ERP assessment of semantic memory in Alzheimer's disease

ELSEVIER

INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY

International Journal of Psychophysiology 27 (1997) 201-214

ERP assessment of semantic memory in Alzheimer’s disease

Marisol Castaiiedaa, Feggy Ostrosky-Solisa’*, Martha PCrez”, Maria Antonieta Bobesb, Luz Esther Rangel’

a Departamento de Psicofisiologia, Far&ad de Psicologia, Universidad National Autdnoma de M&co, Riwra a’e Cupia 11 O- 71, Lomas de Reforma, I 1930 M&co DF, Mexico

hlnstituto de Neurociencias, La Habana, Cuba

‘Centro de Atencih Diumo ‘Francisco Espinozn Figueroa i Franz Hab 119, Col Alfonso xiii, Del Alvaro Obregon, Mako DF, Mexico

Received 11 February 1997; revised 1 July 1997; accepted 1 July 1997

Abstract

This study used the technique of Event-Related Potentials (ERPs), specifically the component N400, to evaluate

semantic functions in Alzheimer’s disease (AD). ERPs of 10 patients with probable AD and 10 asymptomatic elderly control subjects were recorded during a semantic categorization task using pictures as stimuli, 50% of the stimuli were congruent and the other 50% were incongruent. Significant differences for the incongruent ERPs, with a diminished N400 component, was observed in the patients group whereas the amplitude of the congruent ERPs was similar in both groups. The characteristics of the N400 in the patients with probable AD suggest that there is a lack of efficiency in accessing information and shows that there are deficient associative connections within the semantic network. 0 1997 Elsevier Science B.V.

Keywor&: Event-related potentials; N400; Picture categorization; Semantic memory; Alzheimer’s disease

*Corresponding author. Tel.: + 52 5 2517656; fax: + 52 5 5502560; e-mail: [email protected]

0167-8760/97/$17.00 0 1997 Elsevier Science B.V. All rights reserved.

PII SO167-8760(97)00064-O

202 M. Castaiieda et al. /International Journal of Psychophysiology 27 (1997) 201-214

1. Introduction.

Dementia is among the highest occurrences of illnesses of the Central Nervous System in old age, and the most frequent cause of this syndrome is Alzheimer’s disease (AD) (Cummings and Benson, 1992). AD is a progressive and de- generative disorder of difficult diagnosis, charac- terized by a gradual loss of various cognitive functions, the most characteristic of which are the disruptions in semantic memory (Nebes, 1989).

Memory implies a biological function which allows for the registry, retention and the evoca- tion of information stored at a previous time. Recently, there has been a variety of theoretical models that have divided memory into multiple systems that differ in the nature of the information they store, how they represent this information and in the types of operations carried out within each system. One approach to partitioning memory that has had a major effect on the field is the distinction between semantic memory and episodic memory (Tulving, 1984, 1987). Semantic memory consists of an organized body of knowledge which includes words, concepts, mean- ings, associations and the rules for handling these symbols and concepts, whereas episodic memory provides the additional capacity to acquire and retain the knowledge of unique and personal ex- periences or events occurring at a specific time and within a specific context.

According to several studies, it has been stated that episodic memory is impaired both in AD and in normal aging (although to a very different degree), while semantic memory is severely dis- rupted in AD and remains essentially intact in the normal elderly population (see Nebes, 1989 for a review; Ostrosky-Solis et al., 1994). The evidence that AD patients have semantic memory impairments not found in the normal elderly comes from the word-finding problems evident in the patient’s spontaneous speech as well as in their performance on tests of verbal fluency and object naming (Weingartner et al., 1981 Bayles and To- moeda, 1983; Martin and Fedio, 1983; Grober et al., 1985; Nicholas et al., 1985; Huff et al., 1986; Ober et al., 1986; Butters et al., 1987; Kempler et

al., 1987). Two hypothesis have been offered to explain these semantic deficits. The first one sug- gests that patients have a procedural deficit and somehow this deficit prevents accessing the contents of semantic memory, whereas the second explanation supports the existence of a degraded semantic store where the actual contents of semantic memory are degraded (see Chenery, 1995 for a review).

