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A Cognitive Neuroscience View of

Schizophrenic Thought Disorder


by Manfred Spitzer

Abstract work models of the processes in question can provide a


framework for the development and testing of further
The experimental association psychology approach to hypotheses.
mental associations has been the conceptual back- The purpose of this article is to provide an example
ground for the concept of schizophrenia. Cognitive of how cognitive neuroscience can contribute to the
neuroscience methods and concepts can be used to understanding of various phenomena usually summarized
study various forms of schizophrenic thought disorder. under the concept of formal thought disorder. Data from
In particular, the concepts of semantic associative and several studies on the nature of associative processes in
working memory can be applied fruitfully to schizo- normal subjects and schizophrenia patients will be pre-
phrenia research. Semantic associative networks can sented. Schizophrenic thought disorder is often character-
be simulated with self-organizing feature maps. ized by a decreased accuracy of lexical access combined
Dysfunctional lexical access can be modeled in terms with decreased working memory. These dysfunctions may
of low signal-to-noise ratio in intra- or between-net- be related, and they may be caused by dysfunctional map-
work information processing. Evidence for the crucial like semantic networks in frontal and temporal cortical
role of dopamine in this function is presented, and a areas. The structure of semantic networks, as revealed by
general neurocomputational model of schizophrenic experimental psychological, neuropsychological, and
thought disorder is developed. This model capitalizes fMRI studies, bears close resemblance to self-organizing
on basic aspects of neural information processing (i.e., feature maps, that is, a type of neural network. In these
neuromodulation and neuroplasticity) and allows a maps, the influence of noise on plasticity can be demon-
parsimonious explanation of a number of otherwise strated, and these findings can be related to the neuromod-
inexplicable or unrelated clinical phenomena and ulatory function of dopamine, which regulates the signal-
experimental results. to-noise ratio in network information processing. Taken
Schizophrenia Bulletin, 23(l):29-50,1997. together, the presented view allows a comprehensive and
parsimonious explanation of a number of otherwise inex-
plicable or unrelated phenomena. In particular, it demon-
strates how cognitive neuroscience methods and concepts
Cognitive neuroscience is the most recent name of the
can bridge the gap between mind and brain, between clin-
endeavor to understand the nature of mind and how it is
ical phenomena and underlying brain pathology
related to the brain (Gardner 1985; Posner and Raichle
(Callaway 1992).
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
Disordered Thought: Past and Present
(such as event-related potentials [ERPs] and functional Disrupted thought processes have long been described in
magnetic resonance imaging [fMRI]), together with ade- association psychology terms and studied by the method
quate experimental psychological procedures and behav- of the word association test: A subject reads or hears a
ioral measurements, can provide detailed spatio-temporal
information about where and when a specific cognitive
process is computed in the brain. This information can be
Reprint requests should be sent to Dr. M. Spitzer, Psychhitrische
linked to neuroanatomical data, and finally, neural net- Universiliitsklinik. Voss-Slr. 4. 6 l )l 15 Heidelberg, Germany.

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Schizophrenia Bulletin, Vol. 23, No. I, 1997 M. Spitzcr

word and responds by saying the first word that comes to Semantic Priming and Lexical Access in
mind. In this word-association paradigm, "black" pro-
duces "white," "lemon" produces "sour," and "sour" pro-
Semantic Networks
duces "sweet." The investigation of associative processes In their seminal paper on word associations, Kent and
with this test was introduced into the field of psychiatry Rosanoff (1910) pointed out the major limitation of the
by Emil Kraepelin, after he had worked for 2 years in the method of free associations. Specific types of word asso-
world's first psychological laboratory, directed by ciations can only be distinguished post hoc. In other
Wilhelm Wundt. By the turn of the century, a great num- words, the experimenter cannot first specify a certain
ber of word-association studies with normal subjects and association and then test it. To avoid this difficulty, the
patients had been conducted, and they influenced the for- technique of lexical decision can be used. The subject
mation of the concepts of dementia praecox by Kraepelin decides whether a given string of characters is a word or
and of schizophrenia by Eugen Bleuler (for reviews, see not. To investigate certain types of associations, specific
Spitzer 1992; Spitzer and Mundt 1994). word pairs are presented either simultaneously or one
In particular, schizophrenic thinking was character- after the other. Then the effect of the relationship between
ized by loose, mediated, indirect, or oblique associations, the words on the lexical decision task regarding one of
that is, by dysfunctional associative processes. For exam- them can be measured in terms of the time it takes to per-
ple, Bleuler (1911/1950) noted that, in the utterances of form the task (reaction time [RT]) and the errors the sub-
schizophrenia patients, "the associations tend to proceed ject makes.
along new lines" and "indirect associations . . . receive A robust phenomenon that has been discovered using
unusual significance" (p. 14). "I suspect that only the lack this technique of lexical decision is semantic priming
of sufficient observation has been responsible for our (Meyer and Schvaneveldt 1971; Neely 1991). A word is
inability to demonstrate them [indirect associations] more recognized faster if it is preceded by a meaningfully
frequently in the thought-processes of our patients" related word. For example, "black" is recognized faster as
(p. 14). In addition, thought can be overly abstract or a word if it is presented shortly after "white" than if it is
overly concrete, as several researchers have pointed out presented shortly after a nonrelated word such as "soft"
(Cameron 1939; Feinberg and Garman 1961). (see figure 1).
In the Diagnostic and Statistical Manual of Mental This experimental paradigm has been applied to the
Disorders-4th edition (DSM-IV; American Psychiatric study of associations in schizophrenia patients with and
Association 1994), schizophrenic thought disorder is without thought disorder by a number of authors (Maher
characterized by disturbed associational processes, as can et al. 1987; Manschreck et al. 1988; Chapin et al. 1989;
be seen from the description of characteristic features of Fisher and Weinman 1989; Spitzer et al. 1994c; see also
schizophrenic thought: Kwapil et al. 1990). In these studies, thought disorder was
Disorganized thinking ("formal thought disorder," diagnosed using standardized rating scales, such as the
"loosening of associations") has been argued by some Schedule for Affective Disorders and Schizophrenia
(Bleuler, in particular) to be the single most important (SADS; Spitzer and Endicott 1978) and the Brief
feature of schizophrenia. . . . The person may "slip Psychiatric Rating Scale (BPRS; Overall and Gorham
off the track" from one topic to another ("derailment"
or "loose associations"); answers to questions may be 1962). Most notably, Maher et al. and Manschreck et al.
obliquely related or completely unrelated ("tangen- discovered an increased semantic priming effect in schiz-
tiality"). [p. 276] ophrenia patients who suffered from formal thought disor-

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 | |k|1|o|| |
" I . 1- 1 * 1
..LU- .^,1,-U..

stimulus onset asynchrony (SOA) reaction time (RT)

