Neuropsychological evidence for multiple implicit memory systems: a comparison of Alzheimer's, Huntington's, and Parkinson's disease patients

The performances of patients with dementia of the Alzheimer type (DAT), patients with Huntington's disease (HD), and demented and nondemented patients with Parkinson's disease (PD) were compared on 2 tests of implicit memory that do not require the conscious recollection of prior study episodes: (1) a pursuit-rotor motor learning task and (2) a lexical priming test. The HD patients were found to be impaired on the motor learning but not the lexical priming task, whereas the DAT patients evidenced the opposite relationship on these tasks. The demented, but not the nondemented, PD patients were found to be impaired on both tests of implicit memory. For both the HD and PD patients, deficits on the motor learning task correlated significantly with severity of dementia but not with level of primary motor dysfunction. The noted double dissociation between HD and DAT patients indicates that different forms of implicit memory, all of which are intact in amnesia, are dependent upon distinct neuroanatomic systems. Motor skill learning may be mediated by a corticostriatal system, whereas verbal priming may depend upon the integrity of the neocortical association areas involved in the storage of semantic knowledge. The results for the PD patients suggest that the demented PD patients have endured damage to the neurologic systems subserving both motor learning and lexical priming.     

Strategy-based semantic priming in Alzheimer's dementia

The ability to engage semantic search strategies was assessed in a group of patients with dementia of the Alzheimer's type (DAT) (n = 11) and a group of age-matched control subjects (n = 13). The subjects performed a semantic priming task in which attentional priming was induced by manipulating the expected relationship between the primes and targets. Older control subjects were able to predict target words on the basis of expectancy, regardless of the semantic relationship between the prime and target. The DAT patients were also able to predict targets on the basis of expectancy, but only when the prime and target were semantically related. These results suggest that the structure of semantic memory remains intact in DAT, and that semantic memory retrieval may be facilitated by providing DAT patients with appropriate search strategies.     

Repetition effects in a lexical decision task: the role of episodic memory in the performance of alcoholic Korsakoff patients

To examine the contribution of episodic memory to the successful verbal priming performance of Korsakoff patients, we adapted a lexical decision task which holds constant the processing demands during study and testing. Words and nonwords were repeated at a lag of 0, 1, 3, 8 and 15 items and the decrease in response latency was taken as a measure of priming. In Experiment 1, Korsakoff patients showed repetition priming of a magnitude similar to that obtained by alcoholic controls, even at a lag of 15 intervening items. Experiment 2 explored the effect of word frequency on repetition priming. Korsakoff patients again showed normal priming up to lags of 15, and, as expected, these repetition effects were larger for low frequency than for high frequency words. This outcome was felt to be more consistent with an episodically based familiarity account than with a semantic activation account. Finally, Korsakoff patients were found to be impaired in their ability to use episodic memory in an explicit memory task that used the same material under comparable presentation conditions (Experiment 3). Contemporary processing models of episodic memory are discussed as possible explanations for the successful implicit memory performance by amnesic patients on this task.     

Lexical and semantic priming deficits in patients with Alzheimer's disease

Two experiments utilizing priming procedures examined the status of semantic memory in demented and amnesic patients. In the first investigation, lexical priming was assessed in patients with dementia of the Alzheimer type (DAT), Huntington's Disease (HD), alcoholic Korsakoff's syndrome (KS), and in intact control subjects. Subjects were first exposed to a list of words in a rating task and then required to complete three-letter stems with the "first word that comes to mind". Half of the stems could be completed with the previously presented words and the other half were used to assess baseline guessing rates. Recall and recognition of incidentally exposed words was also assessed. Although all three patient groups were impaired on tests of recall and recognition, only the DAT patients exhibited a priming deficit on the stem-completion task. In the second experiment, DAT, HD, and intact control subjects were administered a semantic priming test which required the subject to "free associate" to the first words of previously presented semantically associated word pairs. The results for this association task showed that DAT patients were significantly less likely to produce the second word of the semantically related pair than were the other subject groups. The results of these two experiments suggest that the memory capacities of DAT patients are characterized by a breakdown in the structure of semantic memory and that this impairment is evident on some "automatic" as well as "effortful" processing tasks.     

