Functional changes in brain activity during priming in Alzheimer's disease

Patients with Alzheimer's disease (AD) are often impaired on certain forms of implicit memory, such as word-stem completion priming (WSCP). Lesion data suggest that deficient WSCP may be associated with abnormal functioning in the posterior neocortex. Using positron emission tomography (PET), we here provide direct support for this view. Compared with normal old adults, AD patients showed reduced priming on a word-stem completion task. The normal old showed decreased activity in right occipital cortex (area 19), whereas the AD patients showed increased activity in this region during priming. To the extent that decreased activity during priming reflects an experience-dependent reduction of the neuronal population involved, these results indicate that shaping of the relevant neurons is slower in AD, possibly as a result of inadequate initial stimulus-processing.     

Neural correlates of word-stem priming

The purpose of this study was to identify the neural correlates of implicit memory in a word-stem completion task. Given that both explicit and implicit retrieval tend to occur in this type of memory task, conventional analyses of old/new event-related potential effects are equivocal. To overcome this problem, depth of processing was manipulated and subjective awareness measured. From 400 ms poststimulus, event-related potentials evoked by stems completed with studied words were more positive than those evoked by stems completed with unstudied items. This difference was maximal at parietooccipital electrode sites. Event-related potentials were not modulated by either depth of processing or awareness. Behavioral and event-related potential data converged to indicate that the old/new effect reflects processes either contributing to, or contingent upon, implicit memory retrieval.     

Dissociation of conscious and unconscious repetition priming effect on event-related potentials

Although the neural basis of the unconscious priming effect has previously been investigated, the results of these studies have possibly been contaminated by a conscious priming effect. The aim of the present study was to dissociate the effects of conscious and unconscious priming on event-related potential (ERP) by using the process-dissociation procedure. A prime word was presented briefly, followed by a word-stem, in each trial. Under the inclusion condition, subjects were instructed to complete the word-stem using the prime word, while under the exclusion condition subjects were asked to complete the word-stem with a word not seen as prime. The behavioral priming effect was obtained under both conditions, indicating that the prime words were processed unconsciously and influenced the word-stem completion task. We found that two ERP components were affected by repetition priming. First, the N400 amplitude was decreased by word repetition under the inclusion condition, but not under the exclusion condition. This result suggests that N400 would reflect conscious lexical processing, but not unconscious lexical activation. Second, the negativity at left front lateral region was enhanced by word repetition under the exclusion condition. We discuss this finding herein in relation to the activity of the left inferior prefrontal cortex with regard to word semantic processing.     

Skill learning and repetition priming in Alzheimer's disease.

While perceptual-motor learning occurs normally in Alzheimer's disease (AD) patients, their ability to acquire the skill of reading transformed text has not been well delineated. AD patients and matched controls were timed as they read two blocks of words presented in mirror image. Control subjects displayed both skill learning and repetition priming, whereas AD patients displayed only repetition priming. Skill learning in AD patients was associated with their ability to complete verbal analogies. They displayed the expected impairment in recognition for the words from the mirror reading task. The failure of AD patients to acquire the mirror reading skill can be understood through a task analysis and may reflect an underlying deficit in abstract reasoning that precludes the development of appropriate pattern analyzing strategies needed to transform rotated text.     

Automatic and controlled uses of memory in Alzheimer's disease

This study used the process-dissociation procedure (Jacoby, 1991) to examine the contribution of automatic and controlled uses of memory to a stem completion task in 16 patients with Alzheimer's disease (AD) and a matched group of healthy elderly subjects (EC). In an inclusion task subjects attempted to use a studied word to complete three-letter word stems, in an exclusion task they were instructed to complete stems with unstudied words. Relative to patients with AD, EC subjects produced more target word completions under inclusion conditions, and less target word completions under exclusion conditions. The probability of the AD group using studied words to complete stems was invariant across inclusion and exclusion conditions. Estimates derived from the process-dissociation calculations, showed that the performance of the AD patients was mediated entirely by automatic uses of memory, whereas for EC subjects controlled and automatic processes codetermined task performance. Both estimates of controlled and to a lesser extent automatic uses of memory were greater for the EC than the AD subjects, indicating that the stem completion impairment in AD may not be entirely attributable to a deficiency in controlled memory processes but also due to reduced automatic processing.     

Successive memory test performance and priming in Alzheimer's disease: evidence from the word-fragment completion task

This study assessed the performance of patients with Alzheimer's disease and healthy controls in a successive memory test paradigm. Subjects studied lists of words. Following study, tests of recognition (an explicit memory task) and primed word fragment completion (an implicit memory task) were administered. Since the same words were used in the two tasks, we were able to calculate the degree of dependence between recognition performance and primed word fragment completion. AD patients evidenced impaired recognition memory. In contrast, priming was intact. The pattern of correlation between the two tasks was similar in healthy controls and in AD. Independence between recognition and fragment completion was obtained when recognition preceded the fragment completion task, but not when fragment completion preceded recognition.     

