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Visual Perceptual and Working Memory Impairments in Schizophrenia
Cenk Tek, MD;
James Gold, PhD;
Teresa Blaxton, PhD;
Christopher Wilk, MSc;
Robert P. McMahon, PhD;
Robert W. Buchanan, MD
Arch Gen Psychiatry. 2002;59:146-153.
ABSTRACT
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Background Impairments in working memory have been proposed to underlie a broad
range of cognitive deficits seen in schizophrenia. Visual working memory impairments
are frequently reported in schizophrenia. Investigations of visual working
memory generally assume intact visual information processing, despite evidence
of visual perceptual impairments in schizophrenia. In this study, we evaluated
the integrity of the perceptual system for object and spatial visual information
and the relevant working memory system, after adjusting for individual perceptual
performance differences.
Methods Thirty patients with schizophrenia and 20 healthy control subjects underwent
testing using a task of perceptual discrimination of spatial and object visual
stimuli. For testing visual working memory, a delay was introduced to the
perceptual discrimination task. A thresholding procedure was used so that
each subject adequately perceived the information during the working memory
test.
Results Subjects with schizophrenia exhibited impaired performance relative
to controls for object and spatial visual perceptual discrimination. The extent
of impairment was greater for the object than for the spatial test. After
controlling for perceptual impairments, the subjects with schizophrenia exhibited
impaired performance relative to controls for the spatial working memory test
but not the object working memory test.
Conclusions Findings implicate dysfunction of posterior brain areas that mediate
visual perceptual processing and the prefrontal areas involved in the active
maintenance of information during delay intervals. However, the systems that
govern object and spatial visual perception and working memory appear to be
affected differentially by schizophrenia.
INTRODUCTION
WORKING memory is a multicomponent cognitive system that serves to hold
briefly a limited amount of information "online" and to manipulate that information
so that it is available for further cognitive processing or to guide response
selection.1 Although working memory can be
considered a discrete cognitive function, this elementary capacity is generally
thought to be necessary for a wide range of complex cognitive functions such
as language comprehension, learning, reasoning, and planning. Patients with
schizophrenia typically demonstrate marked deficits on such complex tasks,
as well as on more elementary working memory tasks.2-11
Thus, it has been proposed that an impairment of working memory may be responsible
for much of the observed cognitive disturbance of the illness.12
In addition, working memory deficits have also been related to symptomatic
aspects of the illness, including thought disorder and negative symptoms.7, 12 Thus, delineation of the nature of
working memory dysfunction in schizophrenia may shed important light on the
neural substrates of the illness.
Many monkey and human working memory studies have used versions of delayed
response and delayed match to sample tasks.13
In these tasks, the subject is first presented with some type of informative
cue or stimulus, followed by a delay during which the cue is removed. The
subject then must make a response using a mental representation of the original
cue to guide response selection. Correct response selection is dependent on
at least 2 potentially independent cognitive processes, ie, the cue must be
encoded accurately, and this information must be precisely maintained during
the delay interval. Results of single-cell recording studies in nonhuman primates
and human functional imaging studies have demonstrated that a widely distributed
cortical network mediates the performance of these types of delay tasks.13-16 In
human imaging studies, it has been possible to separate transient brain activity
related to perceptual encoding/analyses (primarily localized in posterior
regions) from sustained activity that is most directly related to information
maintenance during delay intervals (localized in the prefrontal cortex).15-16
The organization of visual information processing system in humans and
other primates is domain specific. Visual processing of spatial (ie, location
of stimuli or "where" information) and object (ie, color and shape of stimuli
or "what" information) information involves 2 functionally and anatomically
segregated systems in the brain.17 As evidenced
by lesion studies in monkeys and functional imaging studies in humans, after
the perceptual sensory information reaches to primary visual area in occipital
cortex, the object information is relayed to occipitotemporal cortex for further
processing (ventral stream) as opposed to spatial information, which is relayed
to occipitoparietal cortex (dorsal stream).17-20
Goldman-Rakic13 and Wilson21
et al have proposed that visual working memory is organized in domain-specific
fashion, similar to the visual information-processing system in humans and
other primates. This domain specificity is consistent with the anatomic connectivity
of subregions of the prefrontal cortex. Dorsal prefrontal areas are reciprocally
connected with inferior/posterior parietal regions thought to subserve spatial
processing, and ventral prefrontal areas are reciprocally connected to inferior
temporal visual areas that are thought to mediate processing of color, pattern,
and facial information (ie, object processing). Thus, working memory performance
requires the integrated function of posterior sites involved in the perceptual
processing of target stimuli, with prefrontal regions that play a specific
role in the maintenance of representations in the absence of perceptual stimuli.
