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Sensory Information Processing in Neuroleptic-Naive First-Episode Schizophrenic Patients
A Functional Magnetic Resonance Imaging Study
Dieter F. Braus, MD;
Wolfgang Weber-Fahr, PhD;
Heike Tost, MSc;
Matthias Ruf, MSc;
Fritz A. Henn, PhD, MD
Arch Gen Psychiatry. 2002;59:696-701.
ABSTRACT
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Background Schizophrenic disorders are thought to involve widespread abnormalities
in information processing. The present study used functional magnetic resonance
imaging and a simple and robust paradigm that involved auditory and visual
activation to examine basic sensory input circuits. Our aim was to determine
which stages of the input processing network are disturbed in first-episode
schizophrenic patients.
Methods Twelve neuroleptic-naive inpatients (paranoid subtype) were compared
with 11 healthy subjects by means of echo-planar functional magnetic resonance
imaging. In a block design, the paradigm included the simultaneous presentation
of a moving 6-Hz checkerboard and auditory stimuli in the form of drumbeats.
The subjects were asked to simply look and listen.
Results In comparison with control subjects, patients showed reduced activation
in the right thalamus, the right prefrontal cortex, and the parietal lobe
(restricted to the dorsal visual pathway) bilaterally. There were no notable
differences in the primary visual cortex or the object-specific occipitotemporal
pathway. In addition, patients presented with a reduced signal change to auditory
stimulation in the left acoustic cortex.
Conclusions The present study supports the concept of widespread cortical and subcortical
deficits in schizophrenia. Our findings suggest abnormal functioning early
in the information processing and in high-order association cortices already
at illness onset, before the administration of medication or the most confounding
effects of illness duration. The main regions have been implicated in visual
motion perception and discrimination as well as in attention to sensorial
events and perceptual synthesis.
INTRODUCTION
THE SCHIZOPHRENIA spectrum is widely recognized as a heterogeneous disorder.
Investigators have consistently tried to identify the neurobiological substrate
of information processing deficits that are characteristic of most schizophrenic
patients.1-3 It
has been hypothesized that there are widespread abnormalities in the early
stages of information processing leading to a cascade of "downstream" effects
on higher cortical functions, such as sustained attention, working memory,
concept formation, or social functioning.4
The goal of the present study was to use functional magnetic resonance
(fMR) imaging5 to demonstrate abnormality in
information processing circuits in first-episode, neuroleptic-naive schizophrenic
patients. In general, functional imaging findings in acutely ill schizophrenic
patients have been criticized, as patients might be unable to understand and
perform complicated cognitive tasks. Keeping this in mind, the present study
was designed with the use of a simple and robust input paradigm requiring
little cognitive effort, which would allow an evaluation of elementary information
processing. The paradigm chosen included the simultaneous presentation of
2 sensory stimuli without information content, (1) an alternating visual checkerboard
(6 Hz) as well as (2) an acoustic stimulus consisting of drumbeats. The use
of 2 different modalities should involve both the information flow through
the thalamus to the low- and high-order sensory cortices (V1-V5 and A1, A2)
in the temporal and occipital lobes and processing in the frontoparietal cortices.
Two inputs were chosen to stimulate perceptual synthesis and to maximize activation
of the heteromodal association cortices. Thus far, the functional interaction
of the information processing stream via visual and acoustic input channels
has not been directly studied in schizophrenia. Therefore, this study may
serve as a starting point for further research aimed at identifying functional
differences in the various levels of information processing deficits. We hypothesized
that even minimal cognitive effort might disclose dysfunction in different
levels of the information processing network, particularly in the thalamus
and frontoparietal association areas.
