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Deficits in language-mediated mental operations in patients with schizophrenia
Schizophrenia Research 53 (2002) 171±179
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De®cits in language-mediated mental operations in patients with schizophrenia Bruce E. Wexler a,*, Nelson Donegan a, Alexander A. Stevens b, Sharif A. Jacob a a
Connecticut Mental Health Center, Department of Psychiatry, Yale University School of Medicine, 34, Park Street, New Haven, CT 06519, USA b Department of Psychiatry, Oregon Health Sciences University, Portland, OR, USA Received 17 August 2000; revised 6 February 2001; accepted 14 February 2001
Abstract We found previously that a subgroup of schizophrenic patients who passed screening tests of attentional competence showed memory de®cits on word memory tasks, but were comparable with controls on tone memory tasks. To better understand the nature of language-speci®c memory de®cits in this subgroup of patients, the present experiment was designed to bypass early perceptual processing of verbal material and determine if patients continue to show impaired performance on verbal memory tasks. Patients who passed the screening tests (`discriminator' patients; DSz) received four serial position tasks. In two, familiar sounds or line drawings were presented and subjects were required to remember the word associated with each stimulus item. In the other two, subjects received hard-to-label auditory and visual stimuli (birdsongs or snow¯akes). DSz patients showed large memory de®cits compared with controls when required to remember words associated with the familiar sounds or drawings, providing clear evidence of de®cits in verbal memory processes independent of sensory processing of verbal stimuli. The interaction between diagnosis and labeling was highly signi®cant, con®rming that these patients have particular dif®culty with verbal as opposed to non-verbal memory. This was particularly striking on the auditory tests where two patients out-performed all controls on the birdsong test, but were below all controls on the easy-to-label sounds test. The verbal memory tests were easier than the non-verbal memory tests for controls, thus deconfounding task dif®culty and de®cit speci®city. q 2002 Elsevier Science B.V. All rights reserved.
1. Introduction An important question in research on schizophrenia is whether the broad cognitive de®cits observed with many test batteries (Levin et al., 1989; Hoff et al., 1992; Saykin et al., 1991, 1994) are characteristic of the population of patients or whether the group
* Corresponding author. Tel.: 11-203-789-7344; fax: 11-203789-7206. E-mail address: [email protected] (B.E. Wexler).
averaging obscures the existence of subgroups with limited and distinct cognitive abnormalities. In our previous work we have provided evidence consistent with the latter interpretation, i.e. that schizophrenia is a heterogeneous disorder (Wexler et al., 1998; Stevens et al., 2000). For example, we have been able to consistently identify a subgroup of schizophrenic patients who demonstrate selective verbal memory de®cits; their performance on word memory tests is inferior to controls, whereas their performance on procedurally equivalent non-verbal memory tests is comparable with controls.
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In a study of auditory verbal and non-verbal memory in schizophrenic patients (Wexler et al., 1998) we ®rst divided the patients into two groups based on their ability to perform as well as controls on a simple screening test of pitch discrimination. The screening test required perceptual, motivational, and attentional competence while imposing minimal demands on memory. Patients who performed as well as controls on the screening test (`discriminators' or DSz patients) also performed as well as controls on tone memory tests, but had signi®cant de®cits on word memory tests, even though the tone tests were clearly more dif®cult than the word tests for healthy controls. Because the discriminator patients had suf®cient perceptual, attentional, and motivational capacities to perform as well as controls on the more dif®cult non-verbal tests, their poorer performance on verbal memory tests could not be attributed to these general performance factors. In addition, these ®ndings indicate that their memory de®cits were not global, but were speci®c to verbal material over this range of tests. Not surprisingly, patients who failed the screening test (`nondiscriminators') did very poorly on both verbal and non-verbal memory tests. Subsequent work in our lab has focused on the scope and nature of the verbal learning de®cit in DSz patients. Stevens et al. (2000) again found the selective de®cit on the auditory word memory test as compared to the auditory tone memory test. In addition, DSz patients were signi®cantly impaired on a similar word memory test in which the items were presented visually. One interpretation of these ®ndings is that the patients' problems on the word memory tests arise at a stage of information processing common to both auditory and visual verbal memory (e.g., creating an acoustical representation of a word and entering it into a rehearsal loop or `buffer') rather than at earlier stages of sensoryspeci®c stimulus encoding. An alternate possibility is that patients have early auditory and visual sensory processing de®cits that are language-speci®c and cause performance de®ciencies on the word memory tests when the words are spoken or presented visually. The present project was designed to test the hypothesis that DSz patients have de®cits in verbal memory processing subsequent to the initial sensory/modality-speci®c encoding of spoken or printed words. To do this, we developed word
memory tasks in which subjects were presented with nonverbal stimuli (familiar sounds or pictures) that reliably activated the representation of the target word in the subjects' memory (e.g., when the sound `moo' was presented the subject kept the word `COW' in memory). Thus, the items presented were nonverbal stimuli, but the memoranda were words. This allowed us to bypass early auditory stages of speech processing or visual analysis of written words but at the same time assess subjects' ability to remember the designated words. If the selective verbal memory de®cits in DSz patients arise from perceptual de®cits, e.g., initial encoding of verbal stimuli, as for example appears to be the case with certain children who have language acquisition disorders (e.g. Merzenich et al., 1996), they should perform well on tests that bypass these early stages of language processing. If, on the other hand, their de®cits arise at later stages of verbal information processing (e.g. automatic or controlled memory processes), they should continue to show pronounced de®cits even in the tests where the stimuli that are presented are non-verbal but the to-beremembered items are the associated words. 2. Subjects and methods Subjects: Twenty-three clinically stable and medicated outpatients who met DSM-IV criteria for schizophrenia and 15 controls without history of psychiatric illness were studied. Subjects were excluded if they met the criteria for substance abuse within the previous six months, were using alcohol or drugs regularly, had a history of neurologic illness, or were not native English speakers. Patients and controls did not differ in age, sex, parental education, or handedness. All gave written informed consent to participate. Method: All tests were presented via a Power Macintosh G3 computer using Psyscope (Carnegie Mellon University, Department of Psychology, Pittsburgh, PA, 1994). Hearing test: Subjects were screened for adequate hearing by testing their ability to detect sounds at intensities one-half those used in the screening test of attentional and perceptual competence. Subjects were required to raise the hand corresponding to the
B.E. Wexler et al. / Schizophrenia Research 53 (2002) 171±179