Several functional imaging studies, but not all, have suggested a similar
domain-specific (spatial vs object) organization of visual working memory
function in the human brain (for detailed reviews13, 22-23
but also24). Although the claim of domain specificity
remains controversial in the literature, the study of spatial vs object working
memory potentially provides a means of assessing the functional integrity
of broadly distributed, but partially segregated, cortical networks that involve
regions implicated in schizophrenia.
Strong evidence exists that patients with schizophrenia demonstrate
impairments on a variety of visual working memory tasks. Impairments have
been documented using spatial paradigms (subjects are asked to remember the
location of 1 or more irregular shapes, dots, or letters, etc) in patients
with chronic illness, medication-naïve first-episode patients, nonmedicated
patients, first-degree relatives who are not ill, and patients with schizophrenia
spectrum personality disorder.2, 7-9,25-31
Thus, this appears to be a reliable deficit. Fewer studies have examined working
memory for nonspatial visual stimuli (object stimuli, eg, subjects are asked
to remember the shape or color of 1 or more objects); available studies suggest
impaired performance in this domain as well.8
The cognitive processes that are responsible for the observed impairments,
however, have not been clearly established. In studies using auditory tones
and weight stimuli, Javitt et al32-33
reported that patients with schizophrenia demonstrate marked impairments in
the ability to discriminate between target and probe stimuli separated by
minimal delay periods. Further, they found no evidence of additional retention-related
impairments when patients and controls were matched for ability to encode
and/or discriminate target stimuli using minimal delays. Based on these data,
Javitt et al33 have argued that the working
memory deficit in schizophrenia may often be attributable to basic perceptual
encoding deficits, implicating dysfunction of posterior sensory processing
areas. Contrary to this argument, Wexler et al11
and Stevens et al34 have demonstrated auditory
tone working memory impairments in schizophrenia, even after they eliminated
subjects who demonstrated perceptual tone discrimination impairments. The
extensive interest in working memory disturbance in schizophrenia has been
driven by the notion that these elementary delayed tasks provide a means of
studying the functional integrity of the prefrontal cortex. Thus, determining
the origins of the schizophrenia behavioral impairment in working memory tasks
is important for understanding cognitive impairments in schizophrenia and
delineating the anatomy implicated.
Both experiments presented herein were designed to evaluate the integrity
of perceptual processing of object and spatial information in patients with
schizophrenia and the retention of such information during a brief delay.
To isolate specific retention impairments, delayed performance was tested
using a thresholding procedure adapted from psychophysics that was designed
to ensure that the information is perceived adequately during the working
memory test. We initially identified the minimum duration that each subject
needed to view the targets to recognize them subsequently above a certain
criterion performance. We then tested the working memory using every subject's
own specific threshold for object or spatial condition. This design provides
for a clear examination of the precision of encoding processes and allows
for a separate examination of delayed performance, controlling for the impact
of encoding differences across groups.
SUBJECTS AND METHODS
SUBJECTS
The patient study group, recruited from the Outpatient Research Program
of the Maryland Psychiatric Research Center, Baltimore, Md, consisted of 30
clinically stable subjects who met DSM-IV35 criteria for schizophrenia. This patient population
has been shown to be similar to the community mental health clinic population
in the area.36 A best-estimate diagnostic approach
was used in which information from the Structured Clincial Interview for DSM-IV Axis I Disorders37
is supplemented by information from family informants, previous psychiatrists,
and medical records. Patients with a DSM-IV diagnosis
of current alcohol and other substance use verified with results of blood
screens, mental retardation, or a medical-neurologic condition for which the
pathologic features or their treatment would likely confound the neuropsychological
test results were excluded from the study. On average, patients were aged
42.9 (± 7.2) years, with illness duration of 22.0 (± 8.1) years
(mean age of onset, 21.0 ± 5.0), Brief Psychiatric Rating Scale38 total score of 37.0 ± 11.7, and Schedule for
the Assessment of Negative Symptoms39 score
of 24.7 ± 13.8. All patients underwent testing while receiving antipsychotics,
and 24 patients (80%) were receiving atypical antipsychotics.
