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Original Article |

Impaired Visual Object Recognition and Dorsal/Ventral Stream Interaction in Schizophrenia FREE

Glen M. Doniger, PhD; John J. Foxe, PhD; Micah M. Murray, PhD; Beth A. Higgins, BSc; Daniel C. Javitt, PhD
[+] Author Affiliations

From the Cognitive Neurophysiology Laboratory, Cognitive Neuroscience and Schizophrenia Program, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY (Drs Doniger, Foxe, Javitt, and Murray and Ms Higgins); Department of Psychology, New York University, New York, NY (Dr Doniger); Department of Neuroscience and Department of Psychiatry and Behavioral Science, Albert Einstein College of Medicine, Bronx, NY (Dr Foxe); and Department of Psychiatry, New York University School of Medicine (Dr Javitt).


Arch Gen Psychiatry. 2002;59(11):1011-1020. doi:10.1001/archpsyc.59.11.1011.
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Published online

Background  Schizophrenia is associated with well-documented deficits in high-order cognitive processes such as attention and executive functioning. The integrity of sensory-level processing, however, has been evaluated only to a limited degree. Our study evaluated the ability of patients with schizophrenia to recognize complete objects based on fragmentary information, a process termed perceptual closure. Perceptual closure processes are indexed by closure negativity (Ncl), a recently defined event-related potential(ERP) component that is generated within the visual association cortex. This study assessed the neural integrity of perceptual closure processes in schizophrenia by examining Ncl generation. Generation of the preceding positive(P1) and negative (N1) ERP components was also examined.

Methods  We evaluated 16 patients with chronic schizophrenia and 16 healthy comparison subjects. Successively less fragmented images were presented during high-density ERP recording, which permitted the monitoring of brain activity during perceptual closure processes prior to object recognition. Analyses were performed at parieto-occipital and occipitotemporal sites consistent with dorsal and ventral stream generators of P1, N1, and Ncl.

Results  Patients with schizophrenia showed significant impairment in the ability to recognize fragmented objects, along with impaired generation of Ncl. The amplitude of visual P1 was significantly reduced, particularly over dorsal stream sites. In contrast, the generation of visual N1 was intact.

Conclusions  Patients with schizophrenia are profoundly impaired in perceptual closure as indicated by both impaired performance and impaired Ncl generation. The selective impairment in dorsal stream P1 is consistent with prior reports of impaired magnocellular processing in schizophrenia. By contrast, intact ventral N1 generation suggests that the initial stages of ventral stream processing are relatively preserved and that impaired magnocellular dorsal stream functioning in schizophrenia may lead to secondary dysregulation of ventral stream object recognition processing.

Figures in this Article

SCHIZOPHRENIA MANIFESTS itself in symptoms that encompass a wide range of human mental activities.1 Deficits in high-order processes such as working memory and executive processing have been extensively studied. In contrast, relatively little attention has been paid to disturbances in perceptual processing, as can be demonstrated in the auditory, visual, and somatosensory modalities.2 In the visual modality, patients with schizophrenia show deficits in eye tracking and motion perception and require prolonged viewing time to recognize briefly presented stimuli.35 Patients also demonstrate increased sensitivity to visual backward masking, which is associated with impaired functioning of the magnocellular visual pathway.68 Severity of visual-processing deficits in schizophrenia correlates with poor outcome on social-functioning measures.9 Therefore, mechanisms underlying visual-processing dysfunction in schizophrenia may be informative regarding the underlying cause of the disease.

One process that may be particularly amenable to neurophysiological dissection is perceptual closure.10 This term refers to the apparent filling-in of missing information by the visual system during partial viewing conditions.11,12 This process, for example, allows one to recognize a complete object (eg, a cat) even when that object is partially hidden from view (eg, located behind a venetian blind).

The process of object recognition/perceptual closure can be studied in a laboratory setting using fragmented images and is indexed by the generation of a specific event-related potential (ERP) component termed closure negativity (Ncl). The Ncl increases gradually in amplitude as stimuli are presented in progressively less fragmented forms using an ascending method of limits (Figure 1). At the point of identification, Ncl amplitude increases discontinuously, suggesting that Ncl generation indexes the perceptual closure process.13,14

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Figure 1.

Stimulus configuration. A, Images displayed from least complete to most complete (4 of 8 levels shown). B, Onset of the most fragmented image (level 8) at 0 milliseconds (duration, 750 milliseconds), followed by a yes/no response prompt (R) (duration, 200 milliseconds) at 1550 milliseconds. A no response resulted in presentation of the next-level image 2.2 seconds after the response prompt. A yes response terminated the sequence for the subject's verbal response.

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A prior study demonstrated that patients with schizophrenia were impaired in their ability to recognize fragmented images even though they benefited equally to controls from manipulations such as object repetition or word priming.10 This pattern suggests that object recognition deficits in schizophrenia are due to a bottom-up disruption of processing at the level of the visual association cortex rather than top-down dysregulation. The goal of our study was to evaluate the degree to which object recognition deficits in schizophrenia are accompanied by impaired generation of the visual Ncl component.

