A Cognitive Neuroscience View of
Schizophrenic Thought Disorder
by Manfred Spitzer
work models of the processes in question can provide a
framework for the development and testing of further
hypotheses.
The purpose of this article is to provide an example
of how cognitive neuroscience can contribute to the
understanding of various phenomena usually summarized
under the concept of formal thought disorder. Data from
several studies on the nature of associative processes in
normal subjects and schizophrenia patients will be presented. Schizophrenic thought disorder is often characterized by a decreased accuracy of lexical access combined
with decreased working memory. These dysfunctions may
be related, and they may be caused by dysfunctional maplike semantic networks in frontal and temporal cortical
areas. The structure of semantic networks, as revealed by
experimental psychological, neuropsychological, and
fMRI studies, bears close resemblance to self-organizing
feature maps, that is, a type of neural network. In these
maps, the influence of noise on plasticity can be demonstrated, and these findings can be related to the neuromodulatory function of dopamine, which regulates the signalto-noise ratio in network information processing. Taken
together, the presented view allows a comprehensive and
parsimonious explanation of a number of otherwise inexplicable or unrelated phenomena. In particular, it demonstrates how cognitive neuroscience methods and concepts
can bridge the gap between mind and brain, between clinical phenomena and underlying brain pathology
(Callaway 1992).
Abstract
The experimental association psychology approach to
mental associations has been the conceptual background for the concept of schizophrenia. Cognitive
neuroscience methods and concepts can be used to
study various forms of schizophrenic thought disorder.
In particular, the concepts of semantic associative and
working memory can be applied fruitfully to schizophrenia research. Semantic associative networks can
be simulated with self-organizing feature maps.
Dysfunctional lexical access can be modeled in terms
of low signal-to-noise ratio in intra- or between-network information processing. Evidence for the crucial
role of dopamine in this function is presented, and a
general neurocomputational model of schizophrenic
thought disorder is developed. This model capitalizes
on basic aspects of neural information processing (i.e.,
neuromodulation and neuroplasticity) and allows a
parsimonious explanation of a number of otherwise
inexplicable or unrelated clinical phenomena and
experimental results.
Schizophrenia Bulletin, 23(l):29-50,1997.
Cognitive neuroscience is the most recent name of the
endeavor to understand the nature of mind and how it is
related to the brain (Gardner 1985; Posner and Raichle
1994; Gazzaniga 1995). The discipline encompasses an
arsenal of methods, each of which provides information
about a certain aspect of cognitive processes. The use of
electrophysiological and functional imaging techniques
(such as event-related potentials [ERPs] and functional
magnetic resonance imaging [fMRI]), together with adequate experimental psychological procedures and behavioral measurements, can provide detailed spatio-temporal
information about where and when a specific cognitive
process is computed in the brain. This information can be
linked to neuroanatomical data, and finally, neural net-
Disordered Thought: Past and Present
Disrupted thought processes have long been described in
association psychology terms and studied by the method
of the word association test: A subject reads or hears a
Reprint requests should be sent to Dr. M. Spitzer, Psychhitrische
Universiliitsklinik. Voss-Slr. 4. 6 l )l 15 Heidelberg, Germany.
29
Schizophrenia Bulletin, Vol. 23, No. I, 1997
M. Spitzcr
word and responds by saying the first word that comes to
mind. In this word-association paradigm, "black" produces "white," "lemon" produces "sour," and "sour" produces "sweet." The investigation of associative processes
with this test was introduced into the field of psychiatry
by Emil Kraepelin, after he had worked for 2 years in the
world's first psychological laboratory, directed by
Wilhelm Wundt. By the turn of the century, a great number of word-association studies with normal subjects and
patients had been conducted, and they influenced the formation of the concepts of dementia praecox by Kraepelin
and of schizophrenia by Eugen Bleuler (for reviews, see
Spitzer 1992; Spitzer and Mundt 1994).
In particular, schizophrenic thinking was characterized by loose, mediated, indirect, or oblique associations,
that is, by dysfunctional associative processes. For example, Bleuler (1911/1950) noted that, in the utterances of
schizophrenia patients, "the associations tend to proceed
along new lines" and "indirect associations . . . receive
unusual significance" (p. 14). "I suspect that only the lack
of sufficient observation has been responsible for our
inability to demonstrate them [indirect associations] more
frequently in the thought-processes of our patients"
(p. 14). In addition, thought can be overly abstract or
overly concrete, as several researchers have pointed out
(Cameron 1939; Feinberg and Garman 1961).
In the Diagnostic and Statistical Manual of Mental
Disorders-4th edition (DSM-IV; American Psychiatric
Association 1994), schizophrenic thought disorder is
characterized by disturbed associational processes, as can
be seen from the description of characteristic features of
schizophrenic thought:
Semantic Priming and Lexical Access in
Semantic Networks
In their seminal paper on word associations, Kent and
Rosanoff (1910) pointed out the major limitation of the
method of free associations. Specific types of word associations can only be distinguished post hoc. In other
words, the experimenter cannot first specify a certain
association and then test it. To avoid this difficulty, the
technique of lexical decision can be used. The subject
decides whether a given string of characters is a word or
not. To investigate certain types of associations, specific
word pairs are presented either simultaneously or one
after the other. Then the effect of the relationship between
the words on the lexical decision task regarding one of
them can be measured in terms of the time it takes to perform the task (reaction time [RT]) and the errors the subject makes.
A robust phenomenon that has been discovered using
this technique of lexical decision is semantic priming
(Meyer and Schvaneveldt 1971; Neely 1991). A word is
recognized faster if it is preceded by a meaningfully
related word. For example, "black" is recognized faster as
a word if it is presented shortly after "white" than if it is
presented shortly after a nonrelated word such as "soft"
(see figure 1).
This experimental paradigm has been applied to the
study of associations in schizophrenia patients with and
without thought disorder by a number of authors (Maher
et al. 1987; Manschreck et al. 1988; Chapin et al. 1989;
Fisher and Weinman 1989; Spitzer et al. 1994c; see also
Kwapil et al. 1990). In these studies, thought disorder was
diagnosed using standardized rating scales, such as the
Schedule for Affective Disorders and Schizophrenia
(SADS; Spitzer and Endicott 1978) and the Brief
Psychiatric Rating Scale (BPRS; Overall and Gorham
1962). Most notably, Maher et al. and Manschreck et al.
discovered an increased semantic priming effect in schizophrenia patients who suffered from formal thought disor-
Disorganized thinking ("formal thought disorder,"
"loosening of associations") has been argued by some
(Bleuler, in particular) to be the single most important
feature of schizophrenia. . . . The person may "slip
off the track" from one topic to another ("derailment"
or "loose associations"); answers to questions may be
obliquely related or completely unrelated ("tangentiality"). [p. 276]
Figure 1. Typical sequence of events in a single trial of a lexical decision task
fixation point
prime
optional blank screen
target
response
—|«|w|»[r
{ • | • |« | f | | |h |
..LU-
stimulus onset asynchrony (SOA)
30
reaction time (RT)
|k|1|o|«|» |
" I . 1- 1 * 1
.^,1,-U..
Cognitive Neuroscience View
Schizophrenia Bulletin, Vol. 23, No. 1, 1997
der, as compared with non-thought-disordered schizophrenia patients and normal control subjects. In the experiment, normal associations are presented (e.g.,
"black-white") and their effect on RTs is compared with
nonrelated word pairs (e.g., "cloud—cheese"). Since schizophrenia patients, at least in the view propagated by
Bleuler, suffer from intrusions of nonstandard associations into their utterances, they should, if anything, show
less benefit in RTs from associated word pairs. In other
words, why should thought disorder, which is characterized by a disruption of normal associations, produce an
increase in benefit due to normal associations?