A group of 20 healthy controls participated in the study. Controls underwent
screening by means of a standardized procedure with detailed medical history,
blood screens for drug abuse, complete psychiatric evaluation including Structured
Clincial Interview for DSM-IV Axis I Disorders,37 and physical and neurologic examinations. Controls
were excluded if they had (1) past or present DSM-IV
Axis I or schizophrenia spectrum Axis II disorder; (2) a family history of
psychotic illness in their first- or second-degree relatives ascertained by
means of a standardized demographics checklist; or (3) any other medical illness
known to affect brain function.
Patient and control groups were comparable for age (42.9 ± 7.2
and 40.0 ± 11.4 years, respectively; t48 = 1.14 [P = .26]), and education (12.8 ±
1.8 and 13.8 ± 1.7 years, respectively; t48 = 1.98 [P = .06]). There were more male
subjects in the control than the patient group (25/30 [83%] vs 10/20 [50%];  2 = 6.35 [P = .01]).
All subjects were provided a complete description of the proposed study
and gave written informed consent before study participation. Patients were
required to demonstrate an understanding of study demands, risks, and their
rights to withdraw in response to probe questions before signing consent documents.
The Institutional Review Board of the University of Maryland School of Medicine,
Baltimore, approved the study protocol and consent procedures. Controls were
compensated for study participation.
PROCEDURES
The perceptual discrimination and working memory abilities of all subjects
were assessed with variants of a basic paradigm validated by Smith et al40 as measures of object and spatial working memory
in a positron emission tomography study with normal controls. It has also
been used for previous clinical behavioral studies by Postle et al.41 The basic paradigm is described first, followed by
the specific variants used to assess perceptual discrimination and working
memory. In this paradigm, subjects were first asked to focus on a fixation
cross in the middle of a blank computer screen. This fixation cross remained
on the screen throughout the experiment. Then, a target display composed of
the 2 abstract figures was presented. Stimuli were gray irregular polygons
randomly chosen from 60 shapes adapted from Vanderplas and Garvin.42 After a delay interval, a single-probe stimulus was
presented. Subjects were asked to judge whether the probe matched the target
in shape (object) or location (spatial), depending on task instructions. In
object trials, each experiment featured an initial presentation of 2 targets
irrelevant to each other, and then a probe shape that was similar to (25%
of the trials), dissimilar to (25% of the trials), or the same as (50% of
the trials) one of the previously presented targets. In the spatial trials,
stimuli were presented in randomly determined positions placed on the circumference
of an imaginary circle around the fixation cross with a radius of 3.2°
of visual angle. In 50% of the trials, the probe was in the same location
as one of the targets, in 25% it was near (15°-25° distant) one of
the targets, and in 25% it was far (40°-50° distant) from the nearest
target. In the spatial trials, probes were never the same shape as any of
the targets, half being similar and half being dissimilar. In object trials,
probes were never in the same location as any of the targets, half being near
and half being far. Subjects indicated their response using 2 keys, one clearly
marked yes (match) and another clearly marked no (nonmatch). Accuracy was
measured and no limits were set for response time.
Perceptual Discrimination Task Conditions
The goal of this condition was to assess perceptual discrimination abilities,
minimizing the role of working memory (Figure
1). To do this, we assessed subjects' perceptual performance by
using 8 different target exposure durations (TED) ranging from 17 to 2505
milliseconds. The study blocks were presented in a pseudorandom array so that
a short TED block (17, 167, 334, and 501 milliseconds) followed a long TED
block (1002, 1503, 2004, and 2505 milliseconds). A Latin square design was
used to ensure that all TEDs were tested in all positions within the session
across participants. This target exposure was followed by a 250-millisecond
delay interval before the presentation of the probe stimulus. This delay duration
was selected to impose a minimal working memory load but to avoid backward
masking interference effects that might have occurred at shorter delays. A
total of 40 spatial and 40 object trials were tested at each TED. Thus, 640
trials were obtained for the spatial and object conditions, 8 blocks of 40
trials each. Before acquiring study data, subjects performed practice blocks
of object and spatial trials using TEDs of 3 seconds to ensure comprehension
of task demands.