One way to solve the issue of procedural vs. storage deficits, is to examine the performance of patients with Dementia of Alzheimer’s Type (DAT) on semantic priming tasks. With this methodology, it is possible to study the effect that a context has on the processing of a stimulus. Semantic priming may be obtained in normal subjects with tasks using pictures as primes (Irwin and Lupker, 19831, on lexical decision tasks (Meyer et al., 1975) and on word naming tasks (Warren, 1977).

Some studies that have assessed the ability of DAT subjects on semantic priming tasks have reported intact priming (Hartman, 1991; Ober et al., 19911, some no priming (Huff et al., 1988; Ober and Shenaut, 1988; Salmon et al., 19881, some excessive or hyperpriming (Chertkow et al., 1989; Nebes et al., 1989; Balota and Duchek, 1991), some a mixture of both no priming and intact facilitation (Albert and Milberg, 1989) and some a dissociation between intact associative- level priming and disturbed semantic priming (Glosser and Friedman, 1991).

Additional information on the semantic processing in DAT patients can be obtained by study- ing a component of the Event-Related Potentials (ERPs) called N400. In recent years it has been shown that ERPs are a valuable non-invasive tool for evaluating the neural function of the nervous system linked to sensorial, perceptual and/or cognitive processes. In contrast to behavioral measurements (such as reaction time) the ERPs give a continuous monitoring of cerebral activity during the processing of information. Described by Kutas and Hillyard 1980, 1984), the N400 is a negative deflection produced around 400 ms post-stimulus which has been observed to occur with semantic processing or detection of semantic

M. Castarieda et al. /International Journal of Psychophysiology 27 (1997) 201-214 203

anomalies in sentences with incongruent endings (i.e. ‘I drank coffee with milk and HAM’), while it is not observed in sentences with congruent endings (i.e. ‘I drank coffee with milk and SUGAR’). This component has also been presented by using as stimuli pairs of written words (Harbin et al., 19841, spoken words (Neville, 1985) and drawings (Barrett and Rugg, 1990) generating a broader N400 in incongruent situations than in congruent ones. In contrast to semantic anomalies, physi- cally deviant words (e.g. printed in boldface type) elicited a positive potential rather than a negativity. Other non-semantic deviations, such as musi- cal or grammatical violations also failed to elicit the N400 (Besson and Macar, 1987; Osterhout and Holcomb, 1992; Hagoort et al., 1993).

The exact mental operation that is indexed by the N400 is still a matter of controversy. Some authors have viewed the N400 as an index of the ease of lexical access, with more negative respon- ses when less contextual pre-activation of the eliciting word is present (Kutas and Hillyard, 1984). Several psycholinguistic experiments have demonstrated that it is associated with some as- pects of lexical processing especially in relation to the eliciting word meaning. The N400 amplitude has proven to be sensitive to factors that are known to influence the speed of lexical access and word recognition, such as frequency, repetition, semantic priming and semantic context (see Ku- tas and Van Petten, 1994). Another interpretation of the N400 views this waveform as a reflection of post-lexical processes, such as the integration of the products of lexical access with the context (Rugg et al., 1988 Halgren, 1990; Rugg, 1990; Brown and Hagoort, 1993; Holcomb, 1993; Chwilla et al., 1995). This implies that an N400 effect will occur when the lexical integration process is hampered as a result of a mismatch between the semantic specifications of a particu- lar word and the semantic specifications of its preceding word or sentence context.

Up until now, very few studies have used the N400 to assess the semantic abilities in DAT patients. Hamberger et al. (1995) used a lexical decision task with sentences as stimuli and found that the N400 amplitude was identically respon-

sive to semantic relatedness in young normal and DAT groups although DAT patients produced significantly greater number of errors, therefore they concluded that the disruption in semantic processing occurs at some point between the elic- itation of the N400 and the generation of the reaction time response. According to Hamberger et al. (1995) these results reflect both an index of the adequate access and organization of information in the semantic memory. Thus the alteration must be at the level of the behavioral-response organization.