Replication studies, one conducted in another language and another using a different experimental paradigm, confirmed the result of an increased semantic priming effect in schizophrenia patients (Kwapil et al. 1990;
Spitzer et al. 1994c). The data from two studies on semantic priming are displayed in figure 2.
The semantic priming effect in normal subjects has
been interpreted as evidence for a networklike organization of the mental lexicon. According to these models,
semantic (and possibly other) features of words are represented as "nodes" in a neuronal network. In the course of
an utterance, these semantic units become activated for a
short period of time and thereafter either decay rapidly or
are actively inhibited (Collins and Loftus 1975; Neely
1977, 1991; Miller and Glucksberg 1988; Levelt 1989).
This model of lexical access further asserts that concepts
activated in a semantic network by a prime serve as a
source of activation that spreads to related concepts. Such
spreading of activation to nearby nodes in the semantic
network lowers their thresholds of being activated. If one
of these concepts is denoted by a word as a target in a lexical decision paradigm, this target will be recognized
faster (i.e., semantic priming will occur) because it is
already activated to some degree.
This view of lexical access and semantic priming
allows a parsimonious explanation of both the increased
semantic priming effect and the occurrence of unusual
associations in thought-disordered schizophrenia patients.
During the course of lexical access, activation spreads
faster and farther in the semantic network than under normal circumstances. This acceleration causes the increased
activation of normal associations (and hence, an increased
semantic priming effect) as well as the intrusion of
oblique and unusual associations into utterances, because
activity may spread quickly to more distant nodes.
Indirect Semantic Priming: A More
Sensitive Measure
While the finding of an increased semantic priming effect
in thought-disordered schizophrenia patients can be
regarded as an important first step, it may not provide the
best possible evidence to support the hypothesis of activated associations in schizophrenic thought disorder for a
number of reasons.
First, it has been argued on methodological grounds
that difference scores in accuracy and latency may be
"inflated" in schizophrenia patients due to a comparatively slower and more variable (or worse, both) performance of patients, a well-established observation regarding
almost any task (Chapman et al. 1994). While in the first
study of lexical decision by Maher et al. (1987) the RTs in
the nonassociated condition were not significantly different for schizophrenia patients and control subjects (possibly a result of the small sample size and a sampling
effect), subsequent data from their laboratory (rvlaher
1993; personal communication, May 1993) and from our
respective study (Spitzer et al. 1994c) generally show
schizophrenia patients' RTs to be slower.
Second, from a clinical point of view, it has been
known for more than 80 years that schizophrenia patients
produce fewer close associates in word-association tests
(Kent and Rosanoff 1910) and tend to produce more indirect, or mediated, associations instead. Hence, a measure
of indirect associations appears appropriate. As Bleuler
noted:
Figure 2. Semantic priming in normal control
subjects, non-thought-disordered (NTD) and
thought-disordered (TD) schizophrenia patients
160
Manschreck et al. 1988
140-
Spitzer etal. 1994 c
120'.
"tn
c
I soc
CO
60-
<D
CO
4020
0
controls
NTD schizophrenic
patients
TD schizophrenic
patients
Data from two studies carried out in two languages. Although
effect size was greater in the study of Spitzer et al. (1994c) (carried out in German), the pattern of results is strikingly similar in
both studies.
31
Schizophrenia Bulletin, Vol. 23, No. 1, 1997
M. Spitzcr
In experimental investigations of association, we find
a notable frequency of "mediate associations." . . .
The above mentioned example [a patient had associated the death of a relative to the word "wood"], the
association "wood (wood-coffin)—dead cousin," may
be considered as a mediate association. . . . In an
experiment using words inscribed on a revolving
drum, Reis . . . found mediate association in the sense
that instead of "war"-"dispute," "cattle"-"horse" was
read. [Bleuler 1911/1950, pp. 26-27]
We recently replicated Bleuler's results, using a standard word-association task given to 20 normal control
subjects and 20 schizophrenia patients (Spitzer et al., submitted for publication a). Compared with the normal control subjects, the thought-disordered schizophrenia
patients showed fewer standard associations, fewer associations driven by meaning, and more indirect associations (see figure 3).
Third, according to the network model of semantic
priming, the spreading of activation dissipates with distance, and there is empirical evidence that such an inverse
relationship exists between semantic distance and the
amount of activation in normal subjects (den Heyer and
Briand 1986). Therefore, from a psycholinguistic perspective, closely associated words, which are automatically
activated in normal control subjects and in schizophrenia
patients, may not be the best stimuli to prove the heightened activation of the associative network in schizophrenia. With closely related primes and targets as the crucial
condition, only "comparably more" activation of closely
associated words can be predicted. In contrast, if heightened activation implies not only faster spread but also farther spread of activation in the semantic network, then the
prediction can be derived that far associations—instead of
close associations—should be a more effective discriminator between normal and activated associative networks.
In conclusion, indirect associates to a word, instead of
close associates, might be more appropriate stimuli for
testing the activated association hypothesis of schizophrenic thought disorder. Examples of such indirect associations are "chalk (white)-black" and "lemon
(sour)-sweet." In general, indirect associations can be
defined as word pairs in which the connection between the
words is obvious only via a mediating associated word.
Applied to the lexical decision paradigm, this means that
the target is an association to an association of the prime.
According to this line of thought, semantic priming
effects should be measured as far away from the prime
node as possible. In other words, a more indirect relation
between prime and targetiis better for the purposes of
measuring the spread of activation—at least from the
point of view of avoiding ceiling effects. However,
semantic networks presumably are the result of the individual's personal history and, hence, are in no way stan-
Figure 3. Word associations in the standard
word-association paradigm as used by Jung
(1906/1973) and others
15
NTD
100
(b) semantic
associations
95-:
O
CD
8"
TD
90 i
85^
80-:
75
NTD
frequenc;
(c) indirect
associations
yP
in
CD in
M l I I Iin
7J
TD
44
34
2-i
14
0 -
|
1
NTD
TD
Frequency of (a) standard associations, statistically defined by
Kent and Rosanoff (1910) as the association given most frequently by a large group of normal subjects; (b) semantic-conceptual associations, defined by Jung (1906/1973) with respect to the
relation of the content of the stimulus word and the response
word; and (c) indirect associations. Data from 20 normal control
(C) subjects and 9 non-thought-disordered (NTD) and 11 thoughtdisordered (TD) schizophrenia patients (after Spitzer et al., submitted for publication a).
32
Cognitive Neuroscience View
Schizophrenia Bulletin, Vol. 23, No. 1, 1997
dardized. Therefore, the transitions from one node to
another always occur with a certain probability and are
never fully determined. By the same token, the transition
from one node to the next occurs with a probability that
equals the product of the probabilities of transition
between nodes 1 and 2 and between nodes 2 and 3.
Because the stimuli for semantic priming tasks are
derived from semantic association norms, we cannot be
sure that, in a given person, the two items presented correspond to two close nodes in the individual semantic network. This uncertainty is one reason why the semantic
priming task might never be a good diagnostic tool, that
is, successfully applicable at the individual level (but see
below).
An example can be found in the word-association
norms as published by Palermo and Jenkins (1964), which
is still one of the classic sources for such data (see table
1). The most common association to "fingers" in 871 college students (377 male and 494 female) was "hand" or
"hands," given by 457 students (52.5%). Hence, when we
give "fingers" as the prime and "hand" as the target, we
can assume that for about half the subjects in our sample
these stimuli tap a close semantic relationship and therefore will produce a priming effect. From the same source,
we can derive that the standard association to "hand" is
"foot," given by 228 students (26.2%). "Feet" is given by
7 students (0.8%). "Finger" and "fingers" are the second
most frequent association to "hand," given by 202 students (23.2%). To go one step further, the standard association to "foot" is "shoe," given by 255 students (29.3%).