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Figure 1. Perceptual discrimination test.
Target display includes 2 abstract figures and a fixation cross. After the
250-millisecond delay, trial screen includes the fixation cross and only 1
abstract figure as the probe. Depending on the trial block, subjects are asked
whether the probe stimulus is at the same location regardless of the shape
(spatial trial) or the same shape regardless of the location (object trial)
as one of the stimuli shown previously on the target screen. TED indicates
target exposure duration.
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Visual Working Memory Task
The goal of this condition was to assess the impact of increased retention
interval on performance, controlling for individual differences in perceptual
discrimination ability (Figure 2).
To ensure that subjects could adequately perceive the spatial and object target
stimuli before delay testing, an individualized thresholding procedure was
developed adapting a 1-up/1-down staircase procedure from psychophysics literature.43 This is an adaptive thresholding method in which
a component of a task (eg, stimulus intensity or stimulus duration) is increased
or decreased by a predetermined size or proportion at each step until a predetermined
target measure is reached. In our thresholding procedure, the subjects underwent
testing using blocks of 20 trials at each step, and the TED of the blocks
was decreased or increased 50% until the subject achieved a criterion level
of performance of 80% to 90% correct on 2 consecutive blocks. All subjects
started the staircase procedure with a TED of 3 seconds, and all trials used
a 250-millisecond delay. The lowest TED at which a participant was able to
meet an 80% to 90% criterion was considered his or her threshold and was the
TED used in the working memory condition. Separate thresholding procedures
were done for object and spatial conditions. Thus, subjects typically had
different TEDs in their object and spatial working memory tests. The threshold
for object and spatial tasks are found on average after 9 blocks of 20 trials
(range, 5-22 blocks). The computer program for this paradigm had a minimal
stimulus exposure duration of 17 milliseconds.40
Because of this technical limitation, findings for 2 controls in the object
condition and 9 subjects (7 controls and 2 schizophrenic patients) in the
spatial condition were above 90% correct with the duration of 17 milliseconds.
The working memory of these subjects was tested using the 17-millisecond TED.
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Figure 2. Perceptual thresholding procedure
and visual working memory tests. During perceptual thresholding procedure,
perceptual discrimination test in Figure 1 was repeated (separately for spatial
and object), starting with the 3000-millisecond target exposure duration (TED).
After every 20-trial block, the TED halved if the subject performed at greater
than 90% accuracy or doubled if the performance was below 80%. The staircase
is continued until a subject performed at a range of 80% to 90% and the step
size reached 17 milliseconds. The threshold TED found at the end of this thresholding
procedure was used in the working memory test. Working memory test was identical
with the perceptual discrimination test with the exception of use of threshold
TED and a 3000-millisecond delay.
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Subjects then underwent testing at their individual threshold TED with
a delay interval of 3000 milliseconds. The TED was kept fixed at the threshold
level for each subject, for each condition. A total of 320 trials were administered
in the spatial and object conditions in a series of 4 trial blocks each.40 Task order was balanced across subjects.
STATISTICAL ANALYSES
The data from the perceptual discrimination task were analyzed as follows:
to take account of the repeated observations per participant, with missing
data at 1 level for 1 participant, percentage of accuracy was predicted with
the use of a mixed model for repeated measures44
using an unstructured covariance matrix. To model immediate response as a
function of condition, group, and TED, the initial model fitted included TED
x condition, condition x group, group x TED, and group x
condition x TED interactions. To allow for nonlinear effects of exposure
duration, TED was represented in these models by a set of indicator variables.
Backward stepwise selection was used to simplify this model; by eliminating
nonsignificant higher-order interactions, this stepwise selection procedure
allowed more power (error degrees of freedom) to test the remaining interactions
and main effects. All main-effect terms were retained in the final model,
as were any interactions for which P<.10. The
final model was used to estimate least squares means at specified combinations
of group, condition, and/or exposure duration, averaged over all levels of
the remaining effects with equal weights for the data from each participant
in each cell.
