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.     

Preserved priming in auditory perceptual identification in Alzheimer's disease

To examine the status of auditory perceptual priming in Alzheimer's disease (AD), this study examined the performance of AD patients in auditory perceptual identification of words. In Experiment 1, the processing operations required to perform the tasks at study and test were matched, whereas in Experiment 2, processing operations at study and test were mismatched. AD patients showed normal priming in both experiments, despite impaired recognition memory. These findings extend to the auditory domain the finding of intact perceptual implicit memory in AD. Preserved auditory priming in AD may reflect the operation of a pre-semantic, phonological representation system, localized to posterior neocortical areas that are functionally spared in AD.     

The underlying mechanisms of semantic memory loss in Alzheimer's disease and semantic dementia

Patients with Alzheimer's disease (AD) and patients with semantic dementia (SD) both exhibit deficits on explicit tasks of semantic memory such as picture naming and category fluency. These deficits have been attributed to a degradation of the stored semantic network. An alternative explanation attributes the semantic deficit in AD to an impaired ability to consciously retrieve items from the semantic network. The present study used an implicit lexical-decision priming task to examine the integrity of the underlying semantic network in AD and SD patients matched for degree of impairment on explicit semantic memory tasks. The AD (n=11) and SD (n=11) patient groups were matched for age, education, level of dementia and impairment on four explicit semantic memory tasks. Healthy elderly participants (n=22) were matched for age and education. Semantic priming effects were evaluated for three types of semantic relationships (attributes, category coordinates, and category superordinates) and compared to lexical associative priming. Healthy controls showed significant priming across all conditions. In contrast, AD patients showed normal superordinate priming, and significant (although somewhat reduced) coordinate priming, but no attribute priming. SD patients showed no priming effect for any semantic relationship. All groups showed significant associative priming. The results indicate that SD patients do indeed have substantial degradation of semantic memory, while AD patients have a partially intact network, accounting for priming in superordinate and coordinate conditions. These findings suggest that AD patients' impairment on explicit semantic tasks is the product of deficient explicit retrieval in combination with a partially degraded semantic network.     

Intact haptic priming in normal aging and Alzheimer's disease: evidence for dissociable memory systems

This study is the first to report complete priming in Alzheimer's disease (AD) patients and older control subjects for objects presented haptically. To investigate possible dissociations between implicit and explicit objects representations, young adults, Alzheimer's patients, and older controls performed a speeded object naming task followed by a recognition task. Similar haptic priming was exhibited by the three groups, although young adults responded faster than the two older groups. Furthermore, there was no difference in performance between the two healthy groups. On the other hand, younger and older healthy adults did not differ on explicit recognition while, as expected, AD patients were highly impaired. The double dissociation suggests that different memory systems mediate both types of memory tasks. The preservation of intact haptic priming in AD provides strong support to the idea that object implicit memory is mediated by a memory system that is different from the medial-temporal diencephalic system underlying explicit memory, which is impaired early in AD. Recent imaging and behavioral studies suggest that the implicit memory system may depend on extrastriate areas of the occipital cortex although somatosensory cortical mechanisms may also be involved.     

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.     

Directed and divided attention in Alzheimer's disease: impairment in shifting of attention to global and local stimuli.

This study investigated the relative performance of Alzheimer's disease (AD) patients and normal controls on directed and divided attention reaction time (RT) tasks that involved the use of global-local stimuli (e.g., a large '1' made from small '2s'). Relative to normals, AD patients displayed disproportionately greater impairment on the divided attention task compared to the directed attention task. On the divided attention task, when the target remained at the same global-local level across consecutive trials, the AD patients displayed a greater facilitation effect than did the controls when responding to the second stimulus. However, when the target changed levels across consecutive trials (i.e., from the global to the local, or vice versa) the AD patients' RTs to the second stimulus were disproportionately slower than were the controls' RTs. These results demonstrated that AD patients are impaired in disengaging and shifting attention across levels of perceptual organization within the same stimulus.     

False item recognition in patients with Alzheimer's disease

Recent evidence suggests that patients with Alzheimer's disease (AD), as compared with normal individuals, exhibit increased false recognition by stimulus repetition in the Deese-Roediger-McDermott (DRM) task or associative recognition memory tasks, probably due to impaired recollection-based monitoring. However, because of possible alternative explanations for the findings of these previous studies, the evidence for impaired recollection-based monitoring in AD patients remains inconclusive. In this study, we employed stimulus repetition in old/new recognition judgments of single-item picture memory without a factor of association between the stimuli and examined whether AD patients showed increased false item recognition as compared with healthy controls. AD patients and healthy controls studied single-item pictures presented either once or three times. They were later asked to make an old/new recognition judgment in response to (a) Same pictures, pictures identical to those seen at encoding, (b) Similar lures, novel pictures similar to but not identical to those seen at encoding, and (c) Dissimilar lures, novel pictures not similar to those seen at encoding. For Same pictures, repeated presentation of stimuli increased the proportion of “old” responses in both groups. For Similar lures, repeated presentation of stimuli increased the rate of “old” responses in AD patients but not in control subjects. The results of the present study clearly demonstrated elevated false recognition by stimulus repetition in single-item recognition in AD patients. The present findings strongly support the view that AD patients are impaired in their ability to use item-specific recollection in order to avoid false recognition.     