While these data demonstrate that associations are
not necessarily symmetric (compare "fingers-hand(s)"
[52.5%] with "hand-finger(s)" [23.2%]), the only way to
obtain a rough estimate of the associations of a word that
is not among the 200 stimulus words (e.g., "toe") is to
check which stimulus words elicited it as an association.
Finally, the percentage score given for a specified associa-
tion to a word is only a crude measure of semantic proximity. The sketch of a small part of a semantic network
depicted in figure 4 may be derived from table 1.
The relatedness of two indirectly related words can
be estimated by multiplying two proximity scores (following the rules of probability theory). In this manner, the
relation between "fingers" and "foot" (via "hand") is
0.525 X 0.270 = 0.142. Even if we consider the second
pathway from "fingers" to "foot" (via "toe") as an additional source of associative strength, we can add only very
little (0.157 X 0.254 = 0.040); note that we have to
assume that the relation between "foot" and "toe" is symmetric. If we go just one step further and prespecify
highly indirectly related word pairs ("fingers-shoe"), the
likelihood that the presupposed associational chain from
Figure 4. Semantic network sketch derived
from table 1
Theoretically, the numbers next to the arrows out of each node
should add up to 1, so much is obviously missing. In the tables
provided by Palermo and Jenkins (1964), a given word produced
on average about 86 different associations in subjects whose age
ranged from childhood to early adulthood. Only the first to fourth
most frequent of these are depicited.
Table 1. Examples of standard word associations and their frequency (in percent) in 871 college
students
Stimulus
word
Fingers
Hand
Foot
Shoes
Standard (most
frequent)
association
Second most
frequent
association
Third most
frequent
association
Fourth most
frequent
association
Fifth most
frequent
association
hand(s)
52.5%
foot (feet)
27.0%
shoe(s)
30.0%
feet (foot)
42.5%
toe(s)
15.7%
finger(s)
23.2%
toe(s)
25.4%
sock(s)
16.0%
nail(s)
5.4%
arm
17.0%
hand
16.3%
stocking(s)
6.5%
thumb(s)
5.1%
glove
6.1%
leg
13.1%
lace(s)
4.8%
five
4.8%
ring
5.6%
walk
3.8%
walk
2.6%
Note.—Adapted from Palermo and Jenkins 1964.
33
Schizophrenia Bulletin, Vol. 23, No. 1, 1997
M. Spitzer
the first word to the third next word is implemented in a
given individual's semantic network is very small (0.14 X
0.30 = 0.04).
The measurement of indirect semantic priming is delicate. In fact, the measurement of highly indirect semantic
priming (from a word to its third next association) is
doomed to failure because the likelihood of prespecified
associative chains decreases sharply with the number of
nodes involved in such chains. Hence, the optimal way of
measuring indirect semantic priming likely consists of
linking the associate to the associate and making sure that
only strong associations are used. Figure 5 illustrates the
benefits of using indirect associations as opposed to direct
associations to measure differences in the spread of activation in semantic networks during lexical access. In short,
the indirect semantic priming paradigm avoids the possible
ceiling effects of the direct semantic priming paradigm.
Our study of indirect and direct semantic priming in
50 normal control subjects and 50 schizophrenia patients
(21 non-thought-disordered and 29 thought-disordered),
using the lexical decision method, provided evidence that
indirect semantic priming may be a better measure of
spreading activation than direct semantic priming (Spitzer
et al. 1993a). We know that semantic priming is a robust
phenomenon independent of the duration of stimuli
(Spitzer et al. 1994c). Indirect priming, in contrast, is sensitive to the timing of stimuli. We used two stimulus-onset
asynchronies (SOAs) (200 and 700 ms) and found no significant indirect semantic priming effect in normal subjects
at the short SOA but a significant effect at the long SOA
(see figure 6). These results were interpreted as evidence
for the spreading activation model of semantic and indirect
semantic priming. In normal subjects, this spreading of
activation reaches more distant nodes only after several
hundred milliseconds. In contrast, thought-disordered
schizophrenia patients displayed a significant indirect
semantic priming effect in the short SOA condition, which
was interpreted as a sign of the fast and far-spreading activation in this group.
We further analyzed the data using ratios (percentage
RT gain caused by the related or indirectly related words,
respectively). The difference in direct semantic priming
between thought-disordered schizophrenia patients and
normal subjects—particularly at the long SOA—can be
exclusively attributed to the general slowness of the
patients. If this slowness is taken into account by calculating ratios, no difference in the priming effect is visible
(Spitzer et al. 1993a). However, when ratios were calculated for the indirect semantic priming effect, the overall
results were similar to the difference score results (see
figure 7).
In general, this study provided strong support for the
spreading activation model of thought disorder and priming phenomena. It suggested that indirect semantic priming in lexical decision tasks with a short SOA is an adequate measure of the fast, far-spreading activation in
semantic networks of thought-disordered schizophrenia
patients.
Figure 6. Indirect semantic priming effect1
Figure 5.
network
The spread of activation in a semantic
semantic priming
focused activation
unfocused
activation
indirect semantic priming
.064
.019
'Significance levels indicate results of unprotected two-tailed
f-tests of priming effects against zero (*p < 0.05; **p < 0.001;
***p < 0.0001). SOA = stimulus-onset asynchronies; TD = thought
disordered.
The effect size of the indirect semantic priming effect is considerably smaller than the effect size of the direct semantic priming
effect. Nonetheless, indirect semantic priming discriminates better
between focused and unfocused activation of the network.
Reprinted with permission from Spitzer et al. 1993a. Copyright ©
Elsevier Science Publishers, 1993.
34
Schizophrenia Bulletin, Vol. 23, No. 1, 1997
Cognitive Neurosciencc View
Figure 7.
Indirect semantic priming effect1
The Spreading Activation Hypothesis of
Thought Disorder: Further Evidence
Indirect semantic priming at short SOAs appears to be the
most straightforward measure of faster, farther-spreading
activation in semantic networks of thought-disordered
schizophrenia patients, but additional data also provide
support for this view. In this section, three lines of evidence will be discussed: the study of spontaneous and
experimentally elicited utterances, the results of other psychological measures, and the study of semantic processes
on awakening from different sleep stages.
Maher (see Maher and Spitzer 1993) has proposed a
model of formal thought disorder that rests on observations of the nature of intrusions (slips of the tongue) into
spontaneous speech. Such intrusions occur in normal subjects and in schizophrenia patients, and they often involve
items from previous utterances. According to the networkactivation model, such intrusions represent patterns of
reverberating network activation caused by previous utterances. If the characteristics of semantic network activation
are changed such that there is either more activation or less
inhibition or both, or merely a less focused activation,
thought disorder occurs.
.011
1
Significance levels indicate results of unprotected two-tailed
Mests of priming effects against zero (*p < 0.05; **p < 0.001;
***p < 0.0001). SOA = stimulus-onset asynchronies; TD = thought
disordered.
Reprinted with permission from Spitzer et al. 1993a. Copyright ©
Elsevier Science Publishers, 1993.
Figure 8. Semantic and indirect semantic priming effects
Nothing is more important in psychopathology than
the replication of new and unexpected findings, since the
field is littered with spurious results. Data from a followup
study on direct and indirect semantic priming in a divided
visual field paradigm (Spitzer et al., submitted for publication d) can be analyzed for this purpose. The study was the
first attempt to investigate hemispheric differences in
direct and indirect semantic priming in control subjects
and schizophrenia patients. The SOA was 250 ms, and data
were obtained from 36 control subjects and 22 nonthought-disordered and 14 thought-disordered schizophrenia patients. When the data were collapsed across both
hemispheres, the results were strikingly similar to the previous study (figure 8). Semantic priming was higher in
thought-disordered patients than in controls, but again, the
differences between the groups were smaller when percent
scores were calculated. In contrast, the differences in indirect semantic priming between thought-disordered patients
and control subjects were clearly visible regardless of
whether a percentage score or a difference score was used.