Visual object priming differs from visual word priming: an ERP study

Implicit memory is inferred from repetition priming effects in tasks such as word identification, word fragment completion, and perceptual recognition with masking or brief exposures. In this experiment, we explored whether the visual word and object repetition priming effects can be reflected by features of ERP and whether visual word repetition priming differs from visual object repetition priming. We have observed that (1) pre-exposure to recognizable stimuli (both word and object picture) shortened the response time in identifying their repetitions; (2) repetition of unrecognized scrambles of words or object pictures did not show any effects on ERP patterns; (3) ERPs distinguished recognizable from unrecognizable stimuli; and, (4) repetitions of both words and pictures strongly influenced the patterns of ERPs, though the ERPs to word stimuli differed from the ERPs to picture stimuli.     

Implicit, explicit, and semantic memory functions in Alzheimer's disease and Huntington's disease.

A priming task involving a word-stem completion paradigm was administered to patients with Alzheimer's disease (AD), patients with Huntington's disease (HD), and normal control subjects. The task was done under conditions of both implicit and explicit recall. Explicit and implicit recall were positively correlated in all three groups. After controlling for explicit recall ability through ANCOVA, AD patients were found to be normally susceptible to the effects of priming on implicit recall. HD patients, however, exhibited significantly increased susceptibility to priming, suggesting that they may have carried out the implicit task in a manner different from that of normals and AD patients. In a second experiment, AD patients were found to supply words of significantly lower association strength than the other two groups in a "free association" task using words from a published list of word association norms. This apparent degradation of semantic memory was found to be strongly correlated with explicit recall performance, suggesting that explicit, implicit, and semantic memory functions decline in parallel in AD. Results are discussed with respect to the difficulties inherent in attempts to demonstrate selective impairments of conceptually distinct forms of memory.     

Masked word repetition results in increased fMRI signal: a framework for understanding signal changes in priming

Evidence from multiple paradigms has converged on the finding that stimulus repetition most often results in decreases in neural activity. The mechanisms of these decreases, however, are not yet well understood. The current study attempted to determine, through the use of masked word repetition priming, whether decreases in activity levels occur in response to pre- or post-prime identification processes. fMRI was performed while participants engaged in a lexical decision task where words were primed with a briefly presented and masked word. Masked word priming resulted in increased fMRI signal in regions of cortex associated with the perceptual identification of the target words. This finding provides evidence suggesting that the impact of repetition priming on the fMRI signal may depend upon whether or not the prime is identified.     

Preserved priming but insensitivity to perceptual fluency on recognition judgments in Alzheimer's disease

Background: Previous research on Alzheimer's disease (AD) has not yielded a consensus regarding the preservation of automatic memory processes, although there is a consensus that conscious recollection processes are impaired in AD. Methods: In the present study, we examined perceptual specificity effects (PSEs) in word recognition judgments (explicit memory task; Experiment 1) and word fragment completion (implicit memory task; Experiment 2) performed by individuals with mild AD and elderly adults without dementia (controls). Results: In recognition judgments, control subjects, but not individuals with AD, demonstrated PSEs (Experiment 1). In contrast, neither group showed PSEs on word fragment completion and their priming magnitudes were comparable (Experiment 2). Conclusions: The findings suggest that perceptually automatic processes in explicit memory judgments and implicit memory processes are different and that the former are specifically impaired in AD.     

Impaired acquisition of a mirror-reading skill in Alzheimer's disease

Several studies using the mirror-reading paradigm have shown that procedural learning and repetition priming may be preserved in the early stages of Alzheimer's disease (AD) (e.g., Deweer et al., 1994). According to the classical interpretation, improved reading time for repeated words is sustained by a repetition priming effect, while procedural learning is demonstrated when this improvement is also observed for new words. Following Masson (1986), the hypothesis tested in the present study was that improved reading of new words could also be due to a repetition priming effect rather than to the acquisition of a mirror-reading skill. Indeed, because the same letters are presented throughout the task, a repetition priming effect for the letters could suffice to explain the improvement in performance. To test this hypothesis, we administered to 30 healthy young and elderly subjects and to 30 AD patients a new mirror-reading task in two phases: an acquisition phase comprising pseudo-words constructed with one part of the alphabet, and a test phase in which both pseudo-words constructed with the same part of the alphabet and pseudo-words constructed with another part of the alphabet were presented. If the new pseudo-words composed with repeated letters were read faster, it would reflect a repetition priming effect; if pseudo-words composed of ‘new’ letters were read faster, it would reflect a procedural learning effect. The results show comparable repetition priming effects in AD patients and in healthy elderly subjects, whereas only healthy subjects showed a procedural learning effect. These results suggest, contrary to previous studies, that the learning of a new perceptual skill may not always be preserved in AD.     