ear in which they heard a 10 ms word fragment (da or ga). Subjects had to correctly report the onset and location of all 12 fragments in order to ªpass' the test. Screening test for basic attentional and perceptual competence: Subjects were required to judge whether two 200 ms pure tones separated by a 100 ms interstimulus interval were the same or different in pitch. When different, frequencies were in one of ®ve ratios: 0.67, 0.75, 0.85, 0.9, or 0.95. Individual tone frequencies ranged from 325±1994 Hz. There were 10 practice trials and 60 test trials; on 30 test trials the tones were the same and on 30 trials they were different. In each of six ten-trial blocks, half of the trials were `same' and half `different' trials, with each of the ®ve frequency ratios appearing once in each block and with trial types randomly distributed across the block. Memory testsÐauditory: Two self-paced serial position tasks were presented. (We used serial position tasks because the format allows one to develop verbal and nonverbal memory tests with procedurally equivalent task demands.) One had complex, dif®cult-to-label stimuli (bird songs). The second used common sounds and subjects were instructed to remember the word most commonly associated with the sound (e.g. the sound `moo' was presented and subjects were instructed to remember the word `COW'). In the bird song task, each trial began with three approximately 2 s recorded bird songs presented with a 1 s inter stimulus interval (ISI). After a delay of 3 or 9 s a probe test-stimulus was presented by playing one of the three songs that had appeared in the preceding list. Subjects were instructed to indicate the list position of the repeated bird song by pressing the appropriate number key. Subjects received a total of 24 trials, 12 at each of the two retention intervals. Within each set of 12 trials, the probe test song was equally often the same as the ®rst, second, or third song in the preceding list. Across the session of 24 trials, the six trial types (two retention intervals by three probe test positions) were presented in a random sequence. From the collection of 24 bird songs, each song appeared in the list of to-be-remembered items on three trials. Before proceeding to the verbal memory test, subjects were told that they were to take a `quiz' and that they could not proceed with the rest of the experiment until they scored 100%. The 24 1±2 s
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common sounds to be used in the subsequent memory test were presented one at a time followed 500 ms later by the word people most often give to the sound, which was printed on the computer screen (e.g. ªmooº ! COW). Subjects read the word out loud and then pressed the spacebar to hear the next sound. The sounds were then presented again and subjects asked to say the appropriate word without it appearing on the computer screen. Immediately after the subject said what they thought was the correct word, the experimenter told them if they were correct or incorrect, and, if incorrect, provided the correct word. All controls and 13 of the 14 DSz patients correctly supplied the words that had been paired with the 24 stimuli the ®rst time through. The one patient who was not 100% correct mislabeled six stimuli the ®rst time through and achieved a level of 100% correct after a single correction of errors. To con®rm that the correct words had remained readily available to subjects throughout the ensuing memory test, the quiz was repeated at the conclusion of the memory test. All subjects gave the correct words to all the sound stimuli. In the serial position test, each trial began with the presentation of four of the 24 common sounds, presented with a 1 s ISI. (On initial practice trials, subjects were encouraged to remember the words corresponding to the familiar sounds presented within each list in the same order in which they were cued.) After a delay of 3 or 9 s, a target word associated with one of the recorded sounds appeared on the screen (e.g. the word CAT might be presented if the sound `meow' had appeared in the preceding list). When the probe test word appeared, subjects indicated its corresponding position in the sequence by pressing the appropriate number key. Thus, if a subject heard the actual sounds corresponding to `meow', `ding-dong', `caw', and `bang', they were to remember the words CAT, DOORBELL, CROW, and GUN, in that order. If they were subsequently presented with the probe test word CROW, they should press the `3' key. There were 24 trials, balanced and ordered randomly with regard to the two retention intervals and the four possible target positions. Each of the 24 sounds appeared as a list item on four trials. Memory testsÐvisual: Two self-paced serial position tasks were presented. One had complex, dif®cult-to-label stimuli (snow¯akes). The second
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used line drawings of familiar objects, and subjects were instructed to remember the associated word (e.g. a drawing of a cat was presented and subjects were required to remember the word `CAT'). In the snow¯akes serial position task, 24 black and white pictures of snow¯akes served as the stimuli. At the start of each trial, three different pictures of snow¯akes were presented, each one appearing on the computer screen for 700 ms (600 ms ISI). On the probe test, one of the three pictures was shown again after a delay of 3 or 9 s. Subjects were instructed to remember the three snow¯akes in the order presented and to indicate the serial position of the repeated snow¯ake by pressing the appropriate number key. Subjects received a total of 24 trials, 12 at each of the two retention intervals. Within each set of 12 trials, the probe test picture was equally often the ®rst, second, or third picture in the preceding list. Across the session of 24 trials, the six trial types (two retention intervals and three test positions) were presented in a random sequence. Each snow¯ake appeared as a list item on three trials. Before proceeding to the verbal memory test, subjects were told that they were to take a `quiz' and that they could not proceed with the rest of the experiment until they scored 100%. The 24 line drawings of familiar objects to be used in the memory test were each presented for 500 ms, and were followed 500 ms later by the word people most often give to the picture, which was printed on the computer screen (e.g. picture of a tree ! `TREE'). Subjects read the word out loud and then pressed the spacebar to see the next picture. The pictures were then presented again and subjects asked to say the appropriate label without it appearing on the computer screen. All controls and all DSz patients gave the correct words for all 24 drawings the ®rst time through. To con®rm that the verbal labels had remained readily available to subjects throughout the ensuing memory test, the quiz was repeated at the conclusion of the memory test. All subjects gave the correct word for each of the 24 drawings. In the memory test, each trial began with presentation of 4 line drawings of the common objects (e.g., a picture of a dog, a tree, a car, and a ¯ower). Each drawing was presented for 700 ms (500 ms ISI). (On initial practice trials, subjects were encouraged to remember the words corresponding to the familiar
drawings in each list in the order in which they were cued.) After a delay of 3 or 9 s, a target word corresponding to one of the drawings in the list appeared on the screen. When the probe test word appeared, subjects indicated its corresponding position in the sequence by pressing the appropriate number key. There were 24 trials balanced and ordered randomly with regard to the two retention intervals and four possible target positions. Each of the 24 drawings appeared as a list item on four trials. General procedure: Subjects were tested individually in two sessions, except for four DSz subjects who performed all tests in one session. In the ®rst session, the simple hearing test (with no practice trials) and the screening test of attention and perception (with 10 practice trials) were given, in that order. In the second session half the subjects took the auditory memory tests ®rst, followed by the visual memory tests, while the remaining half did the visual tests ®rst and then the auditory tests. Subjects were allowed to practice until they could demonstrate that they understood the instructions. Results of the four patients who took all tests in one session were nearly identical to those of the other patients and all DSz patients were therefore considered together in the data analyses. Data analysis: All subjects scored 100% on the hearing test. Subjects were separated into discriminators (DSz, n 14) and non-discriminators (NDSz, n 9) on the basis of scores on the pitch discrimination screening test of basic attentional and perceptual competence (Fig. 1). The distribution of patient scores was bimodal, and a score of 80% was used as the cutoff. All controls scored above this value. Differences among DSz patients and controls on the memory tests were evaluated by analysis of variance. Students' two-tailed t-tests were used for post hoc comparisons. DSz patients were very closely matched to healthy controls in age (means 38 vs. 38 years.), personal education (13.4 vs. 13.6 years.), mother's education (13.6 vs. 14.5 years.), or father's education (14 vs. 14.1 years.), but did include a nonsigni®cantly higher proportion of men (8/14 vs. 5/15). At the time of assessment, mean DSz patient symptom ratings on the PANSS (Kay et al., 1987) were: 13.6 positive; 11.5 negative; and 22.8 general. Five DSz patients were on typical neuroleptics, six on atypical neuroleptics, three on typical and atypical neuroleptics, and six on anticholinergic agents, all within
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11.4; time between most recent hospitalization and study testing was 5.0 ^ 5.0 years.; and duration of most recent hospitalization was 70.2 ^ 119.0 days.