Taken together, these studies make it unlikely that
increased indirect semantic priming in thought-disordered
schizophrenia patients is a chance finding. Nonetheless,
we are conducting a third study in another language
(English) to further validate the results of the studies.
£300
300
E 250-;
1200-1
I 150 J
E 100-
3
o
!
50-
NTD
TD
NTD
TD
NTD
TD
NTD
TD
Figures a and b show difference scores; c and d display ratios;
C = normal control; NTD = non-thought disordered; TD = thought
disordered.
35
M. Spitzer
Schizophrenia Bulletin, Vol. 23, No. 1, 1997
Another task consisted in finding similarities or overlapping features of different items or concepts, which were
of a different semantic distance. Schizophrenia patients
could also perform this task better than normal controls,
particularly when the items were semantically distant.
Within the framework of the spreading activation model of
lexical access and the hypothesis of faster and farther
spread of activity in some schizophrenia patients (the
thought-disordered-non-thought-disordered distinction
was not usually made in studies of schizophrenia patients
during the 1960s and 1970s), these results can easily be
interpreted. In (supposedly thought-disordered) schizophrenia patients, activation in semantic networks spreads
quickly to uncommon meanings, making activation overlap more likely, even when two distant nodes are involved
(see figure 10).
As early as 1910, Kraepelin published a monograph
on thought disorder during dream states. Dreams share
some features with disorders of formal thought, including
The spreading activation model of thought disorder
presupposes an intact semantic network. It is the access to
the network, not the network itself, that is malfunctioning.
Evidence for this view was recently provided by Allen et
al. (1993), who conducted a verbal fluency study with
schizophrenia patients. When the task was given once, the
patients produced fewer words than normal subjects.
However, when the task was given five times and word
responses were pooled, the number of appropriate words
produced was comparable to the number given by normal
subjects.
Several authors have suggested that pauses in spontaneous speech provide clues to the psychological processes
of speech production, including lexical access (GoldmanEisler 1958; Butterworth 1973). Several studies established that two variables determine the length of withinsentence pauses: contextual probability (redundancy) and
frequency of occurrence of the following word. People
make more and longer pauses before words of low use and
low redundancy (Goldman-Eisler 1958; Maclay and
Osgood 1959; Mercer 1976). If thought-disordered schizophrenia patients suffer from a faster and farther spread of
activation, the pauses before words in spontaneous speech
that are not suggested by the context should be comparatively shorter. We tested this hypothesis in 36 normal subjects and 32 schizophrenia patients (23 thought-disordered
and 9 non-thought-disordered) by measuring the pauses in
speech elicited by having the subjects describe a picture
(Spitzer et al. 1994a). In the groups of normal subjects and
non-thought-disordered schizophrenia patients, the mean
duration of pauses before nouns within sentences was significantly different, depending on whether the nouns were
constrained by context or not. Pauses were shorter before
nouns suggested by context and significantly longer before
nouns not suggested by the context. In thought-disordered
patients, however, no such difference was detected (see
figure 9).
The major finding of this study was a decreased context-sensitivity of within-clause pauses in thought-disordered schizophrenia patients when compared with nonthought-disordered schizophrenia patients and normal control subjects. In particular, contextually unconstrained lexical items seem to "pop" into the minds of thought-disordered schizophrenia patients due to the heightened or
unfocused activation of semantic associative networks.
The Russian psychologist Poljakov reported a series
of experimental studies of schizophrenia patients
(Poljakov 1973). In one of the tasks, the subjects had to
solve problems by taking into account unusual meanings
of words. Schizophrenia patients seemed to have faster
access to these meanings and were able to solve some of
the tasks better than normal subjects.
Figure 9. Duration of pauses (means and standard error of the mean) before context nouns
and rare (noncontext) nouns
600
500-
controls
NTD patients
TD patients
Results obtained by 36 control subjects and 8 non-thoughtdisordered (NTD) and 22 thought-disordered (TD) schizophrenia
patients. One TD patient and one NTD patient did not produce
any rare nouns; therefore, their data are not included in the analysis. Differences in pause length before context nouns and rare
nouns were significant in the control subjects (p = 0.02) and in the
NTD schizophrenia patients (p = 0.0004), who were also generally slow and produced long pauses. No such difference was
observed in the TD patients (two-factor analysis of variance with
context dependency and group as independent variables with significant interaction). (F= 6.0; df = 2,63; p = 0.0041; significance
levels of post hoc comparisons reported.)
36
Schizophrenia Bulletin, Vol. 23, No. 1, 1997
Cognitive Neuroscience View
Figure 10. Focused and unfocused activation of
a semantic network
Self-Organizing Semantic Maps
To shed light on the neurocomputational and neurobiological mechanism possibly underlying thought disorder in schizophrenia patients, two crucial concepts will be
discussed in this and the next section: the concept of selforganizing maps, as applied to semantic input, and the
concept of neuromodulation.
A self-organizing map is a type of computational
neural network, which is also called a Kohonen network
after its inventor, the Finnish engineer Teuvo Kohonen
(Kohonen 1982, 1989). This type of network is characterized by connections in the output layer that allow lateral
inhibition, an essential feature of the human cortex that
enables the network to generate maplike representations
spontaneously, without the need for any feedback,
"teacher," or "supervision" (for a general introduction to
neural networks, see Spitzer 1995).
Self-organizing maps can be used to generate orderly
maplike representations of semantic input. Ritter and
Kohonen (1989) developed a computer-simulated network
with the names and characteristics of animals. With this
input, the network formed a map of the 16 animals.
Animals with similar features were closely together, and
dissimilar animals were far apart. The authors commented
on this result: "Although highly idealized, this result is
very suggestive of how a self-organizing system can learn
to spatially guide the formation of memory traces in such a
way that its final physical layout forms a direct image of
the hierarchy of the most important 'concept relationships' " (p. 248). The map looked similar to figure 4.
In their second experiment, the authors presented
short sentences in vectorized form to a similar network.
This time, the network organized this input according to
not only semantic but also grammatical features of the
words. Nouns, adverbs, and verbs were put on distinctive
areas of the map, and within these areas the words were
organized by semantic features (see figure 11). As in maps
inferred from psychological experimental data, antonyms
are represented close together because words of opposite
meaning are likely to be used in similar contexts. The
authors conclude:
Network symbolized by flat grid, activity is shown as peaks along
the vertical axis. Shown is the pattern of activity in a semantic network in which two items become activated. In a focused process
(top), no overlap of activity occurs and no common features "pop"
to mind; overlap and common features are found in the unfocused
activation conditions (bottom).
incoherent actions and amalgamated objects and persons.
Kraepelin analyzed more than 200 examples of disordered
utterances that occurred within dreams (mostly his own)
and found them to be remarkably similar to thought (or
language) disorder in psychosis.
We conducted two studies of the effects of different
sleep stages on semantic priming performance directly after
awakenings (Spitzer et al. 199I, 1993b). In both studies, an
increased semantic priming effect was found in subjects
who had just spent a few minutes in rapid eye movement
(REM) sleep. This result was interpreted as evidence for
unfocused activation of semantic areas during REM sleep,
which is in line with some computational hypotheses about
the function of REM sleep (Crick and Mitchison 1983).
In this work we have now shown that the principle of
self-organizing maps can also be extended to higher
levels of processing, where the relationships between
items are more subtle and less apparent from their
intrinsic features, a property that is characteristic of
symbolic expressions. Symbols, in general, do not
contain metrically relatable components. Consequently, meaningful topographic maps of symbols
must no longer display intrinsic features, but instead
the logical similarities of their inputs. It turns out,
however, that organized mappings of symbolic data
may still ensue from the same basic adaptation laws,
37
M. Spitzcr
Schizophrenia Bulletin, Vol. 23, No. 1, 1997
provided that the symbolic input data are presented
together with a sufficient amount of context, that then
defines the similarity relationships between them.