On another study, Margolin 0987) measured the reaction time of patients with DAT and observed that in contrast to normal elderly subjects, the patients did not show semantic priming when the context was the picture of an object, but did show priming when the context was a word rather than a picture. It is known that there are differences between the processing of words and drawings (Potter and Faulconer, 1975), by using pictures the linguistic process of decoding printed words is bypassed, thus the follow-up of these data could contribute with significant information on the limitations of the semantic functioning in DAT patients.

In the present study a group of patients with probable DAT was compared to a group of normal elderly control subjects in a semantic categorization task that used pictures of common objects and animals as stimuli. The ERPs associated with picture semantic processing were examined in order to determine if the N400 component was altered in the patients. If alterations in the amplitude and/or latency of the N400 were observed, then these abnormalities would be a direct reflection of the procedural routines in the patients and the situation in the semantic storage. Special attention was directed to the amplitude characteristics of N400. The comparison of N400 amplitude was carried out separately for congruent and incongruent trials. Specific contrasts were performed to establish if the N400 amplitude found in the DAT patients during the semantic categorization task, was due to an enhanced negativity for congruent trials, or an enhanced positivity for incongruent trials.

204 M. Castafieda et al. /International Journal of Psychophysiology 27 (1997) 201-214

2. Method

2.1. Subjects

Ten patients with probable DAT (four men and six women; 59-89 years old, mean age 75.4, mean years of education 9.9) who attended the Center for Alzheimer’s Disease ‘Francisco Espinoza Figueroa’ in Mexico City, and 10 normal elderly subjects (five men and five women; 54-82 years old, mean age 67.8, mean years of education 8.6) participated in the study. All subjects were right handed, had normal to corrected vision and none of the patients were taken psychoactive medica- tion. The inclusion criteria for the normal group were: (1) absence of dementia according to the criteria of DSM-IV (American Psychiatric Associ- ation, 1995); (2) a score of at least 23 in the Mini-Mental State Examination (MMS) (Folstein et al., 1975); (3) absence of psychiatric or neurological diseases; and (4) scored within normal range on a neuropsychological battery, that was developed, standardized and validated in a Span- ish speaking population (Ostrosky-Solis et al., 1997). The battery assessed the domains of attention, memory, language, visual perception, visuos- patial process and executive functions. The battery was administered by a trained certified neu- ropsychologist.

The diagnosis of probable DAT was made according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Dis- orders Association (McKhann et al., 1984), on the neuropsychological test results and on the patient’s level of functioning in daily activities. Patients were mildly to moderately impaired, MMS scores were between 14 and 22, and duration of illness was between 6 months and 3 years. On the neuropsychological battery patients scored more than two standard deviations below standardized norms on measures of delay recall of verbal and visual material, on confrontation naming, verbal fluency and on executive functions. Other possible sources of dementia were excluded by appropriate laboratory evaluations, such as computed tomography, electroen- cephalography, blood count, serum B12, hepatic,

renal and thyroid function test. Their scores on the Hachinski Ischemic Rating Scale (Hachinski et al., 1975) were used to aid in excluding multin- farct dementia.

2.2. Material

The stimuli consisted of 118 pairs of drawings of objects and animals (Snodgrass and Vander- wart, 1980) which had been adapted in denomina- tion, familiarity and imaginability in the Mexican population (Aveleyra et al., 1996). The figures, which were 8 cm’, were presented in a computer monitor. Since subjects sat approximately 1 m away from the monitor, the drawings sustained a vertical and horizontal angle of 4.6”. Fifty percent of the pairs were semantically related and consti- tuted the congruent condition (they could be cat- egorized in a supraordinated group, i.e. zebra-deer), while the other 50% of the pairs had no semantic relation and formed the incongruent condition (i.e. trumpet-shoe).