SUBJECTS AND METHODS
SUBJECTS
Twelve inpatients (6 men and 6 women; average [±SD] age, 25.1
± 4.8 years; school education, 10.6 ± 1.8 years) living in the
community of Mannheim, Germany, and satisfying DSM-IV
as well as International Classification of Diseases, 10th
Revision (ICD-10) criteria for schizophrenia along with 11 healthy
control subjects (6 men and 5 women; average age, 29.4 ± 6.2 years;
school education, 12.0 ± 1.4 years) participated in this study. Control
subjects were recruited through advertisements; all patients entered the study
after first psychiatric hospitalization. All were right-handed according to
the Edinburgh Handedness Inventory.6 All inpatients
were neuroleptic-naive, having their first schizophrenic episode with the
predominance of delusions, hallucinations, and distrust. Particular care was
taken to exclude patients with a history of neurologic disorders or substance
abuse. All patients had undergone thorough neurologic examination, showing
no abnormalities. Urine screening for drug usage was negative. All stabilized
patients were rediagnosed 6 months after the initial examination, and the
diagnosis was stable in all cases.
The healthy volunteers were given a structured screening interview.
Exclusion criteria included a history of significant medical, neurologic,
or psychiatric illnesses as well as substance abuse. Written informed consent
was obtained after the purpose of the study and the procedures had been explained
to all participants. The study was approved by the local university ethics
committee.
PROCEDURE
The fMR imaging paradigm included the simultaneous presentation of a
flickering 6-Hz checkerboard and auditory stimuli in the form of drumbeats,
with the specific instruction just to look and listen. Visual stimuli were
generated by a computer (Apple PowerBook; Apple Computer Corp, Cupertino,
Calif; MacStim; David Darby, PhD, FRACP, West Melbourne, Australia) and displayed
on a back projection plane at the foot end of the scanner via a liquid crystal
display projector (Sharp Electronics Corporation, Mahway, NJ). Subjects were
in a supine position and viewed the screen through an adjustable mirror fixed
to the head coil. Acoustic stimuli were presented through customized magnetic
resonance headphones. The 2 experimental conditions (stimulation and fixation)
were recorded in 5 sequences of 10 measurements in alternating order.
IMAGE ACQUISITION
Images were acquired on a standard clinical 1.5-T MR imager (Siemens
AG, Munich, Germany). For fMR imaging, a standard echo planar imaging sequence
(repetition time, 1.8 milliseconds; echo time, 66 milliseconds;  =
90°; T2* contrast) with an in-plane resolution of 64 x 64 pixels
(19 slices; 3-mm thickness; gap factor, 0.3; field of view, 220 x 220
mm) was used. For anatomic reference, a 3-dimensional magnetization prepared
rapid gradient echo image data set was acquired. The fMR imaging slices were
oriented axially parallel to the anterior commissure–posterior commissure
line according to Talairach and Tournoux.7
Each functional T2* slice was imaged 100 times in a total period of 310 seconds.
A vacuum pad was used to improve head fixation and to minimize involuntary
head movement.
DATA ANALYSIS
For data analysis we used a general linear model as employed by SPM99
software (Wellcome Department of Cognitive Neurology, University College,
London, London, England).8 Our inferences were
based on P values adjusted for the volume of interest
by means of random field theory. We used a 2-stage analysis procedure where
the contrasts reflecting activations in each subject were entered into a second-level
analysis to emulate a random-effect analysis. This allows us to generalize
our inferences to the populations from which our control subjects and patients
were drawn. We first looked at the main effects of visual and auditory stimulation
in both groups and then analyzed the interaction or differences in activation.
The first 5 volumes of each functional time series were discarded because
of T1 effects. All volumes were realigned to the remaining first volume as
correction for interscan movements by means of a rigid body transformation
with 6 parameters (3 rotations and 3 translations). A T1-weighted 3-dimensional
magnetization prepared rapid gradient echo (1.05 x 1.05 x 1-mm
voxel size) was coregistered to the first T2* image. This procedure ensures
that the functional (fMR) and structural data are part of the same coordinate
system. The structural image was spatially normalized to a standard template
by means of a 12-parameter affine transformation with additional nonlinear
components,9-10 where the deformations
were modeled with smooth (spatial) basis functions (ie, 3-dimensional discrete
cosine basis function set). The nonlinear transformation was subsequently
applied to the T2* data. The data were smoothed with a 12-mm full width at
half maximum isotropic gaussian kernel for individual analysis and for group
analysis. Data were analyzed by modeling the different conditions (stimulation
and fixation) as boxcar functions convoluted with the hemodynamic response
function (individual threshold P<.001) in the
context of a general linear model.