The Wilcoxon rank sum test was used to compare threshold TEDs and perceptual
performance at threshold TEDs. A repeated-measures analysis of variance (ANOVA)
in a group x condition design was used to assess group differences in
working memory performance. Post hoc analyses using the Wilcoxon rank sum
test were performed for each condition. Since not all the subjects could be
thresholded adequately due to technical limitations summarized above, the
repeated-measures ANOVA and the post hoc tests were repeated with the subjects
whose perceptual thresholds were successfully identified (ie, at the end of
thresholding at a range of 80%-90% accuracy). Spearman rank correlations between
threshold TED and working memory performance were calculated by group and
condition. Mixed-model analysis was performed using a commercially available
statistical software package (PROC MIXED, version 8.0; SAS Institute Inc,
Cary, NC). Other analyses were performed using a separate package (SPSS 10.0;
SPSS Inc, Chicago, Ill). All statistical tests were performed at  =
.05 (2-tailed).
RESULTS
PERCEPTUAL DISCRIMINATION TASK
Observed mean percentage accuracy by TED and processing task (normal
controls vs subjects with schizophrenia) is presented for object condition
in Figure 3A and for spatial condition
in Figure 3B.
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Figure 3. A, Object visual information processing
task. B, Spatial visual information processing task. TED indicates target
exposure duration.
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In backward stepwise selection, the 3-way group x condition x
TED interaction was found to be nonsignificant (F7,48 = 0.95 [P = .48]) and dropped from the model, after which the 2-way
group x TED interaction was tested and dropped (F7,48 = 1.08
[P = .39]). All other terms met the criterion of P<.10 for staying in the model, so that the final model
included terms for group (F1,48 = 46.93 [P<.001]),
condition (F1,48 = 82.14 [P<.001]),
TED (F7,48 = 26.42 [P<.001]), group
x condition (F1,48 = 4.66 [P = .03]),
and condition x TED interaction (F7,48 = 7.43 [P<.001]).
The final model was used to estimate adjusted mean accuracy of immediate
response by condition and group, averaged across TED. These means and related
analyses are presented in Table 1. Averaging across exposure and condition, mean accuracy was lower in schizophrenic
patients than in normal controls (76.2% vs 86.1%, respectively). However,
the control-schizophrenic difference in average performance was significantly
greater (test for group x condition) in the object (11.5% difference)
than in the spatial (8.3% difference) condition. Thus, although volunteers
with schizophrenia demonstrated impairment in object and spatial perceptual
discrimination, the extent of the impairment was greater in the perceptual
processing of object visual information.
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Adjusted Mean Perceptual Performance in Schizophrenic and Control Groups
by Object vs Spatial Condition*
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The performance of both groups improved with increasing TED, as shown
in Figure 3. However, the magnitude
of this improvement was not identical in both conditions (as seen in the test
for condition x TED interaction). Performance in the spatial condition
appears to reach a plateau, with little further improvement with greater TED,
more quickly than does performance in the object condition.
VISUAL WORKING MEMORY
Threshold Performance Levels
On average, patients required considerably longer than controls to attain
the performance criterion of 80% to 90% in the thresholding procedure for
the spatial (mean threshold TED, 692 ± 1083 vs 109 ± 130 milliseconds;
Wilcoxon rank sum test, 385.5 [df = 1; P = .01]) and the object (mean threshold TED, 1937 ± 1808 vs
569 ± 568 milliseconds; Wilcoxon rank sum test, 299 [df = 1; P<.001]) conditions. Despite these
large average differences, there was considerable overlap in the distribution
of threshold TED between groups. Controls did not differ from patients in
accuracy at the threshold TED for the object condition (86.0% ± 3.8%
for controls vs 84.5% ± 3.5% for patients; Wilcoxon rank sum test,
696 [df = 1; P = .16]).
In the spatial condition, controls performed better than patients at the threshold
TED (89.0% ± 5.5% vs 85.0% ± 4.2%; Wilcoxon rank sum test, 636.5
[df = 1; P = .01]). This
difference is likely attributable to the fact that a substantial number of
controls and some patients achieved accuracy of greater than 90% at the lowest
exposure duration used (17 milliseconds).
Working Memory Performance
The repeated-measures ANOVA of delayed object and spatial performance
yielded main effects of condition (F1,48 = 24.30 [P<.001]) and diagnosis (F1,48 = 10.87 [P = .002]) and an interaction between condition and diagnosis (F1,48 = 4.18 [P = .046]). The nature of this
critical interaction is seen in Figure 4.