Closure negativity, the Nc1, occurs with an approximate peak latency of 290 milliseconds and is localized over lateral occipital scalp regions overlying a system of visual association regions termed the lateral occipital complex (LOC). The visual system has 2 main subdivisions.15,16 The dorsal stream receives input primarily from the magnocellular division of the lateral geniculate nucleus (LGN) and extends from early visual areas through the occipito-parietal cortex. This system is specialized for processing location information along with properties such as movement, depth, and positional relationships (the "where" system). In contrast, the ventral stream receives input primarily from the parvocellular division of the LGN and extends through the occipitotemporal cortex. This system is specialized for the processing of object form (the "what" system). Featural processing is thus more complex within the ventral stream, and transmission times are slower in ventral than in dorsal visual pathways.1719 The LOC occupies the highest tier of the ventral visual stream and plays a critical role in object recognition. The relatively long latency of Ncl along with its bilateral occipitotemporal distribution suggests that it indexes activity within the LOC. Impaired Ncl generation would reflect impaired activation of the LOC, which is related to impaired perceptual closure in schizophrenia.

In the paradigm used for our study, Ncl is preceded by additional components that reflect prior stages of visual information processing. The surface-positive component (P1) peaks at approximately 100 milliseconds and arises from generators in both dorsal and ventral streams.2025 The dorsal contribution to P1 is best represented at parieto-occipital electrodes(eg, PO5/PO6), whereas the ventral contribution is distributed over the occipitotemporal electrodes (eg, T5/T6). Dorsal activity begins prior to ventral activity. The negative deflection (N1) peaks at around 164 milliseconds and reflects initial stages of form discrimination in the LOC.15,2628 Surface distributions of N1 and Ncl are therefore similar. Our study assesses not only Ncl generation in schizophrenia but also the generation of earlier ERP components.

In addition to receiving ventral stream input, the LOC receives crossover input from the dorsal visual stream. From behavioral studies alone, it is impossible to determine whether perceptual closure deficits in schizophrenia reflect intrinsic dysfunction of the LOC as compared with impaired afferent information flow. Patients with schizophrenia show consistent deficits on tasks that assess dorsal stream functioning, including velocity discrimination, coherent motion, eye tracking, and spatial localization.3,4,29,30 In contrast, early processing within ventral stream visual regions may be intact. By assessing P1 and N1 along with Ncl, this study evaluates the degree to which deficits in Ncl generation are driven by impaired information flow through dorsal as opposed to ventral visual stream regions.

SUBJECTS

Written informed consent was obtained from 16 individuals (3 women) with chronic schizophrenia and 16 healthy control subjects (4 women) following a full description of the study procedures. Demographic information for patients and controls is given in Table 1. Patients with schizophrenia and control subjects were of similar age (mean ± SD, 38.3 ± 8.8 years and 33.7 ± 10.9 years for patients and controls, respectively; t30 = 1.31; P = .20). All subjects reported normal or corrected-to-normal vision. A subset of the control subjects (n = 9) had participated in our prior studies.13,14 Controls were free of psychiatric illness or symptoms by self-report using criteria from the Structured Clinical Interview for DSM-III-R–Non-Patient Edition,31 and denied alcohol or substance abuse. Patients with schizophrenia were recruited from inpatient and outpatient facilities associated with the Nathan Kline Institute for Psychiatric Research, Orangeburg, NY. All patients were taking medication at the time of testing. Positive and Negative Syndrome Scale ratings were performed by a single rater. Factors were defined according to White et al.32 Although all patients were receiving antipsychotic medication at the time of testing, there was no significant correlation between dose and ERP amplitude.

Table Graphic Jump LocationTable 1. Demographic and Clinical Characteristics of Patients With Schizophrenia*
STIMULI AND TASK

The stimuli and procedure were identical to those in our previous study.13 Subjects were presented with between 350 and 400 sets of line drawings of animate and inanimate objects obtained from previous studies.33,34 Each set consisted of 7 to 8 images with progressively greater fragmentation. Images from each set were presented in accordance with the ascending method of limits, from least complete (levels 7 and 8) to most complete (1evel 1), as shown in Figure 1A.35 After the presentation of each fragmented image, a yes/no cue appeared, prompting a forced-choice response either orally or by pressing a button. Following yes responses, the picture sequence for that set was terminated, and subjects were required to verbally name the picture. Thereafter, a sequence incorporating a new picture set was presented. The entire experiment consisted of 35 to 40 blocks, each containing 10 picture sequences. Each image appeared for 750 milliseconds, followed by a blank screen for 800 milliseconds, followed by a yes/no response prompt, as shown in Figure 1B. Subjects' response window extended for 2300 milliseconds from the onset of the prompt. Use of the response prompt diminishes the effect of motor responses on sensory ERP.

MEASUREMENTS AND ANALYSES

High-density ERPs were acquired from 64 scalp electrodes (impedance <5 kΩ) referenced to the nose using an electrode cap (Electrocap International, Inc; Eaton, Ohio). Electrical activity was amplified (amplification ×20 000, bandpass: 0.05-100 Hz) and digitized at 500 Hz (SynAmp amplifiers; Neuroscan, Herdon, Va). Activity was continuously recorded to a disk along with digital stimulus event markers. Epochs (−100 to 700 milliseconds) were created offline.

Epochs with amplitude exceeding ±100 µV at any electrode site during the −100- to 450-millisecond interval were excluded from further averaging. Mean ± SD rejection rates of trials across conditions were 6.7% ± 7.5% for controls and 23.7% ± 16.1% for patients. The mean ± SD number of accepted sweeps per condition for control subjects was 362 ± 37 for identification (ID), 354 ± 41 for 1-prior (1 level of fragmentation prior to ID), 342 ± 36 for 2-prior (2 levels prior to ID), and 305 ± 43 for 3-prior (3 levels prior to ID). The mean ± SD number of accepted sweeps per condition for patients with schizophrenia was 275 ± 80 for ID, 265 ± 78 for 1-prior, 250 ± 74 for 2-prior, and 223 ± 73 for 3-prior. The ERP averages typically become stable following 20 to 30 sweeps. The number of sweeps collected was sufficient to reduce contributions of the background EEG by 1.5 to 2.5 orders of magnitude.