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Cognitive Neuroscience View Schizophrenia Bulletin, Vol. 23, No. 1, 1997

der, as compared with non-thought-disordered schizophre- This model of lexical access further asserts that concepts
nia patients and normal control subjects. In the experi- activated in a semantic network by a prime serve as a
ment, normal associations are presented (e.g., source of activation that spreads to related concepts. Such
"black-white") and their effect on RTs is compared with spreading of activation to nearby nodes in the semantic
nonrelated word pairs (e.g., "cloudcheese"). Since schiz- network lowers their thresholds of being activated. If one
ophrenia patients, at least in the view propagated by of these concepts is denoted by a word as a target in a lex-
Bleuler, suffer from intrusions of nonstandard associa- ical decision paradigm, this target will be recognized
tions into their utterances, they should, if anything, show faster (i.e., semantic priming will occur) because it is
less benefit in RTs from associated word pairs. In other already activated to some degree.
words, why should thought disorder, which is character- This view of lexical access and semantic priming
ized by a disruption of normal associations, produce an allows a parsimonious explanation of both the increased
increase in benefit due to normal associations? semantic priming effect and the occurrence of unusual
Replication studies, one conducted in another lan- associations in thought-disordered schizophrenia patients.
guage and another using a different experimental para- During the course of lexical access, activation spreads
digm, confirmed the result of an increased semantic prim- faster and farther in the semantic network than under nor-
ing effect in schizophrenia patients (Kwapil et al. 1990; mal circumstances. This acceleration causes the increased
Spitzer et al. 1994c). The data from two studies on seman- activation of normal associations (and hence, an increased
tic priming are displayed in figure 2. semantic priming effect) as well as the intrusion of
The semantic priming effect in normal subjects has oblique and unusual associations into utterances, because
been interpreted as evidence for a networklike organiza- activity may spread quickly to more distant nodes.
tion of the mental lexicon. According to these models,
semantic (and possibly other) features of words are repre-
sented as "nodes" in a neuronal network. In the course of Indirect Semantic Priming: A More
an utterance, these semantic units become activated for a
short period of time and thereafter either decay rapidly or
Sensitive Measure
are actively inhibited (Collins and Loftus 1975; Neely
While the finding of an increased semantic priming effect
1977, 1991; Miller and Glucksberg 1988; Levelt 1989).
in thought-disordered schizophrenia patients can be
regarded as an important first step, it may not provide the
Figure 2. Semantic priming in normal control best possible evidence to support the hypothesis of acti-
subjects, non-thought-disordered (NTD) and vated associations in schizophrenic thought disorder for a
thought-disordered (TD) schizophrenia patients number of reasons.
First, it has been argued on methodological grounds
160
that difference scores in accuracy and latency may be
Manschreck et al. 1988
140-
"inflated" in schizophrenia patients due to a compara-
Spitzer etal. 1994 c
tively slower and more variable (or worse, both) perform-
120- ance of patients, a well-established observation regarding
"tn '.
almost any task (Chapman et al. 1994). While in the first
c
study of lexical decision by Maher et al. (1987) the RTs in
the nonassociated condition were not significantly differ-
I so-
ent for schizophrenia patients and control subjects (possi-
c bly a result of the small sample size and a sampling
CO 60-
<D
CO
effect), subsequent data from their laboratory (rvlaher
40- 1993; personal communication, May 1993) and from our
respective study (Spitzer et al. 1994c) generally show
20
schizophrenia patients' RTs to be slower.
0 Second, from a clinical point of view, it has been
controls NTD schizophrenic TD schizophrenic known for more than 80 years that schizophrenia patients
patients patients
produce fewer close associates in word-association tests
(Kent and Rosanoff 1910) and tend to produce more indi-
Data from two studies carried out in two languages. Although rect, or mediated, associations instead. Hence, a measure
effect size was greater in the study of Spitzer et al. (1994c) (car-
ried out in German), the pattern of results is strikingly similar in of indirect associations appears appropriate. As Bleuler
both studies. noted:

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Schizophrenia Bulletin, Vol. 23, No. 1, 1997 M. Spitzcr

In experimental investigations of association, we find Figure 3. Word associations in the standard


a notable frequency of "mediate associations." . . . word-association paradigm as used by Jung
The above mentioned example [a patient had associ- (1906/1973) and others
ated 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 stan-
dard word-association task given to 20 normal control
subjects and 20 schizophrenia patients (Spitzer et al., sub-
mitted for publication a). Compared with the normal con-
trol subjects, the thought-disordered schizophrenia
patients showed fewer standard associations, fewer asso- 15
ciations driven by meaning, and more indirect associa- NTD TD
tions (see figure 3).
Third, according to the network model of semantic
priming, the spreading of activation dissipates with dis-
100
tance, and there is empirical evidence that such an inverse (b) semantic
relationship exists between semantic distance and the 95-: associations
amount of activation in normal subjects (den Heyer and
Briand 1986). Therefore, from a psycholinguistic perspec- 90 i
tive, closely associated words, which are automatically O

activated in normal control subjects and in schizophrenia CD


85^
patients, may not be the best stimuli to prove the height- 8"
ened activation of the associative network in schizophre- 80-:
nia. With closely related primes and targets as the crucial
condition, only "comparably more" activation of closely 75
associated words can be predicted. In contrast, if height- NTD TD
ened activation implies not only faster spread but also far-
ther spread of activation in the semantic network, then the
prediction can be derived that far associationsinstead of
close associationsshould be a more effective discrimi-
nator between normal and activated associative networks. 7J (c) indirect
M l I I Iin

In conclusion, indirect associates to a word, instead of associations yP


CD in

close associates, might be more appropriate stimuli for


in

testing the activated association hypothesis of schizo-


frequenc;

phrenic thought disorder. Examples of such indirect asso- 44


ciations are "chalk (white)-black" and "lemon 34
(sour)-sweet." In general, indirect associations can be 2-i
defined as word pairs in which the connection between the
words is obvious only via a mediating associated word.
14
Applied to the lexical decision paradigm, this means that 0 - | 1

the target is an association to an association of the prime. NTD TD


According to this line of thought, semantic priming
effects should be measured as far away from the prime Frequency of (a) standard associations, statistically defined by
Kent and Rosanoff (1910) as the association given most fre-
node as possible. In other words, a more indirect relation quently by a large group of normal subjects; (b) semantic-concep-
between prime and targetiis better for the purposes of tual associations, defined by Jung (1906/1973) with respect to the
measuring the spread of activationat least from the relation of the content of the stimulus word and the response
word; and (c) indirect associations. Data from 20 normal control
point of view of avoiding ceiling effects. However, (C) subjects and 9 non-thought-disordered (NTD) and 11 thought-
semantic networks presumably are the result of the indi- disordered (TD) schizophrenia patients (after Spitzer et al., sub-
vidual's personal history and, hence, are in no way stan- mitted for publication a).

