Processing sentence context in women with schizotypal personality
disorder: An ERP study
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Citation
Niznikiewicz, Margaret A., Michelle Friedman, Martha E. Shenton,
Martina Voglmaier, Paul G. Nestor, Melissa Frumin, Larry
Seidman, John Sutton, and Robert W. McCarley. 2004. Processing
Sentence Context in Women with Schizotypal Personality
Disorder: An ERP Study. Psychophysiology 41, no. 3: 367–371.
doi:10.1111/1469-8986.2004.00173.x.
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doi:10.1111/1469-8986.2004.00173.x
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June 18, 2017 7:31:25 AM EDT
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Published in final edited form as:
Psychophysiology. 2004 May ; 41(3): 367–371. doi:10.1111/1469-8986.2004.00173.x.
Processing sentence context in women with schizotypal
personality disorder: An ERP study
MARGARET A. NIZNIKIEWICZa,b, MICHELLE FRIEDMANb, MARTHA E. SHENTONa,b,c,
MARTINA VOGLMAIERb, PAUL G. NESTORa, MELISSA FRUMINb,c, LARRY SEIDMANb,
JOHN SUTTONb, and ROBERT W. MCCARLEYa,b,c
a Department of Psychiatry, Harvard Medical School, Neuroscience Laboratory, Brockton/West
Roxbury VAMC, Brockton, Massachusetts, USA
b
Massachusetts Mental Health Center, Boston, Massachusetts, USA
c
Department of Radiology, Brigham and Women Hospital, Boston, Massachusetts, USA
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Abstract
Accumulating evidence suggests that schizophrenic patients do not use context efficiently. Also,
studies suggest similarities in clinical and cognitive profiles between schizophrenic and schizotypal
personality disorder (SPD) individuals, and epidemiological studies point to a genetic link between
the two disorders. This study examined electrophysiological correlates of processing sentence
context in a group of SPD women in a classical N400 sentence paradigm. The study assessed if the
dysfunction in context use found previously in schizophrenia and male SPD also exists in female
SPD. We tested 17 SPD and 16 matched normal control women. The results suggest the presence of
abnormality in context use in female SPD similar to that previously reported for male schizophrenic
and SPD individuals, but of lesser degree of severity. In SPD women, relative to their comparison
group, a more negative N400 was found only to auditory congruent sentences.
Descriptors
Sentence processing; Schizotypal personality disorder women; Context; Event-related potentials;
Language; N400
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Language dysfunction in schizophrenia is regarded as one of the primary features of this
disease. Speech in schizophrenic patients is often characterized by loose and bizarre
associations, lack of coherence, and inability to maintain a theme. It has been recently proposed
that these features of schizophrenic speech are the result of dysfunction in semantic memory
operations. The two processes suggested to be abnormal are the activation in semantic memory
networks (Manschreck et al., 1988; Moritz et al., 1999; Spitzer, Braun, Maier, Hermle, &
Maher, 1993) and the use of context (Cohen, Barch, Carter, & Servan-Schreiber, 1999; ServanSchreiber, Cohen, & Steingard, 1996). Both epidemiological and genetic evidence suggests a
similar genetic vulnerability for schizophrenia and schizotypal personality disorder (Kendler,
1988; Kety, Rosenthal, Wendler, & Schulsinger, 1968). Also, similar but less severe
impairments have been found in several areas of language function such as semantic
categorization, semantic clustering, and levels of recall (Condray and Steinhauer, 1992;
Trestman et al., 1995; Voglmaier, Seidman, Salisbury, & McCarley, 1997). This study focused
Address reprint requests to: Margaret A. Niznikiewicz, Ph.D., Psychiatry 116A, 940 Belmont St., VA Boston Healthcare System/Brockton
division, Brockton, MA 02301, USA. [email protected]; or to Robert W. McCarley, MD, Psychiatry 116A, 940
Belmont St., VA Boston Healthcare System/Brockton division, Brockton, MA 02301, USA. [email protected].
NIZNIKIEWICZ et al.