Baseline was defined as the mean voltage across −100 to 20 milliseconds. A priori analyses13,14 examined between-group differences in amplitude of P1, N1, and Ncl. For P1 and N1, amplitude measures were derived from a 20-millisecond window centered at the estimated peak latency for each component (P1: 100 milliseconds; N1: 164 milliseconds). For Ncl, a broader component, amplitude measures were derived from a 40-millisecond window centered at its estimated peak latency of 290 milliseconds.13 Analyses were performed across 3 pairs of scalp electrodes (parietal sites P5 and P6, parieto-occipital sites PO5 and PO6, and occipitotemporal sites T5 and T6). Data from 1 patient with schizophrenia were excluded from all tests that included site T6 because of a broken contact at that electrode site.

The ERP data were also inspected post hoc for further components of interest. Two additional components, an early and late bilateral frontal positivity, were identified. The amplitude of the early frontal positivity was measured within a 20-millisecond window centered at its estimated peak latency of 126 milliseconds at 3 pairs of frontocentral sites (F1/F2, F3/F4, and FC1/FC2). Data from 1 patient were excluded from all tests that included site F2 because of a broken contact at that electrode site. The amplitude of the late frontal positivity (onset, approximately 300 milliseconds) was tested at F3/F4.

Components were analyzed using repeated-measures multivariate analysis of variance (MANOVA) equivalent to Wilks λ (SPSS statistical software; SPSS Inc, Chicago, Ill), with a between-subject factor of group (patients or controls) and within-subject factors including hemisphere and electrode location, as appropriate. Values in the text represent mean ± SD.

BEHAVIORAL RESULTS

Stimuli were presented starting with the most fragmented version of each picture (level 7/8) and progressing to lower levels of fragmentation, terminating when subjects were able to identify the object or when the object was presented in its entirety (level 1). Control subjects correctly identified pictures 88% of the time, with a modal ID level of 3, consistent with prior findings.13,14 Patients with schizophrenia correctly identified pictures 85% of the time, with a modal ID level of 1. Hence, although patients with schizophrenia were nearly as accurate as controls when they did identify objects, they required significantly more information to do so. Figure 2 illustrates the between-group performance difference.

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Figure 2.

Behavioral performance: mean level of fragmentation at which object recognition was achieved for patients (n= 16) and controls (n = 16). For patients, P<.005. Error bars indicate SEM.

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ELECTROPHYSIOLOGICAL RESULTS
Closure Negativity: Nc1

Figure 3A shows group-averaged visual evoked potentials (VEPs) for the conditions at levels ID, 1-prior, 2-prior, and 3-prior. As in previous studies, waveforms from control subjects revealed a robust increase in activity in the 240- to 340-millisecond-latency range, corresponding to the Ncl component.

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Figure 3.

Closure negativity (Ncl)effect. A, Group-averaged (n = 16) voltage waveforms for controls (left plot) and patients with schizophrenia (right plot) at a right-hemisphere parieto-occipital electrode (P6) at the level of object identification (ID) and at 3 prior levels. B, Topographic voltage maps of the difference waveform between levels ID and 1-prior at 290 milliseconds after stimulus onset for controls (top row) and patients with schizophrenia (bottom row). Different scales were used for patients and controls to equate for overall amplitude reduction in patients. Each isocontour line represents a division. Red isocontour lines indicate positive values; purple lines, negative values. A light-blue disk indicates the location of electrode P6 shown in A. Robust bilateral negative foci characteristic of Ncl are evident over the occipitotemporal scalp for control subjects but are markedly decreased in patients with schizophrenia, even at a reduced scale.

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The Ncl amplitude was determined in both patients and controls by the construction of difference waves between the ERP for ID and 1-prior and for ID and 2-prior, followed by the determination of mean amplitude values within specified latency ranges. Mean values for both groups are shown in Table 2.

Table Graphic Jump LocationTable 2. Event-Related Potential Mean Area Measurements in Control Subjects and Patients With Schizophrenia*

Between-group differences were evaluated by MANOVA across 3 symmetric pairs of electrode locations (P5/P6, T5/T6, and PO5/PO6). A highly significant main effect for group (P<.008 for all) was found in both ID/1-prior and ID/2-prior analyses. Scalp topographic distributions for patients and controls are shown in Figure 3B. Group × electrode location (ID/1-prior: F2,28 =0.41; P = .67; ID/2-prior: F2,28 = 1.54; P = .23) and group × hemisphere (ID/1-prior: F1,29 = 2.35; P = .14; ID/2-prior: F1,29 = 0.67; P = .42) interactions were not significant between patients and controls, indicating similar topography of the potential in both groups. Mean ± SD Ncl amplitude combined across hemispheres (P5/P6) for patients was −30.1 ± 33.4 µV/ms(95% confidence interval [CI], −9.1 to –45.5), which was decreased by more than 60% (t30 = 3.31; P = .002) relative to control subjects (−76.9 ± 49.1 µV/ms[95% CI, −50.8 to –103.1]).