2.3. Procedure

The task of the subjects was to discriminate between the congruent and incongruent pairs of pictures. During the experiment, the subjects sat in a comfortable chair in front of the computer monitor and were asked to minimize body and eye movements. They were instructed about the task with a training phase which consisted of 10 pairs of drawings not present in the task of ERPs recordings. The first figure of the pair served as the context for the second figure, which was the stimulus on which ERPs were registered. The electroencephalographic recording was synchro- nized with the presentation of the second drawing and the following sequence of events composed each test: the letter string XXXX was presented as a warning stimuli, the first picture (Sl) was presented for 1 s, followed by a 180-ms blackout, following the blank interval a second picture (S2) was presented (1 s duration) and the screen was again blanked. After the blank screen, the word ‘RESPONDA’ (answer) appeared and the subjects responded verbally (yes or no> if the stimulus (S2) was related to the previous one (Sl). The

M. Castaieda et al. / IntemationalJournal of Psychophysiology 27 (1997) 201-214 205

Stimulus Onset Asynchrony (SOA) between onset of Sl and onset of S2 was therefore equal to 1180 ms. The response was delayed until EEG recording was finished in order to reduce artifacts, thus reaction time was not measured. Average ERPs were obtained only for stimuli S2 in both congruent and incongruent conditions.

2.4. Electrophysiological recording

Electrophysiological data acquisition and analysis were carried out on a Neuroscan System. Scalp electrical activity was recorded from 32 monopolar derivations according to the lo-20 International System. An electrode cap (Electra-Cap Interna- tional) was used. All electrodes were referenced to linked ear lobes and an additional bipolar derivation recorded EOG placed at the inner and outer canthi of the right eye. Electrode impedance was always below 5 Kfl. The signal was filtered between 0.5 and 30 Hz (3 dB down). In each trial 256 points of digitized EEG (12 bit resolution) were recorded at a sampling rate of 256 Hz, totalling 1 s and stored on a magnetic disk for off-line analysis. A pre-stimulus baseline of 100 ms was obtained in each trial and data acquisition continued 900 ms after stimulus onset. Only trials on which a correct behavioral response was made were used to form the averages. Also trials on which EOG activity exceeded a peak-to-peak amplitude of +50 to -50 pV, or on which satura- tion of one or more channels of the analog-digital converter occurred, were also excluded (ap- prox. 15% of trials were lost due to such artifacts).

For every subject, averaged ERPs for each recording site were obtained for each stimulus condition. Average ERPs at the congruent condition and incongruent condition were 29 trials for both groups. These ERPs were submitted to low- pass digital (zero phase distortion) filtering with an upper cut of 5.5 Hz. All data points were corrected (prior to plotting or measurement) by subtracting the average pre-stimulus amplitude value. In other words, all amplitude values were measured with respect to the average amplitude of the pre-stimulus value corresponding to each ERP.

2.5. Statistical analysis

Discrimination behavior was analyzed using the Signal Detection Theory measures d’ and the log,, of /3 @wets, 1964). The use of d’ permits an assessment of the accuracy of performance with- out contamination from variations in criterion (response bias), which could be important between controls and patients. Both behavioral and ERPs measured were submitted to analysis of variance (ANOVA). For the ERPs measured, 11 electrode sites where the negativity was largest were selected (Fz, Cz, Pz, Fc3, Cp3, T3, Tp7, Fc4, Cp4, T4 and Tp8). For some analysis, homologous left and right electrodes were collapsed as Anterior to Posterior sites (frontal, central, parietal) and Coronal sites (left, midline, right). Amplitude and latency values were subjected to repeated measures ANOVA using Group (normal elderly and DAT patients) as between subject variable and two within subject variable conditions (congruent vs. incongruent) and Anterior to Posterior (frontal, central, parietal) or Coronal (left, midline, right). The Greenhouse-Geisser procedure was used, when appropriate, to mitigate violations of sphericity assumptions in the repeated measures design (Keselman and Rogan, 1980). When neces- sary significant interactions were reassessed with repeated measures ANOVAs of normalized amplitude as outlined by McCarthy and Wood (1985); only interactions that were significant on the normalized amplitude measures are reported.

3. Results

3.1. Behavior

Both groups were able to discriminate between congruent and incongruent pictures, as reflected by the mean d’ (Table 1) which was significantly different from zero (t-tests, P < 0.001). The mean d’ differed between groups, as confirmed by an

ANOVA, Fi i&l = 10.04, P < 0.0005. The mean percent of hits was very high for the normal elderly group and lower for the DAT group but always above 50%, these data differed between groups as confirmed by an ANOVA, Fl.18 = 14.43,


Table 1 Behavioral results (d’, Hits % and log,, p) obtained in the semantic matching task in both groups studied

d’

Hits (% Congr.) Hits (% Incon.)