Reversed negative priming following frontal lobe lesions

The present study investigated whether lesions to the prefrontal cortex would lead to impaired inhibitory control in selective attention. Patients with uni- and bilateral frontal lobe damage and age-matched control participants were compared in an identity negative priming task involving letter naming. Whereas all control groups revealed robust negative priming and distractor interference, the majority of patients showed positive instead of negative priming and not all of them were more susceptible to interference. These results suggest that frontal lobe lesions disrupt distractor inhibition and cannot be explained in terms of a retrieval deficit. However, the level of interference may not only be determined by inhibition but also by excitation of the target stimulus.     

Preserved conceptual priming in Alzheimer's disease

We assessed Alzheimer's disease (AD) and healthy older adult control (HC) group performance on: (1) a conceptual priming task, in which participants had to make a semantic decision as to whether a degraded picture of an object encountered previously belonged to the category of living or non-living things; and (2) a recognition memory task. The AD group showed a dissociation between impaired performance on the recognition task and preserved priming for semantic decisions to degraded pictures. We argue that it is not whether priming is conceptual or perceptual that is important for the observation of priming in AD, rather it is the nature of the response that is required (c.f., Gabrieli et al., 1999).     

Impaired Acquisition and Rapid Forgetting of Patterned Visual Stimuli in Alzheimer's Disease

Whether or not rate of forgetting is accelerated in Alzheimer's disease (AD) is controversial. This study examined recognition of visual patterns in patients with AD and in controls at 10 min relative to a learning baseline measured after a 10-s delay (delayed recognition ratio, DRR). Comparable baseline performances were attained in the two groups by manipulating stimulus exposure times. Comparisons between 25 AD and 48 age-matched controls demonstrated lower DRR in AD when initial recognition, which was statistically worse in AD, was covariated. DRR was also lower in an analysis of subgroups closely matched on initial performance. The findings suggest that forgetting is accelerated in AD because multiple aspects of memory processing, including storage, are impaired.     

Impaired acquisition and rapid forgetting of patterned visual stimuli in Alzheimer's disease

Whether or not rate of forgetting is accelerated in Alzheimer's disease (AD) is controversial. This study examined recognition of visual patterns in patients with AD and in controls at 10 min relative to a learning baseline measured after a 10-s delay (delayed recognition ratio, DRR). Comparable baseline performances were attained in the two groups by manipulating stimulus exposure times. Comparisons between 25 AD and 48 age-matched controls demonstrated lower DRR in AD when initial recognition, which was statistically worse in AD, was covariated. DRR was also lower in an analysis of subgroups closely matched on initial performance. The findings suggest that forgetting is accelerated in AD because multiple aspects of memory processing, including storage, are impaired.     

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.     

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.     

Priming of color and position during visual search in unilateral spatial neglect

We examined priming of visual search by repeated target location or color in two patients with left visual neglect and extinction, following strokes centered on the right inferior parietal lobe. Both patients, like the healthy controls we tested, showed intact priming, with performance speeded when either the location or color of a singleton target was repeated over successive trials in a standard search condition (Experiment 1). This was observed both from and to targets on the contralesional (left) side. Moreover, priming of search was still observed even when a return of fixation back to display-center was required between successive trials (Experiment 2). When briefer displays were used (Experiment 3), the patients often failed to detect left targets. This situation revealed an important dissociation: Whereas location priming only arose from preceding left targets that had been consciously detected, color priming (possibly arising within the intact ventral stream) did not depend on awareness of the preceding target. There was considerable color priming from missed targets. These findings demonstrate relatively intact priming of visual search by color and location in patients with right parietal damage, and also reveal that location priming may differ from color priming in requiring awareness.     

Implicit and explicit memory in Alzheimer's disease and Parkinson's disease

Several tasks examined implicit and explicit memory in demographically matched samples of Alzheimer's (AD) and Parkinson's disease (PD) patients, and healthy elderly subjects. A fragmented pictures test, word stem-completion repetition priming, and a pursuit-rotor tracking task, followed by explicit memory tests, were given. AD patients were impaired on all explicit tests and on word stem-completion priming, but were intact on pursuit-rotor tracking and the skill learning (SL) component of the fragmented pictures test. PD patients were significantly better than AD patients on all explicit memory tests, but were selectively impaired on the SL component of the fragmented pictures test. Finally, a mirror-reading test was given to the PD patients and control subjects, with no significant differences found in performances between the two groups. Results are discussed in terms of hypothetical cognitive processes and brain circuits underlying different implicit and explicit memory domains.     