The groups differed in the level at which they achieved object recognition, with patients often requiring the complete picture. A control analysis, therefore, evaluated the degree to which this difference might have contributed to between-group differences in Ncl amplitude. Patients with schizophrenia showed significantly reduced Ncl amplitudes even when data were considered only from pictures identified at a noncomplete level; that is, level 2 or higher (ID/1-prior: F1,29 = 5.80; P =.03; ID/2-prior: F1,29 = 6.30; P = .02). Thus, the between-group difference in Nclamplitude could not be attributed to the differential level of fragmentation at which ID was achieved in both groups.

The P1 Component

The P1 was defined as mean area within a 90- to 110-millisecond-latency range. Figure 4A shows P1 waveforms from electrodes overlying dorsal (PO5) and ventral (T5) visual stream areas. Figure 4B shows scalp distributions for each group. A set of 3 MANOVAs(2 groups × 2 hemispheres × 3 electrode locations) tested for between-group differences in P1 amplitude at levels ID, 1-prior, and 2-prior, respectively. Mean amplitudes for P1 are reported in Table 2. All 3 analyses revealed a highly significant main effect for group, reflecting reduced P1 amplitude in patients relative to controls. Mean ± SD P1 amplitude at the ID level combined across hemispheres(PO5/PO6) in patients was 68.9 ± 46.6 µV/ms (95% CI, 44.1-93.7), which was decreased by more than 65% (t30 =3.29; P = .003) relative to that of control subjects(23.1 ± 30.4 µV/ms [95% CI, 6.9-39.3]).

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Figure 4.

Positive (P1) effect. A, Group-averaged waveforms at dorsal (PO5) and ventral (T5) left-hemisphere electrodes for controls (n = 16) and patients with schizophrenia (n = 16). Although patients showed comparable P1 amplitude at dorsal and ventral sites, control subjects showed greater amplitude at the dorsal relative to the ventral site. B, Topographic voltage maps at 100 milliseconds for the object identification level (ID) waveform for controls (top row) and patients with schizophrenia (middle row) and for the difference waveform for level ID for controls and patients (bottom row). Red isocontour lines indicate positive values; purple lines, negative values. Patients with schizophenia show a marked decrease in P1 amplitude relative to controls that can be attributed to dysfunction in dorsal P1 generators.

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To test for between-group differences in the apparent increase in P1 amplitude from 2-prior to 1-prior to ID, a 4-way MANOVA was performed (2 groups × 3 levels × 2 hemispheres × 3 electrode locations). As in the individual MANOVAs, there was a highly significant main effect for group (F1,29 = 18.14; P = .001). There was also a highly significant main effect for level (F2,28 = 7.60; P = .002) but no group × hemisphere (F1,29 =0.27; P = .61) or group × level (F2,28 = 0.07; P = .93) interaction, indicating a similar degree of impairment in P1 generation across levels for patients with schizophrenia.

All MANOVAs revealed a highly significant group × electrode location interaction (F>6.11 for all; P<.007 for all). To determine the basis for the interaction, follow-up analyses were conducted on 2 electrode pairs: the most dorsal pair (PO5/PO6) and the most ventral pair (T5/T6). Activity at both pairs of sites peaked at approximately 100 milliseconds for both groups. As shown in Figure 4A, controls demonstrated greater activity at dorsal vs ventral sites, whereas patients had similar amplitudes.

A MANOVA (2 groups × 2 hemispheres × dorsal/ventral stream electrode location) tested for differential contribution of putative P1 generators at level ID across groups. A significant main effect for group was found (F1,29 = 8.57; P = .007), as was a significant group × dorsal/ventral stream interaction (F1,29 = 12.11; P = .002). This significant interaction may reflect the greater contribution of dorsal as opposed to ventral generators to the reduced P1 in patients with schizophrenia.

To further examine the group × dorsal/ventral stream interaction, separate MANOVAs (2 groups × 2 hemispheres) were performed for dorsal and ventral stream electrode locations. Between-group differences were greater at dorsal (F1,30= 10.85; P = .004) than ventral (F1,29 = 5.17; P = .04) electrode locations. Because of spatial overlap between dorsal and ventral contributions, multivariate analysis of covariance (MANCOVA) was performed. The main effect for group persisted for dorsal sites following MANCOVA for ventral sites (F1,27 = 4.82; P = .04). In contrast, this main effect was no longer significant following MANCOVA for dorsal sites (F1,27 = 1.37; P = .25), indicating a primary contribution of the dorsal sites to the between-group deficit.

The N1 Component

The N1 was defined as mean area within a 154- to 174-millisecond-latency range (Figure 3A). A set of 3 MANOVAs(2 groups × 2 hemispheres × 3 electrode locations) tested for between-group differences in N1 amplitude at levels ID, 1-prior, and 2-prior, respectively. Each of these analyses revealed a nonsignificant main effect for group, reflecting normal N1 generation in the patient group, as shown in Table 2. Furthermore, a 4-way MANOVA (2 groups × 3 levels × 2 hemispheres × 3 electrode locations) resulted in nonsignificant group × level (F2,28 =0.18; P = .80), group × hemisphere (F1,29 = 0.08; P = .80), and group × electrode location (F2,28 = 1.24; P = .30) interactions. In addition, the 95% CI for N1 averaged across P5 and P6 electrodes was highly similar between patients (95% CI, −21.9 to –64.9) and control subjects (95% CI, −22.9 to –61.7).