Specific effects were tested by applying appropriate linear contrasts
to the parameter estimates for each condition, resulting in a T-statistic
for each individual voxel. The statistical parametric map constitutes the
T-values. The contrast used was +1 for visual and auditory stimulation and
–1 for the fixation condition. Data were analyzed by including the contrast
images of all subjects of each group (first-episode patients and control subjects)
into a second-level group analysis with a threshold of P<.05 corrected for the entire volume or the volume of interest.11-12 One-sample t
tests were performed to test for in-group correspondences and 2-sample t tests to identify areas that are less active in schizophrenic
patients compared with control subjects.
RESULTS
The study groups did not differ significantly with respect to age, sex,
or educational achievement. On average, patients were investigated 6.5 months
after inception of prodromal signs. Patients presented with moderate psychotic
symptoms as indicated by the Brief Psychiatric Rating Scale (mean ±
SD score, 49.9 ± 5.7). None of the participants had ever received neuroleptic
medication before being enrolled in the study. Overall head motions were evaluated
with SPM99 software. Two patients and 1 control subject had to be excluded
because of motion artifacts exceeding 1.5 mm in the x, y, or z direction.
Structural MR images and showed no abnormalities in any of the participants.
GROUP ANALYSIS OF HEALTHY SUBJECTS
Comparing visual and acoustic stimulation and fixation, the group analysis
showed a significant (P<.05) activation of the
primary visual cortex (V1) and extrastriate areas (V2-V5) as well as the superior
temporal auditory cortices A1 and A2 (Table
1). A stimulation-induced enhancement of local blood oxygen level–dependent
MR signals could also be traced subcortically bilaterally in dorsolateral
thalamic areas corresponding to the lateral and medial geniculate nuclei.
Increased activation was also seen in the dorsolateral prefrontal cortex,
where a pronounced right-sided activation in the inferior portion was detected.
Figure 1 shows
the localization of the activation overlaid onto a glass brain.
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Table 1. SPM Group Analysis*
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Figure 1. Anatomic correlates of the stimulus-induced
activation patterns in 10 healthy control subjects (A) and 10 first-episode
schizophrenic patients (B). The patient group shows a reduced right thalamic
blood oxygen level–dependent response (B, red arrow) in addition to
a lack of prefrontal activation seen in control subjects (A, red arrow) (SPM99
software; Wellcome Department of Cognitive Neurology, University College,
London, London, England, group analysis, P<.05,
corrected for volume of interest).
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GROUP ANALYSIS OF FIRST-EPISODE SCHIZOPHRENIC PATIENTS
The group analysis of the different perceptual conditions in the neuroleptic-naive
first-episode patient group showed a significant activation in the primary
visual (V1), extrastriate (V2-V5), and auditory cortices (A1, A2) of the brain.
Thalamic activation patterns were more pronounced in the lateral and medial
geniculate nuclei of the left hemisphere. A significant blood oxygen level–dependent
response of prefrontal areas was totally missing in our patient group. Table 1 shows the amount and the localization
of stimulus-induced activations.
INTERACTION ANALYSIS
The application of a rigorous interaction analysis allows the selective
detection of cerebral areas that are less active in the schizophrenic sample
and enhanced in healthy control subjects. The schizophrenic patients showed
a markedly reduced response of the right posterior thalamic relay nuclei,
which are concerned with subcortical processing of sensory information (lateral
and medial geniculate nuclei). Higher-order extrastriate cortices of the middle
occipital and inferior parietal lobes corresponding to the dorsal visual processing
pathway were found to be hypoactive in the patients bilaterally. Furthermore,
a reduced prefrontal activation level of the right frontal eye field and the
intermediate frontal gyrus corresponding to Brodmann area 46 was detected
along with a reduced blood oxygen level–dependent-response in the left
acoustic cortices of the superior temporal lobe (Table 2). Figure 1 and Figure 2 outline the "hypoactive" cortical
regions of the first-episode schizophrenic patients from a lateral and posterior
angle on a normalized brain.
