Automatic Semantic Facilitation in Alzheimer's Disease

Abstract

To explore the nature of semantic deficit in Alzheimer's disease patients (AD patients) we compared two tasks that are known to be very different with respect to the type of attentional demand and conscious effort they require: lexical decision (automatic) in a semantic priming paradigm and semantic relatedness judgements (intentional). In order to minimise post-lexical facilitation we devised a semantic priming experiment that met an automatic condition as much as possible, and we selected patients without severe word recognition deficits. AD patients showed reduced accuracy in the semantic relatedness judgements as compared to controls. Some effect of priming was found, but this was weaker than in normals. AD patients also differed from controls on targets preceded by a nonlinguistic prime (neutral condition) where their reaction times were slower as compared to neutral condition.     

Affective semantic priming in patients with schizophrenia

Affective semantic priming was examined in normal controls and patients with schizophrenia using a lexical decision task with four affective categories of related word pairs: neutral, happy, fearful and sad. Results demonstrated a striking and reliable effect of affective category upon semantic priming. Neutral and happy prime targets yielded significant semantic priming. Fearful and sad pairs showed no or modest semantic priming facilitation. Schizophrenia patients did not differ from normal controls on their priming scores to any of the four affective categories. These results support the notion that the associative mechanisms that bind negative valence words are distinct in nature; they also clarify that patients with schizophrenia do not show increased sensitivity to affect, and more specifically negative affective context during priming paradigms. This study further indicates the importance of replicating novel findings and reporting negative results.     

Comprehension of lexical ambiguity in healthy aging, mild cognitive impairment, and mild Alzheimer's disease

Two experiments examined processing of lexical ambiguity in healthy older control (HC), mild cognitive impairment (MCI) and Alzheimer's disease (AD) participants. In Experiment 1, groups of HC, MCI and AD participants took part in an ERP study in which they read lexically ambiguous items presented in a subordinate context and primed by the same item presented in a dominant context. Ambiguous items were homonyms (e.g., bank), metaphorical polysemes (e.g., star), or metonyms (e.g., rabbit). All participants exhibited smaller N400s for items preceded by a related prime. In addition, HC participants exhibited a smaller N400 for metonyms than for metaphorical polysemes or homonyms; this effect was diminished in MCI and AD participants. In Experiment 2, HC and MCI participants completed a primed lexical decision task where targets related to the subordinate meaning/sense of ambiguous items were preceded by primes biasing the dominant meaning/sense (e.g., financial-bank-river). In contrast to the results of Experiment 1, both HC and MCI participants showed priming for metonymic items, but not homonyms or metaphorical polysemes. These results suggest that basic knowledge of multiple senses of metonyms is preserved in MCI, but the processing advantage conveyed by this semantic richness is diminished in MCI and AD.     

ERP analyses of task effects on semantic processing from words

Semantic (positive) priming refers to the facilitated processing of a probe word when preceded by a related prime word, and is a widely used technique for investigating semantic activation. However, the effect is interrupted or eliminated when attention is directed to low-level features of the prime word, such as its letters, a result which has been used to question the automaticity of semantic processing. We investigated this issue using both behavioural [reaction time (RT)] and electrophysiological measures [event-related potentials (ERPs)]. Subjects performed semantic categorization (living vs. nonliving) and letter search ("A" or "E") tasks on prime words followed by lexical decision on the probe. RT results showed the expected elimination of semantic priming following letter search. However, both prime tasks were affected by the semantic category of the prime, indicating that the meaning was processed. The ERP results supported this conclusion: an early component previously associated with automatic semantic processing [the Recognition Potential (RP)] was sensitive to the category of the prime word irrespective of the prime task. However, a later component (N400) was significantly affected by the task, in both the prime (categorization task) and probe words (semantic priming). The results dissociate rapid, automatic semantic processing from semantic priming. We suggest that a later inhibitory control mechanism suppresses this semantic activation when it is not relevant to the task, and that this produces the loss of semantic priming.     