The groups differed significantly in the spatial working memory condition
(Wilcoxon rank sum test, 587.5 [df = 1; P<.001]), whereas performance in the object condition did not (Wilcoxon
rank sum test, 699 [df = 1; P
= .19]). Spatial and object working memory performances were not correlated
with each other for controls and patients (r = -0.16
[P = .50] and r = 0.27 [P = .15], respectively). Total scores on the Brief Psychiatric
Rating Scale and Schedule for the Assessment of Negative Symptoms were not
significantly correlated with object (r = 0.24 [P = .20] and r = 0.08 [P = .68], respectively) or spatial (r = -0.31
[P = .10] for both) working memory performance.
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Figure 4. A, Spatial working memory task.
Mean performance for patients was 73.84% (SD, 6.92%); for normal control subjects,
80.32% (SD = 4.18%) (Wilcoxon rank sum test, 446.5 [df = 1; P<.001]). B, Object working memory task. Mean performance
for patients with schizophrenia was 70.77% (SD = 6.38); for controls, 72.91%
(SD = 4.40%) (Wilcoxon rank sum test, 540.5 [df =
1; P = .54]). The box represents the interquartile
range, which contains the 50% of values. The whiskers are lines that extend
from the box to the highest and lowest values, excluding outliers. A line
across the box indicated the median.
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Although the thresholding strategy ensured that the perceptual demands
of the working memory task was met by both groups in both conditions, a criticism
might arise from the fact that the control group exhibited significantly better
threshold performance in the spatial condition before entering working memory
testing. We addressed this by repeating the working memory data analysis after
excluding 11 subjects (9 controls and 2 patients) for whom the thresholding
strategy was unsuccessful because of technical limitations. After this, control
and schizophrenic groups exhibited comparable performance in the object (85.91
± 3.02 vs 84.64 ± 3.52, respectively; Wilcoxon rank sum test,
523.5 [df = 1; P = .24])
and spatial (85.91 ± 3.41 vs 84.29 ± 3.25, respectively; Wilcoxon
rank sum test, 518 [df = 1; P
= .18]) conditions. Results of the repeated-measures ANOVA, similar to those
of the whole-group analysis, demonstrated main effects of condition (F1,37 = 20.64 [P<.001]) and diagnosis (F1,37 = 6.65 [P = .01]) and an interaction between
condition and diagnosis (F1,48 = 6.88 [P
= .01]). Patients with schizophrenia were impaired in spatial working memory
(72.97 ± 6.24 vs 80.29 ± 3.09; Wilcoxon rank sum test, 446.5
[df = 1; P<.001]) but
not in object working memory (70.67 ± 6.35 vs 71.71 ± 3.69;
Wilcoxon rank sum test, 540.5 [df = 1; P = .54]) performances.
COMMENT
In this study, we documented an impairment in visual perceptual performance
for patients with schizophrenia relative to normal control subjects. Perceptual
impairment for patients with schizophrenia was greater for the object than
for the spatial perceptual task. We also documented a domain-specific spatial
working memory deficit in patients with schizophrenia. The spatial working
memory impairment was observed even after between-group differences in perceptual
processing were controlled for, suggesting a genuine deficit in the retention
of spatial material.
We observed deficits in the perceptual discrimination of object form
and spatial location in patients with schizophrenia. These data are consistent
with a growing body of work documenting deficits in a number of fairly elementary
sensory and perceptual tasks among patients with the illness.32, 45-52
Several recent studies have highlighted deficits in the discrimination of
motion, trajectory, or location cues, suggesting a relatively specific deficit
in the dorsal visual-processing stream.46-48
The present data suggest that the impairment extends to the ventral system
as well: patients demonstrated more pronounced deficits in the object condition
than in the spatial condition. Consistent with earlier studies of visual perception
in schizophrenia, patients needed longer stimulus exposures to achieve perceptual
performance comparable with that of normal controls.49-52
However, since the impairment was evident even after extended encoding times,
a slowing of visual processing cannot plausibly account for the extent of
perceptual impairment observed. Instead, it appears that patients have deficits
in the precise encoding of visual stimuli, with maximal impairments when fine-feature
processing is needed. Given the role of attention in the modulation of sensory
processing, it is not possible to parse the source of the patient behavioral
deficit further as reflecting a fundamental perceptual or attentional defect.
In this type of task, effective behavioral performance requires the integrated
function of attention in the service of perception.