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on the processes of reconciling word meaning with sentence context in a group of Schizotypal
Personality Disorder (SPD) women. Previously, abnormal context use has been observed in
schizophrenia both in behavioral (Barch et al., 1999; Cohen et al., 1999; Braver et al., 2001)
and event-related brain potential (ERP) studies of language processing (Condray, Steinhauer,
Cohen, van Kammen, & Kasparek, 1999; Niznikiewicz et al., 1997, 1999; Salisbury,
O’Donnell, McCarley, Nestor, & Shenton, 2000; Sitnikova, Salisbury, Kuperberg, & Holcomb,
2002).
Context processing in sentences is a complex operation that involves both working memory
resources as well as complex computations allowing us to fit upcoming words into available
sentence meaning and make judgments about it (e.g., Federmeier & Kutas, 1999; Gaskell &
Marlsen-Wilson, 2001; Holcomb, Kounios, Anderson, & West, 1999; Van Berkum, Hagoort,
& Brown, 1999).
N400, a negative-going potential appearing about 400 ms after the presentation of a target
word, has been used extensively to study contextual processes in both normal and clinical
populations (e.g., Niznikiewicz et al., 1997; Van Petten, 1993). N400 is more negative if the
upcoming word does not fit the context (e.g., She spread her bread with socks.) relative to
when it does (e.g., She spread her bread with butter.).
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In this study, we examined context processing in SPD women. It is the last in a series of studies
in which the use of the same experimental materials and procedures enabled us to assess
language dysfunction across severity spectrum, from male schizophrenic to female SPD
populations. It is also the first study that we are aware of to examine ERP correlates of language
processing in SPD women. In the previous studies (Niznikiewicz et al., 1997, 1999) difficulties
in using context efficiently were found in both male schizophrenics, as indicated by a more
negative N400 to both congruent and incongruent sentences in auditory and visual modality,
and in male SPDs, as indicated by a more negative N400 to congruent sentences in both
modalities. In this study, we turned to SPD women, especially given previous reports of less
severe impairment in women in the ERP paradigms examining attentional and memory
updating processes (i.e., P300; Hirayasu, Samura, Ohta, & Ogura, 2000; Turetsky, Colbath, &
Gur, 1998), as well as on behavioral measures of verbal function in both;schizophrenia (e.g.,
Goldstein et al., 1998; Ragland, Gur, Klimas, McGrady, & Gur, 1999) and SPD (Voglmaier
et al., 2003).
Methods
Participants
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Seventeen right-handed women were diagnosed with Schizotypal Personality Disorder using
the SCID (Spitzer, Williams, Gibbon, & First, 1990a) and DSM-IIIR (American Psychiatric
Association, 1987) criteria. Diagnostic reliability was evaluated using the kappa statistics; the
reliability between the raters was .87. The SPD women were included in the study based on a
newspaper advertisement soliciting individuals who were shy, had few friends, and felt they
had special powers. Overall, 472 responders to the advertisement were screened. The 17 women
who participated in this study met full SPD criteria, that is, they fulfilled five or more of the
nine DSM-IIIR items (they also met DMS-IV criteria). Sixteen comparison women, matched
for age and IQ, participated in the study, and were selected from a pool of volunteers recruited
from a newspaper advertisement. They were also screened with the SCID (Spitzer, Williams,
Gibbon, & First, 1990b). All participants spoke English as their first language. All study
participants signed a written consent form after familiarizing themselves with a detailed
description of the study. The inclusion and exclusion criteria were the same as in Niznikiewicz
et al. (1997, 1999).
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The average age of the SPD participants was 40.7 years (range 23–53 years, SD = 10.7), the
average IQ was 110 (range 80–131, SD = 13.5), and parental SES was 3.4 (range 1–5, SD =
1.3). IQ was estimated based on the WAIS verbal score and block design scores, and the SES
was computed based on Hollingshead Four Factor Index of Social Status. The comparison
group’s age was 35.8 years (range 22–51 years, SD = 8.8), IQ was 117.7 (range 109–135,
SD = 14.3), and parental SES was 3.75 (range 2–5, SD = 1.1). The two groups did not differ
statistically on any of these measures.