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Cognitive Neuroscience View Schizophrenia Bulletin, Vol. 23, No. 1, 1997

dardized. Therefore, the transitions from one node to tion to a word is only a crude measure of semantic prox-
another always occur with a certain probability and are imity. The sketch of a small part of a semantic network
never fully determined. By the same token, the transition depicted in figure 4 may be derived from table 1.
from one node to the next occurs with a probability that The relatedness of two indirectly related words can
equals the product of the probabilities of transition be estimated by multiplying two proximity scores (fol-
between nodes 1 and 2 and between nodes 2 and 3. lowing the rules of probability theory). In this manner, the
Because the stimuli for semantic priming tasks are relation between "fingers" and "foot" (via "hand") is
derived from semantic association norms, we cannot be 0.525 X 0.270 = 0.142. Even if we consider the second
sure that, in a given person, the two items presented corre- pathway from "fingers" to "foot" (via "toe") as an addi-
spond to two close nodes in the individual semantic net- tional source of associative strength, we can add only very
work. This uncertainty is one reason why the semantic little (0.157 X 0.254 = 0.040); note that we have to
priming task might never be a good diagnostic tool, that assume that the relation between "foot" and "toe" is sym-
is, successfully applicable at the individual level (but see metric. If we go just one step further and prespecify
below). highly indirectly related word pairs ("fingers-shoe"), the
An example can be found in the word-association likelihood that the presupposed associational chain from
norms as published by Palermo and Jenkins (1964), which
Figure 4. Semantic network sketch derived
is still one of the classic sources for such data (see table
from table 1
1). The most common association to "fingers" in 871 col-
lege 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 there-
fore 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 stu-
dents (23.2%). To go one step further, the standard associ-
ation 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 Theoretically, the numbers next to the arrows out of each node
obtain a rough estimate of the associations of a word that should add up to 1, so much is obviously missing. In the tables
is not among the 200 stimulus words (e.g., "toe") is to provided by Palermo and Jenkins (1964), a given word produced
on average about 86 different associations in subjects whose age
check which stimulus words elicited it as an association. ranged from childhood to early adulthood. Only the first to fourth
Finally, the percentage score given for a specified associa- most frequent of these are depicited.

Table 1. Examples of standard word associations and their frequency (in percent) in 871 college
students
Standard (most Second most Third most Fourth most Fifth most
Stimulus frequent) frequent frequent frequent frequent
word association association association association association
Fingers hand(s) toe(s) nail(s) thumb(s) five
52.5% 15.7% 5.4% 5.1% 4.8%
Hand foot (feet) finger(s) arm glove ring
27.0% 23.2% 17.0% 6.1% 5.6%
Foot shoe(s) toe(s) hand leg walk
30.0% 25.4% 16.3% 13.1% 3.8%
Shoes feet (foot) sock(s) stocking(s) lace(s) walk
42.5% 16.0% 6.5% 4.8% 2.6%
Note.Adapted from Palermo and Jenkins 1964.

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Schizophrenia Bulletin, Vol. 23, No. 1, 1997 M. Spitzer

the first word to the third next word is implemented in a (see figure 6). These results were interpreted as evidence
given individual's semantic network is very small (0.14 X for the spreading activation model of semantic and indirect
0.30 = 0.04). semantic priming. In normal subjects, this spreading of
The measurement of indirect semantic priming is deli- activation reaches more distant nodes only after several
cate. In fact, the measurement of highly indirect semantic hundred milliseconds. In contrast, thought-disordered
priming (from a word to its third next association) is schizophrenia patients displayed a significant indirect
doomed to failure because the likelihood of prespecified semantic priming effect in the short SOA condition, which
associative chains decreases sharply with the number of was interpreted as a sign of the fast and far-spreading acti-
nodes involved in such chains. Hence, the optimal way of vation in this group.
measuring indirect semantic priming likely consists of We further analyzed the data using ratios (percentage
linking the associate to the associate and making sure that RT gain caused by the related or indirectly related words,
only strong associations are used. Figure 5 illustrates the respectively). The difference in direct semantic priming
benefits of using indirect associations as opposed to direct between thought-disordered schizophrenia patients and
associations to measure differences in the spread of activa- normal subjectsparticularly at the long SOAcan be
tion in semantic networks during lexical access. In short, exclusively attributed to the general slowness of the
the indirect semantic priming paradigm avoids the possible patients. If this slowness is taken into account by calculat-
ceiling effects of the direct semantic priming paradigm. ing ratios, no difference in the priming effect is visible
Our study of indirect and direct semantic priming in (Spitzer et al. 1993a). However, when ratios were calcu-
50 normal control subjects and 50 schizophrenia patients lated for the indirect semantic priming effect, the overall
(21 non-thought-disordered and 29 thought-disordered), results were similar to the difference score results (see
using the lexical decision method, provided evidence that figure 7).
indirect semantic priming may be a better measure of In general, this study provided strong support for the
spreading activation than direct semantic priming (Spitzer spreading activation model of thought disorder and prim-
et al. 1993a). We know that semantic priming is a robust ing phenomena. It suggested that indirect semantic prim-
phenomenon independent of the duration of stimuli ing in lexical decision tasks with a short SOA is an ade-
(Spitzer et al. 1994c). Indirect priming, in contrast, is sen- quate measure of the fast, far-spreading activation in
sitive to the timing of stimuli. We used two stimulus-onset semantic networks of thought-disordered schizophrenia
asynchronies (SOAs) (200 and 700 ms) and found no sig- patients.
nificant indirect semantic priming effect in normal subjects
at the short SOA but a significant effect at the long SOA
Figure 6. Indirect semantic priming effect1
Figure 5. The spread of activation in a semantic
network

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;
The effect size of the indirect semantic priming effect is consider- ***p < 0.0001). SOA = stimulus-onset asynchronies; TD = thought
ably smaller than the effect size of the direct semantic priming disordered.
effect. Nonetheless, indirect semantic priming discriminates better Reprinted with permission from Spitzer et al. 1993a. Copyright
between focused and unfocused activation of the network. Elsevier Science Publishers, 1993.

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Cognitive Neurosciencc View Schizophrenia Bulletin, Vol. 23, No. 1, 1997

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 evi-
dence will be discussed: the study of spontaneous and
experimentally elicited utterances, the results of other psy-
chological 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 observa-
tions of the nature of intrusions (slips of the tongue) into
spontaneous speech. Such intrusions occur in normal sub-
jects and in schizophrenia patients, and they often involve
.011 items from previous utterances. According to the network-
activation model, such intrusions represent patterns of
reverberating network activation caused by previous utter-
1
Significance levels indicate results of unprotected two-tailed ances. If the characteristics of semantic network activation
Mests of priming effects against zero (*p < 0.05; **p < 0.001; are changed such that there is either more activation or less
***p < 0.0001). SOA = stimulus-onset asynchronies; TD = thought
disordered. inhibition or both, or merely a less focused activation,
Reprinted with permission from Spitzer et al. 1993a. Copyright thought disorder occurs.
Elsevier Science Publishers, 1993.

Nothing is more important in psychopathology than Figure 8. Semantic and indirect semantic prim-
ing effects
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 300 300
visual field paradigm (Spitzer et al., submitted for publica- E 250-;
tion d) can be analyzed for this purpose. The study was the 1200-1
first attempt to investigate hemispheric differences in I 150 J
direct and indirect semantic priming in control subjects E 100-
3 !
and schizophrenia patients. The SOA was 250 ms, and data o 50-
were obtained from 36 control subjects and 22 non-
NTD TD NTD TD
thought-disordered and 14 thought-disordered schizophre-
nia patients. When the data were collapsed across both
hemispheres, the results were strikingly similar to the pre-
vious 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 indi-
rect semantic priming between thought-disordered patients
and control subjects were clearly visible regardless of
whether a percentage score or a difference score was used.
NTD TD NTD TD
Taken together, these studies make it unlikely that
increased indirect semantic priming in thought-disordered
schizophrenia patients is a chance finding. Nonetheless,
Figures a and b show difference scores; c and d display ratios;
we are conducting a third study in another language C = normal control; NTD = non-thought disordered; TD = thought
(English) to further validate the results of the studies. disordered.