Frontal Activity

Both groups showed a frontal positivity starting soon after Ncl onset (approximately 230 milliseconds). There was no apparent between-group or between-level difference in this positivity, and no increase in the amplitude of this component was apparent across stimulus levels. Visual inspection of the VEPs revealed an early frontal positivity (peak, approximately 126 milliseconds) in the schizophrenia group that was absent in the control group. Mean amplitude of this positivity across levels ID, 1-prior, 2-prior, and 3-prior was computed for each subject. Significant activity was found in patients (t15>2.87 for all; P<.01 for all) but not in controls (t15<1.45 for all; P>.17 for all). A between-group MANOVA (2 groups × 2 hemispheres × 3 electrode locations) failed to yield a significant main effect for group (F1,29 = 2.79; P = .10), but the group × electrode location interaction reached significance (F2,28 = 4.47; P = .03). Given that this early frontal positivity became apparent post-hoc and that the group effect failed to reach significance, a full analysis must await future studies targeted at eliciting the positivity.

Finally, a late frontal positivity was observed in both groups starting at approximately 300 milliseconds and continuing until the end of the epoch, as shown in Figure 5. This sustained modulation, which occurred exclusively at level ID, probably relates to maintenance of the response decision until onset of the response prompt and was similar in both groups. A MANOVA (2 groups × 3 levels × 2 hemispheres) yielded a highly significant main effect of level (F2,29 = 20.10; P = .001) but no main effect of group (F1,30 =1.57; P = .22) or hemisphere (F1,30 =.004; P = .95) and no group × level (F2,29 = 0.8; P = .46) or hemisphere × level (F2,29 = 0.76; P = .50) interaction.

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Figure 5.

Frontal activity. Group-averaged(n = 16) voltage waveforms for controls (left plot) and patients with schizophrenia(right plot) at a left-hemisphere frontal electrode (F3) at the level of object identification (ID) and at 3 prior levels.

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The Ncl is a newly defined component of the VEP that indexes perceptual closure processes over ventral stream object recognition areas of the visual system.13,14 To our knowledge, this study provides the first demonstration of reduced Ncl amplitude in schizophrenia. The deficit is selective in that generation of the preceding N1 component, which is also generated over ventral object recognition areas, is not impaired. Moreover, the deficit in Nclgeneration is consistent with impaired perceptual closure ability observed previously10 and in this study.

As we have previously shown, the scalp distribution of Ncl is consistent with generators within the LOC. Impaired Ncl generation thus suggests brain dysfunction at the level of the LOC. Dysfunction within the LOC may account for other well-documented sensory-processing deficits in schizophrenia, including prolonged duration thresholds for object recognition and increased sensitivity to visual backward masking.7,3638 As with these other deficits, it remains to be determined whether the LOC itself is dysfunctional or whether prior stages of information processing may also be impaired.

Information concerning mechanisms of LOC dysfunction can be obtained by analyzing the integrity of VEPs that precede Ncl in response to fragmented stimuli. The N1, a component that indexes perceptual discrimination within the LOC,27,3941 was normal in amplitude across all conditions. In contrast, P1, a component with both dorsal and ventral stream generators, was significantly reduced in amplitude, especially over dorsal stream sites. This pattern of ERP deficits permits specific hypotheses to be developed concerning brain processes underlying impaired visual sensory processing in schizophrenia.

The normal amplitude of the visual N1 observed in our study is consistent with the results of prior VEP studies on schizophrenia42 and distinguishes visual N1, which is normal in schizophrenia, from auditory N1, which is reduced.43 Therefore, a consistent finding in the visual system in schizophrenia may be that the initial stages of ventral stream processing are intact, whereas later stages are impaired.

Visual N1 is thought to reflect general feature discrimination mediated by ventral stream object recognition areas such as the LOC. For example, N1 is larger when subjects must discriminate between classes of objects based on intrinsic physical characteristics vs when subjects need only determine whether an object is present or absent.28,44 Furthermore, in the fragmented-image task used in our study, N1 is larger for identified repeated images than for the same images at first presentation, suggesting that discrimination between repeated objects vs perceptual closure of novel objects represents discrete stages of processing.14 Similarly, perceptual discrimination of illusory shapes (Kanisza figures) also gives rise to N1 enhancement.45,46 The finding of normal N1 generation despite impaired Ncl generation localizes the information-processing deficit in schizophrenia in both time and space. Further analysis of the perceptual closure deficit may help identify dysfunctional brain processes, as well as dysfunctional brain regions, in schizophrenia.

The finding of intact N1 generation also argues against differential levels of attention or task engagement as an explanation for our findings. The N1 amplitude, in general, is greater for attended stimuli as compared with nonattended stimuli or a neutral condition.47,48 The finding that N1 amplitude was similar between patients and controls therefore argues that the 2 groups had similar levels of task engagement.

In contrast to N1, which was unaffected, P1 amplitude was significantly and substantially reduced in the patients with schizophrenia. The P1 arises from generators in both dorsal and ventral stream structures,2025 whereas N1 arises primarily from ventral stream structures. Topographical analyses were conducted to better characterize the basis for the P1 reduction. Although significant reductions were observed over both dorsal and ventral stream structures, the degree of reduction was greater over dorsal than over ventral stream sites. Moreover, the P1 reduction persisted over dorsal structures following MANCOVA for ventral sites but disappeared over ventral structures following MANCOVA for dorsal sites. Thus, the P1 data suggest relatively preserved initial ventral stream processing but substantially impaired processing within the dorsal stream, even at latencies as short as 100 milliseconds following stimulus onset.