3. Results
Fig. 1. Scores of individual patients on the screening test of basic attentional and perceptual competence. The distribution is discontinuous. Patients with scores above 80% were considered to have passed the test, were labeled discriminators of DSz patients, and are the ones included in the analyses of memory test performance.
conventional dose ranges. Age (mean ^ SD) at time of ®rst psychiatric hospitalization for DSz patients was 21 ^ 3.5 years.; time between ®rst hospitalization and study testing was 18.6 ^ 7.1 years.; total number of psychiatric hospitalizations was 11.9 ^
Fig. 2a presents the overall levels of performance for the patient and control group when the items to be remembered were birdsongs or words associated with familiar sounds and Fig. 2b presents subjects level of performance when the stimuli were snow¯akes or words associated with familiar pictures. In order to compare DSz patients and healthy controls on all four memory tests, a three-way ANOVA was performed (collapsing across retention intervals and serial position) with diagnosis as a between-subjects factor and memoranda (words vs. dif®cult to label sounds or images) and modality (auditory vs. visual) as within-subject factors. There was a signi®cant main effect of group, re¯ecting the greater overall performance of controls compared with DSz patients [F(1,27) 34.4, p , 0.0001]. There was a reliable main effect of memoranda re¯ecting better performance when the memoranda were words [F(1,27) 121, p , 0.001], and an interaction between modality and memoranda due to the fact that the effect of memoranda was greater on the auditory than on the visual tests [F(1,27) 14.8, p , 0.001]. The interaction of primary interest, between memoranda and group, was
Fig. 2. (a) and (b) Mean group performance for DSz patients and control subjects on the auditory tests with dif®cult-to-label birdsongs and easyto-name familiar sounds (a), and on the visual tests with dif®cult-to-label snow¯akes and easy-to-name familiar objects.
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Fig. 3. Individual scores for healthy controls and DSz patients on the auditory tests with dif®cult-to-name birdsongs and easy-to-label familiar sounds.
also highly signi®cant, due to the fact the patient performance de®cit relative to controls was signi®cantly greater on the easier tests with verbal memoranda than they were on the more dif®cult tests with hard-to-label stimuli [F(1,27) 17.1, p , 0.0005]. In addition, the three-way interaction of group, memoranda, and modality was signi®cant, F(1,27) 5.3, p , 0.05, re¯ecting the fact that the interaction of memoranda with group was robust in the auditory tasks (Fig. 2a) but much less apparent in the visual tasks (Fig. 2b). For the auditory tasks, the group £ memoranda interaction was highly reliable, F(1,27) 29.25, p , 0.0001. In contrast, the same interaction was not signi®cant in the visual tasks, F(1,27) 1.36, p . 0.25. Thus, while on both the auditory and visual tests the patient de®cit was greater on the easier tests with verbal memoranda, this effect was signi®cant only on the auditory tests. The striking differences between the controls and the DSz patients in the auditory memory test with easy-to-name familiar sounds is evident in Fig. 2a (93 vs. 63%, respectively, p , 0.0005). In contrast, the difference between the two groups was much smaller on the birdsong test (69 vs 61%, respectively), although reliable, p , 0.05. It is also evident that the labeled familiar sounds test was much easier for the controls than the birdsong test Ð an improvement of 24 percentage points. In contrast, the DSz patients improved only 2 percentage points. All controls
scored higher on the auditory test with verbal memoranda than they did on the bird song test, while this was true of less than half of DSz patients (Fig. 3). Two of the DSz patients scored as well or better than the best controls on the bird song test yet performed worse than all of the controls on the auditory test with verbal memoranda. DSz patient scores on the word test with easy-toname familiar objects serving as retrieval cues (Fig. 2b) was markedly below that of controls (96 vs. 72%, p , 0.0005), again con®rming the presence of a verbal memory de®cit that is independent of early sensory processing of verbal stimuli. In the test with snow¯akes, DSz patient scores were also markedly below controls (70 vs. 49%, p , 0.005). In ANOVAs with gender as an additional betweensubjects factor, the main effect of gender and interactions of gender with other factors were all non-signi®cant. Secondary analyses examined the effects of retention interval (3 vs. 9 s) and of serial position of the target on task performance. Neither DSz patients nor controls showed any effect of retention interval on the tests with easy-to-name stimuli. Both groups showed similar performance declines (p , 0.05) with increasing retention intervals on the birdsong and snow¯ake tests. Serial position effects were signi®cant on all tests, but the only evidence of group differences in this effect was on the familiar sounds test. Here DSz patients showed a greater
B.E. Wexler et al. / Schizophrenia Research 53 (2002) 171±179
recency effect than did healthy controls, but this may have been due to ceiling effects in the controls. DSz patients with lower scores on the labeled sounds test tended to have higher ratings of positive symptoms (Pearson r 20.48, p , 0.10), negative symptoms (r 20.51, p , 0.08), and general symptoms (r 20.66, p , 0.02). Similar correlations were evident between the difference between the labeled sounds and the birdsong tests (i.e. the selective de®cit in language-mediated auditory test performance) and positive (r 20.51, p , 0.08), negative (r 20.58, p , 0.04), and general symptom scores (r 20.53, p , 0.06). Correlations between ratings of hallucinations in particular and scores on the labeled sounds test (r 20.50, p , 0.08) and the difference between the labeled sounds and birdsongs tests (r 20.54, p , 0.06) were similar to the correlations with other symptoms. Correlations between overall memory performance (i.e., the sum of scores on all four serial position tasks) and positive (r 20.30, p . 0.32) and negative (r 20.35, p . 0.24) symptoms were lower than the correlations between labeled sounds or labeled sounds-birdsong scores and symptoms, but the correlation between total memory and the general symptom score (r 20.64, p , 0.02) was comparable. 4. Discussion In previous studies we identi®ed a subgroup of patients with schizophrenia (DSz patients) who have selective de®cits in verbal memory (Wexler et al., 1998; Stevens et al., 2000). The present study used newly developed tests to determine whether their poorer performance on verbal memory tasks was due to language speci®c de®cits in early stages of sensory processing (encoding) or later, language speci®c memory processes. The strategy was to bypass early, perceptual processing of verbal stimuli. To do this, tasks were developed that used easy-toname non-verbal auditory and visual stimuli as retrieval cues for highly associated word targets. In this way, the target words could be activated and rehearsed, without having been presented as spoken or printed words. Thus, language-based memory mechanisms were activated while initial sensory processing of linguistic stimuli was bypassed. DSz patients showed marked de®cits on both the auditory