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Schizophrenia Bulletin, Vol. 23, No. 1, 1997 M. Spitzer

The spreading activation model of thought disorder Another task consisted in finding similarities or over-
presupposes an intact semantic network. It is the access to lapping features of different items or concepts, which were
the network, not the network itself, that is malfunctioning. of a different semantic distance. Schizophrenia patients
Evidence for this view was recently provided by Allen et could also perform this task better than normal controls,
al. (1993), who conducted a verbal fluency study with particularly when the items were semantically distant.
schizophrenia patients. When the task was given once, the Within the framework of the spreading activation model of
patients produced fewer words than normal subjects. lexical access and the hypothesis of faster and farther
However, when the task was given five times and word spread of activity in some schizophrenia patients (the
responses were pooled, the number of appropriate words thought-disordered-non-thought-disordered distinction
produced was comparable to the number given by normal was not usually made in studies of schizophrenia patients
subjects. during the 1960s and 1970s), these results can easily be
Several authors have suggested that pauses in sponta- interpreted. In (supposedly thought-disordered) schizo-
neous speech provide clues to the psychological processes phrenia patients, activation in semantic networks spreads
of speech production, including lexical access (Goldman- quickly to uncommon meanings, making activation over-
Eisler 1958; Butterworth 1973). Several studies estab- lap more likely, even when two distant nodes are involved
lished that two variables determine the length of within- (see figure 10).
sentence pauses: contextual probability (redundancy) and As early as 1910, Kraepelin published a monograph
frequency of occurrence of the following word. People on thought disorder during dream states. Dreams share
make more and longer pauses before words of low use and some features with disorders of formal thought, including
low redundancy (Goldman-Eisler 1958; Maclay and
Osgood 1959; Mercer 1976). If thought-disordered schizo-
phrenia patients suffer from a faster and farther spread of Figure 9. Duration of pauses (means and stan-
activation, the pauses before words in spontaneous speech dard error of the mean) before context nouns
that are not suggested by the context should be compara- and rare (noncontext) nouns
tively shorter. We tested this hypothesis in 36 normal sub-
jects and 32 schizophrenia patients (23 thought-disordered
and 9 non-thought-disordered) by measuring the pauses in 600
speech elicited by having the subjects describe a picture
(Spitzer et al. 1994a). In the groups of normal subjects and 500-
non-thought-disordered schizophrenia patients, the mean
duration of pauses before nouns within sentences was sig-
nificantly 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 con-
text-sensitivity of within-clause pauses in thought-disor-
dered schizophrenia patients when compared with non-
thought-disordered schizophrenia patients and normal con-
controls NTD patients TD patients
trol subjects. In particular, contextually unconstrained lexi-
cal items seem to "pop" into the minds of thought-disor-
dered schizophrenia patients due to the heightened or Results obtained by 36 control subjects and 8 non-thought-
unfocused activation of semantic associative networks. disordered (NTD) and 22 thought-disordered (TD) schizophrenia
patients. One TD patient and one NTD patient did not produce
The Russian psychologist Poljakov reported a series any rare nouns; therefore, their data are not included in the analy-
of experimental studies of schizophrenia patients sis. Differences in pause length before context nouns and rare
nouns were significant in the control subjects (p = 0.02) and in the
(Poljakov 1973). In one of the tasks, the subjects had to NTD schizophrenia patients (p = 0.0004), who were also gener-
solve problems by taking into account unusual meanings ally slow and produced long pauses. No such difference was
of words. Schizophrenia patients seemed to have faster observed in the TD patients (two-factor analysis of variance with
context dependency and group as independent variables with sig-
access to these meanings and were able to solve some of nificant interaction). (F= 6.0; df = 2,63; p = 0.0041; significance
the tasks better than normal subjects. levels of post hoc comparisons reported.)

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Cognitive Neuroscience View Schizophrenia Bulletin, Vol. 23, No. 1, 1997

Figure 10. Focused and unfocused activation of Self-Organizing Semantic Maps


a semantic network
To shed light on the neurocomputational and neuro-
biological mechanism possibly underlying thought disor-
der in schizophrenia patients, two crucial concepts will be
discussed in this and the next section: the concept of self-
organizing 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 character-
ized 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 rela-
tionships' " (p. 248). The map looked similar to figure 4.
Network symbolized by flat grid, activity is shown as peaks along In their second experiment, the authors presented
the vertical axis. Shown is the pattern of activity in a semantic net-
work in which two items become activated. In a focused process short sentences in vectorized form to a similar network.
(top), no overlap of activity occurs and no common features "pop" This time, the network organized this input according to
to mind; overlap and common features are found in the unfocused
activation conditions (bottom).
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
incoherent actions and amalgamated objects and persons.
are represented close together because words of opposite
Kraepelin analyzed more than 200 examples of disordered
meaning are likely to be used in similar contexts. The
utterances that occurred within dreams (mostly his own)
authors conclude:
and found them to be remarkably similar to thought (or
language) disorder in psychosis. In this work we have now shown that the principle of
We conducted two studies of the effects of different self-organizing maps can also be extended to higher
levels of processing, where the relationships between
sleep stages on semantic priming performance directly after items are more subtle and less apparent from their
awakenings (Spitzer et al. 199I, 1993b). In both studies, an intrinsic features, a property that is characteristic of
increased semantic priming effect was found in subjects symbolic expressions. Symbols, in general, do not
who had just spent a few minutes in rapid eye movement contain metrically relatable components. Con-
(REM) sleep. This result was interpreted as evidence for sequently, meaningful topographic maps of symbols
must no longer display intrinsic features, but instead
unfocused activation of semantic areas during REM sleep,
the logical similarities of their inputs. It turns out,
which is in line with some computational hypotheses about however, that organized mappings of symbolic data
the function of REM sleep (Crick and Mitchison 1983). may still ensue from the same basic adaptation laws,