Semantic priming for coordinate distant concepts in Alzheimer's disease patients

Semantic priming paradigms have been used to investigate semantic knowledge in patients with Alzheimer's disease (AD). While priming effects produced by prime-target pairs with associative relatedness reflect processes at both lexical and semantic levels, priming effects produced by words that are semantically related but not associated should reflect only semantic activation processes. This study was aimed at further investigating automatic semantic priming effects in AD patients when semantically related concepts with little to no lexical association are used. Twenty patients with mild to moderate AD and 20 matched controls (NCs) performed a lexical decision task on 30 concept pairs (15 in the living and 15 in the non-living domain) in an automatic semantic priming paradigm. In order to investigate the relationship between priming alteration and semantic damage, we chose concepts from a database. This allowed us to quantify semantic indexes relative to the structural representation at the feature level.No priming was found in NCs or mild AD patients, probably because feature similarity was insufficient in the concept pairs used. Similar to the hyperpriming observed in previous studies, the appearance of priming in the moderate AD group suggests early semantic damage in which attribute knowledge is partially affected. Furthermore, the finding that priming was predicted by the level of sharing (in the semantic system) of features common to the two concepts in the pairs indicates that the level of redundancy of attribute information is the main factor responsible for resiliency to neurological damage in AD.     

Effects of task structure on category priming in patients with Parkinson's disease and in healthy individuals

Lexical decision tasks have been used to study both shifts of attention and semantic processing in Parkinson's Disease (PD). Whereas other laboratories have reported normal levels of semantic priming among PD patients, our laboratory has reported abnormally large levels. In this study, two experiments were performed to determine the influence of task structure on the extent of semantic priming during lexical decision-making and pronunciation tasks among PD patients and neurologically healthy controls. In Experiment 1, the effect of Prime Dominance (the ratio of category to neutral trials) on lexical decision-making was studied. Although equal numbers of word and nonword trials were presented, half of the PD patients and controls were studied under Category Prime Dominance (category : neutral prime ratio of 2:1) and half were studied under Neutral Prime Dominance (category : neutral prime ratio of 1:2). In Experiment 2, PD and control participants were studied on lexical decision-making and pronunciation tasks where twice as many words as nonword trials were presented, consistent with other studies from our laboratory. In Experiment 1, we found no group differences in the magnitude of priming and no effect of Prime Dominance. Moreover, the findings were similar in pattern and magnitude to results published by Neely (1977). In Experiment 2, we observed larger priming effects among PD patients than among controls, but only on the lexical decision (LD) task. These results support the hypothesis that abnormally large category-priming effects appear in LD studies of PD patients when the number of word trials exceeds the number of nonword trials. Furthermore, increased lexical priming in PD appears to be due to processes operating during the decision-making period that follows presentation of the lexical target.     

Effects of Task Structure on Category Priming in Patients With Parkinson's Disease and in Healthy Individuals

Lexical decision tasks have been used to study both shifts of attention and semantic processing in Parkinson's Disease (PD). Whereas other laboratories have reported normal levels of semantic priming among PD patients, our laboratory has reported abnormally large levels. In this study, two experiments were performed to determine the influence of task structure on the extent of semantic priming during lexical decision-making and pronunciation tasks among PD patients and neurologically healthy controls. In Experiment 1, the effect of Prime Dominance (the ratio of category to neutral trials) on lexical decision-making was studied. Although equal numbers of word and nonword trials were presented, half of the PD patients and controls were studied under Category Prime Dominance (category : neutral prime ratio of 2:1) and half were studied under Neutral Prime Dominance (category : neutral prime ratio of 1:2). In Experiment 2, PD and control participants were studied on lexical decision-making and pronunciation tasks where twice as many words as nonword trials were presented, consistent with other studies from our laboratory. In Experiment 1, we found no group differences in the magnitude of priming and no effect of Prime Dominance. Moreover, the findings were similar in pattern and magnitude to results published by Neely (1977). In Experiment 2, we observed larger priming effects among PD patients than among controls, but only on the lexical decision (LD) task. These results support the hypothesis that abnormally large category-priming effects appear in LD studies of PD patients when the number of word trials exceeds the number of nonword trials. Furthermore, increased lexical priming in PD appears to be due to processes operating during the decision-making period that follows presentation of the lexical target.     