[p. 251]
Evidence is also accumulating for the existence of
semantic maps in various cortical areas, including reports
of patients with brain damage who display a loss of only a
small fraction of their semantic memory. These patients
have no cognitive deficit except for the naming of living
things, of vegetables, or of items inside the house (for
recent reviews and discussions, see Farah and Wallace
1992; Caramazza et al. 1994; de Renzi and Lucchelli
1994). These cases appear to be rare, but the increasing
number of patients with category-specific naming deficits
suggests that a negative observation bias may have contributed, and may still be contributing, to the rarity of the
phenomenon. In fact, as early as 1966, Goodglass et al.
found a high incidence of dissociations between categories in a quantitative study of category-specific, wordcomprehension deficits, which led them to conclude that
in aphasic patients such dissociations may be the rule
rather than the exception. Farah and Wallace (1992) correctly conclude that such patterns of deficits suggest that
the representations are organized at least in part by
semantics and that these representations must be localized
to some degree.
Evidence for the formation of maps of various
aspects of the outside world in the human cortex can be
derived from a number of sources. First, we know that the
building blocks of self-organizing networks—high, flexible connectivity and lateral inhibition—are realized in the
cortex (Thomson and Deuchars 1994; Rauschecker 1995),
which can be regarded as a computational surface that
represents any coherent input as a map (Kohonen 1982).
Maps of motor and somatosensory information were
described several decades ago by Penfield and Rasmussen
(1950); more recently, multiple maps have been reported
(Merzenich and Sameshima 1993). Multiple retinotopic
and tonotopic maps have been discovered in the primate
cortex, and there is evidence that such maps exist in the
human cortex. In other words, a neurocomputational
mechanism for the formation of maps has been proposed,
and the existence of quite a number of such maps has
been demonstrated by neurobiology research.
Finally, we recently conducted a study using functional magnetic resonance imaging. The subjects were
asked to covertly name either animals or furniture items
displayed to them on a computer video projection device.
In most subjects, we found areas showing increased cortical activation caused by naming animals or furniture.
Often, animal and furniture areas were near each other,
and in many cases, several such areas were found in one
subject—mostly (but not exclusively) in the left frontal
and temporal lobes. This study provides direct evidence
that maplike semantic representations can be detected
noninvasively in human subjects (Spitzer et al. 1995b;
Spitzerand Kammer 1996; Spitzer et al. 1996a).
Recently, we conducted computer simulations of
change in self-organizing feature maps (Spitzer et al.
1995a). Such change should happen, for example, if a part
of a map is deafferented. Under such circumstances, the
representations of input patterns are rearranged on the
"computational surface" such that there is a computationally optimal distribution on the map. Such rearrangements
are the computational equivalent of cortical neuroplasticity, which has been found in a number of experiments on
cortical sensory maps (Merzenich et al. 1983, 1988;
Jenkins et al. 1990; Allard et al. 1991; Recanzone et al.
1992a, 1992/7, 1992c; Pascual-Leone and Torres 1993).
The rearrangement is highly dependent on the noise level
of the input and the noise level within the system. Without
noise, rearrangement (neuroplasticity) occurs slowly, but
internal and external noise drives reorganization.
In sum, there is a biologically plausible computational mechanism for the formation of maplike represen-
Figure 11. Semantic map generated
spontaneously by a Kohonen network
(Ritter and Kohonen 1989)
water
•
meat
•
beer
•
bread
dog horse
•
cat
•
•
little
•
•
fast
Bob
•
slowly
•
much
Jim
often
•
well
poorly
•
Mary
eats^
works
%^.
/
phones
buys
•
•
•
•
hates
visits
runs
drinks
•
walks
•
likes
Words were organized according to semantic and grammatical
features. Note the similarity to the "cartoon" semantic network
depicted in figure 4.
38
Schizophrenia Bulletin, Vol. 23, No. 1, 1997
Cognitive Neuroscience View
capacity—may appear desirable under any circumstances,
but it can also at times be counterproductive and cause
other forms of psychopathology (Spitzer 1995). As discussed above, network models suggest that noise is an
important factor driving neuroplasticity. In semantic networks, the relative absence of noise, for example, produced by a state of moderate anxiety, may cause a more
focused activation of ideas, concepts, and meanings.
Accordingly, stress and anxiety can lead to the production
of an increased number of standard associations (such as
"black-white," "doctor-nurse") in normal subjects (Mintz
1969).
If dopamine modulates the signal-to-noise ratio in
cortical networks, if such networks are involved in the
storage of semantic information in the form of maps, and
if these maps are accessed during semantic information
processing more or less reliably (i.e., with more or less
noise involved), the ingestion of L-dopa, a precursor of
dopamine and norepinephrine, should cause an increase in
the focus of activation in semantic networks and, hence, a
decrease in the effects of spreading activation.
To directly test this hypothesis, we conducted a study
on indirect semantic priming in normal volunteers
(Kischka et al. 1996). In a double-blind placebo-controlled design, a speeded lexical decision task with
directly and indirectly related word pairs as well as with
nonrelated word pairs was used to assess the effect of 100
mg of L-dopa (plus 25 mg benserazide, a peripheral decarboxylase inhibitor) on the time course of spreading activation in normal subjects. If dopamine causes a sharper
focus of lexical activation, we reasoned, the small indirect
priming effect that normal subjects display at longer
SOAs should decrease. The results of the study were in
line with this hypothesis. When a long SOA was used to
elicit indirect priming in normals, L-dopa produced a significant decrease of the indirect semantic priming effect
from 29 ms (4.8%) to 7 ms (1%). A small, nonsignificant
reduction of semantic priming indicated, again, that this
measure may be less sensitive to changes in the spreading
of activation in semantic networks (figure 12). This study
provided direct support for the hypothesis that dopamine
increases the signal-to-noise ratio in semantic networks,
causing a decreased spreading of activation during the
process of lexical access. Indirectly, these data provide
some support for the hypothesis that formal thought disorder is the result of a decreased dopaminergic tone.
L-Dopa is a precursor of dopamine and norepinephrine, and both substances have been implicated in
modulating the signal-to-noise ratio in cortical networks
(Chiodo and Berger 1986; Servan-Schreiber et al. 1990;
Grace 1991) but it is hard to discern the effects of the two
catecholamines. However, neuroanatomical considera-
tations of any coherent input to the cortex. Such maps
have been discovered in the animal and human cortex,
and the dynamically adapting behavior of these maps to
new input has been documented. Moreover, the existence
of semantic maps (a localized representation of semantic
information in the brain) is suggested by converging evidence from neuropsychological, computational, psycholinguistic, and functional neuroimaging data. Finally,
neural network simulations provide evidence for the
importance of noise in the rearrangement of such cortical
representations (neuroplasticity).
Signal-tO'Noise, L-Dopa, Psilocybin, and
Indirect Semantic Priming
While the postsynaptic effects of dopamine in the human
cortex have not yet been fully determined (Glowinski et
al. 1984; Thierry et al. 1988), Cohen and ServanSchreiber (1992, 1993) have evidence suggesting that
dopamine and norepinephrine act as neuromodulators
amplifying strong signals and dampening weak ones
(Morrison and Hof 1992), that is, they modulate one general parameter of cortical information processing, its signal-to-noise ratio. According to this model, a decreased
dopaminergic activation of cortical areas leads to a
decrease of the functional focus of cortical neuronal network activity and thereby reduces their ability to produce
appropriate output (Servan-Schreiber et al. 1990).