37
Schizophrenia Bulletin, Vol. 23, No. 1, 1997 M. Spitzcr

provided that the symbolic input data are presented Evidence is also accumulating for the existence of
together with a sufficient amount of context, that then semantic maps in various cortical areas, including reports
defines the similarity relationships between them. of patients with brain damage who display a loss of only a
[p. 251]
small fraction of their semantic memory. These patients
Evidence for the formation of maps of various have no cognitive deficit except for the naming of living
aspects of the outside world in the human cortex can be things, of vegetables, or of items inside the house (for
derived from a number of sources. First, we know that the recent reviews and discussions, see Farah and Wallace
building blocks of self-organizing networkshigh, flexi- 1992; Caramazza et al. 1994; de Renzi and Lucchelli
ble connectivity and lateral inhibitionare realized in the 1994). These cases appear to be rare, but the increasing
cortex (Thomson and Deuchars 1994; Rauschecker 1995), number of patients with category-specific naming deficits
which can be regarded as a computational surface that suggests that a negative observation bias may have con-
represents any coherent input as a map (Kohonen 1982). tributed, and may still be contributing, to the rarity of the
Maps of motor and somatosensory information were phenomenon. In fact, as early as 1966, Goodglass et al.
described several decades ago by Penfield and Rasmussen found a high incidence of dissociations between cate-
(1950); more recently, multiple maps have been reported gories in a quantitative study of category-specific, word-
(Merzenich and Sameshima 1993). Multiple retinotopic comprehension deficits, which led them to conclude that
and tonotopic maps have been discovered in the primate in aphasic patients such dissociations may be the rule
cortex, and there is evidence that such maps exist in the rather than the exception. Farah and Wallace (1992) cor-
human cortex. In other words, a neurocomputational rectly conclude that such patterns of deficits suggest that
mechanism for the formation of maps has been proposed, the representations are organized at least in part by
and the existence of quite a number of such maps has semantics and that these representations must be localized
been demonstrated by neurobiology research. to some degree.
Finally, we recently conducted a study using func-
tional magnetic resonance imaging. The subjects were
Figure 11. Semantic map generated asked to covertly name either animals or furniture items
spontaneously by a Kohonen network displayed to them on a computer video projection device.
(Ritter and Kohonen 1989) In most subjects, we found areas showing increased corti-
cal activation caused by naming animals or furniture.
water meat dog horse
Often, animal and furniture areas were near each other,

and in many cases, several such areas were found in one
beer bread subjectmostly (but not exclusively) in the left frontal
cat and temporal lobes. This study provides direct evidence
that maplike semantic representations can be detected
little noninvasively in human subjects (Spitzer et al. 1995b;
fast Bob Spitzerand Kammer 1996; Spitzer et al. 1996a).
much Jim Recently, we conducted computer simulations of
change in self-organizing feature maps (Spitzer et al.
slowly often
1995a). Such change should happen, for example, if a part
eats^ Mary of a map is deafferented. Under such circumstances, the
well works %^. representations of input patterns are rearranged on the
"computational surface" such that there is a computation-
ally optimal distribution on the map. Such rearrangements
/
poorly phones are the computational equivalent of cortical neuroplastic-
buys visits
ity, 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.
runs 1992a, 1992/7, 1992c; Pascual-Leone and Torres 1993).
drinks hates
The rearrangement is highly dependent on the noise level
walks likes
of the input and the noise level within the system. Without
noise, rearrangement (neuroplasticity) occurs slowly, but
internal and external noise drives reorganization.
Words were organized according to semantic and grammatical
features. Note the similarity to the "cartoon" semantic network In sum, there is a biologically plausible computa-
depicted in figure 4. tional mechanism for the formation of maplike represen-

38
Cognitive Neuroscience View Schizophrenia Bulletin, Vol. 23, No. 1, 1997

tations of any coherent input to the cortex. Such maps capacitymay appear desirable under any circumstances,
have been discovered in the animal and human cortex, but it can also at times be counterproductive and cause
and the dynamically adapting behavior of these maps to other forms of psychopathology (Spitzer 1995). As dis-
new input has been documented. Moreover, the existence cussed above, network models suggest that noise is an
of semantic maps (a localized representation of semantic important factor driving neuroplasticity. In semantic net-
information in the brain) is suggested by converging evi- works, the relative absence of noise, for example, pro-
dence from neuropsychological, computational, psy- duced by a state of moderate anxiety, may cause a more
cholinguistic, and functional neuroimaging data. Finally, focused activation of ideas, concepts, and meanings.
neural network simulations provide evidence for the Accordingly, stress and anxiety can lead to the production
importance of noise in the rearrangement of such cortical of an increased number of standard associations (such as
representations (neuroplasticity). "black-white," "doctor-nurse") in normal subjects (Mintz
1969).
If dopamine modulates the signal-to-noise ratio in
Signal-tO'Noise, L-Dopa, Psilocybin, and cortical networks, if such networks are involved in the
Indirect Semantic Priming storage of semantic information in the form of maps, and
if these maps are accessed during semantic information
While the postsynaptic effects of dopamine in the human
processing more or less reliably (i.e., with more or less
cortex have not yet been fully determined (Glowinski et
noise involved), the ingestion of L-dopa, a precursor of
al. 1984; Thierry et al. 1988), Cohen and Servan-
dopamine and norepinephrine, should cause an increase in
Schreiber (1992, 1993) have evidence suggesting that
the focus of activation in semantic networks and, hence, a
dopamine and norepinephrine act as neuromodulators
decrease in the effects of spreading activation.
amplifying strong signals and dampening weak ones
To directly test this hypothesis, we conducted a study
(Morrison and Hof 1992), that is, they modulate one gen-
on indirect semantic priming in normal volunteers
eral parameter of cortical information processing, its sig-
(Kischka et al. 1996). In a double-blind placebo-con-
nal-to-noise ratio. According to this model, a decreased
dopaminergic activation of cortical areas leads to a trolled design, a speeded lexical decision task with
decrease of the functional focus of cortical neuronal net- directly and indirectly related word pairs as well as with
work activity and thereby reduces their ability to produce nonrelated word pairs was used to assess the effect of 100
appropriate output (Servan-Schreiber et al. 1990). mg of L-dopa (plus 25 mg benserazide, a peripheral decar-
While the standard dopamine hypothesis attributes boxylase inhibitor) on the time course of spreading activa-
schizophrenic psychopathology to elevated dopamine lev- tion in normal subjects. If dopamine causes a sharper
els, several authors have proposed that negative symp- focus of lexical activation, we reasoned, the small indirect
toms in schizophrenia are due to a decrease in dopaminer- priming effect that normal subjects display at longer
gic activity (Crow 1980; Mackay 1980; Carlsson 1988; SOAs should decrease. The results of the study were in
Weinberger et al. 1988; Heritch 1990; Davis et al. 1991; line with this hypothesis. When a long SOA was used to
Grace 1991). In particular, Davis et al. (1991) proposed elicit indirect priming in normals, L-dopa produced a sig-
that negative symptoms are caused by low prefrontal nificant decrease of the indirect semantic priming effect
dopamine activity, which leads to excessive dopamine from 29 ms (4.8%) to 7 ms (1%). A small, nonsignificant
activity in mesolimbic dopaminergic neurons, which may reduction of semantic priming indicated, again, that this
eventually lead to positive symptoms. Similarly, Grace measure may be less sensitive to changes in the spreading
(1991) suggested that schizophrenia patients suffer from a of activation in semantic networks (figure 12). This study
diminished "tonic" striatal dopamine release, consecutive provided direct support for the hypothesis that dopamine
up-regulation of striatal postsynaptic dopamine receptors increases the signal-to-noise ratio in semantic networks,
and, hence, increased responses to "phasic" striatal causing a decreased spreading of activation during the
dopaminergic activation due to environmental stress. This process of lexical access. Indirectly, these data provide
would result in both low dopaminergic negative symptoms some support for the hypothesis that formal thought disor-
and stress-related hyperdopaminergic positive symptoms. der is the result of a decreased dopaminergic tone.
Our data on the effect of treatment on priming effects L-Dopa is a precursor of dopamine and norepi-
suggest that a neuroleptic-induced reduction of symptoms nephrine, and both substances have been implicated in
also leads to a normalization of semantic priming (Spitzer modulating the signal-to-noise ratio in cortical networks
et al. 1994c) and indirect semantic priming, in particular (Chiodo and Berger 1986; Servan-Schreiber et al. 1990;
(Spitzer et al., submitted for publication c). Grace 1991) but it is hard to discern the effects of the two
A high signal-to-noise ratiowithout any modulatory catecholamines. However, neuroanatomical considera-