Impaired fear conditioning in Alzheimer's disease

Classical conditioning of the fear response is a basic form of nondeclarative (nonconscious) memory that mediates both normal and pathological responses to aversive stimuli. Because fear conditioning critically depends on the amygdala, a medial temporal lobe structure that frequently undergoes significant pathological changes early in the course of Alzheimer's disease (AD), we hypothesized that fear conditioning would be impaired in patients with mild to moderate AD. We examined simple classical fear conditioning in a group of 10 patients with probable AD and 14 demographically matched, neurologically intact elderly controls. During conditioning, one stimulus (e.g. a green rectangle, the conditioned stimulus (CS+)), was paired with an aversive stimulus (a loud noise, the unconditioned stimulus (US)) using a partial reinforcement conditioning schedule. The opponent color (e.g. red rectangle), the CS-, was never paired with the US. The elderly controls acquired robust fear responses as demonstrated by their differential skin-conductance responses to the CS+ and CS-. In contrast, the AD group showed a marked impairment in conditioning, failing to exhibit significant conditioned fear responses. This failure to acquire conditioned responses could not be attributed to diminished responding by patients, relative to controls, to the aversive US. The results indicate that fear conditioning, an amygdala-dependent form of memory, is impaired in AD. These findings complement previous reports of impairments in declarative emotional memory in AD by demonstrating that a basic form of nondeclarative emotional memory is also impaired in AD.     

Effects of stimulus predictability and interstimulus gap on saccades in Alzheimer's disease

OBJECTIVES: Studies of saccadic eye movement impairment in Alzheimer's disease (AD) have largely focused on simple reflexive eye movements and the antisaccade task. The effects of manipulating stimulus timing have been little studied. METHODS: Fourteen patients with mild to severe AD and 11 age-matched controls were studied on the antisaccade task, while latencies on simultaneous, gap and predictable tasks were recorded from 11 patients and 11 controls. Dementia severity was assessed with the Mini-Mental State Examination. RESULTS: As a group, patients' latencies were significantly higher and more variable on the simultaneous and gap tasks. Predictable task performance was similar in mean but significantly more variable. Grossly anticipatory responses by patients were common on the predictable, simultaneous and gap tasks. Exclusion of these from subject means revealed that AD patients, when making target-driven saccades, demonstrated a gap effect of similar magnitude to normal subjects. Patients made significantly fewer correct antisaccades and significantly more reflexive errors not followed by a corrective antisaccade than did controls. CONCLUSIONS: The frequent presence of grossly anticipatory saccades may reflect dysfunction of fixation mechanisms possibly involving projections from frontal lobe to superior colliculus. The less frequently seen, marked prolongation of latency may reflect changes in posterior parietal mechanisms mediating reflexive saccade generation. The presence of the gap effect demonstrates a continued ability to benefit from externally controlled stimulus disengagement. Patients' ability to make appropriately timed saccades to targets of known locations was particularly impaired, but the target sequence itself was at least grossly correctly learned. Larger studies may be able to identify clinically distinct populations of AD patients.     

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.     

Automatic affective stimulus processing is intact after unilateral resection of the anterior temporal lobe in humans

Only hundreds of milliseconds after an incoming stimulus is perceived, we make an evaluation of whether it is good or bad. This evaluation seems to occur automatically and can significantly influence behavior. According to several functional imaging studies, the amygdala, which is localized in the temporal lobes of the brain, is an important structure for the automatic processing of affective stimuli. To investigate how critical a role the amygdala plays in this process, we had 20 participants with unilateral resection of the temporal lobe and 20 controls perform an affective priming task. Both controls and patients demonstrated shorter response latencies on trials where prime and target had the same valence than on trials where prime and target had the opposite valence. This finding is generally known as the affective priming effect and is considered to reflect automatic stimulus evaluation. More specifically, it is assumed that the valence of the prime stimulus is activated automatically and exerts an influence on the speed by which the target stimulus is evaluated. Given that the affective priming effect is equally large in both groups, our results suggest that the automatic processing of stimulus valence is intact in participants who sustained unilateral resection of the temporal lobe.     

Category specific deficits in Alzheimer's disease: fact or artefact?

Impairments in semantic memory commonly occur in Alzheimer's Disease (AD) but do these occur along category-specific lines? We administered a confrontation naming task comprising living and nonliving items to 68 individuals with AD and 59 age-matched control participants, in a study designed to address some of the methodological issues affecting investigation of category effects. In Experiment 1, stimuli were matched for familiarity and word frequency and also visual complexity, and the AD group showed a differential deficit in nonliving things. In Experiment 2, however, living and nonliving stimuli were matched for age-of-acquisition, name agreement, word frequency, and naming accuracy of elderly controls and there was no categorical impairment in the AD group. The AD group was subdivided first into mild and moderate AD, and then into normal or impaired overall naming groups and performance was reanalysed, but there was still no significant category deficit in any group. Converging evidence was provided by hierarchical regressions across items, as age-of-acquisition, name agreement and word frequency were significant predictors of naming performance in mild and moderate AD groups, but category was not. In Experiment 3, stimulus items were matched for familiarity and naming accuracy of elderly controls when their performance was off-ceiling, and again no differential effect of category was found. When we reduced slightly how closely matched stimuli were for familiarity we then found a differential impairment in living things in the AD group. When reviewing the changing pattern of results from use of different stimulus sets, we concluded that the main determinant of whether or not a categorical impairment of either sort is found in AD is which stimulus properties are controlled during stimulus selection. We conclude that AD does not generally lead to a selective category loss in semantic knowledge.