Relationship between nicotinic receptors and cognitive function in early Alzheimer's disease: a 2-[18F]fluoro-A-85380 PET study

Neuronal nicotinic acetylcholine receptors (nAChRs) are critical for higher order cognitive processes. Post-mortem studies suggest reductions in nAChRs (particularly the alpha(4)beta(2) subtype) with ageing and in Alzheimer's disease (AD). This study aimed to; (1) quantify nAChR distribution in vivo with 2-[18F]fluoro-A-85380 (2-FA) in 15 early AD patients compared to 14 age-matched, healthy controls (HC) and (2) correlate nAChR distribution with cognitive performance in both groups. All participants were non-smokers and underwent cognitive testing along with a dynamic PET scan after injection of 200 MBq of 2-FA. Brain regional 2-FA binding was assessed through a simplified estimation of Distribution Volume (DV(S)). The AD group differed significantly from HC on all cognitive measures employed, with impairments on measures of attention, working memory, language, executive function, visuospatial ability, verbal learning and verbal memory (p<.05). Contrary to post-mortem data this study found no evidence of in vivo nAChR loss in early AD despite significant cognitive impairment. Furthermore, no correlation between nAChR and cognitive performance was found for either group. The findings of the current study suggest preservation of nAChRs early in AD supporting previous studies. It is possible that while the clinical 2-FA PET method described here may be insensitive in detecting changes in early AD, such changes may be detected in more advanced stages of the illness.     

Order information and free recall: evaluating the item-order hypothesis

The item-order hypothesis proposes that order information plays an important role in recall from long-term memory, and it is commonly used to account for the moderating effects of experimental design in memory research. Recent research (Engelkamp, Jahn, & Seiler, 2003; McDaniel, DeLosh, & Merritt, 2000) raises questions about the assumptions underlying the item-order hypothesis. Four experiments tested these assumptions by examining the relationship between free recall and order memory for lists of varying length (8, 16, or 24 unrelated words or pictures). Some groups were given standard free-recall instructions, other groups were explicitly instructed to use order information in free recall, and other groups were given free-recall tests intermixed with tests of order memory (order reconstruction). The results for short lists were consistent with the assumptions of the item-order account. For intermediate-length lists, explicit order instructions and intermixed order tests made recall more reliant on order information, but under standard conditions, order information played little role in recall. For long lists, there was little evidence that order information contributed to recall. In sum, the assumptions of the item-order account held for short lists, received mixed support with intermediate lists, and received no support for longer lists.     

Generation and memory for contextual detail

Generation enhances item memory but may not enhance other aspects of memory. In 12 experiments, the author investigated the effect of generation on context memory, motivated in part by the hypothesis that generation produces a trade-off in encoding item and contextual information. Participants generated some study words (e.g., hot-c__) and read others (e.g., hot-cold). Generation consistently enhanced item memory but did not enhance context memory. More specifically, generation disrupted context memory for the color of the target word but did not affect context memory for location, background color, and cue-word color. The specificity of the negative generation effect in context memory argues against a general item-context trade-off. A processing account of generation meets greater success. In addition, the results provide no evidence that generation enhances recollection of contextual details.     

Do readers make inferences about conversational topics?

When we read that two protagonists in a story chatted together for a couple of minutes, do we draw inferences about the topic of the conversation on the basis of information presented earlier in the text? Participants read passages in which protagonists part and later reunite; the passages ended with a sentence either that implied conversation or did not. In Experiment 1, participants' continuation sentences indicated that inferences about the topic of conversation were drawn. Recognition probe data in Experiment 2 provided more immediate evidence of such inferences. Experiment 3 addressed a possible confound in Experiment 2 and again provided evidence that readers inferred the continuation of the conversation. In Experiments 4 and 5, we investigated the effect of having the targeted conversational topic be a secret that should not be shared between the protagonists. The results are discussed in terms of the collaboration between passive, memory-based text processing and schema-driven comprehension processes.     

The effect of negation on deductive inferences

Research shows that negation can suppress the activation of propositions presented explicitly in text, but does negation have a similar effect on propositions that can be inferred? That is, does negation inhibit the inference process? Four experiments investigated whether a deductive inference that produces a negated conclusion (therefore not a) is made as readily as a similar inference form that yields an affirmative conclusion (therefore a). A combination of naming latencies, verification times, and reading times indicate that negation does not affect the deductive inference process itself, although it may inhibit the activation of inferred concepts.     