Establishing a relationship between activity reduction in human perirhinal cortex and priming

Perirhinal neurons exhibit reduced firing rates with stimulus repetition, a phenomenon termed “repetition suppression.” However, relationships between perirhinal repetition suppression and behavioral expressions of memory remain unclear. We used anatomically constrained functional magnetic resonance imaging (fMRI) to assess relationships between perirhinal activity and priming, a type of implicit memory. Priming was expressed as speeded animacy judgments for old versus new words. Concurrently, old words elicited less neural activity in bilateral perirhinal cortex. The magnitude of the left perirhinal activity reduction selectively predicted the magnitude of behavioral priming in an across‐subjects hierarchical linear regression analysis. These findings have implications for considering how perirhinal cortex may contribute to different neurocognitive functions, possibly including both implicit memory and familiarity‐based recognition. This study documents the first evidence linking behavioral measures of priming to information processing in perirhinal cortex. © 2009 Wiley‐Liss, Inc.     

Neuronal correlates of familiarity-driven decisions in artificial grammar learning

It has been proposed on the basis of behavioural data that grammaticality judgments in implicit artificial grammar learning paradigms are largely driven by priming based on fragment familiarity. A prediction that follows from this account is that neural deactivation, a common correlate of repetition priming, should be observed for grammatical compared to ungrammatical stimuli. We conducted an event-related fMRI study to investigate neuronal correlates of such fragment-based priming. In a study phase, participants performed a short-term memory task on a series of strings of pseudofont characters. Scanning was performed in a subsequent test phase in which participants classified new strings as either grammatical or ungrammatical. Test strings differed systematically from training strings in terms of exemplar and fragment similarity. Behaviourally, participants classified strings as grammatical based on fragment familiarity. Differential activity was evident during string classification as reduced activity in left lateral occipital complex and bilateral lingual gyri for strings with high fragment familiarity compared to strings with low fragment familiarity. Thus, consistent with the hypothesis, neuronal facilitation in extrastriate occipital regions may constitute one basis of implicit grammaticality decisions based on fragment priming.     

Impaired production priming and intact identification priming in Alzheimer's disease.

This study examined the distinction between identification and production processes in repetition priming for 16 patients with Alzheimer's disease (AD) and 16 healthy old control participants (NC). Words were read in three study phases. In three test phases, participants (1) reread studied words, along with unstudied words, in a word-naming task (identification priming); (2) completed 3-letter stems of studied and unstudied words into words in a word-stem completion task (production priming); and (3) answered yes or no to having read studied and unstudied words in a recognition task (explicit memory). Explicit memory and word-stem completion priming were impaired in the AD group compared to the NC group. After correcting for baseline slowing, word-naming priming magnitude did not differ between the groups. The results suggest that the distinction between production and identification processes has promise for explaining the pattern of preservation and failure of repetition priming in AD.     

Implicit learning in patients with Alzheimer's disease

We examined implicit memory using priming and procedural learning tasks in patients with probable Dementia-Alzheimer's Type (DAT) to examine whether priming and procedural processes could be dissociated and whether task specificity was a factor in DAT patient performance. Priming was tested using a word recognition paradigm (perceptual priming) and by repeated administrations of a fragmented objects test (long term priming). Procedural learning was tested using repeated and random sequences on a choice serial reaction time task and by repeated administration of a puzzle map of the United States. DAT patients were compared to hospitalized depressed patients, patients suffering from Progressive Supranuclear Palsy (PSP), and normal controls. We found that DAT patients demonstrated marginal but significant implicit learning on both procedural learning and perceptual priming tasks. DAT patients performed relatively better on the procedural learning task than a perceptual priming task compared to PSP patients, suggesting that priming of meaningful stimuli is subserved by cortical structures whereas procedural motor responses to simple serial visual stimulus patterns can be maintained by subcortical systems. Furthermore, our findings suggest that priming and procedural processes can be dissociated and that task specificity is a factor in interpreting the results of implicit learning paradigms in DAT patients. The implications of these results for models of knowledge representation and memory processes as well as the way they can serve as models for testing nootropic drug effects are discussed.     