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Table 2. SPM Interaction Analysis (Activation Control Subjects >First-Episode
Patients)*
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Figure 2. Visualization of the interaction
analysis results (SPM99 software; Wellcome Department of Cognitive Neurology,
University College, London, London, England, P<.05,
corrected for volume of interest). Compared with schizophrenic patients (n
= 10), the spatial extent of activation patterns in healthy subjects (n =
10) is significantly increased in the highlighted anatomic areas of the prefrontal
areas (frontal eye field, Brodmann area 46) (A) and the dorsal visual processing
pathway (B).
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COMMENT
Using a very simple perceptual fMR imaging paradigm that minimized the
effect of cognitive effort and motivation, we examined the circuitry involved
in the fundamental processing of simultaneous visual and auditory information
in neuroleptic-naive first-episode schizophrenic patients compared with control
subjects. We were able to demonstrate functional deficits in the first relay
station of the right thalamus as a sign of abnormalities in early stages of
information processing. This observation is consistent with positron emission
tomographic studies,13-14 lending
further support to the concept indicating both deficits in sensory gating
in schizophrenia15 and a dysfunction in cortical-thalamic-cerebellar
circuitry as proposed by Andreasen et al.16
In addition, cortical response to auditory stimulation in the left superior
temporal gyrus was reduced in our acutely ill patients, with at least 9 of
them experiencing auditory hallucinations. This latter result is in full agreement
with fMR imaging data from David et al17 showing
that response of the temporal cortex to exogenous auditory stimulation was
markedly reduced in patients experiencing auditory hallucinations, regardless
of medication. The major new finding of the present study is that, after simultaneous
visuoauditory stimulation, schizophrenic patients activate to a lesser extent
than do normal subjects bilaterally in the inferoposterior parietal cortex
and regions of the right prefrontal cortex. In contrast to this specific hypofunction
of the dorsal visual pathway, we did not find any differences in the primary
visual cortex or the object-specific occipitotemporal stream.
One emerging architectural principle of functional brain organization
in information processing is that neuronal responses expressed at any level
in a perceptual hierarchy reflect an interaction between "bottom-up"–driven
afferents from lower subcortical and cortical areas and backward "modulatory"
inputs from higher cortical regions that mediate top-down contextual effects.18-20 A compelling example
is attentional modulation of responses in functionally specialized areas.
Vision is an especially fruitful domain for studying distributed neural systems
in the human brain. Major functions are comparable with those in nonhuman
primates, with the neuroanatomy and neurophysiology of the monkey visual system
being well known.21
The differential visual impairments produced by focal lesions in clinical
cases suggest that the human visual cortex, like that of the monkey, may be
similarly organized into 2 anatomically distinct and functionally specialized
ventral and dorsal processing pathways. Occipitotemporal lesions include visual
object agnosia, while those produced by occipitoparietal lesions include disorders
in velocity detection and discrimination as well as attention deficits, visuospatial
neglect, and dysfunction of spatial working memory.22-23
Both processing streams have reciprocal connections with regions beyond the
modality-specific visual system.24 Anatomic
studies have shown that projections from areas in the dorsal stream terminate
around the frontal eye field and the principal sulcus of the dorsolateral
prefrontal cortex (Brodmann area 46) reciprocated by a top-down feedback projection
via the prefrontal cortex.25 On the other hand,
there is evidence that thalamocortical and corticocortical loops play a causal
role in cooperative and competitive neural interactions26
and that frontoparietal connections are mediating spatial working memory27 as well as visual awareness and the organization
of voluntary behavior contingent on sensory cues.28-29
It has been suggested that, in addition to thalamic gating, the maintenance
of context and spatial working memory may underlie various deficits in information
processing and attention observed in schizophrenic patients.30-32
This in turn would imply disturbances in the above-mentioned neural network
in schizophrenic patients.33
This study showed a very specific profile of abnormal activation in
the posterior parietal cortex and regions of the right prefrontal cortex (the
right frontal eye field and Brodmann area 46) in schizophrenic patients. This
points to a limited dysfunction in the dorsal visual processing stream, as
opposed to the object-specific ventral visual pathway. The parietal and frontal
regions implicated in our study are very similar to those activated during
attention to visual motion in normal subjects18
as well as smooth-pursuit eye movements.34
Furthermore, these areas have been shown to be specifically involved in the
formation of perceptual states and the awareness of sensory stimuli.29 Attentional deficits35-36
and impairments in the visual perception of motion signals37
as well as in smooth-pursuit eye movements38-39
are well documented in schizophrenia. The homology between our functional
results and those behavioral markers may represent their underlying neurobiology.