39
Schizophrenia Bulletin, Vol. 23, No. 1, 1997 M. Spitzer

tions indicate dopamine as the more likely candidate for (Spitzer et al. 1996/?), we hypothesized that it might defo-
the modulation of semantic processes. cus semantic networks (i.e., decrease the signal-to-noise
In our study on the effects of the hallucinogenic agent ratio), which should lead to an increased indirect semantic
psilocybin, which acts on the serotonin system and has priming effect. As shown in figure 12b, psilocybin has the
subjective effects of "broadening" conscious experiences opposite effects of L-dopa; it produced a nonsignificant
increase in semantic priming and a significant increase in
Figure 12. Semantic and indirect semantic indirect semantic priming. Although the design of this
priming effects in a speeded lexical decision study (single group, repeated measures) was different from
task in which target words were displayed 700 the design of the L-dopa study, the opposite effects of these
ms after the prime words neuromodulatory agents deserves further exploration.

More Precise Mental Chronometry:


r
Placebo
9-i
L-dopa ERPs
8-:
1... .1.... 1....

To further clarify the time course of cerebral language


~J
effect (%)

p<.05 processing, we applied the method of ERPs to the investi-


gation of the time course of lexical activation in normal
1
Ol

subjects and schizophrenia patients (Spitzer et al., submit-


ted for publication d). The rationale for using the ERP
A '
method in conjunction with a semantic and indirect seman-
tic priming paradigm follows.
2'-

_ , [I
L
1. RT studies provide only a first, crude measure of
differences in the time course of mental information proc-
essing. In the example shown in figure 13, the lexical
0-: decision task involves perceptual, language-related, and
semantic priming indirect semantic priming
motor output components. Since it is known that schizo-
phrenia 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 deci-
sion RTs (measurements that supposedly concern seman-
tic processes). Hence, any RT differences between control
subjects and schizophrenia patients in measures such as
semantic priming must be compromised by this error vari-
ance.
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 lan-
guage-related components. Sentences with semantically
anomalous endings produce a negative deflection of the
scalp ERP at about 400 ms after stimulus onset. More-
over, this N400 component also occurs when only seman-
semantic priming indirect semantic priming tically 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 pro-
Data obtained from 31 normal subjects under placebo (n = 17) or duces a clear ERP signal in normals and suggests the use
100 mg L-dopa (n = 14). a. L-Dopa reduced direct semantic prim-
ing effect only to a small, nonsignificant degree, but the indirect of ERP measurements for the further clarification of the
semantic priming effect was significantly lower under L-dopa than time course of lexical access in schizophrenia patients.
under placebo (p < 0.05, one-tailed f-test); b. In contrast to
L-dopa, the hallucinogenic agent psilocybin increased direct
We recently completed our first study (Spitzer et al.,
semantic priming (numerically) and indirect semantic priming (sig- in press) in which ERPs were recorded from 20 scalp
nificantly), n.s. = not significant. electrodes while subjects (20 schizophrenia patients and

40.
Cognitive Neuroscience View Schizophrenia Bulletin, Vol. 23, No. 1, 1997

Figure 13. Rationale for use of event-related potentials (ERPs) in research concerning cognitive
functions

behavioral paradigm (RTs and error rates)

stimulus response
(e.g., the second word in a semantic priming task) (e.g., a keypress)

perceptual? semantic? motor?

doctornurse
skycheese priming
effect

+> + +
200 400 time 600 800 1000 ms

event related potentials (ERP)

perceptual motor

/ ^ ~ v_
__
skycheese

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 con-
trast, 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 Most notably, peak and latency data for the indirect prim-
indirect semantic priming task as described above (with ing condition suggest that indirectly related word pairs are
an SOA of 200 ms). In line with previous research on processed differently by the two groups. Normal subjects
incongruous semantics of sentences and words, an N400 showed an N400 that was almost identical to the N400
component was obtained in the nonrelated condition for produced by nonrelated words; schizophrenia patients
the majority of the subjects in both groups (17 controls showed no N400 in this condition. In other words, schizo-
and 12 schizophrenia patients). At most, only a small phrenia patients treat indirectly related words like related
N400 component was detected in the related condition. words and normal subjects treat these words like unre-