Verbal memory processes in schizophrenia patients and biological relatives of schizophrenia patients: intact implicit memory, impaired explicit recollection

Verbal memory deficits are arguably the most common cognitive abnormalities in biological relatives of schizophrenia patients. Because verbal memory is a complex cognitive function, it is necessary to differentiate its intact and compromised aspects in order to reveal aberrant neural systems that reflect genetic risk in relatives of schizophrenia patients. Using an experimental verbal memory task, we examined encoding, free-recall, repetition priming, and recognition of verbal material in 22 schizophrenia patients, 22 first-degree biological relatives of schizophrenia patients, and 23 nonpsychiatric control participants. Schizophrenia patients exhibited intact repetition priming, but worse size judgment task performance (encoding), recall, and recognition than the control participants. Biological relatives of schizophrenia patients exhibited intact size judgment task performance, repetition priming, and recognition, but a free-recall deficit. Although size judgment task performance at encoding was associated with recall of verbal material in schizophrenia and control groups, in the relative group encoding performance was associated with the degree of repetition priming. Findings are consistent with impaired explicit recollection of verbal material, but intact implicit verbal memory in schizophrenia patients and biological relatives of schizophrenia patients.     

Sparing of perceptual implicit memory despite suppression of the electrophysiological word repetition effect: a study with general anesthetic isoflurane.

OBJECTIVE: Much effort has been devoted to the search for the neurophysiological correlates of implicit memory. A commonly held view is that the early portion (250-500 ms) of the event-related potential (ERP) word repetition effect reflects processes important for perceptual implicit memory whereas the latter portion reflects processes implicated in explicit memory. It is, however, difficult to disentangle with certainty the relative contributions of each form of memory on ERPs since both forms co-exist in normal subjects. To dissociate ERP effect related to implicit and explicit memory, we used isoflurane sedation in normal subjects to suppress explicit remembering while sparing implicit memory. These ERPs were compared with those of non-medicated control subjects. METHODS: Thirteen subjects performed an incidental encoding task for words presented auditorily during the inhalation of a subanesthetic dose of isoflurane. After termination of isoflurane administration, we assessed free recall and recorded ERPs during a syllable completion task (implicit memory) and during a passive listening task (ERP repetition effect). Eleven non-medicated control subjects were tested in a similar manner. RESULTS: The controls showed robust early and late ERP repetition effect. The isoflurane group had implicit memory without free recall and showed no ERP repetition effect. CONCLUSIONS: These findings failed to show an association between any part of the repetition effect and perceptual implicit memory. The results are consistent with the view that processes linked to explicit memory contribute to the ERP repetition effect since there was a marked difference in free recall between the control and isoflurane groups. SIGNIFICANCE: The present study shows that the reversible alterations of memory by general anesthetics can be used to study the neurophysiological correlates of memory processes.     

Explicit memory and repetition priming in depression. Preliminary findings

Explicit memory and repetition priming, a form of implicit memory, were examined in depressed patients and controls. Explicit memory of depressed patients was severely impaired, whereas repetition priming was intact. These results are consistent with the hypothesis that the impairment of memory in depression is linked to a failure of effort-demanding cognitive processes. Repetition priming might be useful in differentiating between depression and dementia.     