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and visual versions of these tests, providing conclusive evidence of de®cits in language-based memory processes per se. Patient de®cits were greater on the tests with easyto-name stimuli and verbal memoranda than on the tests with hard-to-label stimuli and non-verbal memoranda. For healthy subjects, the tests with verbal memoranda were much easier than the tests with nonverbal memoranda. Thus, the patient de®cit was greater on the tests that were easier for the controls, deconfounding de®cit-speci®city and task-dif®culty as in our previous studies (Wexler et al., 1998; Stevens et al., 2000). In fact, the tests with easy-toname stimuli and verbal memoranda were so easy for the healthy subjects that ceiling effects may have underestimated the degree of patient de®cits. One way to understand these de®cits is that DSz patients are less able than healthy controls to retrieve appropriate words from memory. Such a disability would be consistent with our earlier ®ndings that DSz patients do as well as healthy controls on tone memory tests, yet have de®cits on word memory tests (Wexler et al., 1998; Stevens et al., 2000). When a word is spoken, the pattern of sounds must activate a representation of the word, i.e. the word has to be retrieved from an internal lexicon. In contrast, on the tone or birdsong tests, in which it is not possible to verbally label the stimuli, it is the actual sound pattern that must be remembered. Thus a relative inability to retrieve verbal tags would put patients at a disadvantage on the word but not on the tone or birdsong tests. Such a de®cit could arise from an inability to activate the appropriate representation and/or an inability to inhibit activation of inappropriate representations (Spitzer, 1997; Engle et al., 1999). Impaired retrieval of language-related internal representations could also account for the ®nding that patients with schizophrenia show less consistent categorical perception of ambiguous auditory stimuli than do healthy controls (Cienfuegos et al., 1999). In that study, subjects were required to identify auditory stimuli as being either the phoneme `ba' or the phoneme `da'. When a range of stimuli were presented falling along the acoustic continuum between `ba' and `da', healthy subjects abruptly switched from perceiving `ba' to perceiving `da'. Such categorical perception would appear to be based on activation of one or the other pre-existing
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internal phonemic representations by the auditory input. Patients with schizophrenia performed normally when the acoustic stimuli were at one end or the other of the acoustic continuum, but were less consistent (i.e. show a less abrupt transition) in categorization of stimuli from the middle of the continuum. Stimuli from the middle of the continuum would less strongly and less selectively activate the internal (categorical) phonemic representation both because they are less familiar and because they are more likely to activate multiple internal representations. If retrieval mechanisms in patients are impaired, lack of familiarity and increased ambiguity would both lead to less consistent activation of internal representations. This view of the patients' performance de®cit might lead one to predict that their de®cits would be greater on verbal memory tests in which the to-beremembered word is activated by a non-verbal retrieval cue (e.g. a familiar sound) than when the to-be-remembered word is itself presented, since the association between the sound of the word and its internal verbal label is much more heavily practiced than is the association between the non-verbal retrieval cue and its internal verbal label. This appears to be the case. In our previous studies, when the to-beremembered words were spoken, DSz patients scored 76 and 75% correct, compared with control values of 89 and 86% (Wexler et al. 1998; Stevens et al., 2000). In the present study, when the to-be-remembered words were cued by the easy-to-name sounds, DSz patients only scored 63% correct while controls scored 93%. The same pattern is evident in on-going work in our laboratory when both the word and labeled sounds serial position tasks are given to the same patients. This explanation may also be extended to our earlier observation that patients did more poorly on a visual than an auditory word serial position task (Stevens et al., 2000). Again, the association between the sound pattern corresponding to a word and the internal verbal label is more practiced than is the association between the pattern of visual stimuli corresponding to a word (i.e. the printed letters) and the verbal tag, especially in patients who may not read very much and in whom the effects of illness may have been evident when learning to read but not when learning to understand speech. Patients are able to use language and attach verbal labels to sounds and images. In a previous study we
demonstrated their ability to repeat back, accurately, words they heard or saw (Stevens et al., 2000), and in the present study they could accurately retrieve verbal labels for the familiar sounds and pictures. However, in the previous study they were signi®cantly less accurate than controls in reading the words. More importantly, we hypothesize that the patient de®cit in internal verbal labeling is more easily demonstrable when the labeling function is part of more complex tasks, such as our serial position memory tasks, that require division and integration of neurocognitive resources. It is not clear whether the proposed disability in activating verbal labels to sensory input is part of a more general de®cit in retrieval from long-term memory or is a de®cit speci®c to language-related processes. In either case, its impact on cognitive function would be profound, as the use of internal language mechanisms to enhance cognition is an essential aspect of a wide range of normal human brain functions (e.g. Vygotsky, 1978; Walker and Hulme, 1999). In the present study, for example, when healthy subjects were able to activate verbal labels for auditory input on the familiar sounds test, they scored 93% correct compared with only 69% correct on the unlabelable birdsongs test. In summary, by devising tests that use non-verbal stimulus cues to bypass sensory encoding of linguistic stimuli but still activate verbal memoranda, we provide evidence of de®cits in language-based memory processes in attentionally competent patients with schizophrenia. We suggest that the verbal memory de®cit in these patients re¯ects a disability in retrieving verbal labels from an internal lexicon. Given the importance of internal language mechanisms in human neurocognitive function, such a disability could have widespread consequences for patients with schizophrenia. References Cienfuegos, A., Shelley, A., March, L., Javitt, D.C., 1999. Impaired categorical percepton of synthetic sounds in schizophrenia. Soc. Biol. Psychiatry 45, 82±88. Engle, R.W., Kane, M.J., Tuholsk, S.W., 1999. Individual differences in working memory capacity and what they tell us about controlled attention, general ¯uid intelligence, and functions of the prefrontal cortex. In: Shah, P., Miyake, A. (Eds.), Models of working memory. Cambridge University Press, Cambridge, pp. 102±134.