41
Schizophrenia Bulletin, Vol. 23, No. 1, 1997 M. Spitzer

lated words (Spitzer et al., in press, submitted for publica- Litman et al. 1991; Shimamura et al. 1991) and brain
tion d). Moreover, latency data for the N400 peak clearly imaging methods (Weinberger et al. 1988), and because
reproduced previous RT data results but displayed consid- delayed response tasks require the subject to use newly
erably less variability. Therefore, the N400 component stored information for each trial, such tasks seem suitable
under conditions of different semantic distances between to tap working memory deficits in schizophrenia patients
prime and target word may be a suitable measure of dys- (Goldman-Rakic 1991). Moreover, working memory
functional associative processes in schizophrenia patients. deficits have been directly demonstrated in schizophrenia
We are currently carrying out a replication study using a patients using various delayed response tasks (Park and
64-electrode array (Tucker 1993) to obtain additional spa- Holzman 1992; Spitzer 1993; Park, in press).
tial information on lexical information processing in In short, working memory has a limited capacity,
schizophrenia patients. lasts only a few seconds, and is relevant for goal-directed
behavior. Its anatomical basis in the frontal cortex, receiv-
ing and sending projections to other cortical areas, is
Context, Working Memory, and the established, it has been related to dopamine function in
Frontal Lobes animal and human studies, and there is evidence of its
dysfunction in schizophrenia patients.
The frontal lobes are considered the site of working mem- Individual differences in working memory have
ory, temporary storage of relevant contextual information already been used to account for differences in sentence
from the recent past, about the general plan, or regarding comprehension among normal individuals (Just and
aspects of an object or event that are not part of what is Carpenter 1992). As these authors point out, "Working
actually perceived. memory plays a critical role in storing the intermediate
The most salient feature of working memory is its and final products of a reader's or listener's computations
ever-changing content. In contrast to the large capacity as she or he constructs and integrates ideas from the
and longevity of semantic memory, working memory, by stream of successive words in a text or spoken discourse"
definition, has a limited capacity and items are stored only (p. 122). According to their capacity theory of compre-
for seconds (Baddeley 1992). For example, when we hension, the capacity of working memory constrains com-
make a phone call, we look up the number in a phone prehension, and hence, a dramatically reduced working
book, keep it in working memory to dial it, and forget it memory capacity (presumably present in schizophrenia
immediately thereafter. Working memory has been com- patients) should lead to marked defects in language pro-
pared to a "scratch pad" and to the random access mem- duction and understanding.
ory of a computer, which holds the most immediately The results of the above-mentioned pauses study may
needed information. bear on the issue of dysfunctional working memory in
Goldman-Rakic and others have argued on the schizophrenia. Thought-disordered schizophrenia patients
grounds of behavioral data from human subjects and ani- were obviously unable to maintain the relevant context and
mal research and from the results of single cell recordings therefore did not use it appropriately for sentence produc-
from monkeys that holding information over a short tion. This led to noncontextually constrained words intrud-
period of time involves the functioning of the frontal cor- ing into the utterances quickly, as could be detected by the
tex (Funahashi et al. 1989; Goldman-Rakic 1990; pause length measure. In the following section, a further
Goldman-Rakic et al. 1990; Goldman-Rakic and Friedman experiment is reported that may exemplify how dysfunc-
1991). In particular, the cooling of the dorsolateral pre- tional working and associative memory can be linked to
frontal cortex in monkeys induced reversible deficits in schizophrenic psychopathology and how experimental
the performance of visual, tactual, and cross-modal delay methods can be used for the fine-grained analysis of such
tasks, implying that this anatomical site is crucial for pathology.
supramodal short-term memory (Fuster 1991, 1993, The results from the study of Park and Holzman
1995). Moreover, this type of short-term memory has (1992) are not in line with the view presented here. They
been linked to dopamine activity in this brain area in report abnormal results in a group of schizophrenia
human beings (Luciana et al. 1992). Because dopamine patients only in a spatial working memory task, while the
functioning is clearly involved in the pathogenesis of patients produced normal results in a digit-span test, sup-
schizophrenia (see above), because frontal cortex dys- posedly tapping into verbal working memory. However,
function in schizophrenia has already been demonstrated Just and Carpenter (1992) report a lack of correlation of
by neuropsychological tests such as the Wisconsin Card the digit-span test with their reading comprehension task,
Sorting Task (Heaton 1981) (see Goldberg et al. 1991; which "indicates that the standard digit span task does not

42
Cognitive Neuroscience View Schizophrenia Bulletin, Vol. 23, No. 1, 1997

draw on the same resources as those used in most lan- the activation of literal and metaphoric meanings of
guage comprehension tasks" (p. 125). In particular, the metaphoric statements, the method of lexical decision was
authors distinguish two aspects of verbal working mem- used in schizophrenia patients and normal control subjects
ory, the "articulatory loop," as proposed by Baddeley (Spitzer 1993; for details, see Spitzer et al. 1994b).
(1986), and a "central executive," which was only Forty-three normal control subjects and 35 schizo-
vaguely defined and empirically addressed by Baddeley. phrenia patients performed a visual lexical decision task
While the former is clearly involved in digit-span per- shortly after listening to a proverb. The stimulus material
formance and has been located in the left superior tempo- consisted of 60 metaphorical statements as primes and of
ral lobe, according to a positron emission tomography the following targets (see table 2): 10 words concretely
(PET) study (Frackowiak 1994), the latter has always related to the last or to the most prominent word of the
been suggested to reside in the frontal lobes. Moreover, proverb, 10 metaphorically (abstractly) related words, 10
Just and Carpenter cite neuropsychological data support- nonrelated words (5 concrete words and 5 abstract
ing a dissociation between the digit-span task and the cog- words), and 30 nonwords. For each metaphoric statement,
nitive processes of sentence comprehension. Finally, a three words and three nonwords were selected, and differ-
recent study by Maher et al. (1995) demonstrated that ent versions of the test were set up such that each prime
schizophrenic deficits in a verbal memory task that taps sentence was followed by each of the targets. The order of
into context effects (the Miller-Selfridge paradigm) corre- the conditions in each experiment was initially random-
lated most highly with structural deficits in the frontal ized and then remained constant. -The different versions
lobes as assessed with MRI. In the next section, the were used at random for patients and subjects to exclude
results of an experimental study of a specific type of for- the effects of particular stimulus words. The target word
mal thought disorder (concretism) are discussed in the was displayed 1,200 ms after the auditory prime.
framework of associative and working memory just
described. The abstract and concrete priming effects in both
groups are displayed in figure 14, which shows a group-
dependent difference in the priming effect of concrete and
Concretism abstract meanings: In normal control subjects both the
concrete and the abstract meanings produce a significant
The failure of many schizophrenia patients to take the priming effect; in schizophrenia patients only a concrete
"abstract attitude" (Goldstein 1944), that is, the prefer- priming effectlarger than in the normal control sub-
ence for the literal (denotative) meaning as opposed to the jectscould be detected. These effects were not caused
metaphorical (connotative) meaning has been reported by by the concreteness or abstractness of the words per se,
a number of authors (Meadow et al. 1953; Chapman since RTs to the abstract and concrete words in the nonre-
1960; Holm-Hadulla and Haug 1984; Cutting and Murphy lated condition did not reveal significant RT differences.
1990). The phenomenon is usually described as "con- The main findings of this experiment can be inter-
cretism" or "concrete thinking" and can be demonstrated preted as follows.
with experimental approaches, such as interpreting
proverbs or selecting word pairs that fit together. Contrary I. A comparatively large concrete priming effect in
to such an "underinclusive" bias, the tendency to overgen- schizophrenia patients is in line with the above-mentioned
eralize a given concept ("overinclusive" thinking) has results of lexical decision studies on semantic and indirect
been noted as a characteristic of schizophrenia by several semantic priming. Hence, it can be considered further evi-
authors (Cameron 1939; Payne 1962, 1966). Over- dence in favor of the semantic network spreading activa-
inclusive thinking was characterized by "an inability to tion hypothesis of schizophrenic thought disorder. The
preserve conceptual boundaries, so that ideas which are concrete meaning of a metaphoric statement is not only
only distantly related, or even irrelevant to a concept
become incorporated into it. . . . Because of this, thinking Table 2. Conditions in the "concretism"
becomes more abstract and less precise" (Payne 1966, pp. experiment
78-79). In DSM-IV, the following description is given:
Conditions Examples of target words
"their [the patients'] speech may be generally understand-
able but digressive, vague, or overly abstract or concrete" Concretely related snow
Abstractly related risk
(p. 278). The seemingly contradictory findings of a bias in
Nonrelated (concrete/abstract) chair/grief
the semantic preferences of schizophrenia patients toward
Nonword toble
the more abstract and toward the more concrete meaning
Note.The examples refer to target words that followed the audi-
of a word or an utterance need explanation. To probe for tory prime "He is skating on thin ice."