The selective impairment of dorsal P1 generation observed in our study is consistent with the results of a recent steady-state VEP study that showed reduced responses to magnocellularly biased (dorsal stream) stimuli but intact responses to parvocellularly biased (ventral stream) stimuli.49

The P1 is known to be modulated by spatial attention.47,48 However, it is unlikely that differences in spatial attention account for our findings because there was no spatial attention manipulation. Furthermore, the attentional modulation of P1 has not been observed for stimuli presented centrally, as in this study. Finally, N1 effects typically accompany P1 spatial attention effects.50,51 As noted previously, no N1 deficits were observed in our study.

Because of the highly specific pattern of ERP deficit observed in this study, it is possible to propose a rela tively specific, circuit-based model to account for our findings. The ventral visual stream receives not only direct parvocellular projections from the LGN but also indirect crossover projections from the dorsal stream.18,5255 Because transmission is much more rapid in the dorsal stream than the ventral stream, crossover input to higher-tier ventral stream regions such as the LOC may precede direct parvocellularly mediated input.1719 It has been proposed that the faster transmission and spatial-coding properties of the dorsal stream are ideal for "spotlighting" relevant information for transmission to ventral stream regions, so that crossover input from the dorsal stream may modulate activity within ventral stream structures.18,5355

These theories raise the possibility that impaired Ncl generation reflects impaired modulation of the LOC via crossover input from the dorsal stream, rather than intrinsic LOC dysfunction. Such a model would explain the relatively intact preliminary processing within the LOC, as reflected in the normal N1 generation. In addition, it would suggest that a single underlying deficit (magnocellular dorsal stream dysfunction) could account for both the P1 and Ncl deficits observed in our study. This model would also explain the behavioral finding that patients with schizophrenia are particularly impaired in the ability to use motion information for object recognition.30

Impaired dorsal stream processing, as reflected by deficient dorsal P1 generation, may also explain deficits that patients with schizophrenia show in processing local vs global stimulus features. The P1 amplitude is enhanced when subjects are required to process local vs global features of hierarchical stimuli (eg, large arrows composed of smaller arrows),5658 reflecting greater activation of the dorsal stream in these conditions. The results of these ERP studies are consistent with those of lesion studies demonstrating that dorsal stream (inferior parietal) lesions impair the ability to alternate between local and global processing, whereas frontal lesions do not.59

Patients with schizophrenia have a selective deficit in the ability to process hierarchical stimuli at the local level.60,61 Such a deficit is consistent with the reduced P1 amplitude observed in this study and suggests that the perceptual closure deficit may be due in part to the reduced ability of patients to process local features of the fragmented stimuli.

Although prefrontal dysfunction is known to play an important role in the pathophysiologic characteristics of schizophrenia,6265 it is unlikely that such deficits contribute appreciably to such abnormalities in our study. No perceptual closure–related activity was observed over the frontal cortex in either group until after the onset of Ncl. Furthermore, post-Ncl activity in the frontal cortex was evident exclusively when object recognition had been achieved14 and did not differ between groups. This late activity is likely related to maintenance of the yes/no decision once closure either had or had not been achieved. These findings are consistent with the results of a recent functional magnetic resonance imaging study showing closure-related activity in the fusiform gyrus and occipitotemporal sulcus but not in frontal regions during object recognition.66

Interestingly, the earliest frontal activity was observed in the patients with schizophrenia. This activity (peak, approximately 126 milliseconds) was evident immediately following the reduced posterior P1 observed in these patients and may reflect attempted frontal compensation for impaired automatic stimulus processing within the visual sensory regions (Figure 5).

A limitation of our study is that all patients with schizophrenia were receiving medication at the time of testing.67 However, visual-processing deficits in schizophrenia have been shown irrespective of whether patients were taking medication.7 In addition, our study showed no significant correlation between antipsychotic medication dose and behavioral or ERP measures.

In summary, to our knowledge, this is the first study to demonstrate neural dysfunction in perceptual closure processes in schizophrenia. The main finding of our study is profound impairment in Ncl (peak, approximately 290 milliseconds), a novel ERP component generated over the LOC that has been shown to grow incrementally with reduced levels of fragmentation prior to object recognition.13,14 In addition, there was a decrease in amplitude of the early P1 component that was greater over dorsal than ventral structures in patients with schizophrenia, indicating selective dysfunction of dorsal stream P1 generators. Decreases in Ncl and P1 were in stark contrast to the intervening N1 component, which was of normal amplitude and time course in these patients, suggesting intact ventral stream processing prior to Ncl. This study thus supports earlier work showing a dysfunction of magnocellular dorsal stream processing in schizophrenia.13,14 Furthermore, it suggests that a primary deficit in magnocellular dorsal stream processing may lead to secondary impairment of object recognition processes within ventral stream object-processing regions such as the LOC. Finally, it indicates a specific time course for interactions between dorsal and ventral processing that may be relevant to the pathophysiologic characteristics of information-processing dysfunction in schizophrenia.

Submitted for publication July 17, 2001; final revision received February 11, 2002; accepted February 22, 2002.

Supported by National Research Service Award MH12691 (Dr Doniger) and grants RO1 MH49334 and K02 MH01439 from the National Institute of Mental Health, Bethesda, Md; and by a Clinical Scientist Award (Dr Javitt) from the Burroughs Wellcome Fund, Research Triangle Park, NC.