B.E. Wexler et al. / Schizophrenia Research 53 (2002) 171±179 Hoff, A.L., Riordan, H., O'Donell, D., Stritzke, P., Neale, C., Boccio, A., Anand, A.K., DeLisi, L.E., 1992. Anomalous lateral sulcus asymmetry and cognitive function in ®rst-episode schizophrenia. Schiz. Bull. (2), 257±272. Kay, S.R., Fiszbein, A., Opler, L., 1987. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schiz. Bull. 13, 261±276. Levin, S., Yurgelun-Todd, D., Craft, S., 1989. Contributions of clinical neuropsychology to the study of schizophrenia. J. Abn. Psychol. 98 (4), 341±356. Merzenich, M.M., Jenkins, W.M., Johnston, C.S., Miller, S.L., Tallal, P., 1996. Temporal processing de®cits of language-learning impaired children ameliorated by training. Science 271, 77± 81. Saykin, A.J., Gur, R.C., Gur, R.E., Mozley, P.D., Mozley, L.H., Resnick, S.M., Kester, B., Sta®niak, P., 1991. Neurological function in schizophrenia: selective impairment in memory and learning. Arch. Gen. Psychiatry 48, 618±624. Saykin, A.J., Sahtasel, D.L., Gur, R.E., Kester, D.B., Mozley, L.H.,
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Sta®niak, P., Gur, R.C., 1994. Neuropsychological de®cits in neuroleptic naõÈve patients with ®rst-episode schizophrenia. Arch. Gen. Psychiatry. 51, 124±131. Spitzer, M., 1997. A cognitive neuroscience view of schizophrenic thought disorder. Schiz. Bull. 23, 29±50. Stevens, A.A., Donegan, N.H., Anderson, M., Goldman-Rakic, P.S., Wexler, B.E., 2000. Verbal memory de®cits in schizophrenia: the contribution of proactive interference, phonological processing and stimulus modality. J. Abn. Psychol. 109 (461), 471. Vygotsky, L.S., 1978. Mind in society: the development of higher psychological processes. Harvard University Press, Cambridge MA. Walker, I., Hulme, C., 1999. Concrete words are easier to recall than abstract words: Evidence for a semantic contribution to shortterm serial recall. J. Exp. Psychology (5), 1256±1271. Wexler, B.E., Stevens, A.A., Bowers, S.A., Sernyak, M.J., Goldman-Rakic, P.S., 1998. Word and tone working memory de®cits in schizophrenia. Arch. Gen. Psychiatry 55, 1093±1096.
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De®cits in language-mediated mental operations in patients with schizophrenia Bruce E. Wexler a,*, Nelson Donegan a, Alexander A. Stevens b, Sharif A. Jacob a a
Connecticut Mental Health Center, Department of Psychiatry, Yale University School of Medicine, 34, Park Street, New Haven, CT 06519, USA b Department of Psychiatry, Oregon Health Sciences University, Portland, OR, USA Received 17 August 2000; revised 6 February 2001; accepted 14 February 2001
Abstract We found previously that a subgroup of schizophrenic patients who passed screening tests of attentional competence showed memory de®cits on word memory tasks, but were comparable with controls on tone memory tasks. To better understand the nature of language-speci®c memory de®cits in this subgroup of patients, the present experiment was designed to bypass early perceptual processing of verbal material and determine if patients continue to show impaired performance on verbal memory tasks. Patients who passed the screening tests (`discriminator' patients; DSz) received four serial position tasks. In two, familiar sounds or line drawings were presented and subjects were required to remember the word associated with each stimulus item. In the other two, subjects received hard-to-label auditory and visual stimuli (birdsongs or snow¯akes). DSz patients showed large memory de®cits compared with controls when required to remember words associated with the familiar sounds or drawings, providing clear evidence of de®cits in verbal memory processes independent of sensory processing of verbal stimuli. The interaction between diagnosis and labeling was highly signi®cant, con®rming that these patients have particular dif®culty with verbal as opposed to non-verbal memory. This was particularly striking on the auditory tests where two patients out-performed all controls on the birdsong test, but were below all controls on the easy-to-label sounds test. The verbal memory tests were easier than the non-verbal memory tests for controls, thus deconfounding task dif®culty and de®cit speci®city. q 2002 Elsevier Science B.V. All rights reserved.
1. Introduction An important question in research on schizophrenia is whether the broad cognitive de®cits observed with many test batteries (Levin et al., 1989; Hoff et al., 1992; Saykin et al., 1991, 1994) are characteristic of the population of patients or whether the group
* Corresponding author. Tel.: 11-203-789-7344; fax: 11-203789-7206. E-mail address: [email protected] (B.E. Wexler).
averaging obscures the existence of subgroups with limited and distinct cognitive abnormalities. In our previous work we have provided evidence consistent with the latter interpretation, i.e. that schizophrenia is a heterogeneous disorder (Wexler et al., 1998; Stevens et al., 2000). For example, we have been able to consistently identify a subgroup of schizophrenic patients who demonstrate selective verbal memory de®cits; their performance on word memory tests is inferior to controls, whereas their performance on procedurally equivalent non-verbal memory tests is comparable with controls.
0920-9964/02/$ - see front matter q 2002 Elsevier Science B.V. All rights reserved. PII: S 0920-996 4(01)00194-3
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In a study of auditory verbal and non-verbal memory in schizophrenic patients (Wexler et al., 1998) we ®rst divided the patients into two groups based on their ability to perform as well as controls on a simple screening test of pitch discrimination. The screening test required perceptual, motivational, and attentional competence while imposing minimal demands on memory. Patients who performed as well as controls on the screening test (`discriminators' or DSz patients) also performed as well as controls on tone memory tests, but had signi®cant de®cits on word memory tests, even though the tone tests were clearly more dif®cult than the word tests for healthy controls. Because the discriminator patients had suf®cient perceptual, attentional, and motivational capacities to perform as well as controls on the more dif®cult non-verbal tests, their poorer performance on verbal memory tests could not be attributed to these general performance factors. In addition, these ®ndings indicate that their memory de®cits were not global, but were speci®c to verbal material over this range of tests. Not surprisingly, patients who failed the screening test (`nondiscriminators') did very poorly on both verbal and non-verbal memory tests. Subsequent work in our lab has focused on the scope and nature of the verbal learning de®cit in DSz patients. Stevens et al. (2000) again found the selective de®cit on the auditory word memory test as compared to the auditory tone memory test. In addition, DSz patients were signi®cantly impaired on a similar word memory test in which the items were presented visually. One interpretation of these ®ndings is that the patients' problems on the word memory tests arise at a stage of information processing common to both auditory and visual verbal memory (e.g., creating an acoustical representation of a word and entering it into a rehearsal loop or `buffer') rather than at earlier stages of sensoryspeci®c stimulus encoding. An alternate possibility is that patients have early auditory and visual sensory processing de®cits that are language-speci®c and cause performance de®ciencies on the word memory tests when the words are spoken or presented visually. The present project was designed to test the hypothesis that DSz patients have de®cits in verbal memory processing subsequent to the initial sensory/modality-speci®c encoding of spoken or printed words. To do this, we developed word
memory tasks in which subjects were presented with nonverbal stimuli (familiar sounds or pictures) that reliably activated the representation of the target word in the subjects' memory (e.g., when the sound `moo' was presented the subject kept the word `COW' in memory). Thus, the items presented were nonverbal stimuli, but the memoranda were words. This allowed us to bypass early auditory stages of speech processing or visual analysis of written words but at the same time assess subjects' ability to remember the designated words. If the selective verbal memory de®cits in DSz patients arise from perceptual de®cits, e.g., initial encoding of verbal stimuli, as for example appears to be the case with certain children who have language acquisition disorders (e.g. Merzenich et al., 1996), they should perform well on tests that bypass these early stages of language processing. If, on the other hand, their de®cits arise at later stages of verbal information processing (e.g. automatic or controlled memory processes), they should continue to show pronounced de®cits even in the tests where the stimuli that are presented are non-verbal but the to-beremembered items are the associated words. 2. Subjects and methods Subjects: Twenty-three clinically stable and medicated outpatients who met DSM-IV criteria for schizophrenia and 15 controls without history of psychiatric illness were studied. Subjects were excluded if they met the criteria for substance abuse within the previous six months, were using alcohol or drugs regularly, had a history of neurologic illness, or were not native English speakers. Patients and controls did not differ in age, sex, parental education, or handedness. All gave written informed consent to participate. Method: All tests were presented via a Power Macintosh G3 computer using Psyscope (Carnegie Mellon University, Department of Psychology, Pittsburgh, PA, 1994). Hearing test: Subjects were screened for adequate hearing by testing their ability to detect sounds at intensities one-half those used in the screening test of attentional and perceptual competence. Subjects were required to raise the hand corresponding to the