Memory impairment differs in frontotemporal dementia and Alzheimer's disease

The aim of this study was to assess short-term and long-term explicit memory and implicit memory in frontotemporal dementia (FTD; frontal variant) and to compare FTD and Alzheimer's disease (AD) patients with similar severity of dementia. Fifteen FTD patients [mean age: 68 years; Mini-Mental State (MMS): 24], 30 probable AD patients (mean age: 72 years; MMS: 23) and 12 healthy subjects participated in the study. The three groups were comparable in terms of gender and educational level. Short-term memory was assessed with the digit span and Corsi block-tapping tests. Explicit verbal memory was assessed with the Grober and Buschke test, and implicit memory with a verbal priming task and a fragmented picture test. FTD patients demonstrated a genuine memory deficit with impaired digit span, encoding deficit and retrieval strategy difficulties, but preserved implicit verbal and visual priming. Memory patterns differed in AD and FTD: short-term memory and free recall were similarly decreased in FTD and AD but cues provided more benefit to FTD than to AD; encoding was more impaired and the forgetting rate was faster in AD than in FTD; priming was lower in AD than in FTD. AD patients with clinical and imaging frontal lobe dysfunction tended to have lower memory performance and to differ even more from FTD patients than AD patients without frontal lobe dysfunction.     

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.     

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.     

Flash Visual Evoked Potentials of Various Derivations in Dementia of the Alzheimer Type and Vascular Dementia

Background : Recently, evoked potentials have been used for objective monitoring of the cortical function in dementia. The aim of this study was to distinguish dementia of the Alzheimer type (DAT) from vascular dementia (VaD) using flash visual evoked potentials of various derivations.
Methods : A total of 70 patients consulting Tachikawa Medical Center Kashiwazaki Kosei Hospital were divided into four groups, normal adult (29.5 ± 8.5 years, n=16), normal elderly (77.2 ± 4.7 years, n=17), VaD (81.1 ± 8.1 years, n=17) and DAT (77.4 ± 5.6 years, n=20). Red flash stimulation was provided by a pair of goggles. Visual evoked potentials (VEPs) to flash were recorded in accordance with the International 10–20 Electrode System.
Results : The latencies of N130 and P190 of frontal and central derivations were significantly reduced in DAT compared with all other groups (p<0.05). The N130 and P190 latencies were markedly delayed in the normal elderly group compared with the normal adult group (p<0.05). The P3 (P100) latency of occipital derivation was significantly delayed in normal elderly, VaD and DAT groups compared with the normal adult group (p<0.05). In the DAT group, the P190 latency was shortened at central and frontal derivations compared with that at occipital derivation (p<0.05).
Conclusions : The N130 and P190 latencies decreased at frontal and central derivations in DAT. While the reason is still unclear, dysfunction in the central visual system induced by the degeneration of neuronal populations in DAT may cause the apparently reduced latency. Flash VEPs of frontal and central derivations may be useful for the differential diagnosis of DAT from VaD.     

Cross-modal semantic and homograph priming in healthy young, healthy old, and in Alzheimer's disease individuals.

Two experiments are reported that explore the influence of strength of the prime-target relationship on the observed priming effects in young, healthy old, and individuals diagnosed with dementia of the Alzheimer type (DAT). In Experiment 1, participants were auditorily presented primes (FURNITURE) and after varying delays presented visual targets that were (1) high-strength related (e.g., SOFA), (2) low-strength related (e.g., RUG), or (3) unrelated control words (e.g., COW or DEER). The results indicated that the DAT individuals produced relatively larger priming effects that both the young and the healthy old, but these data could be accommodated by increases in effect size due to general slowing of response latencies. In Experiment 2, the same cross-modal priming paradigm was used with ambiguous words presented as primes (e.g., BANK) and either high-dominant (e.g., MONEY) or low-dominant (e.g., RIVER) words as targets. The results of Experiment 2 produced a qualitatively distinct pattern of priming that indicated DAT individuals only produced priming for high-dominant targets and not for low-dominant targets, whereas, the healthy control groups produced equivalent priming for both high- and low-dominant targets. The discussion focuses on the implication that these results have for the interpretation of semantic priming effects, in general, along with implications for the apparent semantic memory loss in DAT individuals.     

Memory processing in Alzheimer's disease.