Ageing affects brain activity in highly educated older adults: An ERP study using a word-stem priming task

In this event-related evoked potentials (ERP) study, the neural correlates of a group of highly educated older adults were compared with those of a group of young adults while performing a word-stem completion priming task under semantic and lexical encoding conditions. The results revealed that both age groups exhibited robust priming. The older participants showed better performance than the young adults. Both groups exhibited ERP repetition effects at posterior sites, but only the older adults showed additional frontal activity. The results suggest that highly performing older adults compensate for their lower level of parieto-occipital functioning, reflected by smaller P300 amplitude at posterior sites, by recruiting frontal sites as a mode of brain adaptation.     

Exploring different routes of recovery from memory in Alzheimer's disease: evidence for preserved long-term priming

Studies investigating implicit memory in Alzheimer's disease suggest that priming abilities disappear over time. This study investigates long-term priming in Alzheimer's disease. A total of 20 patients with Alzheimer's disease and 20 controls underwent the Free and Cued Selective Reminding test. After a 30-minute delay, participants were submitted to a word identification task comprising the studied words and new words. The patients exhibited a long-term priming effect similar to that presented by the comparison group. Therefore, whereas explicit retrieval is definitely impaired in Alzheimer's disease, implicit processes allowing the retrieval of that same information operate relatively normally, including after a long delay.     

The neural substrates of visual implicit memory: do the two hemispheres play different roles?

Identification of visually presented words is facilitated by implicit memory, or visual priming, for past visual experiences with those words. There is disagreement over the neuro-anatomical substrates of this form of implicit memory. Several studies have suggested that this form of priming relies on a visual word-form system localized in the right occipital lobe, whereas other studies have indicated that both hemispheres are equally involved. The discrepancies may be related to the types of priming tasks that have been used because the former studies have relied primarily on word-stem completion tasks and the latter on tasks like word-fragment completion. The present experiments compared word-fragment and word-stem measurements of visual implicit memory in patients with right occipital lobe lesions and patients with complete callosotomies. The patients showed normal visual implicit memory on fragment completion tests, but essentially no visual priming on standard stem completion tests. However, when we used a set of word stems that had only one correct solution for each test item, as was true of the items in the fragment completion tests, the patients showed normal priming effects. The results indicate that visual implicit memory for words is not solely dependent upon the right hemisphere, rather it reflects changes in processing efficiency in bilateral visual regions involved in the initial processing of the items. However, under conditions of high lexical competition (i.e., multiple completion word stems), the lexical processes, which are dominant in the left hemisphere, overshadow the visual priming supported by the left hemisphere.     

Lexical and conceptual components of stem completion priming in patients with Alzheimer's disease.

This study evaluated the hypothesis of dissociation between normal lexical but deficient conceptual repetition priming in patients with Alzheimer's disease (AD). For this purpose, we administered to patients with AD and age-matched normal controls the Stem Completion task. In Experiment 1, the level of word processing during study was manipulated by requiring subjects to count vowels (graphemic condition) or generate meanings (semantic condition) of target words. In Experiment 2, the presentation modality was varied during the study to obtain an intramodal and crossmodal repetition priming. Probably due to a floor effect of performance in the graphemic condition, in Experiment 1, AD patients exhibited lower priming than normal controls for the semantically processed words but comparable priming for the graphemically processed ones. In contrast, in Experiment 2, AD patients were poorly primed both in the intra- and crossmodal conditions. Results question the hypothesis of a lexical/conceptual dissociation in the repetition priming exhibited by AD patients and call for other explicative hypotheses of the dissociation between normal and deficient forms of repetition priming in degenerative dementia.     

The disconnection syndrome in the Alzheimer’s disease: The cross-modal priming example

Implicit memory is generally supposed to be preserved in Alzheimer’s disease (AD). Yet, some implicit priming effects are impaired and others are not. The preserved/impaired priming effects are often interpreted according to the perceptual/conceptual or identification/production distinctions. Perceptual–identification priming paradigms shall be preserved and conceptual–production priming paradigms impaired. A third interpretation is yet possible based on the disconnection syndrome hypothesis which states that patients with AD should fail tasks requiring relatively complex brain communications. In this case, patients with AD should not demonstrated a significant perceptual priming effect in an identification task if this one involved complex brain communications. The present study tests this latter hypothesis with two cross-modal priming experiments using a categorization task. A visual meaningless mask presented with half of the auditory primes tested the nature of the cross-modal priming effect. The control group exhibited significant priming effects for unmasked primes. The interference effect of the mask demonstrated that the priming effect was perceptually driven. Patients with AD did not present any priming effect nor mask interference. The present findings therefore showed that perceptual priming using an identification task could be impaired in AD supporting the disconnection syndrome hypothesis.     