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ear in which they heard a 10 ms word fragment (da or ga). Subjects had to correctly report the onset and location of all 12 fragments in order to ªpass' the test. Screening test for basic attentional and perceptual competence: Subjects were required to judge whether two 200 ms pure tones separated by a 100 ms interstimulus interval were the same or different in pitch. When different, frequencies were in one of ®ve ratios: 0.67, 0.75, 0.85, 0.9, or 0.95. Individual tone frequencies ranged from 325±1994 Hz. There were 10 practice trials and 60 test trials; on 30 test trials the tones were the same and on 30 trials they were different. In each of six ten-trial blocks, half of the trials were `same' and half `different' trials, with each of the ®ve frequency ratios appearing once in each block and with trial types randomly distributed across the block. Memory testsÐauditory: Two self-paced serial position tasks were presented. (We used serial position tasks because the format allows one to develop verbal and nonverbal memory tests with procedurally equivalent task demands.) One had complex, dif®cult-to-label stimuli (bird songs). The second used common sounds and subjects were instructed to remember the word most commonly associated with the sound (e.g. the sound `moo' was presented and subjects were instructed to remember the word `COW'). In the bird song task, each trial began with three approximately 2 s recorded bird songs presented with a 1 s inter stimulus interval (ISI). After a delay of 3 or 9 s a probe test-stimulus was presented by playing one of the three songs that had appeared in the preceding list. Subjects were instructed to indicate the list position of the repeated bird song by pressing the appropriate number key. Subjects received a total of 24 trials, 12 at each of the two retention intervals. Within each set of 12 trials, the probe test song was equally often the same as the ®rst, second, or third song in the preceding list. Across the session of 24 trials, the six trial types (two retention intervals by three probe test positions) were presented in a random sequence. From the collection of 24 bird songs, each song appeared in the list of to-be-remembered items on three trials. Before proceeding to the verbal memory test, subjects were told that they were to take a `quiz' and that they could not proceed with the rest of the experiment until they scored 100%. The 24 1±2 s
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common sounds to be used in the subsequent memory test were presented one at a time followed 500 ms later by the word people most often give to the sound, which was printed on the computer screen (e.g. ªmooº ! COW). Subjects read the word out loud and then pressed the spacebar to hear the next sound. The sounds were then presented again and subjects asked to say the appropriate word without it appearing on the computer screen. Immediately after the subject said what they thought was the correct word, the experimenter told them if they were correct or incorrect, and, if incorrect, provided the correct word. All controls and 13 of the 14 DSz patients correctly supplied the words that had been paired with the 24 stimuli the ®rst time through. The one patient who was not 100% correct mislabeled six stimuli the ®rst time through and achieved a level of 100% correct after a single correction of errors. To con®rm that the correct words had remained readily available to subjects throughout the ensuing memory test, the quiz was repeated at the conclusion of the memory test. All subjects gave the correct words to all the sound stimuli. In the serial position test, each trial began with the presentation of four of the 24 common sounds, presented with a 1 s ISI. (On initial practice trials, subjects were encouraged to remember the words corresponding to the familiar sounds presented within each list in the same order in which they were cued.) After a delay of 3 or 9 s, a target word associated with one of the recorded sounds appeared on the screen (e.g. the word CAT might be presented if the sound `meow' had appeared in the preceding list). When the probe test word appeared, subjects indicated its corresponding position in the sequence by pressing the appropriate number key. Thus, if a subject heard the actual sounds corresponding to `meow', `ding-dong', `caw', and `bang', they were to remember the words CAT, DOORBELL, CROW, and GUN, in that order. If they were subsequently presented with the probe test word CROW, they should press the `3' key. There were 24 trials, balanced and ordered randomly with regard to the two retention intervals and the four possible target positions. Each of the 24 sounds appeared as a list item on four trials. Memory testsÐvisual: Two self-paced serial position tasks were presented. One had complex, dif®cult-to-label stimuli (snow¯akes). The second
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used line drawings of familiar objects, and subjects were instructed to remember the associated word (e.g. a drawing of a cat was presented and subjects were required to remember the word `CAT'). In the snow¯akes serial position task, 24 black and white pictures of snow¯akes served as the stimuli. At the start of each trial, three different pictures of snow¯akes were presented, each one appearing on the computer screen for 700 ms (600 ms ISI). On the probe test, one of the three pictures was shown again after a delay of 3 or 9 s. Subjects were instructed to remember the three snow¯akes in the order presented and to indicate the serial position of the repeated snow¯ake by pressing the appropriate number key. Subjects received a total of 24 trials, 12 at each of the two retention intervals. Within each set of 12 trials, the probe test picture was equally often the ®rst, second, or third picture in the preceding list. Across the session of 24 trials, the six trial types (two retention intervals and three test positions) were presented in a random sequence. Each snow¯ake appeared as a list item on three trials. Before proceeding to the verbal memory test, subjects were told that they were to take a `quiz' and that they could not proceed with the rest of the experiment until they scored 100%. The 24 line drawings of familiar objects to be used in the memory test were each presented for 500 ms, and were followed 500 ms later by the word people most often give to the picture, which was printed on the computer screen (e.g. picture of a tree ! `TREE'). Subjects read the word out loud and then pressed the spacebar to see the next picture. The pictures were then presented again and subjects asked to say the appropriate label without it appearing on the computer screen. All controls and all DSz patients gave the correct words for all 24 drawings the ®rst time through. To con®rm that the verbal labels had remained readily available to subjects throughout the ensuing memory test, the quiz was repeated at the conclusion of the memory test. All subjects gave the correct word for each of the 24 drawings. In the memory test, each trial began with presentation of 4 line drawings of the common objects (e.g., a picture of a dog, a tree, a car, and a ¯ower). Each drawing was presented for 700 ms (500 ms ISI). (On initial practice trials, subjects were encouraged to remember the words corresponding to the familiar
drawings in each list in the order in which they were cued.) After a delay of 3 or 9 s, a target word corresponding to one of the drawings in the list appeared on the screen. When the probe test word appeared, subjects indicated its corresponding position in the sequence by pressing the appropriate number key. There were 24 trials balanced and ordered randomly with regard to the two retention intervals and four possible target positions. Each of the 24 drawings appeared as a list item on four trials. General procedure: Subjects were tested individually in two sessions, except for four DSz subjects who performed all tests in one session. In the ®rst session, the simple hearing test (with no practice trials) and the screening test of attention and perception (with 10 practice trials) were given, in that order. In the second session half the subjects took the auditory memory tests ®rst, followed by the visual memory tests, while the remaining half did the visual tests ®rst and then the auditory tests. Subjects were allowed to practice until they could demonstrate that they understood the instructions. Results of the four patients who took all tests in one session were nearly identical to those of the other patients and all DSz patients were therefore considered together in the data analyses. Data analysis: All subjects scored 100% on the hearing test. Subjects were separated into discriminators (DSz, n 14) and non-discriminators (NDSz, n 9) on the basis of scores on the pitch discrimination screening test of basic attentional and perceptual competence (Fig. 1). The distribution of patient scores was bimodal, and a score of 80% was used as the cutoff. All controls scored above this value. Differences among DSz patients and controls on the memory tests were evaluated by analysis of variance. Students' two-tailed t-tests were used for post hoc comparisons. DSz patients were very closely matched to healthy controls in age (means 38 vs. 38 years.), personal education (13.4 vs. 13.6 years.), mother's education (13.6 vs. 14.5 years.), or father's education (14 vs. 14.1 years.), but did include a nonsigni®cantly higher proportion of men (8/14 vs. 5/15). At the time of assessment, mean DSz patient symptom ratings on the PANSS (Kay et al., 1987) were: 13.6 positive; 11.5 negative; and 22.8 general. Five DSz patients were on typical neuroleptics, six on atypical neuroleptics, three on typical and atypical neuroleptics, and six on anticholinergic agents, all within
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11.4; time between most recent hospitalization and study testing was 5.0 ^ 5.0 years.; and duration of most recent hospitalization was 70.2 ^ 119.0 days.