IJJg,o P

Elderly

4.32 ( f 0.47)

94.3 ( * 7.9)

95.4 (k6.1)

- 2.43 (k4.69)

DAT

2.55 (* 1.21)

78.7 (+ 10.85)

84.2 (* 15.1)

0.21 tf3.6)

P < 0.0005. Response bias (log,, p > is also shown in Table 1, and was not statistically different among the two groups.

3.2. Event related potentials (ERPs)

The morphology of the waveform was charac- terized by an early negativity, with a peak latency of approximately 100 ms, followed by a positive deflection peaking at approximately 200 ms. This deflection was followed by a second negative deflection, broadly distributed across the scalp, peaking at approximately 300-570 ms (N400), that was larger for incongruent than congruent pictures and finally a positive deflection at approximately 600 ms.

No significant effects in the amplitude or latency of ERPs were found before 300 ms or at 600 ms for any of the factors, thus a direct explanation will be given of what was observed in the N400. In the normal elderly group, after 300 ms, the ERPs related to the incongruent trials generated a substantial negativity which was not observed in the congruent trials. The N400 observed was generated with greater amplitude in centro-parietal regions, with greater activity in the right hemisphere than in the left (Fig. 1). In the DAT group, a substantial reduction in the amplitude of this component was observed and they showed no gradient of significant activity (Fig. 2).

The N400 effect (the mean amplitude of the difference waveforms obtained by subtracting the incongruent trials from the congruent trials) was calculated in the 300~580-ms time window and

adjusted for each group in its respective N400 peak. That is, between 333 and 571 ms for the normal elderly group and between 353 and 531 ms in the DAT group. The negativity of the N400 appears in these different waveforms as a defined peak in the normal elderly group and as a diminished peak in the DAT group as can be seen in Fig. 3.

These data were analyzed applying an ANOVA with Group (normal elderly and DAT patients) as between subject variable and two within subject variable Anterior to Posterior (frontal, central, parietal) and Coronal (left, midline, right). A significant main effect of Group (Fols) = 4.95, P < O.OS>, Anterior to Posterior (F2,36 = 7.71, P < 0.005) and Coronal (FZ,36 = 11.04, P < 0.005) factors were found reflecting the fact that the N400 was largest in the normal elderly group than in DAT group in all the leads analyzed. Statistical analysis also revealed significant differences between the normal elderly group and the DAT group in the mean peak latency of the N400 effect (Fi,is = 3.89, P < 0.05). In the normal elderly group, the mean peak latency was 472 f 56.4 ms whereas in the DAT group the mean peak latency was at 528 + 42 ms.

The analysis of the scalp distribution of the N400 effect for each group showed striking differences in distribution between groups. For the normal elderly group, the maximum negativity was more posterior (main effect of Anterior to Posterior: F2,36 = 15.75, P < 0.001) involving the parietal region, and it was clearly displaced to- wards the right hemisphere (main effect of Coro-

nal (E;O,,O = 8.42, P < O.OOS), while the electroencephalographic activity of DAT group did not reflect significant topographic effects.

The mean amplitude of the congruent and incongruent recordings for the time window from 300 to 580 ms is shown in Table 2 for both groups studied.

As exemplified in Fig. 4, wave morphology on the N400 amplitude values corresponding to the congruent trials were similar in both groups, whereas the wave morphology on the N400 amplitude values corresponding to the incongruent trials for the DAT group were clearly more positive than those of the normal elderly group. Thus the

M. Castarieda et al. /International Journal of Pychophysiology 27 (1997) 201-214 207

TP’

W

+ I - coNauJENr - IN-UENT

Fig. 1. Grand average ERPs elicited by congruent and incongruent pictures in the control elderly (n = 10). At each site the ERPs associated with the congruent trials (thin line) are overlaid on ERPs elicited by incongruent trials (thick lines). Negativity is upward.

reduction in N400 amplitude for the DAT group is due to a diminution of the negativity in the incongruent trials. Only central (Cz) and centro-

parietal (Cp3, Cp4) leads are shown in Fig. 4 but as reported in Table 2, the same pattern was observed for the rest of the leads.