The aim of the present research was to examine automatic and controlled influences on memory processing in patients with Alzheimer's disease using the process-dissociation procedure. In Experiment 1, a source recognition procedure was used, and the patients were found to have significantly reduced estimates of automatic processing and capacity to recognise words seen during the study phase of the procedure. In Experiment 2, a detection of repetition procedure was used to determine whether automatic influences on memory decline as a dementia progressed. The patients showed the expected inability to detect repetition in their responding, but there was no evidence that estimates of automatic processing were predicted by mental status scores or by ratings of the severity of dementia. In the third study, a novel method for estimating parameters in the process-dissociation model, developed from the task used in Experiment 2, was tested in a student sample. In this procedure, participants first produce semantic associates with either high or low relatedness to a list of cue words. These responses are subsequently used in a paired associate learning paradigm to determine independent estimates of recollection and automatic processing. Evidence for the validity of this procedure was found in Experiment 3 and the procedure used to examine memory processing in a sample of persons with dementia (Experiment 4). The patient group was found to have a substantial deficit in controlled recollection and a reduced capacity for automatic memory processing.     

Increased inhibition and decreased facilitation effect during a lexical decision task in children

Widespread theories propose that implicit memory is established in the early stages of development, while explicit memory continues to develop until later stages. However, recent studies have argued that implicit memory changes developmentally. In order to elucidate the differences of implicit memory and semantic memory structures between children and adults, a single-word presentation method was developed using lexical decision tasks in which repeated real words, related real words, unrelated real words and pseudowords were presented in a list. Semantic priming and repetition priming using a single-word presentation method were employed in 25 children and 18 adults. Reaction time (RT) and correct rate for real words following pseudowords served as the base. Inhibition effect was defined as an increase in RT between a real word preceded by an unrelated real word and a real word preceded by a pseudoword. Facilitation effect was defined as a decrease in RT between a real word preceded by a related real word and a real word preceded by a pseudoword. Although the effect sizes of semantic priming did not differ between children and adults, the inhibition effect was larger and the facilitation effect was smaller in children. Repetition priming in children did not differ from that in adults. These findings challenge the idea of developmental invariance in implicit memory, suggesting that the strength of links between nodes in the semantic network increases and the range of spreading activation expands developmentally.     

Generative associative naming in dementia of Alzheimer's type

Forty-eight patients with mild to moderate dementia of Alzheimer's type (DAT) were tested with a generative associative naming task, a task that combines the aspects of fluency and of word association tests. The variables taken into consideration were the number of adequate and inadequate responses, conventionality, word frequency and lexical-semantic relation to the target. DAT patients' performances were compared to those of a group of control subjects matched for sex, age and educational level. As a group, the patients gave fewer adequate responses, more idiosyncratic responses and perseverations, while there was no difference in the qualitative variables. However, the analyses of the performance profiles suggest that, irrespective of the severity of the disease, two major subgroups of DAT patients may be identified: (1) a first subgroup of subjects produced words with a lower conventionality rate and these were mostly in propositional relationship to the target; they also produced a higher rate of idiosyncratic responses and perseverations. (2) A second subgroup of subjects gave more conventional responses, mostly in the hierarchical-categorical relationship. The disorders of the former subgroup seem to correspond to a disrupted access to some relatively spared semantic abilities, whereas those of the latter to a semantic breakdown.     

Exploring semantic memory by investigating buildup and release of proactive interference in healthy older adults and individuals with dementia of the Alzheimer type.

There is debate regarding the integrity of semantic memory in dementia of the Alzheimer type (DAT). One view argues that DAT is associated with a breakdown in semantic memory; the other argues that DAT is associated with predominantly preserved semantic memory and a breakdown in retrieval. The classic release from proactive interference (RPI) paradigm was used to shed light on this debate. Individuals with early-stage DAT (n = 36) and healthy older adult controls (n = 45) participated in an RPI paradigm. Each trial was a Brown-Peterson task in which participants read three-word lists, counted (for 0, 3, 6, or 9 s), and recalled the words. Both groups showed significant proactive interference (PI), but the size of the PI was significantly smaller in the DAT group. The group difference in PI may be due to the faster forgetting rate in the DAT group. Both groups showed significant RPI and there was no group difference in size when RPI was considered in terms of PI levels. Both groups showed PI and RPI in prior list intrusions. The DAT group's significant buildup and release of PI based on semantic categories suggest predominantly preserved semantic memory activity, at least, in early-stage DAT individuals.