3. Results
Fig. 1. Scores of individual patients on the screening test of basic attentional and perceptual competence. The distribution is discontinuous. Patients with scores above 80% were considered to have passed the test, were labeled discriminators of DSz patients, and are the ones included in the analyses of memory test performance.
conventional dose ranges. Age (mean ^ SD) at time of ®rst psychiatric hospitalization for DSz patients was 21 ^ 3.5 years.; time between ®rst hospitalization and study testing was 18.6 ^ 7.1 years.; total number of psychiatric hospitalizations was 11.9 ^
Fig. 2a presents the overall levels of performance for the patient and control group when the items to be remembered were birdsongs or words associated with familiar sounds and Fig. 2b presents subjects level of performance when the stimuli were snow¯akes or words associated with familiar pictures. In order to compare DSz patients and healthy controls on all four memory tests, a three-way ANOVA was performed (collapsing across retention intervals and serial position) with diagnosis as a between-subjects factor and memoranda (words vs. dif®cult to label sounds or images) and modality (auditory vs. visual) as within-subject factors. There was a signi®cant main effect of group, re¯ecting the greater overall performance of controls compared with DSz patients [F(1,27) 34.4, p , 0.0001]. There was a reliable main effect of memoranda re¯ecting better performance when the memoranda were words [F(1,27) 121, p , 0.001], and an interaction between modality and memoranda due to the fact that the effect of memoranda was greater on the auditory than on the visual tests [F(1,27) 14.8, p , 0.001]. The interaction of primary interest, between memoranda and group, was
Fig. 2. (a) and (b) Mean group performance for DSz patients and control subjects on the auditory tests with dif®cult-to-label birdsongs and easyto-name familiar sounds (a), and on the visual tests with dif®cult-to-label snow¯akes and easy-to-name familiar objects.
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Fig. 3. Individual scores for healthy controls and DSz patients on the auditory tests with dif®cult-to-name birdsongs and easy-to-label familiar sounds.
also highly signi®cant, due to the fact the patient performance de®cit relative to controls was signi®cantly greater on the easier tests with verbal memoranda than they were on the more dif®cult tests with hard-to-label stimuli [F(1,27) 17.1, p , 0.0005]. In addition, the three-way interaction of group, memoranda, and modality was signi®cant, F(1,27) 5.3, p , 0.05, re¯ecting the fact that the interaction of memoranda with group was robust in the auditory tasks (Fig. 2a) but much less apparent in the visual tasks (Fig. 2b). For the auditory tasks, the group £ memoranda interaction was highly reliable, F(1,27) 29.25, p , 0.0001. In contrast, the same interaction was not signi®cant in the visual tasks, F(1,27) 1.36, p . 0.25. Thus, while on both the auditory and visual tests the patient de®cit was greater on the easier tests with verbal memoranda, this effect was signi®cant only on the auditory tests. The striking differences between the controls and the DSz patients in the auditory memory test with easy-to-name familiar sounds is evident in Fig. 2a (93 vs. 63%, respectively, p , 0.0005). In contrast, the difference between the two groups was much smaller on the birdsong test (69 vs 61%, respectively), although reliable, p , 0.05. It is also evident that the labeled familiar sounds test was much easier for the controls than the birdsong test Ð an improvement of 24 percentage points. In contrast, the DSz patients improved only 2 percentage points. All controls
scored higher on the auditory test with verbal memoranda than they did on the bird song test, while this was true of less than half of DSz patients (Fig. 3). Two of the DSz patients scored as well or better than the best controls on the bird song test yet performed worse than all of the controls on the auditory test with verbal memoranda. DSz patient scores on the word test with easy-toname familiar objects serving as retrieval cues (Fig. 2b) was markedly below that of controls (96 vs. 72%, p , 0.0005), again con®rming the presence of a verbal memory de®cit that is independent of early sensory processing of verbal stimuli. In the test with snow¯akes, DSz patient scores were also markedly below controls (70 vs. 49%, p , 0.005). In ANOVAs with gender as an additional betweensubjects factor, the main effect of gender and interactions of gender with other factors were all non-signi®cant. Secondary analyses examined the effects of retention interval (3 vs. 9 s) and of serial position of the target on task performance. Neither DSz patients nor controls showed any effect of retention interval on the tests with easy-to-name stimuli. Both groups showed similar performance declines (p , 0.05) with increasing retention intervals on the birdsong and snow¯ake tests. Serial position effects were signi®cant on all tests, but the only evidence of group differences in this effect was on the familiar sounds test. Here DSz patients showed a greater
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recency effect than did healthy controls, but this may have been due to ceiling effects in the controls. DSz patients with lower scores on the labeled sounds test tended to have higher ratings of positive symptoms (Pearson r 20.48, p , 0.10), negative symptoms (r 20.51, p , 0.08), and general symptoms (r 20.66, p , 0.02). Similar correlations were evident between the difference between the labeled sounds and the birdsong tests (i.e. the selective de®cit in language-mediated auditory test performance) and positive (r 20.51, p , 0.08), negative (r 20.58, p , 0.04), and general symptom scores (r 20.53, p , 0.06). Correlations between ratings of hallucinations in particular and scores on the labeled sounds test (r 20.50, p , 0.08) and the difference between the labeled sounds and birdsongs tests (r 20.54, p , 0.06) were similar to the correlations with other symptoms. Correlations between overall memory performance (i.e., the sum of scores on all four serial position tasks) and positive (r 20.30, p . 0.32) and negative (r 20.35, p . 0.24) symptoms were lower than the correlations between labeled sounds or labeled sounds-birdsong scores and symptoms, but the correlation between total memory and the general symptom score (r 20.64, p , 0.02) was comparable. 4. Discussion In previous studies we identi®ed a subgroup of patients with schizophrenia (DSz patients) who have selective de®cits in verbal memory (Wexler et al., 1998; Stevens et al., 2000). The present study used newly developed tests to determine whether their poorer performance on verbal memory tasks was due to language speci®c de®cits in early stages of sensory processing (encoding) or later, language speci®c memory processes. The strategy was to bypass early, perceptual processing of verbal stimuli. To do this, tasks were developed that used easy-toname non-verbal auditory and visual stimuli as retrieval cues for highly associated word targets. In this way, the target words could be activated and rehearsed, without having been presented as spoken or printed words. Thus, language-based memory mechanisms were activated while initial sensory processing of linguistic stimuli was bypassed. DSz patients showed marked de®cits on both the auditory