208 M. Castatieda et al. / IntemationaiJoumnl of Psychophysiology 27 (1997) 201-214

Fd

11 I I

* 0 400 9ooh4

W -- -INcoN(IRuEM

+ I

Fig. 2. Grand average ERPs elicited by congruent and incongruent pictures in the DAT patients (n = 10). At each site the ERPs associated with the congruent trials (thin line) are overlaid on ERPs elicited by incongruent trials (thick lines). Negativity is upward.

All these findings were confirmed in an significant (F,,,, = 4.95, P < 0.05) which reflected

ANOVA performed on the amplitude values. The the more negative values for incongruent record- interaction between Group and Condition was ings with respect to the congruent ones. Planned

M. Castaiieda et al. /International Journal of Pqvchophysiology 27 (1997) 201-214 209

Fig. 3. Grand average difference waveforms (N400 effect) obtained by subtracting ERPs associated to congruent trials from ERPs associated with incongruent trials.

comparisons showed that the significant effect of condition existed in the normal elderly group,

however, this effect was not significant for the DAT group, which confirmed that the N400 was


Table 2

Mean amplitude and standard deviation (in parenthesis) of

the congruent and incongruent recordings for both groups

studied at the 11 electrodes sites selected

Fc3

Fc4

Fz

CP3

CP4 cz

T3

T4

Pz

TP~

TP8

Congruent Incongruent

Elderly DAT Elderly DAT

0.7 (2.1) 2.7 (1.2) 0.1 (1.3) 2.6 (1.7)

1.2 (2.3) 2.5 (1.5) - 0.34 (1.2) 2.2 (1.8)

0.8 (2.1) 2.2 (1.3) - 0.63 (1.6) 2.0 (1.5)

1.9 (2.2) 1.9 (1.3) - 0.03 (1.9) 1.5 (2.0)

2.0 (3.0) 2.3 (1.5) - 0.68 (1.6) l.l(l.8)

1.4 (2.6) 1.9 (1.2) - 0.51(2.1) 1.2 (2.2)

0.3 (1.4) 2.5 (1.6) - 0.05 (1.4) 2.7 (1.7)

0.9 (2.1) 0.9 (0.7) -0.40 (1.1) 1.2 (1.6)

1.7 (2.4) 1.1 (1.1) - 0.28 (1.5) 1.1 (1.3)

0.6 (1.9) 1.2 (1.2) - 0.27 (1.3) 1.2 (1.1)

1.5 (2.7) 1.4 (0.8) -0.17 (1.7) 1.3 (1.0)

diminished in this group. Comparisons done a posteriori confirmed that there were no significant differences in the congruent trials between the normal elderly group and the DAT group but there were significant differences for the incongruent trials (Fr,rs = 9.33, P < 0.05).

4. Discussion

The behavioral results indicated that the DAT group committed more errors than the normal elderly group in the categorization task. It has also been observed in various studies that patients with DAT are less efficient than the control subjects in semantic tasks using both words and pictures (Bayles and Tomoeda, 1983; Huff et al., 1986; Ober et al., 1986; Nebes, 1989). Picture matching is assumed to share with word matching the same mechanisms involving semantic memory and response organization. The fact that categorization is faster with pictures than with words has led to the hypothesis that pictures are more directly connected to semantic memory (Potter and Faulconer, 1975). Thus a possible explanation of the impairments observed in semantic matching for both words and pictures is obtained under the hypothesis that the underlying deficiency is located either in the use of the semantic memory or in the response organization, discarding the theory that the abnormal pairing of pictures arise

from difficulties in identifying the stimulus. This pattern of results has been confirmed by other studies suggesting that the mistakes made by the patients probably arise from deficiencies subse- quent to accessing the information stored in the memory and/or in integrating the information evoked by the context.