We also have replicated previous studies reporting spatial working memory
impairments among patients with schizophrenia.2, 7-9,25-26,28, 53
In addition, we found evidence of impairment in the retention of spatial information,
even after controlling for perceptual deficits, and somewhat unexpectedly,
that this impairment does not extend to the retention of object stimuli. Indeed,
O'Donnell and colleagues47 have previously
reported that patients demonstrated far greater impairment with delayed spatial
than with object tasks. Our findings are also consistent with the work of
Javitt et al32-33 in highlighting
the extent to which sensory/perceptual encoding impairment in schizophrenia
contributes to working memory impairment. However, there also appears to be
additional impairment in the retention of spatial information. A specific
spatial (but not object) working memory impairment in schizophrenia lends
support to the hypotheses that object and spatial visual working memory are
dissociable, likely mediated by partially segregated brain areas, and can
be affected differentially by pathologic processes.13
Although it is tempting to argue that our finding of a selective spatial working
memory deficit suggests dorsal prefrontal dysfunction in schizophrenia,12, 14 similar selective spatial deficits
have been observed in patients with Parkinson disease.41, 54
As noted by Postle et al,41 abnormalities of
the head of caudate could produce a similar deficit, as such lesions might
deafferent the dorsal prefrontal cortex or disrupt the processing of spatial
information in posterior parietal areas that project to the caudate.
It is difficult to explain our findings with a generalized impairment
in schizophrenia. In the perception experiment, although patients demonstrated
more impairment in the more difficult object task than in the easier spatial
task, an artifactual impairment due to differential difficulty is unlikely.
Nearly constant group differences were observed from the shortest to the longest
TED as demonstrated by a lack of group x TED interaction, although performance
in the controls varied substantially across the various TEDs. A difficulty
artifact would be most consistent with robust between-group differences at
the shortest TEDs and an attenuation of differences as difficulty level was
decreased. In the working memory experiment, after the perceptual impairment
was experimentally controlled for, patients differed from controls on the
easier spatial condition and not in the harder object condition. Thus, the
specificity of the impairment is deconfounded from the task difficulty. A
similar pattern was previously demonstrated by Stevens et al34
in an auditory working memory experiment. Together, these studies argue against
a generalized working memory impairment in schizophrenia.
Some potential limitations of the present study should be noted. In
light of the specific visuospatial deficits observed in patients with Parkinson
disease41, 54 and the proposed
role of dopamine in modulating working memory performance,55
a potential concern is that the impairments we observed are a result of antipsychotic
treatment interfering with dopamine function. One may speculate that blockage
or lack of stimulation of certain dopamine receptors might cause specific
spatial working memory impairments. However, spatial working memory deficits
have been documented in unmedicated patients as well as untreated first-degree
relatives.7, 27, 29
Thus, impairment has been observed in the absence of the potential treatment
confound and appears to be an effect of the illness. A second concern is that
the thresholding procedure was compromised by the inability to reduce TED
below 17 milliseconds. The thresholding strategy was successful, ensuring
that all subjects have met the perceptual demands of the working memory task.
However, some subjects exceeded the 90% criterion. An analysis without these
subjects ruled out a carryover effect from spatial perception.
CONCLUSIONS
We have shown visual perceptual processing impairments in schizophrenia.
This impairment was greater for visual information about features of the objects
than for their spatial location. After controlling for perceptual impairments,
patients with schizophrenia exhibited spatial but not object visual working
memory impairments. These dual deficits in perceptual encoding and retention
suggest that the working memory impairment in schizophrenia is multifactorial
and point toward dysfunction in posterior, perceptual processing areas and
possibly prefrontal regions that play a critical role in maintenance of representations
during delays. Future studies using functional imaging techniques may provide
further information on the integrity of these brain areas and/or circuitry
in schizophrenia.
AUTHOR INFORMATION
Accepted for publication April 19, 2001.
Supported in part by grants MH 40279, MH 48225, and MH 60487 from the
Public Health Service, Washington, DC.
We thank Bradley R. Postle, PhD.
Corresponding author and reprints: Cenk Tek, MD, Maryland Psychiatric
Research Center, PO Box 21246, Baltimore, MD 21228 (e-mail: ctek{at}umaryland.edu).
From the Maryland Psychiatric Research Center, Department of Psychiatry,
University of Maryland, Baltimore.
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