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and visual versions of these tests, providing conclusive evidence of de®cits in language-based memory processes per se. Patient de®cits were greater on the tests with easyto-name stimuli and verbal memoranda than on the tests with hard-to-label stimuli and non-verbal memoranda. For healthy subjects, the tests with verbal memoranda were much easier than the tests with nonverbal memoranda. Thus, the patient de®cit was greater on the tests that were easier for the controls, deconfounding de®cit-speci®city and task-dif®culty as in our previous studies (Wexler et al., 1998; Stevens et al., 2000). In fact, the tests with easy-toname stimuli and verbal memoranda were so easy for the healthy subjects that ceiling effects may have underestimated the degree of patient de®cits. One way to understand these de®cits is that DSz patients are less able than healthy controls to retrieve appropriate words from memory. Such a disability would be consistent with our earlier ®ndings that DSz patients do as well as healthy controls on tone memory tests, yet have de®cits on word memory tests (Wexler et al., 1998; Stevens et al., 2000). When a word is spoken, the pattern of sounds must activate a representation of the word, i.e. the word has to be retrieved from an internal lexicon. In contrast, on the tone or birdsong tests, in which it is not possible to verbally label the stimuli, it is the actual sound pattern that must be remembered. Thus a relative inability to retrieve verbal tags would put patients at a disadvantage on the word but not on the tone or birdsong tests. Such a de®cit could arise from an inability to activate the appropriate representation and/or an inability to inhibit activation of inappropriate representations (Spitzer, 1997; Engle et al., 1999). Impaired retrieval of language-related internal representations could also account for the ®nding that patients with schizophrenia show less consistent categorical perception of ambiguous auditory stimuli than do healthy controls (Cienfuegos et al., 1999). In that study, subjects were required to identify auditory stimuli as being either the phoneme `ba' or the phoneme `da'. When a range of stimuli were presented falling along the acoustic continuum between `ba' and `da', healthy subjects abruptly switched from perceiving `ba' to perceiving `da'. Such categorical perception would appear to be based on activation of one or the other pre-existing
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internal phonemic representations by the auditory input. Patients with schizophrenia performed normally when the acoustic stimuli were at one end or the other of the acoustic continuum, but were less consistent (i.e. show a less abrupt transition) in categorization of stimuli from the middle of the continuum. Stimuli from the middle of the continuum would less strongly and less selectively activate the internal (categorical) phonemic representation both because they are less familiar and because they are more likely to activate multiple internal representations. If retrieval mechanisms in patients are impaired, lack of familiarity and increased ambiguity would both lead to less consistent activation of internal representations. This view of the patients' performance de®cit might lead one to predict that their de®cits would be greater on verbal memory tests in which the to-beremembered word is activated by a non-verbal retrieval cue (e.g. a familiar sound) than when the to-be-remembered word is itself presented, since the association between the sound of the word and its internal verbal label is much more heavily practiced than is the association between the non-verbal retrieval cue and its internal verbal label. This appears to be the case. In our previous studies, when the to-beremembered words were spoken, DSz patients scored 76 and 75% correct, compared with control values of 89 and 86% (Wexler et al. 1998; Stevens et al., 2000). In the present study, when the to-be-remembered words were cued by the easy-to-name sounds, DSz patients only scored 63% correct while controls scored 93%. The same pattern is evident in on-going work in our laboratory when both the word and labeled sounds serial position tasks are given to the same patients. This explanation may also be extended to our earlier observation that patients did more poorly on a visual than an auditory word serial position task (Stevens et al., 2000). Again, the association between the sound pattern corresponding to a word and the internal verbal label is more practiced than is the association between the pattern of visual stimuli corresponding to a word (i.e. the printed letters) and the verbal tag, especially in patients who may not read very much and in whom the effects of illness may have been evident when learning to read but not when learning to understand speech. Patients are able to use language and attach verbal labels to sounds and images. In a previous study we
demonstrated their ability to repeat back, accurately, words they heard or saw (Stevens et al., 2000), and in the present study they could accurately retrieve verbal labels for the familiar sounds and pictures. However, in the previous study they were signi®cantly less accurate than controls in reading the words. More importantly, we hypothesize that the patient de®cit in internal verbal labeling is more easily demonstrable when the labeling function is part of more complex tasks, such as our serial position memory tasks, that require division and integration of neurocognitive resources. It is not clear whether the proposed disability in activating verbal labels to sensory input is part of a more general de®cit in retrieval from long-term memory or is a de®cit speci®c to language-related processes. In either case, its impact on cognitive function would be profound, as the use of internal language mechanisms to enhance cognition is an essential aspect of a wide range of normal human brain functions (e.g. Vygotsky, 1978; Walker and Hulme, 1999). In the present study, for example, when healthy subjects were able to activate verbal labels for auditory input on the familiar sounds test, they scored 93% correct compared with only 69% correct on the unlabelable birdsongs test. In summary, by devising tests that use non-verbal stimulus cues to bypass sensory encoding of linguistic stimuli but still activate verbal memoranda, we provide evidence of de®cits in language-based memory processes in attentionally competent patients with schizophrenia. We suggest that the verbal memory de®cit in these patients re¯ects a disability in retrieving verbal labels from an internal lexicon. Given the importance of internal language mechanisms in human neurocognitive function, such a disability could have widespread consequences for patients with schizophrenia. References Cienfuegos, A., Shelley, A., March, L., Javitt, D.C., 1999. Impaired categorical percepton of synthetic sounds in schizophrenia. Soc. Biol. Psychiatry 45, 82±88. Engle, R.W., Kane, M.J., Tuholsk, S.W., 1999. Individual differences in working memory capacity and what they tell us about controlled attention, general ¯uid intelligence, and functions of the prefrontal cortex. In: Shah, P., Miyake, A. (Eds.), Models of working memory. Cambridge University Press, Cambridge, pp. 102±134.
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