The emergent generation effect and hypermnesia: influences of semantic and nonsemantic generation tasks

The generation effect is moderated by experimental design, affecting recall in within-subjects designs but typically not in between-subjects designs. However, N. W. Mulligan (2001) found that the generation effect emerged over repeated recall tests in a between-subjects design, calling into question the generality of this limiting condition. In addition, the generate condition but not the read condition produced hypermnesia (increased recall over tests). The present experiments demonstrate that semantic-based (semantic-associate and category-associate) generation tasks produce this pattern of results whereas nonsemantic (letter transposition, rhyme, word fragment) generation tasks do not. Thus, the emergent generation effect appears to be a byproduct of semantic elaboration rather than a direct product of generation. In addition, high- and low-imagery words produced equivalent hypermnesia and emergent generation effects, arguing against a mediating role for imagistic encoding. Finally, there is no evidence of an emergent generation effect for nonwords, another traditional limiting condition of the generation effect.     

Easily perceived, easily remembered? Perceptual interference produces a double dissociation between metamemory and memory performance

A recent candidate for explaining metamemory judgments is the perceptual fluency hypothesis, which proposes that easily perceived items are predicted to be remembered better, regardless of actual memory performance (Rhodes & Castel Journal of Experimental Psychology: General 137:615–625, 2008). In two experiments, we used the perceptual interference manipulation to test this hypothesis. In Experiment 1, participants were presented with intact and backward-masked words during encoding, followed by a metamemory prediction (a list-wide judgment of learning, JOL) and then a free recall test. Participants predicted that intact words would be better recalled, despite better actual memory for words in the perceptual interference condition, yielding a crossed double dissociation between predicted and actual memory performance. In Experiment 2, JOLs were made after each study word. Item-by-item JOLs were likewise higher for intact than for backward-masked words, despite similar actual memory performance for both types of words. The results are consistent with the perceptual fluency hypothesis of metamemory and are discussed in terms of experience-based and theory-based metamemory judgments.     

Throwing in the dark: improved prediction of action outcomes following motor training without vision of the action

Traditional models of action understanding emphasise the idea that long-term exposure to a wide array of visual patterns of particular actions allows for effective action anticipation or prediction. More recently, a greater emphasis has been placed on the motor system’s role in the perceptual understanding and prediction of action outcomes. There have been attempts to isolate the contributions of visual and motor experience in action prediction, but to date, these studies have relied on comparisons of motor-visual experience to visual-only (observational) experience. We conducted a learning study, where visual experience was directly manipulated during practice. Novice participants practised throwing darts to 3 specific areas of a dartboard. A group trained without vision of their action, only feedback about the final landing position, significantly improved in their ability to predict the landing position of a thrown dart, from temporally occluded video clips. The performance of this ‘no-vision’ group did not differ from a Full-vision group and was significantly more accurate than an observation-only and a no-practice control group (with the latter two groups not improving pre- to post-practice). These results suggest that motor experience specifically modulates the perceptual prediction of action outcomes. This is thought to occur through simulative mechanisms, whereby observed actions are mapped onto the observer’s own motor representations.     

Conceptual implicit memory and environmental context

Changes in environmental context between encoding and retrieval often affect explicit memory but research on implicit memory is equivocal. One proposal is that conceptual but not perceptual priming is influenced by context manipulations. However, findings with conceptual priming may be compromised by explicit contamination. The present study examined the effects of environmental context on conceptual explicit (category-cued recall) and implicit memory (category production). Explicit recall was reduced by context change. The implicit test results depended on test awareness (assessed with a post-test questionnaire). Among test-unaware participants, priming was equivalent for same-context and different-context groups, whereas for the test-aware, the same-context group produced more priming. Thus, when explicit contamination is controlled, changes in environmental context do not impair conceptual priming. Context dependency appears to be a general difference between implicit and explicit memory rather than a difference between conceptual and perceptual implicit memory. Finally, measures of mood indicated no changes in affect across contexts, arguing against mood mediation for the context effects in explicit recall.