43
Schizophrenia Bulletin, Vol. 23, No. 1, 1997 M. Spitzer

Figure 14. Concrete and abstract priming tions, a significant concrete priming effect, but no signifi-
effects (percentage scores) in normal control cant abstract priming effect, was obtained (only a trend
subjects and schizophrenia patients was detectable). This result corresponds with established
differences in decoding time of literal and metaphoric
speech (Chaika 1990) and suggests that the metaphoric
controls meaning needs some time to build up (only then being
patients effective as a prime) in normal control subjects. During
this time, the meanings of the words that make up the
7- entire sentence must be kept in minda task that involves
working memory. To quote again from the seminal paper
by Just and Carpenter (1992):

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 lexi-
e
<D 3
cal level during comprehension are intuitively obvi-
in ous. 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]
1-
Therefore, it appears likely that while the prominent
concrete priming effect in schizophrenia patients indicates
concrete abstract an overactive associative memory, the lack of a significant
abstract priming effect signifies a deficit in language-
Significant semantic priming effects for concretely related words
related working memory.
were found in both groups. The abstractly related word condition
produced a significant priming effect only in control subjects. Two- Generally speaking, the lack of integrative function,
factor analysis of variance with group (controls vs. patients) and goal directedness, adequate attention, drive, and general
condition (abstract vs. concrete) as within-subject factors showed
significant interaction (Spitzer 1993a). 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
more readily accessible than the abstract meaning (be- immediate perceptual clues rather than by internally gen-
cause the abstract meaning has not been produced by the erated and kept goals. Beringer (1924, 1926) already
patient), but also activated to a higher degree than in nor- described the "diminished intentional span" of schizo-
mal control subjects. This difference might explain the phrenia patients as most characteristic of the patient's
clinical observation that schizophrenic concretism is deficits, which may be interpreted as merely another way
somewhat different from concretism displayed by organic of referring to a reduced capacity or accessibility of work-
mental syndrome patients in that schizophrenia patients ing memory in these patients.
may focus on a concrete aspect of a remote feature of a
Other features of schizophrenic thought may also be
concept. best explained by a combined dysfunction of associative
2. The finding of a significant abstract priming effect semantic and working memory. As we have already seen,
only in normal control subjects corresponds directly to the the particular kind of schizophrenic concretism can easily
clinical observation of concretism in schizophrenia be explained as the combined effect of a disinhibited
patients. The study has clearly demonstrated that little or (unfocused) associative memory and a reduced capacity
no abstract meaning is activated in schizophrenia patients of working memory. Furthermore, the clinically highly
more than a second after a metaphoric statement has been relevant aspect of schizophrenic thought and behavior,
uttered; instead, one or a few concrete meanings are highly the patients' ubiquitous lack of sensitivity to context
active. (Chapman et al. 1964; de Silva and Hemsley 1977), can
Data from a parallel experiment (Spitzer et al. 1994fc) easily be accounted for in terms of working and associa-
shed further light on the results. Forty normal control sub- tive memory. The patients' failure to make appropriate use
jects performed the same task with a shorter SOA of 400 of contextual evidence in the production and understand-
ms (i.e., there was no 800-ms pause between the auditory ing of language as well as in goal-directed behavior may
prime sentence and the fixation point). Under these condi- be caused by the inability to keep relevant information in

44
Cognitive Neuroscience View Schizophrenia Bulletin, Vol. 23, No. 1, 1997

mind while pursuing a certain project. This relevant infor- provide localized information on cognitive processes with
mation must be represented in working memory, since it a resolution of a few millimeters. Studies of the effects of
has to be permanently used to guide behavior in the neuromodulators on normal subjects, employing the
absence of immediate perceptual cues or even despite per- behavioral paradigms (and in future studies, in conjunc-
ceptual cues that suggest some alternative behavior. tion with ERPs and fMRI), can be used to bridge the gap
The findings of a nonfocused associative memory and between cognitive neurobiological models of psy-
a reduced capacity of working memory in schizophrenia chopathology. Finally, neuronal network models provide
patients can be linked to cortical deficits, which may insights into computational functions and are needed to
either be structural or functional. A structural deficit in the link the mental and the biological realms. Such computa-
left temporal lobe, an area known to be involved in lan- tional models of mental and biological processes provide
guage processing, has recently been implicated in schizo- a framework for the generation of new hypotheses, which
phrenic pathology (Shenton et al. 1992; McCarley et al. can be readily tested in such models.
1993). Possibly such a defect would cause a decreased In this article, I have applied this logic of cognitive
accuracy of lexical processing and, hence, would be in neuroscience research to the study of language-related psy-
line.with the findings of increased semantic and indirect chopathology. In sum, the results of the experimental stud-
semantic priming, as presented above. A dysfunctional ies on language-related phenomena in schizophrenia
frontal lobe, implicated in schizophrenic symptomatology patients as well as the clinical phenomena that first moti-
(Andreasen et al. 1992; Andreasen 1994), would also vated these experiments can be parsimoniously explained
explain the findings reported above. In particular, one in terms of dysfunctional information processing in, or
might think of the frontal cortex providing contextual between, working and semantic associative memory. The
information (e.g., on the other words in a sentence) that neurobiological equivalent of the working memory deficit
constrains the meaning of the entire phrase and therefore is a dysfunctional, possibly left lateralized, frontal lobe,
the activation of the respective nodes in a semantic net- caused by either a structural deficit or a hypodopaminergic
work, possibly residing in the temporal lobe. If these con- state (or both). The decreased signal-to-noise ratio in
straints are weakenedeither by lower dopaminergic semantic associative networks has its neurobiological
input to the frontal lobe or by fewer connections between equivalent either in the reduced frontal lobe effect just men-
frontal and temporal lobesincreased autonomy of lexi- tioned (possibly caused by the mechanisms mentioned or
cal connections in semantic memory as well as decreased by a structural or functional disconnection) or in an
purpose directedness of the utterances will occur. 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
Conclusions psychopathology.
Within the framework of cognitive neuroscience, the con-
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Spitzer, M.; Thimm, M.; Hermle, L.; Holzmann, P.; Acknowledgments
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Kischka, U.; and Schneider, F. Increased activation of This work was supported by a single investigator's grant
indirect semantic associations under psilocybin. from the Deutsche Forschungsgemeinschaft (DFG Sp
Biological Psychiatry, 39:1055-1057, 1996ft. 364/1-2) and an established investigator's award from the
Spitzer, M.; Walder, S.; and Clarenbach, P. Semantische National Alliance for Research in Schizophrenia and
Bahnung im REM-Schlaf. In: Meier-Ewert, K., and Depression (NARSAD). The author is grateful to two
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Gustav Fischer Verlag, 1993ft. pp. 168-178.
Spitzer, M.; Weisbrod, M.; and Winkler, S. "Lemon
The Author
Sweet: Electrophysiological Correlates of Indirect
Semantic Priming in Normal Volunteers and Schizo- Manfred Spitzer, M.D., Ph.D., is Senior Lecturer in
phrenic Patients." Submitted for publication d. Psychiatry, Section of Experimental Psychopathology,
Spitzer, M.; Weisker, I.; Maier, S.; Hermle, L.; and Maher, Psychiatric Clinic of the University of Heidelberg,
B.A. Semantic and phonological priming in schizophre- Heidelberg, Germany.

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