Stimuli
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Two hundred sentences were presented visually and auditorily. The sentences were 5–8 words
long, and were identical to the sentences used in a previous study of male SPD subjects
(Niznikiewicz et al., 1999). For the full description of language materials and mode of
presentation, see Niznikiewicz et al. (1997, 1999). Briefly, half of the sentences ended with a
word that fit previously presented context, and half of them ended with a word that did not fit
the context; the sentences were presented one word at a time, with an 800-ms offset to onset
interval (ISI). In the auditory modality, the words were spoken by a male voice. The mean
length of words in the auditory modality was 497.5 ms including final words. All words in the
visual modality were presented for 300 ms. The mean length of auditory and visual sentences
was 7,633.75 ms and 6,350 ms, respectively. Two sets of sentences were constructed such that
each participant was exposed to two different sets in the two modalities, but across participants,
the same sentences were presented auditorily and visually. Participants were asked to make a
decision if the sentence just presented made sense by pressing a “yes” or “no” response button
(right and left hand counterbalanced), after they “saw a star on the screen,” 800 ms after the
sentence ended. The accuracy data, that is, the error rates, recorded along with the response
time data, did not differ statistically in the two groups; for auditory modality, t(21) = −1.3,
p<.21, (accuracy: NC = 96.75%, SPD = 94.75%), for visual modality t(20) = −1.74, p<.098
(accuracy: NC = 97.05%, SPDs = 94.7%).
EEG Recording Procedures
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The EEG was recorded using 28 tin-plate electrodes housed in a Neuroscience Electrocap with
a left earlobe reference and positioned according to the International 10–20 system, plus 8
additional interpolated electrodes (Niznikiewicz et al., 1997). Separate electrodes were placed
at the left and right canthi and at supra and infraorbital sites to record horizontal and vertical
eye movements. The electrode impedance was maintained below 4.0 kΩ, and care was taken
that the difference in impedance between right and left ears was less than 0.5 kΩ. The EEG
was recorded using a DC to 40 Hz bandpass (Neuroscan Inc., EEG amplifiers; 24 dB/octave
low-pass slope and 24 dB/octave high-pass slope). The EEG was sampled over the epoch of
924 ms, with 100-ms prestimulus baseline relative to the onset of a target word, and was
digitized at the rate of 256 samples/s. Linked earlobes reference was constructed off-line and
the rereferenced data were used in all analyses.
Data Processing
For the details of data processing we refer the reader to Niznikiewicz et al. (1999). Singlesubject averages were constructed from the EEG epochs recorded to the last words (congruent
and incongruent relative to the context) of presented sentences, and filtered using a digital filter
of 0.01–8 Hz. The N400 was measured as a mean amplitude under the curve and as peak
amplitude to get a measure of peak latency within the window of 300–450 ms poststimulus.
Statistical Analyses
The group differences were most prominent at fronto-central sites. Therefore, the N400 was
measured at Fz, Cz, F3/4, FTC1/2, C3/4, CP1/2, and T3/4. The N400 amplitude and latency
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were submitted to mixed model MANOVA with group as a between variable (2 levels: NC
and SPD), and within factors of modality (2 levels: auditory and visual), sentence type (2 levels:
congruent and incongruent sentence final word), and electrode (12 levels). This omnibus
MANOVA was followed by modality-specific MANOVAs to follow up on the interactions.
For N400 latency, only the results for midline are reported here.
Results
N400 amplitude
There was a three-way interaction between modality, sentence type, and group, F(1,24) = 7.08,
p<.014. Modality-specific MANOVAs revealed a Group × Sentence Type interaction for the
auditory modality, F(1,25) = 5.35, p<.028, and no significant group effects for the visual
modality. There was the main effect of sentence type for both the auditory, F(1,28) = 97.00,
p<.0001, and visual modalities, F(1,24) = 58.54, p<.0001.