While the standard dopamine hypothesis attributes
schizophrenic psychopathology to elevated dopamine levels, several authors have proposed that negative symptoms in schizophrenia are due to a decrease in dopaminergic activity (Crow 1980; Mackay 1980; Carlsson 1988;
Weinberger et al. 1988; Heritch 1990; Davis et al. 1991;
Grace 1991). In particular, Davis et al. (1991) proposed
that negative symptoms are caused by low prefrontal
dopamine activity, which leads to excessive dopamine
activity in mesolimbic dopaminergic neurons, which may
eventually lead to positive symptoms. Similarly, Grace
(1991) suggested that schizophrenia patients suffer from a
diminished "tonic" striatal dopamine release, consecutive
up-regulation of striatal postsynaptic dopamine receptors
and, hence, increased responses to "phasic" striatal
dopaminergic activation due to environmental stress. This
would result in both low dopaminergic negative symptoms
and stress-related hyperdopaminergic positive symptoms.
Our data on the effect of treatment on priming effects
suggest that a neuroleptic-induced reduction of symptoms
also leads to a normalization of semantic priming (Spitzer
et al. 1994c) and indirect semantic priming, in particular
(Spitzer et al., submitted for publication c).
A high signal-to-noise ratio—without any modulatory
39
Schizophrenia Bulletin, Vol. 23, No. 1, 1997
M. Spitzer
tions indicate dopamine as the more likely candidate for
the modulation of semantic processes.
In our study on the effects of the hallucinogenic agent
psilocybin, which acts on the serotonin system and has
subjective effects of "broadening" conscious experiences
(Spitzer et al. 1996/?), we hypothesized that it might defocus semantic networks (i.e., decrease the signal-to-noise
ratio), which should lead to an increased indirect semantic
priming effect. As shown in figure 12b, psilocybin has the
opposite effects of L-dopa; it produced a nonsignificant
increase in semantic priming and a significant increase in
indirect semantic priming. Although the design of this
study (single group, repeated measures) was different from
the design of the L-dopa study, the opposite effects of these
neuromodulatory agents deserves further exploration.
Figure 12. Semantic and indirect semantic
priming effects in a speeded lexical decision
task in which target words were displayed 700
ms after the prime words
9-i
effect (%)
Ol «
~J
1... .1.... 1....
8-:
—
A
'
2'-
0-:
r
•
•
_ •,
•
Placebo
•
L-dopa
More Precise Mental Chronometry:
ERPs
To further clarify the time course of cerebral language
processing, we applied the method of ERPs to the investigation of the time course of lexical activation in normal
subjects and schizophrenia patients (Spitzer et al., submitted for publication d). The rationale for using the ERP
method in conjunction with a semantic and indirect semantic priming paradigm follows.
p<.05
1
[I
•L
semantic priming
indirect semantic priming
semantic priming
indirect semantic priming
1. RT studies provide only a first, crude measure of
differences in the time course of mental information processing. In the example shown in figure 13, the lexical
decision task involves perceptual, language-related, and
motor output components. Since it is known that schizophrenia patients may have early visual processing deficits
(Goldberg et al. 1991) and certainly suffer from motor
output dysfunctions (Manschreck 1992), we can infer that
these processes will add error variance to the lexical decision RTs (measurements that supposedly concern semantic processes). Hence, any RT differences between control
subjects and schizophrenia patients in measures such as
semantic priming must be compromised by this error variance.
2. The ERP method can provide a window into the
otherwise opaque period of time between stimulus and
response and allows for the investigation of specific language-related components. Sentences with semantically
anomalous endings produce a negative deflection of the
scalp ERP at about 400 ms after stimulus onset. Moreover, this N400 component also occurs when only semantically unrelated word pairs are used as stimuli (Kutas and
Van Petten 1994; Nobre and McCarthy 1994). In other
words, the ERP literature suggests that this paradigm produces a clear ERP signal in normals and suggests the use
of ERP measurements for the further clarification of the
time course of lexical access in schizophrenia patients.
We recently completed our first study (Spitzer et al.,
in press) in which ERPs were recorded from 20 scalp
electrodes while subjects (20 schizophrenia patients and
Data obtained from 31 normal subjects under placebo (n = 17) or
100 mg L-dopa (n = 14). a. L-Dopa reduced direct semantic priming effect only to a small, nonsignificant degree, but the indirect
semantic priming effect was significantly lower under L-dopa than
under placebo (p < 0.05, one-tailed f-test); b. In contrast to
L-dopa, the hallucinogenic agent psilocybin increased direct
semantic priming (numerically) and indirect semantic priming (significantly), n.s. = not significant.
40.
Schizophrenia Bulletin, Vol. 23, No. 1, 1997
Cognitive Neuroscience View
Figure 13.
functions
Rationale for use of event-related potentials (ERPs) in research concerning cognitive
behavioral paradigm (RTs and error rates)
stimulus
(e.g., the second word in a semantic priming task)
perceptual?
response
(e.g., a keypress)
motor?
semantic?
doctor—nurse
sky—cheese
priming
effect
•+>
200
400
•+•
•+•
time
600
800
1000 ms
event related potentials (ERP)
motor
perceptual
/ ^ ~
__ •
v_
sky—cheese
differences in
N400 latency
and amplitude
Reaction time (RT) studies provide only a first, crude measure of differences in the time course of mental information processing. In contrast, ERPs provide a detailed temporal account of dynamic cognitive processes from stimulus onset to final motor response.
Manipulation of semantic relation causes a pronounced difference in the two ERP signals 400 ms after stimulus onset.
20 normal control subjects) performed a semantic and
indirect semantic priming task as described above (with
an SOA of 200 ms). In line with previous research on
incongruous semantics of sentences and words, an N400
component was obtained in the nonrelated condition for
the majority of the subjects in both groups (17 controls
and 12 schizophrenia patients). At most, only a small
N400 component was detected in the related condition.
Most notably, peak and latency data for the indirect priming condition suggest that indirectly related word pairs are
processed differently by the two groups. Normal subjects
showed an N400 that was almost identical to the N400
produced by nonrelated words; schizophrenia patients
showed no N400 in this condition. In other words, schizophrenia patients treat indirectly related words like related
words and normal subjects treat these words like unre-
41
Schizophrenia Bulletin, Vol. 23, No. 1, 1997
M. Spitzer
Litman et al. 1991; Shimamura et al. 1991) and brain
imaging methods (Weinberger et al. 1988), and because
delayed response tasks require the subject to use newly
stored information for each trial, such tasks seem suitable
to tap working memory deficits in schizophrenia patients
(Goldman-Rakic 1991). Moreover, working memory
deficits have been directly demonstrated in schizophrenia
patients using various delayed response tasks (Park and
Holzman 1992; Spitzer 1993; Park, in press).
In short, working memory has a limited capacity,
lasts only a few seconds, and is relevant for goal-directed
behavior. Its anatomical basis in the frontal cortex, receiving and sending projections to other cortical areas, is
established, it has been related to dopamine function in
animal and human studies, and there is evidence of its
dysfunction in schizophrenia patients.
Individual differences in working memory have
already been used to account for differences in sentence
comprehension among normal individuals (Just and
Carpenter 1992). As these authors point out, "Working
memory plays a critical role in storing the intermediate
and final products of a reader's or listener's computations
as she or he constructs and integrates ideas from the
stream of successive words in a text or spoken discourse"
(p. 122). According to their capacity theory of comprehension, the capacity of working memory constrains comprehension, and hence, a dramatically reduced working
memory capacity (presumably present in schizophrenia
patients) should lead to marked defects in language production and understanding.
The results of the above-mentioned pauses study may
bear on the issue of dysfunctional working memory in
schizophrenia. Thought-disordered schizophrenia patients
were obviously unable to maintain the relevant context and
therefore did not use it appropriately for sentence production. This led to noncontextually constrained words intruding into the utterances quickly, as could be detected by the
pause length measure. In the following section, a further
experiment is reported that may exemplify how dysfunctional working and associative memory can be linked to
schizophrenic psychopathology and how experimental
methods can be used for the fine-grained analysis of such
pathology.
