippocampal activation during successful recognition of words: a self-paced event-related fMRI study.

In this study, we investigated retrieval from verbal episodic memory using a self-paced event-related fMRI paradigm, similar to the designs typically used in behavioral studies of memory function. We tested the hypothesis that the medial temporal lobe (MTL) is involved in the actual recovery of verbal information (retrieval success) rather than in the attempt to retrieve information (retrieval attempt). To this end, we used a verbal recognition task, distinguishing correctly recognized words, correctly rejected words, and a low-level baseline condition. Directly contrasting correct recognition with correct rejection of words, we found activation in the left fusiform/parahippocampal gyrus, indicating that this region has a distinct role in the successful retrieval of verbal information. Furthermore, our results were in agreement with those of previous imaging studies that compared a fixed-paced verbal recognition task to a baseline condition, showing activation in bilateral inferior frontal cortex, left dorsolateral prefrontal cortex, left anterior insular cortex, and anterior cingulate. This demonstrates the applicability of a self-paced event-related design within imaging studies of memory function.

A Bayesian model for implicit effects in perceptual identification.

Retrieving effectively from memory (REM; R. M. Shiffrin & M. Steyvers, 1997), an episodic model of memory, is extended to implicit memory phenomena, namely the perceptual identification studies reported in R. Ratcliff and G. McKoon (1997). In those studies, the influence of prior study was greatest when words were presented most briefly and when forced-choice targets and foils were most similar. R. Ratcliff and G. McKoon use these data to argue against models in which prior study changes a word's representation. A model in which prior study changes a word's representation by adding context information is fit to their data; at test, the model uses a Bayesian decision process to compare the perceptual and context features associated with the test flash to stored traces. The effects of prior study are due to matching extra context information and are larger when alternatives share many features, thereby reducing noise that attenuates these effects.

Testing the counter model for perceptual identification: effects of repetition priming and word frequency.

The counter model for perceptual identification (Ratcliff & McKoon, 1997) differs from alternative views of word recognition in two important ways. First, it assumes that prior study of a word does not result in increased sensitivity but, rather, in bias. Second, the effects of word frequency and prior study are explained by different mechanisms. In the present experiment, study status and word frequency of target and foil were varied independently. Using a forced-choice task, we replicated the bias effect. However, we also found several interactions between frequency and prior study that are in direct conflict with the counter model. Most important, prior study of both alternatives resulted in an attenuation of the frequency effect and an increase in performance for low-frequency targets, but not for high-frequency targets. These findings suggest that the effects of frequency and prior study are not mediated by completely independent mechanisms.

A criterion-shift model for enhanced discriminability in perceptual identification: a note on the counter model.

The original version of the counter model for perceptual identification (Ratcliff & McKoon, 1997) assumed that word frequency and prior study act solely to bias the identification process (i.e., subjects have a tendency to prefer high-frequency and studied low-frequency words, irrespective of the presented word). In a recent study, using a two-alternative forced-choice paradigm, we showed an enhanced discriminability effect for high-frequency and studied low-frequency words (Wagenmakers, Zeelenberg, & Raaijmakers, 2000). These results have led to a fundamental modification of the counter model: Prior study and high frequency not only result in bias, but presumably also result in a higher rate of feature extraction (i.e., better perception). We demonstrate that a criterion-shift model, assuming limited perceptual information extracted from the flash as well as a reduced distance to an identification threshold for high-frequency and studied low-frequency words, can also account for enhanced discriminability.

Priming in a free association task as a function of association directionality.

Two experiments investigated priming in free association, a conceptual implicit memory task. The stimuli consisted of bidirectionally associated word pairs (e.g., BEACH-SAND) and unidirectionally associated word pairs that have no association from the target response back to the stimulus cue (e.g., BONE-DOG). In the study phase, target words (e.g., SAND, DOG) were presented in an incidental learning task. In the test phase, participants generated an associate to the stimulus cues (e.g., BEACH, BONE). In both experiments, priming was obtained for targets (e.g., SAND) that had an association back to the cue, but not for targets (e.g., DOG) for which such a backward association was absent. These results are problematic for theoretical accounts that attribute priming in free association to the strengthening of target responses. It is argued that priming in free association depends on the strengthening of cue-target associations.