Loss of person-specific knowledge in Alzheimer’s disease: Evidence from priming

Semantic deficits in Alzheimer’s disease (AD) are often more severe for items that are characterized by a unique semantic and lexical association, such as famous people. Whether these deficits are due to the degradation of semantic information or a deficit in the ability to intentionally access semantic knowledge remains controversial. To assess the integrity of the semantic system without explicitly accessing it, a priming paradigm was used. Semantic and repetition priming effects in individuals with AD (n = 7) and age-matched controls (n = 13) were measured in a familiarity judgment task using visually-presented names of famous people. A defective priming effect in AD subjects was observed in the semantic priming but not in the repetition priming condition. Therefore, the semantic impairments observed in AD may indicate a degraded representation of the semantic information concerning famous people.     

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.     

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.     

Lack of inhibition in Parkinson's disease: evidence from a lexical decision task

Persons affected by Parkinson's disease (PD) often show an increased semantic priming effect from target words in lexical decision tasks (hyper-priming) as compared to age-matched controls. In this study, a lexical decision task was used to investigate both semantic priming (Experiment 1) and repetition priming (Experiment 2) from distractor words in PD patients and age-matched controls. With this negative priming procedure, target words in successive trials are never related, and therefore participants always have to switch between unrelated target words. Instead, it is the distractor prime word that is either related or unrelated to the subsequent target, giving the measure of priming. Results showed that PD patients demonstrated a robust effect of positive semantic priming from distractor words. Participants from the control group did not show any semantic priming effect (positive or negative) from distractors. Similarly, PD patients showed positive repetition priming from distractor words, but the control group showed significant repetition negative priming. These results support the view that the hyper-priming effect typically shown by persons with Parkinson's disease is the result of impaired inhibitory processes required to control word activation during reading.     

Can the emotional connotation of concepts modulate the lexico-semantic deficits in Alzheimer's disease?

Semantic memory impairments are a common symptom of Alzheimer's disease (AD) and may occur at a relatively early stage. These disturbances can be evidenced by a hyperpriming effect (greater semantic priming in AD patients than in controls). Up till now, very few studies of semantic memory have included emotionally charged concepts. Our aim was therefore to study the semantic processing of such concepts, as opposed to neutral ones, in early AD. Given that emotional processes are relatively preserved at the beginning of the disease compared with other cognitive functions, we expected that an emotional connotation would influence the spreading activation of words and affect some of the impairments in semantic processing. We administered a semantic priming task (lexical decision task) implicitly assessing semantic memory to 26 patients with AD and 26 normal controls. Primes and targets either had a semantic relationship (e.g. tiger-lion), a semantic and emotional (positive or negative) relationship (e.g. slap-smack) or no relationship at all (e.g. chair-horse), or else belonged to a word-nonword condition (e.g. window-inuly). Compared with controls, the patients showed pathological hyperpriming effects in all conditions, especially in the emotional conditions. Hyperpriming implies a deterioration in specific attributes, as it is difficult to tell two concepts apart once their distinctive attributes have been lost. These results suggest that emotional concepts, like neutral ones, lose some of their distinctive attributes in early AD, and as the emotional processes are preserved, there is greater similarity between close emotional concepts than between close neutral concepts.     

The N400 is modulated by unconsciously perceived masked words: further evidence for an automatic spreading activation account of N400 priming effects

It is a matter of debate whether the N400 component of the event-related brain potential (ERP) is sensitive to unconscious automatic priming mechanisms or to strategic mechanisms only. Recent studies demonstrated N400 modulation by masked primes at a short SOA supporting an automatic spreading activation account. However, it cannot be ruled out that strategic mechanisms based upon partial prime identification contributed to the observed priming effects. The present study was set up to substantiate masked N400 priming effects as an index of automatic spreading activation. It was assessed whether partial identification of the masked words due to backward priming could have supported strategic priming to occur. In experiment 1, ERPs were recorded while subjects performed lexical decisions on targets preceded by masked and unmasked primes at an SOA of 67 ms. Masked words, which were not consciously perceived, as well as visible words were shown to modulate the N400 to meaningfully related target words. Experiment 2 required subjects to perform decisions on visual, lexical and semantic features of masked words presented with or without semantically related context words. Subjects performed at chance in all tasks. Furthermore, the results exclude the possibility that backward priming has rendered the masked words partially visible. The present study therefore demonstrates that N400 priming effects can be reliably obtained from unconsciously perceived masked words at a very short SOA and strengthens the notion that the N400 is modulated by automatic spreading activation and not exclusively by strategic semantic processes.     