Presented in part at the Eighth Annual Meeting of the Cognitive Neuroscience Society, New York, NY, March 26, 2001.

We sincerely thank Gail Silipo for assistance in the collection of demographic and clinical data and Jin Fan for programming assistance. Special thanks to Charles E. Schroeder, PhD, and Joan Gay Snodgrass, MA, for valuable discussions.

Corresponding author and reprints: Daniel C. Javitt, MD, PhD, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd, Orangeburg, NY 10962 (e-mail: javitt@nki.rfmh.org).

Andreasen  NC Schizophrenia: the fundamental questions. Brain Res Brain Res Rev. 2000;31106- 112
Link to Article
Javitt  DCLiederman  ECienfuegos  AShelley  AM Panmodal processing imprecision as a basis for dysfunction of transient memory storage systems in schizophrenia. Schizophr Bull. 1999;25763- 775
Link to Article
Chen  YLevy  DLNakayama  KMatthysse  SPalafox  GHolzman  PS Dependence of impaired eye tracking on deficient velocity discrimination in schizophrenia. Arch Gen Psychiatry. 1999;56155- 161
Link to Article
Chen  YNakayama  KLevy  DLMatthysse  SHolzman  PS Psychophysical isolation of a motion-processing deficit in schizophrenics and their relatives and its association with impaired smooth pursuit. Proc Natl Acad Sci U S A. 1999;964724- 4729
Link to Article
Cornblatt  BAKeilp  JG Impaired attention, genetics, and the pathophysiology of schizophrenia. Schizophr Bull. 1994;2031- 46
Link to Article
Braff  DLSaccuzzo  DP Effect of antipsychotic medication on speed of information processing in schizophrenic patients. Am J Psychiatry. 1982;1391127- 1130
Butler  PBHarkavy-Friedman  JMAmador  XFGorman  JM Backward masking in schizophrenia: relationship to medication status, neuropsychological functioning, and dopamine metabolism. Biol Psychiatry. 1996;40295- 298
Link to Article
Green  MFNuechterlein  KHBreitmeyer  BMintz  J Backward masking in unmedicated schizophrenic patients in psychotic remission: possible reflection of aberrant cortical oscillation. Am J Psychiatry. 1999;1561367- 1373
Kee  KSKern  RSGreen  MF Perception of emotion and neurocognitive functioning in schizophrenia: what's the link? Psychiatry Res. 1998;8157- 65
Link to Article
Doniger  GMSilipo  GRabinowicz  ESnodgrass  JGJavitt  DC Impaired sensory processing as a basis for object recognition deficits in schizophrenia. Am J Psychiatry. 2001;1581818- 1826
Link to Article
Bartlett  FC An experimental study of some problems of perceiving and imagining. Br J Psychol. 1916;8222- 266
Snodgrass  JGFeenan  K Priming effects in picture fragment completion: support for the perceptual closure hypothesis. J Exp Psychol Gen. 1990;119276- 296
Link to Article
Doniger  GMFoxe  JJMurray  MMHiggins  BASnodgrass  JGSchroeder  CEJavitt  DC Activation timecourse of ventral visual stream object-recognition areas: high density electrical mapping of perceptual closure processes. J Cogn Neurosci. 2000;12615- 621
Link to Article
Doniger  GMFoxe  JJSchroeder  CEMurray  MMHiggins  BAJavitt  DC Visual perceptual learning in human object recognition areas: a repetition priming study using high-density electrical mapping. Neuroimage. 2001;13305- 313
Link to Article
Ungerleider  LGMishkin  M Two cortical visual systems. Ingle  DJMansfield  RJWGoodale  MSeds.The Analysis of Visual Behavior Cambridge, Mass MIT Press1982;549- 586
Callaway  EM Local circuits in primary visual cortex of the macaque monkey. Annu Rev Neurosci. 1998;2147- 74
Link to Article
Schroeder  CEMehta  ADFoxe  JJ Determinants and mechanisms of attentional modulation of neural processing. Front Biosci. 2001;6D672- D684
Link to Article
Schroeder  CEMehta  ADGivre  SJ A spatiotemporal profile of visual system activation revealed by current source density analysis in the awake macaque. Cereb Cortex. 1998;8575- 592
Link to Article
Schmolesky  MTWang  YHanes  DPThompson  KGLeutgeb  SSchall  JDLeventhal  AG Signal timing across the macaque visual system. J Neurophysiol. 1998;793272- 3278
Heinze  HJMangun  GRBurchert  WHinrichs  HScholz  MMunte  TFGos  AScherg  MJohannes  SHundeshagen  HGazzaniga  MSHillyard  SA Combined spatial and temporal imaging of brain activity during visual selective attention in humans. Nature. 1994;372543- 546
Link to Article
Mangun  GRHopfinger  JBKussmaul  CLFletcher  EMHeinze  HJ Covariations in ERP and PET measures of spatial selective attention in human extrastriate visual cortex. Hum Brain Mapp. 1997;5273- 279
Link to Article
Murray  MMFoxe  JJHiggins  BAJavitt  DCSchroeder  CE Visuo-spatial neural response interactions in early cortical processing during a simple reaction time task: a high-density electrical mapping study. Neuropsychologia. 2001;39828- 844
Link to Article
Murray  MMFoxe  JJHiggins  BASchroeder  CEJavitt  DC Intact illusory contour processing despite diminished early visual cortical responses in schizophrenia. J Cogn Neurosci Suppl. 2001;104