The noted abnormal frontoparietal activations could also reflect a functional
interaction between visual and auditory cortical processing and a disturbed
modulatory cognitive set in schizophrenia. This would mean that the site of
abnormal activation must not necessarily be identical with the site of pathophysiology.
Our findings are clearly preliminary because of the small number of
unmedicated first-episode patients available for this study and acquired in
a naturalistic design. Because of the fMR imaging method, substracting the
fixation baseline from the stimulation condition, we cannot exclude that patients
showed more baseline activation during the fixation period in the frontoparietal
areas than the control subjects, but equal activation during stimulation,
appearing as a hypoactive response to stimulation. A further drawback of this
study lies in the fact that these acutely ill patients were not examined for
oculomotor and motion-perception deficits or spatial and nonspatial working
memory, partly because of technical limitations and their limited compliance
for extensive technical procedures. Clearly, one future goal should be more
comprehensive studies using large numbers of well-characterized subjects (clinically
and neuropsychologically), with a direct correlation of oculomotor performance
and specific dorsal pathway activation tasks (eg, sinusodial grating or random
dot paradigms) performed inside the magnet.40
Despite its constraints, this study confirms the concept of widespread
cortical and subcortical deficits in schizophrenia. The regions implicated
in our study suggest an abnormal functioning of the thalamus as well as high-order
frontoparietal cortical areas that are restricted to the dorsal visual processing
stream and have been implicated in attention to sensorial events and conscious
perceptual synthesis. With respect to the syndromic nature of schizophrenia,
we suggest that functional alterations within this information processing
network represent a common pathophysiology rather than a common etiology.
Our simple and robust fMR imaging paradigm may be useful for screening at-risk
populations and for observing patients during the introduction of medication
and throughout the longitudinal course of the illness.
AUTHOR INFORMATION
Submitted for publication March 26, 2001; final revision received August
16, 2001; accepted October 15, 2001.
This work was supported by grant DFG: BR 1112/5-1 from the Deutsche
Forschungsgemeinschaft, Bonn, Germany.
We thank Traute Demirakca, MSc, for valuable comments on the manuscript
and Gunilla Oberthür, MTRA, for her help in performing the studies.
Corresponding author and reprints: Dieter F. Braus, MD, Central Institute
of Mental Health (ZI), PO Box 122 120, D-68072 Mannheim, Germany (e-mail: dfbraus{at}zi-mannheim.de).
From the Central Institute of Mental Health (ZI), NMR-Research, Mannheim,
Germany.
REFERENCES
| |
1. Braff DL, Saccuzzo DP. Information processing dysfunction in paranoid schizophrenia: a two-factor
deficit. Am J Psychiatry. 1981;138:1051-1056.
FREE FULL TEXT
2. Holzman PS, Proctor LR, Levy DL, Yasillo NJ, Meltzer HY, Hurt SW. Eye-tracking dysfunctions in schizophrenic patients and their relatives. Arch Gen Psychiatry. 1974;31:143-151.
ISI
| PUBMED
3. Nuechterlein KH, Dawson ME, Green MF. Information-processing abnormalities as neuropsychological vulnerability
indicators for schizophrenia. Acta Psychiatr Scand Suppl. 1994;384:71-79.