Attentional modulation of unconscious "automatic" processes: evidence from event-related potentials in a masked priming paradigm

Automatic processes are usually thought to occur independently of any cognitive resources. This traditional view has been recently challenged by showing that temporal attention to a target stimulus is a prerequisite for "automatic" response priming. The event-related potential (ERP) study reported here extends this research by pursuing a somewhat different approach. In two experiments, it was investigated whether masked semantic priming effects can be modulated by temporal attention to the prime using a cueing procedure. We hypothesized that masked priming is amplified when attention is directed to the stimulus stream in the time window of masked prime presentation, even in the absence of any prime awareness. ERPs were recorded while subjects performed a primed lexical decision task. Target words were preceded by semantically related or unrelated masked prime words, which were not consciously identified. A cue stimulus prompted subjects to direct their attention to the stimulus stream either shortly before the masked prime (short cue interval) or a long time interval before. Priming affected the amplitude of the N400 ERP component, an electrophysiological index of semantic processing. Unrelated prime-target pairs elicited a larger N400 than related pairs (N400 priming effect). Most importantly, this masked N400 priming effect was strongest when the cue interval and the stimulus onset asynchronies were short. The present results show that temporal attention to the prime is a prerequisite for obtaining masked N400 priming effects. They also demonstrate that unconscious automatic processes are susceptible to attentional modulation.     

Backward priming and postlexical processing in the right hemisphere

Postlexical processing in the intact cerebral hemispheres was studied using a divided visual field method. Asymmetrically associated prime-target pairs were presented in forward (PRIEST-MAN) and backward (MAN-PRIEST) directions in a binary lexical decision task. The primes were presented either centrally or laterally, and the targets laterally. The priming effects in the backward conditions were assumed to reflect postlexical semantic processing. The analyses of response times revealed that, in the left visual field, backward priming was equal in both prime conditions, but forward priming was observed for the central primes only. In the right visual field, forward priming was similar in both prime conditions, whereas backward priming was restricted to the central prime condition. The analyses of errors showed an LVF advantage in backward priming and a trend towards an RVF advantage in forward priming in central prime conditions. The results suggest that the right hemisphere is capable of postlexical semantic processing, but may lack an expectancy-based mechanism underlying forward priming.     

Backward Priming and Postlexical Processing in the Right Hemisphere

Postlexical processing in the intact cerebral hemispheres was studied using a divided visual field method. Asymmetrically associated prime-target pairs were presented in forward (PRIEST-MAN) and backward (MAN-PRIEST) directions in a binary lexical decision task. The primes were presented either centrally or laterally, and the targets laterally. The priming effects in the backward conditions were assumed to reflect postlexical semantic processing. The analyses of response times revealed that, in the left visual field, backward priming was equal in both prime conditions, but forward priming was observed for the central primes only. In the right visual field, forward priming was similar in both prime conditions, whereas backward priming was restricted to the central prime condition. The analyses of errors showed an LVF advantage in backward priming and a trend towards an RVF advantage in forward priming in central prime conditions. The results suggest that the right hemisphere is capable of postlexical semantic processing, but may lack an expectancy-based mechanism underlying forward priming.     

Semantic priming of word pronunciation and lexical decision in schizophrenia.

Experimental assessments of semantic memory structure and function in schizophrenic subjects can be a useful approach for delineating some of the information processing deficits in schizophrenia. In this study, a pronunciation and a lexical decision semantic priming experiment were conducted with 19 schizophrenic subjects and 20 normal controls. A short stimulus-onset asynchrony (250 msec) and a relatively low proportion of related prime-target pairs were used in order to examine automatic priming and in order to avoid the contribution of attentional, controlled processes. On the pronunciation task, schizophrenic subjects showed a significant priming effect, equal to the priming shown by normal controls. However, on the lexical decision task, schizophrenics, unlike normal controls, did not show a priming effect which is significantly greater than zero, even though the group difference in priming effect (interaction of priming effect by group) was nonsignificant. The lack of priming on the lexical decision task is consistent with the hypothesis that schizophrenic subjects may show abnormalities in the realm of post-lexical, controlled information processing. The equal-to-normal priming for schizophrenic subjects indicates that the basic structure of the semantic network, including associations among related concepts, is intact in schizophrenia, and that spreading activation also occurs normally.     