The results from the study of Park and Holzman
(1992) are not in line with the view presented here. They
report abnormal results in a group of schizophrenia
patients only in a spatial working memory task, while the
patients produced normal results in a digit-span test, supposedly tapping into verbal working memory. However,
Just and Carpenter (1992) report a lack of correlation of
the digit-span test with their reading comprehension task,
which "indicates that the standard digit span task does not
lated words (Spitzer et al., in press, submitted for publication d). Moreover, latency data for the N400 peak clearly
reproduced previous RT data results but displayed considerably less variability. Therefore, the N400 component
under conditions of different semantic distances between
prime and target word may be a suitable measure of dysfunctional associative processes in schizophrenia patients.
We are currently carrying out a replication study using a
64-electrode array (Tucker 1993) to obtain additional spatial information on lexical information processing in
schizophrenia patients.
Context, Working Memory, and the
Frontal Lobes
The frontal lobes are considered the site of working memory, temporary storage of relevant contextual information
from the recent past, about the general plan, or regarding
aspects of an object or event that are not part of what is
actually perceived.
The most salient feature of working memory is its
ever-changing content. In contrast to the large capacity
and longevity of semantic memory, working memory, by
definition, has a limited capacity and items are stored only
for seconds (Baddeley 1992). For example, when we
make a phone call, we look up the number in a phone
book, keep it in working memory to dial it, and forget it
immediately thereafter. Working memory has been compared to a "scratch pad" and to the random access memory of a computer, which holds the most immediately
needed information.
Goldman-Rakic and others have argued on the
grounds of behavioral data from human subjects and animal research and from the results of single cell recordings
from monkeys that holding information over a short
period of time involves the functioning of the frontal cortex (Funahashi et al. 1989; Goldman-Rakic 1990;
Goldman-Rakic et al. 1990; Goldman-Rakic and Friedman
1991). In particular, the cooling of the dorsolateral prefrontal cortex in monkeys induced reversible deficits in
the performance of visual, tactual, and cross-modal delay
tasks, implying that this anatomical site is crucial for
supramodal short-term memory (Fuster 1991, 1993,
1995). Moreover, this type of short-term memory has
been linked to dopamine activity in this brain area in
human beings (Luciana et al. 1992). Because dopamine
functioning is clearly involved in the pathogenesis of
schizophrenia (see above), because frontal cortex dysfunction in schizophrenia has already been demonstrated
by neuropsychological tests such as the Wisconsin Card
Sorting Task (Heaton 1981) (see Goldberg et al. 1991;
42
Schizophrenia Bulletin, Vol. 23, No. 1, 1997
Cognitive Neuroscience View
the activation of literal and metaphoric meanings of
metaphoric statements, the method of lexical decision was
used in schizophrenia patients and normal control subjects
(Spitzer 1993; for details, see Spitzer et al. 1994b).
Forty-three normal control subjects and 35 schizophrenia patients performed a visual lexical decision task
shortly after listening to a proverb. The stimulus material
consisted of 60 metaphorical statements as primes and of
the following targets (see table 2): 10 words concretely
related to the last or to the most prominent word of the
proverb, 10 metaphorically (abstractly) related words, 10
nonrelated words (5 concrete words and 5 abstract
words), and 30 nonwords. For each metaphoric statement,
three words and three nonwords were selected, and different versions of the test were set up such that each prime
sentence was followed by each of the targets. The order of
the conditions in each experiment was initially randomized and then remained constant. -The different versions
were used at random for patients and subjects to exclude
the effects of particular stimulus words. The target word
was displayed 1,200 ms after the auditory prime.
The abstract and concrete priming effects in both
groups are displayed in figure 14, which shows a groupdependent difference in the priming effect of concrete and
abstract meanings: In normal control subjects both the
concrete and the abstract meanings produce a significant
priming effect; in schizophrenia patients only a concrete
priming effect—larger than in the normal control subjects—could be detected. These effects were not caused
by the concreteness or abstractness of the words per se,
since RTs to the abstract and concrete words in the nonrelated condition did not reveal significant RT differences.
The main findings of this experiment can be interpreted as follows.
draw on the same resources as those used in most language comprehension tasks" (p. 125). In particular, the
authors distinguish two aspects of verbal working memory, the "articulatory loop," as proposed by Baddeley
(1986), and a "central executive," which was only
vaguely defined and empirically addressed by Baddeley.
While the former is clearly involved in digit-span performance and has been located in the left superior temporal lobe, according to a positron emission tomography
(PET) study (Frackowiak 1994), the latter has always
been suggested to reside in the frontal lobes. Moreover,
Just and Carpenter cite neuropsychological data supporting a dissociation between the digit-span task and the cognitive processes of sentence comprehension. Finally, a
recent study by Maher et al. (1995) demonstrated that
schizophrenic deficits in a verbal memory task that taps
into context effects (the Miller-Selfridge paradigm) correlated most highly with structural deficits in the frontal
lobes as assessed with MRI. In the next section, the
results of an experimental study of a specific type of formal thought disorder (concretism) are discussed in the
framework of associative and working memory just
described.
Concretism
The failure of many schizophrenia patients to take the
"abstract attitude" (Goldstein 1944), that is, the preference for the literal (denotative) meaning as opposed to the
metaphorical (connotative) meaning has been reported by
a number of authors (Meadow et al. 1953; Chapman
1960; Holm-Hadulla and Haug 1984; Cutting and Murphy
1990). The phenomenon is usually described as "concretism" or "concrete thinking" and can be demonstrated
with experimental approaches, such as interpreting
proverbs or selecting word pairs that fit together. Contrary
to such an "underinclusive" bias, the tendency to overgeneralize a given concept ("overinclusive" thinking) has
been noted as a characteristic of schizophrenia by several
authors (Cameron 1939; Payne 1962, 1966). Overinclusive thinking was characterized by "an inability to
preserve conceptual boundaries, so that ideas which are
only distantly related, or even irrelevant to a concept
become incorporated into it. . . . Because of this, thinking
becomes more abstract and less precise" (Payne 1966, pp.
78-79). In DSM-IV, the following description is given:
"their [the patients'] speech may be generally understandable but digressive, vague, or overly abstract or concrete"
(p. 278). The seemingly contradictory findings of a bias in
the semantic preferences of schizophrenia patients toward
the more abstract and toward the more concrete meaning
of a word or an utterance need explanation. To probe for
I. A comparatively large concrete priming effect in
schizophrenia patients is in line with the above-mentioned
results of lexical decision studies on semantic and indirect
semantic priming. Hence, it can be considered further evidence in favor of the semantic network spreading activation hypothesis of schizophrenic thought disorder. The
concrete meaning of a metaphoric statement is not only
Table 2. Conditions in the "concretism"
experiment
Conditions
Concretely related
Abstractly related
Nonrelated (concrete/abstract)
Nonword
Examples of target words
snow
risk
chair/grief
toble
Note.—The examples refer to target words that followed the auditory prime "He is skating on thin ice."
43
Schizophrenia Bulletin, Vol. 23, No. 1, 1997
M. Spitzer
Figure 14. Concrete and abstract priming
effects (percentage scores) in normal control
subjects and schizophrenia patients
tions, a significant concrete priming effect, but no significant abstract priming effect, was obtained (only a trend
was detectable). This result corresponds with established
differences in decoding time of literal and metaphoric
speech (Chaika 1990) and suggests that the metaphoric
meaning needs some time to build up (only then being
effective as a prime) in normal control subjects. During
this time, the meanings of the words that make up the
entire sentence must be kept in mind—a task that involves
working memory. To quote again from the seminal paper
by Just and Carpenter (1992):
controls
patients
7-
A somewhat more modern view of working memory
takes into account . . . the storage of partial results in
complex sequential computations, such as language
comprehension. The storage requirements at the lexical level during comprehension are intuitively obvious. A listener or comprehender must be able to
quickly retrieve some representation of earlier words
and phrases in a sentence to relate them to later words
and phrases, [p. 122]
e„
<D 3
in
1-
concrete
Therefore, it appears likely that while the prominent
concrete priming effect in schizophrenia patients indicates
an overactive associative memory, the lack of a significant
abstract priming effect signifies a deficit in languagerelated working memory.