Involvement of the medial temporal lobe in priming for new associations

This study was addressed to the question of whether the medial temporal lobe (MTL) plays a critical role in implicit memory for new associations. Priming for new associations was examined in two different tasks in 18 patients with focal lesions all involving the MTL. In Experiment 1, following a study phase for pairs of unrelated words, subjects performed a perceptual identification task on old, recombined, and new pairs of words presented at brief exposure durations. In contrast to control subjects, and despite a normal level of item priming, the patients failed to show superior identification of the old pairs relative to the recombined pairs, the measure of associative priming. In Experiment 2, subjects engaged in speeded naming of the print color for previously studied words presented in the original color or in a different old color, and for unstudied words. Again, in contrast to control subjects and despite a normal level of item facilitation on color naming reaction time (RT), the patients failed to show priming for recently experienced new associations between words and colors. Explicit recognition memory by the patients was abnormal in both experiments. This study records an absence of priming for new associations, in two different tasks in which the nature of the stimuli was considerably different, in a large group of patients with lesions in the MTL. Although some previous research has reported significant associative priming in other tasks for patients with MTL lesions, the present results suggest that this region is critical for forming new associations of the types assessed here.     

Event-related potentials associated with masked priming of test cues reveal multiple potential contributions to recognition memory

The relationship between recognition memory and repetition priming remains unclear. Priming is believed to reflect increased processing fluency for previously studied items relative to new items. Manipulations that affect fluency can also affect the likelihood that participants will judge items as studied in recognition tasks. This attribution of fluency to memory has been related to the familiarity process, as distinct from the recollection process, that is assumed by dual-process models of recognition memory. To investigate the time courses and neural sources of fluency, familiarity, and recollection, we conducted an event-related potential (ERP) study of recognition memory using masked priming of test cues and a remember/know paradigm. During the recognition test, studied and unstudied words were preceded by a brief, masked word that was either the same or different. Participants decided quickly whether each item had been studied ("old" or "new"), and for items called old, indicated whether they "remembered" (R) the encoding event, or simply "knew" (K) the item had been studied. Masked priming increased the proportion of K, but not R, judgments. Priming also decreased response times for hits but not correct rejections (CRs). Four distinct ERP effects were found. A medial-frontal FN400 (300-500 msec) was associated with familiarity (R, K Hits > CRs) and a centro-parietal late positivity (500-800 msec) with recollection (R Hits > K Hits, CRs). A long-term repetition effect was found for studied items judged "new" (Misses > CRs) in the same time window as the FN400, but with a posterior distribution. Finally, a centrally distributed masked priming effect was visible between 150 and 250 msec and continued into the 300-500 msec time window, where it was topographically dissociable from the FN400. These results suggest that multiple neural signals are associated with repetition and potentially contribute to recognition memory.     

Automatic and attentional mechanisms of semantic priming in Alzheimer's disease

Previous studies using a word-naming task have suggested that in demented patients, semantic priming results only from automatic spreading activation and not from attention-dependent processes. If this is true, then on a lexical-decision task where attention-dependent processes are a major source of the semantic-priming effect, demented patients should show little or no priming. To test this prediction, three groups of 16 subjects (young and normal-old individuals and patients with Alzheimer's disease) were given a Word-Naming and a Lexical-Decision task. In both tasks, the amount of semantic priming (the difference in response time to a word preceded by a semantically unassociated vs. a semantically associated word) was determined. Demented patients showed significantly greater semantic priming than either normal group on both tasks. This result argues against the hypothesis that the semantic priming found in demented patients is due solely to automatic processes.     

Repetition priming in aging and Alzheimer's disease: an integrative review and future directions

Two decades of research examining repetition priming in aging and Alzheimer's disease (AD) has yielded a large body of contradictory findings due to differences between studies in participant and task characteristics. Recent research that has employed methodological advances indicates that this form of implicit memory is preserved in healthy aging. When a priming deficit does occur in studies of aging, it is likely a very early signal of neurological disease. Future directions for research in this area include linking priming ability to known risk factors for development of AD, integrating priming measures into clinical neuropsychological assessment batteries, and implementing programs of cognitive retraining that enhance memory using stimulus repetition techniques.