In the auditory modality, congruent condition, there was a main effect of group, F(1,28) = 4.54,
p<.042; N400 amplitude was more negative (larger) in SPD women relative to the normal
comparison group. No group differences existed in the incongruent condition.
N400 Latency
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In the overall MANOVA, including both auditory and visual modalities, there was a main
effect of group, F(1,25) = 19.23, p<.0001, and a three-way interaction between group, modality,
and sentence type, F(1,25) = 9.19, p<.006. There was a main effect of group in the auditory
modality, F(1,27) = 12.433, p<.002, and a trend level interaction between group and sentence
type in the auditory modality, F(1,27) = 4.02, p<.055. Longer N400 latencies were found in
the SPD group (see Figures 1–3).
In the visual modality, there was an interaction between group and sentence type, F(1,26) =
8.31, p<.008. In the follow-up MANOVA, the main effect of group was found for the congruent
sentence type, F(1,26) = 7.47, p<.01, and no group differences were found in the incongruent
sentence type condition. Again, the N400 latency was prolonged in the SPD relative to normal
comparison subjects.
Discussion
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In this study of processing final words in sentences, more negative N400 amplitude was found
in the SPD women relative to normal women. This group difference was limited to auditory,
congruent sentences. Prolonged N400 latencies were found in the SPD relative to the normal
women in both modalities.
The results reported in this study represent an extension of previous studies on the processing
of context in schizophrenia spectrum disorder within the confines of an identical paradigm.
The one technical difference relates to the replacement of one Neuroscan amplifier (used to
acquire male SPD data) with another (used to acquire female SPD data). The present results
are similar to the ones reported for male schizophrenic subjects (Niznikiewicz et al., 1997),
and for male SPD subjects (Niznikiewicz et al., 1999). The differences among these studies
relate to the degree of dysfunction as documented with the N400 response. In the schizophrenic
male patients, more negative N400 was found to both congruent and incongruent sentence
endings in both visual and auditory modality as compared to the normal males. In male SPD
subjects, the more negative N400 amplitude was found only to the congruent sentence final
words in both modalities. In the current study, the group differences were found only in the
auditory modality for congruent sentence final words.
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Thus, across these three studies, varying degrees of dysfunction, as indexed by the N400, were
found, with the most severe impairment in the male schizophrenic patients and the least severe
impairment in the SPD women. It is therefore possible that a type of impairment represented
by SPD women is primary or “core,” and that as the cognitive system breaks down further,
more severe symptoms emerge. As sentential context processing involves both matching
semantic information and working memory operations, this and previous studies suggest a
scenario where auditorily based operations of matching semantic information with the previous
context are compromised first by a schizophrenia-like disease process. At subsequent stages
the dysfunction includes both the auditory and visual mode of language processing, and then
goes beyond a dysfunction in semantic matching operations. For example, it is possible that
working memory function as related to maintaining sentence context becomes compromised
at more severe stages, as the results of the study in male schizophrenia patients (Niznikiewicz
et al., 1997) would suggest. Future studies including both men and women from among SPD
and schizophrenia sufferers, in various linguistic tasks, are needed to elucidate this model.
Acknowledgments
The work presented in this article was supported by The National Alliance for Research on Schizophrenia and
Depression (M.A.N.), by the National Institute of Mental Health (MH52807 and MH40799 to R.W.M., Research
Scientist Development Award KO2-MH00746 and First Award to M.E.S.), and by the Department of Veterans Affairs
Center for Basic and Clinical Neuroscience Studies of Schizophrenia (R.W.M.).
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Figure 1.
Grand average waveforms of 17 SPD and 16 normal comparison women recorded to the
congruent sentence final words presented in the auditory modality.
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Figure 2.
Grand average waveforms of 17 SPD and 16 normal comparison women recorded to the
incongruent sentence final words presented in the auditory modality.
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Figure 3.
Grand average waveforms of 17 SPD and 16 normal comparison women recorded to the
congruent and incongruent sentence final words presented in the visual modality.
Psychophysiology. Author manuscript; available in PMC 2009 December 16.