PUBMED
4. Saccuzzo DP, Braff DL. Early information processing deficit in schizophrenia. Arch Gen Psychiatry. 1981;38:175-179.
ABSTRACT
5. Ogawa S, Lee TM. Magnetic resonance imaging of blood vessels at high fields. Magn Reson Med. 1990;16:9-18.
ISI
| PUBMED
6. Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia. 1971;9:97-113.
FULL TEXT
|
ISI
| PUBMED
7. Talairach J, Tournoux P. Co-planar Stereotactic Atlas of the Human Brain. Stuttgart, Germany: Georg Thieme Verlag; 1988.
8. Friston KJ, Holmes AP, Poline JB, Grasby PJ, Williams SC, Frackowiak RS, Turner R. Analysis of fMRI time-series revisited. Neuroimage. 1995;2:45-53.
FULL TEXT
|
ISI
| PUBMED
9. Ashburner J, Hutton C, Frackowiak R, Johnsrude I, Price C, Friston K. Identifying global anatomical differences. Hum Brain Mapp. 1998;6:348-357.
FULL TEXT
|
ISI
| PUBMED
10. Ashburner J, Friston KJ. Nonlinear spatial normalization using basis functions. Hum Brain Mapp. 1999;7:254-266.
FULL TEXT
|
ISI
| PUBMED
11. Worsley KJ, Friston KJ. Analysis of fMRI time-series revisited—again. Neuroimage. 1995;2:173-181.
FULL TEXT
|
ISI
| PUBMED
12. Strange BA, Fletcher PC, Henson RN, Friston KJ, Dolan RJ. Segregating the functions of human hippocampus. Proc Natl Acad Sci U S A. 1999;96:4034-4039.
FREE FULL TEXT
13. Buchsbaum MS, Someya T, Teng CY, Abel L, Chin S, Najafi A, Haier RJ, Wu J, Bunney WE Jr. PET and MRI of the thalamus in never-medicated patients with schizophrenia. Am J Psychiatry. 1996;153:191-199.
FREE FULL TEXT
14. Heckers S, Curran T, Goff D, Rauch SL, Fischman AJ, Alpert NM, Schacter DL. Abnormalities in the thalamus and prefrontal cortex during episodic
object recognition in schizophrenia. Biol Psychiatry. 2000;48:651-657.
FULL TEXT
|
ISI
| PUBMED
15. Judd LL, McAdams L, Budnick B, Braff DL. Sensory gating deficits in schizophrenia: new results. Am J Psychiatry. 1992;149:488-493.
FREE FULL TEXT
16. Andreasen NC, Paradiso S, O'Leary DS. "Cognitive dysmetria" as an integrative theory of schizophrenia. Schizophr Bull. 1998;24:203-218.
17. David AS, Woodruff PW, Howard R, Mellers JD, Brammer M, Bullmore E, Wright I, Andrew C, Williams SC. Auditory hallucinations inhibit exogenous activation of auditory association
cortex. Neuroreport. 1996;7:932-936.
ISI
| PUBMED
18. Friston KJ, Buchel C. Attentional modulation of effective connectivity from V2 to V5/MT in
humans. Proc Natl Acad Sci U S A. 2000;97:7591-7596.
FREE FULL TEXT
19. Posner MI, Petersen SE, Fox PT, Raichle ME. Localization of cognitive operations in the human brain. Science. 1988;240:1627-1631.
FREE FULL TEXT
20. Haxby JV, Grady CL, Ungerleider LG, Horwitz B. Mapping the functional neuroanatomy of the intact human brain with
brain work imaging. Neuropsychologia. 1991;29:539-555.
FULL TEXT
|
ISI
| PUBMED
21. Zeki S, Watson JD, Lueck CJ, Friston KJ, Kennard C, Frackowiak RS. A direct demonstration of functional specialization in human visual
cortex. J Neurosci. 1991;11:641-649.