Neural correlates of semantic priming for ambiguous words: an event-related fMRI study

We investigated the neural correlates of semantic priming by using event-related fMRI to record blood oxygen level dependent (BOLD) responses while participants performed speeded lexical decisions (word/nonword) on visually presented related versus unrelated prime-target pairs. A long stimulus onset asynchrony of 1000 ms was employed, which allowed for increased controlled processing and selective frequency-based ambiguity priming. Conditions included an ambiguous word prime (e.g. bank) and a target related to its dominant (e.g. money) or subordinate meaning (e.g. river). Compared to an unrelated condition, primed dominant targets were associated with increased activity in the LIFG, the right anterior cingulate and superior temporal gyrus, suggesting postlexical semantic integrative mechanisms, while increased right supramarginal activity for the unrelated condition was consistent with expectancy based priming. Subordinate targets were not primed and were associated with reduced activity primarily in occipitotemporal regions associated with word recognition, which may be consistent with frequency-based meaning suppression. These findings provide new insights into the neural substrates of semantic priming and the functional-anatomic correlates of lexical ambiguity suppression mechanisms.     

Lack of semantic priming effects in famous person recognition in Mild Cognitive Impairment

IntroductionGrowing evidence indicates that individuals with Mild Cognitive Impairment (MCI) manifest semantic deficits that are often more severe for items that are characterized by a unique semantic and lexical association, such as famous people and famous buildings, than common concepts, such as objects. However, it is still controversial whether the semantic deficits observed in MCI are determined by a degradation of semantic information or by a deficit in intentional access to semantic knowledge. Here we used a semantic priming task in order to assess the integrity of the semantic system without requiring explicit access to this system. This paradigm may provide new insights in clarifying the nature of the semantic deficits in MCI.MethodsWe assessed the semantic and repetition priming effect in 13 individuals with MCI and 13 age-matched controls who engaged in a familiarity judgment task of famous names. In the semantic priming condition, the prime was the name of a member of the same occupation category as the target (Tom Cruise–Brad Pitt), while in the repetition priming condition the prime was the same name as the target (Charlie Chaplin–Charlie Chaplin).ResultsThe results showed a defective priming effect in MCI in the semantic but not in the repetition priming condition. Specifically, when compared to controls, MCI patients did not show a facilitation effect in responding to the same occupation prime-target pairs, but they showed an equivalent facilitation effect when the target was the same name as the prime.ConclusionThe present results provide support to the hypothesis that the semantic impairments observed in MCI cannot be uniquely ascribed to a deficit in intentional access to semantic information. Instead, these findings point to the semantic nature of these deficits and, in particular, to a degraded representation of semantic information concerning famous people.     

Semantic activation within and across the cerebral hemispheres: what's left isn't right

This study examined differences in the spread of semantic activation within and between the cerebral hemispheres. A lateralised lexical decision task using indirect priming was presented to 58 undergraduates with primes and targets separated by 215 or 750 milliseconds (ms). Prime and target words were presented to the same or opposite visual fields and were either directly related (book-read), indirectly related (lion-[tiger]-stripes), or unrelated (cup-street). At 215 ms participants exhibited significant priming effects to directly related words in all conditions except when primes and targets were both presented to the right hemisphere (RH). In contrast, priming to indirectly related words was effective only when primes and targets were presented to opposite hemispheres. At 750 ms, significant priming occurred for directly related words in all conditions, and for indirectly related words when primes were presented to the RH. Results suggest that priming for directly and indirectly related concepts occurs unilaterally in each hemisphere before 215 ms. Both prime types activate semantic networks in the RH within 750 ms, whereas the LH processes information in a more focused manner. This suggests that activation spreads contralaterally from each hemisphere first to directly and then to indirectly related concepts, indicating the importance of incorporating contralateral priming contrasts in lexical decision tasks.