Automatic priming effects for new associations in lexical decision and perceptual identification.

Information storage in semantic memory was investigated by looking at automatic priming effects for new associations in two experiments. In the study phase, word pairs were presented in a paired-associate learning task. Lexical decision and perceptual identification were used to examine priming effects during and after the study phase. There was automatic priming for new associations. The priming effect was greatly reduced when different semantic tasks were used at study and test compared to when identical tasks were used at study and test. The results show that new associations in semantic memory can be accessed automatically but are still context dependent. This suggests that rather than being abstract and static, retrieval from semantic memory interacts dynamically with the context.

Adding new word associations to semantic memory: evidence for two interactive learning components.

The addition of newly learned word associations to semantic memory was investigated in three experiments. In these experiments word pairs were repeatedly presented as prime-target pairs in a lexical decision task. Performance on repeated pairs (both pre-experimentally associated and initially unrelated pairs) was compared to that on neutral pairs. In Experiments 1 and 2, effects of prior study (episodic priming) were observed but since this episodic priming effect was equal for both conditions it could not be concluded that the new associations has been added to semantic memory. In Experiment 3 some evidence was found that the newly learned word associations had been added to semantic memory. This occurred only after presenting the word pairs for several trials in paired-associate learning. The results are interpreted as supporting a model that distinguishes two memory components that mediate the effects of new learning, an episodic and a semantic one.

Episodic memory in dementia of the Alzheimer type and in normal ageing: similar impairment in automatic processing.

A perceptual identification task was used to provide an implicit measure for automatic memory processes. The facilitation of word identification on repeated presentation is taken as a measure of the automatic retrieval of an episode. In addition, recognition memory was tested. The recognition task is an explicit test of memory and relies mainly on controlled processing. In the first experiment 11 patients suffering from probable Alzheimer disease and 11 normal age- and sex-matched controls were tested. Both groups exhibited a rather small facilitation effect (ca 7%) but did not differ in the size of the effect. However, when tested explicitly, a difference in recognition memory existed between the two groups. In the second experiment the performance of 11 normal young subjects was compared to that of 11 normal elderly subjects. Whereas the elderly group showed a small facilitation effect similar to that observed in the first experiment, a considerable facilitation effect was found for the young group. Also, the elderly group had poorer recognition memory than the young group.

Statistical analysis of the Michaelis-Menten equation.

An application of the method of maximum likelihood (ML) is described for analysing the results of enzyme kinetic experiments in which the Michaelis-Menten equation is obeyed. Accurate approximate solutions to the ML equations for the parameter estimates are presented for the case in which the experimental errors are of constant relative magnitude. Formulae are derived that approximate the standard errors of these estimates. The estimators are shown to be asymptotically unbiased and the standard errors observed in simulated data rapidly approach the theoretical lower bound as the sample size increases. The results of a large-scale Monte Carlo simulation study indicate that for data with a constant coefficient of variation, the present method is superior to other published methods, including the conventional transformations to linearity and the nonparametric technique proposed by Eisenthal and Cornish-Bowden (1974, Biochemical Journal 139, 715-720). Finally, the present results are extended to the analysis of simple receptor binding experiments using the general approach described by Munson and Rodbard (1980, Analytical Biochemistry 107, 220-239).

Prostaglandin-like substances in Propionibacterium acnes. VI. Characterization of the lipid fraction by gas chromatography in conjunction with mass spectrometry.

The lipid fraction of P. acnes was submitted to stepwise purification followed by bioassay in order to localize the prostaglandin-like material. GC-MS analysis revealed the occurrence of substances having a part but not a total molecule in common with the prostaglandin family, suggesting that prostaglandin-like substances represent a new group of prostaglandin compounds.

System for the identification of novel prostaglandins.

A system for structural analysis based on thin-layer and gas chromatographic and mass spectrometric data is presented. It permits the rapid and unequivocal identification of structurally closely related prostaglandins and their products containing microbiologically introduced hydroxyl groups at positions C-16, -17, -18, -19, and -20. Novel criteria are described by which distinctions can be made between stereoisomers.