ABSTRACT
22. Park S, Puschel J, Sauter BH, Rentsch M, Hell D. Spatial working memory deficits and clinical symptoms in schizophrenia. Biol Psychiatry. 1999;46:392-400.
FULL TEXT
|
ISI
| PUBMED
23. Petrides M. Visuo-motor conditional associative learning after frontal and temporal
lesions in the human brain. Neuropsychologia. 1997;35:989-997.
FULL TEXT
|
ISI
| PUBMED
24. Desimone R, Schein SJ, Moran J, Ungerleider LG. Contour, color and shape analysis beyond the striate cortex. Vision Res. 1985;25:441-452.
FULL TEXT
|
ISI
| PUBMED
25. Ungerleider LG, Courtney SM, Haxby JV. A neural system for human visual working memory. Proc Natl Acad Sci U S A. 1998;95:883-890.
FREE FULL TEXT
26. Lumer ED, Edelman GM, Tononi G. Neural dynamics in a model of the thalamocortical system, II. Cereb Cortex. 1997;7:228-236.
FREE FULL TEXT
27. Friedman HR, Goldman-Rakic PS. Coactivation of prefrontal cortex and inferior parietal cortex in working
memory tasks revealed by 2D functional mapping in the rhesus monkey. J Neurosci. 1994;14:2775-2788.
ABSTRACT
28. Lumer ED, Friston KJ, Rees G. Neural correlates of perceptual rivalry in the human brain. Science. 1998;280:1930-1934.
FREE FULL TEXT
29. Lumer ED, Rees G. Covariation of activity in visual and prefrontal cortex associated
with subjective visual perception. Proc Natl Acad Sci U S A. 1999;96:1669-1673.
FREE FULL TEXT
30. Wexler BE, Stevens AA, Bowers AA, Sernyak MJ, Goldman-Rakic PS. Word and tone working memory deficits in schizophrenia. Arch Gen Psychiatry. 1998;55:1093-1096.
FREE FULL TEXT
31. Carter CS, Perlstein W, Ganguli R, Brar J, Mintun M, Cohen JD. Functional hypofrontality and working memory dysfunction in schizophrenia. Am J Psychiatry. 1998;155:1285-1287.
FREE FULL TEXT
32. Javitt DC, Shelley AM, Silipo G, Lieberman JA. Deficits in auditory and visual context–dependent processing
in schizophrenia. Arch Gen Psychiatry. 2000;57:1131-1137.
FREE FULL TEXT
33. Braff DL, Swerdlow NR. Neuroanatomy of schizophrenia. Schizophr Bull. 1997;23:509-512.
34. Berman RA, Colby CL, Genovese CR, Voyvodic JT, Luna B, Thulborn KR, Sweeney JA. Cortical networks subserving pursuit and saccadic eye movements in
humans: an FMRI study. Hum Brain Mapp. 1999;8:209-225.
FULL TEXT
|
ISI
| PUBMED
35. Bustillo JR, Thaker G, Buchanan RW, Moran M, Kirkpatrick B, Carpenter WT Jr. Visual information-processing impairments in deficit and nondeficit
schizophrenia. Am J Psychiatry. 1997;154:647-654.
ABSTRACT
36. Cornblatt BA, Keilp JG. Impaired attention, genetics, and the pathophysiology of schizophrenia. Schizophr Bull. 1994;20:31-46.
37. Chen Y, Palafox GP, Nakayama K, Levy DL, Matthysse S, Holzman PS. Motion perception in schizophrenia. Arch Gen Psychiatry. 1999;56:149-154.
FREE FULL TEXT
38. Iacono WG, Lykken DT. Eye tracking and psychopathology. Arch Gen Psychiatry. 1979;36:1361-1369.
ABSTRACT
39. Holzman PS. Recent studies of psychophysiology in schizophrenia. Schizophr Bull. 1987;13:49-75.
40. Rudolph K, Pasternak T. Transient and permanent deficits in motion perception after lesions
of cortical areas MT and MST in the macaque monkey. Cereb Cortex. 1999;9:90-100.
FREE FULL TEXT
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