Generally speaking, the lack of integrative function,
goal directedness, adequate attention, drive, and general
intellectual capacity can be directly related to working
memory dysfunction. If less information can be held for
immediate use, complex tasks cannot be performed and
behavior will generally be guided to a greater extent by
immediate perceptual clues rather than by internally generated and kept goals. Beringer (1924, 1926) already
described the "diminished intentional span" of schizophrenia patients as most characteristic of the patient's
deficits, which may be interpreted as merely another way
of referring to a reduced capacity or accessibility of working memory in these patients.
abstract
Significant semantic priming effects for concretely related words
were found in both groups. The abstractly related word condition
produced a significant priming effect only in control subjects. Twofactor analysis of variance with group (controls vs. patients) and
condition (abstract vs. concrete) as within-subject factors showed
significant interaction (Spitzer 1993a).
more readily accessible than the abstract meaning (because the abstract meaning has not been produced by the
patient), but also activated to a higher degree than in normal control subjects. This difference might explain the
clinical observation that schizophrenic concretism is
somewhat different from concretism displayed by organic
mental syndrome patients in that schizophrenia patients
may focus on a concrete aspect of a remote feature of a
concept.
2. The finding of a significant abstract priming effect
only in normal control subjects corresponds directly to the
clinical observation of concretism in schizophrenia
patients. The study has clearly demonstrated that little or
no abstract meaning is activated in schizophrenia patients
more than a second after a metaphoric statement has been
uttered; instead, one or a few concrete meanings are highly
active.
Data from a parallel experiment (Spitzer et al. 1994fc)
shed further light on the results. Forty normal control subjects performed the same task with a shorter SOA of 400
ms (i.e., there was no 800-ms pause between the auditory
prime sentence and the fixation point). Under these condi-
Other features of schizophrenic thought may also be
best explained by a combined dysfunction of associative
semantic and working memory. As we have already seen,
the particular kind of schizophrenic concretism can easily
be explained as the combined effect of a disinhibited
(unfocused) associative memory and a reduced capacity
of working memory. Furthermore, the clinically highly
relevant aspect of schizophrenic thought and behavior,
the patients' ubiquitous lack of sensitivity to context
(Chapman et al. 1964; de Silva and Hemsley 1977), can
easily be accounted for in terms of working and associative memory. The patients' failure to make appropriate use
of contextual evidence in the production and understanding of language as well as in goal-directed behavior may
be caused by the inability to keep relevant information in
44
Schizophrenia Bulletin, Vol. 23, No. 1, 1997
Cognitive Neuroscience View
provide localized information on cognitive processes with
a resolution of a few millimeters. Studies of the effects of
neuromodulators on normal subjects, employing the
behavioral paradigms (and in future studies, in conjunction with ERPs and fMRI), can be used to bridge the gap
between cognitive neurobiological models of psychopathology. Finally, neuronal network models provide
insights into computational functions and are needed to
link the mental and the biological realms. Such computational models of mental and biological processes provide
a framework for the generation of new hypotheses, which
can be readily tested in such models.
In this article, I have applied this logic of cognitive
neuroscience research to the study of language-related psychopathology. In sum, the results of the experimental studies on language-related phenomena in schizophrenia
patients as well as the clinical phenomena that first motivated these experiments can be parsimoniously explained
in terms of dysfunctional information processing in, or
between, working and semantic associative memory. The
neurobiological equivalent of the working memory deficit
is a dysfunctional, possibly left lateralized, frontal lobe,
caused by either a structural deficit or a hypodopaminergic
state (or both). The decreased signal-to-noise ratio in
semantic associative networks has its neurobiological
equivalent either in the reduced frontal lobe effect just mentioned (possibly caused by the mechanisms mentioned or
by a structural or functional disconnection) or in an
autonomous signal-to-noise decrease in semantic networks.
Cognitive neuroscience provides an array of methods
and concepts that can be fruitfully applied to research in
psychopathology.
mind while pursuing a certain project. This relevant information must be represented in working memory, since it
has to be permanently used to guide behavior in the
absence of immediate perceptual cues or even despite perceptual cues that suggest some alternative behavior.
The findings of a nonfocused associative memory and
a reduced capacity of working memory in schizophrenia
patients can be linked to cortical deficits, which may
either be structural or functional. A structural deficit in the
left temporal lobe, an area known to be involved in language processing, has recently been implicated in schizophrenic pathology (Shenton et al. 1992; McCarley et al.
1993). Possibly such a defect would cause a decreased
accuracy of lexical processing and, hence, would be in
line.with the findings of increased semantic and indirect
semantic priming, as presented above. A dysfunctional
frontal lobe, implicated in schizophrenic symptomatology
(Andreasen et al. 1992; Andreasen 1994), would also
explain the findings reported above. In particular, one
might think of the frontal cortex providing contextual
information (e.g., on the other words in a sentence) that
constrains the meaning of the entire phrase and therefore
the activation of the respective nodes in a semantic network, possibly residing in the temporal lobe. If these constraints are weakened—either by lower dopaminergic
input to the frontal lobe or by fewer connections between
frontal and temporal lobes—increased autonomy of lexical connections in semantic memory as well as decreased
purpose directedness of the utterances will occur.
Conclusions
Within the framework of cognitive neuroscience, the concept of association used by Bleuler and by Kraepelin to
characterize schizophrenic psychopathology becomes
important again. Specific behavioral measures such as
direct and indirect semantic priming allow the measurement of the spread of activation during lexical access in
semantic (and supposedly neural) space over time. The
clinical phenomena of loose, oblique, and derailed associations, of concretism, and of seemingly overabstract
thinking can be accounted for in terms of associative
semantic and working memory. Behavioral paradigms can
guide the search for dysfunctional mental activities (such
as lexical access and holding contextual information),
which can be studied in more detail using the behavioral
paradigms in conjunction with electrophysiological and
functional brain imaging methods. With the former, the
time course of cerebral information processing can be
revealed with millisecond accuracy by recording the scalp
signatures of electrical phenomena accompanying cortical
information processing. Functional imaging techniques
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Koutstaal, W.; Rittenhouse, C ; Maher, B.A.; and Hobson,
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Acknowledgments
This work was supported by a single investigator's grant
from the Deutsche Forschungsgemeinschaft (DFG Sp
364/1-2) and an established investigator's award from the
National Alliance for Research in Schizophrenia and
Depression (NARSAD). The author is grateful to two
anonymous reviewers for their helpful comments.
Spitzer, M.; Walder, S.; and Clarenbach, P. Semantische
Bahnung im REM-Schlaf. In: Meier-Ewert, K., and
Riither, E., eds. Schlafmedizin. Stuttgart, Germany:
Gustav Fischer Verlag, 1993ft. pp. 168-178.
Spitzer, M.; Weisbrod, M.; and Winkler, S. "Lemon—
Sweet: Electrophysiological Correlates of Indirect
Semantic Priming in Normal Volunteers and Schizophrenic Patients." Submitted for publication d.
The Author
Manfred Spitzer, M.D., Ph.D., is Senior Lecturer in
Psychiatry, Section of Experimental Psychopathology,
Psychiatric Clinic of the University of Heidelberg,
Heidelberg, Germany.
Spitzer, M.; Weisker, I.; Maier, S.; Hermle, L.; and Maher,
B.A. Semantic and phonological priming in schizophre-
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