It has been theorized that the N400 is sensitive to semantic processing and that the amplitude of this component varies inversely according to the quantity of activation offered by the semantic context (Kutas and Hillyard, 1980, 1984). In the present study a reduction of the N400 component in the DAT group was observed. This is a result that conforms to prior studies of the N400 component which have used semantic matching tasks in other types of pathologies, such as schizophrenia and aphasia (Babes et al., 1996; Swaab et al., 1997), in which the reduced amplitude and delayed latency of this component indicates alterations at the level of the semantic storage. An aspect that was not sufficiently discussed in previous papers is the basis of this reduction, which could be due to either an increased positivity in incongruent trials (smaller N400 in incongruent trials), an increased negativity in congruent trials (larger N400 in congruent trials) or both. In this study the amplitude measurements in the N400 time window were similar in the normal elderly group and the DAT group for congruent trials, however, at incongruent trials the amplitude was significantly more positive for the DAT group relative to the normal elderly group. Thus, the results of this study indicate that the DAT group reflected both normal and abnormal patterns in ERPs. On one hand, they showed normal ERPs for congruent trials, but on the other, they demonstrated abnormal ERPs for incongruent trials.

The interpretation of this pattern of results depends on the type of hypothesis about the functional meaning of N400 that is accepted. If N400 is considered to reflect pre-lexical priming (Kutas and Hillyard, 1984), then these results suggest that in patients with DAT, less priming is produced by incongruent stimuli, since the amount of negativity should be inversely related to the amount of contextual preactivation. This would

M. Castafieda et al. /International Journal of Psychophysiology 27 (1997) 201-214 211

CONGRUENT

CP3

iNCONGRUENT

CP3

w

I ! I I 0 400 9OoMs

- ELDERLY GROUP - DATGROUP

11 I I 0 400 9ooMs

Fig. 4. Grand average waveforms elicited by congruent and incongruent pictures at central (Cz) and centro parietal leads (CP3 and CP4). The ERPs for the normal elderly and DAT patients are overlapped. Congruent and incongruent ERPs waveforms are shown separately.

seem to indicate that the context in an incongruent stimuli reflects deficient associative connections within the semantic network.

A different interpretation of the results emerges if the N400 is conceived as a reflection of the amount of post-lexical processing (Halgren, 1990).


Under this hypothesis, the results obtained in the DAT group suggest that the incongruent stimuli required equivalent amounts of post-lexical processing as in the congruent stimuli, since the amount of amplitude in both cases is similar. In contrast, the normal elderly group seemed to require less processing for the congruent stimuli since the N400 associated with this condition is smaller than the N400 associated with the incongruent stimuli.

Whatever explanation of the N400 is accepted, the N400 pattern observed in the DAT group shows that the processing of the incongruent stimuli is not facilitated within the semantic network as in the normal elderly group. The dif- ficulty of patients with probable DAT in the processing of incongruent stimuli could be due to the damage in the cortical association areas. Neuro- pathological studies have shown that DAT patients showed marked pathology in temporal, parietal and frontal association cortices. The senile plaques and neurofibrillary tangles of DAT prominently involve the origins and termination of long cortico-cortical associative fibers of the brain (Brun, 1988; Morrison et al., 1986; Lewis et al., 1987) and neurophysiological studies have found that there are changes in brain functional connectivity in DAT and that EEG decrease between parietal and frontal areas due to degen- eration of fibers that connect these two areas (Leuchter et al., 1992). It has been suggested that DAT is a ‘neocortical disconnection syndrome’, where associative areas lose afferent and efferent connections through white matter tracts. This disconnection occurs at the cortical level and is associated with the death of pyramidal neurons that provide corticocortical projections (Pearson et al., 1985; Lewis et al., 1987; Leuchter et al., 1992). These neuropathological characteristics can lead to the deterioration in the associative network, which forms the structural skeleton of the semantic memory. The findings of the present study are consistent with a lack of efficiency in accessing information and show that there are deficient associative connections within the semantic network. The results of this study indicate that there is an alteration in the structure and

organization of the semantic memory in patients with DAT.

Acknowledgements

This research was partially supported by a grant given to Dr. Ostrosky-Solis by DGAPA (IN- 2019941, National University of Mexico.

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ERP assessment of semantic memory in Alzheimer's disease

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