Simpson  GVFoxe  JJVaughan  HG  JrMehta  ADSchroeder  CE Integration of electrophysiological source analyses, MRI and animal models in the study of visual processing and attention. Electroencephalogr Clin Neurophysiol Suppl. 1995;4476- 92
Woldorff  MGFox  PTMatzke  MLancaster  JL Retinotopic organization of early visual spatial attention effects as revealed by PET and ERPs. Hum Brain Mapp. 1997;5280- 286
Link to Article
Allison  TPuce  ASpencer  DDMcCarthy  G Electrophysiological studies of human face perception, I: potentials generated in occipitotemporal cortex by face and non-face stimuli. Cereb Cortex. 1999;9415- 430
Link to Article
Mouchetant-Rostaing  YGiard  MHBentin  SAguera  PEPernier  J Neurophysiological correlates of face gender processing in humans. Eur J Neurosci. 2000;12303- 310
Link to Article
Vogel  EKLuck  SJ The visual N1 component as an index of a discrimination process. Psychophysiology. 2000;37190- 203
Link to Article
Schwartz  BDMaron  BAEvans  WJWinstead  DK High velocity transient visual processing deficits diminish ability of patients with schizophrenia to recognize objects. Neuropsychiatry Neuropsychol Behav Neurol. 1999;12170- 177
Schwartz  BDMaron  BAEvans  WJWinstead  DK Smooth pursuit tracking deficits of patients with schizophrenia at specific within-sine wave bins. Neuropsychiatry Neuropsychol Behav Neurol. 1999;12221- 229
Spitzer  RLWilliams  JBWGibbon  MFirst  MB Structured Clinical Interview for DSM-III-R–Non-Patient Edition (SCID-NP, Version 1.0).  Washington, DC American Psychiatric Press1990;
White  LHarvey  PDOpler  LLindenmayer  JP Empirical assessment of the factorial structure of clinical symptoms in schizophrenia: a multisite, multimodel evaluation of the factorial structure of the Positive and Negative Syndrome Scale: the PANSS Study Group. Psychopathology. 1997;30263- 274
Link to Article
Snodgrass  JGVanderwart  M A standardized set of 260 pictures: norms for name agreement, image agreement, familiarity, and visual complexity. J Exp Psychol [Hum Learn]. 1980;6174- 215
Link to Article
Cycowicz  YMFriedman  DRothstein  MSnodgrass  JG Picture naming by young children: norms for name agreement, familiarity, and visual complexity. J Exp Child Psychol. 1997;65171- 237
Link to Article
Snodgrass  JGCorwin  J Perceptual identification thresholds for 150 fragmented pictures from the Snodgrass and Vanderwart picture set. Percept Mot Skills. 1988;673- 36
Link to Article
Saccuzzo  DPBraff  DL Information-processing abnormalities: trait- and state-dependent components. Schizophr Bull. 1986;12447- 459
Link to Article
Slaghuis  WLBakker  VJ Forward and backward visual masking of contour by light in positive- and negative-symptom schizophrenia. J Abnorm Psychol. 1995;10441- 54
Link to Article
Weiner  RUOpler  LAKay  SRMerriam  AEPapouchis  N Visual information processing in positive, mixed, and negative schizophrenic syndromes. J Nerv Ment Dis. 1990;178616- 626
Link to Article
Bentin  SAllison  TPuce  APerez  EMcCarthy  G Electrophysiological studies of face perception in humans. J Cogn Neurosci. 1996;8551- 565
Link to Article
Eimer  M Effects of face inversion on the structural encoding and recognition of faces: evidence from event-related brain potentials. Brain Res Cogn Brain Res. 2000;10145- 158
Link to Article
Rossion  BGauthier  ITarr  MJDespland  PBruyer  RLinotte  SCrommelinck  M The N170 occipito-temporal component is delayed and enhanced to inverted faces but not to inverted objects: an electrophysiological account of face-specific processes in the human brain. Neuroreport. 2000;1169- 74
Link to Article
Shelley  AMGrochowski  SLieberman  JAJavitt  DC Premature disinhibition of P3 generation in schizophrenia. Biol Psychiatry. 1996;39714- 719
Link to Article
Shelley  AMSilipo  GJavitt  DC Diminished responsiveness of ERPs in schizophrenic subjects to changes in auditory stimulation parameters: implications for theories of cortical dysfunction. Schizophr Res. 1999;3765- 79
Link to Article
Mangun  GRHillyard  SA Modulations of sensory-evoked brain potentials indicate changes in perceptual processing during visual-spatial priming. J Exp Psychol Hum Percept Perform. 1991;171057- 1074
Link to Article
Murray  MMWylie  GRHiggins  BAJavitt  DCSchroeder  CEFoxe  JJ A spatio-temporal dynamics of illusory contour processing: combined high-density electrical mapping, source analysis, and functional magnetic resonance imaging. J Neurosci. 2002;225055- 5073
Murray  MMWylie  GRHiggins  BAJavitt  DCSchroeder  CEFoxe  JJ Spatio-temporal analysis of illusory contour processing: combined high-density electrical mapping, source analysis, and functional magnetic resonance imaging. J Neurosci. 2002;225055- 5073
Luck  SJHillyard  SA The role of attention in feature detection and conjunction discrimination: an electrophysiological analysis. Int J Neurosci. 1995;80281- 297
Link to Article
Luck  SJHillyard  SAMouloua  MWoldorff  MGClark  VPHawkins  HL Effects of spatial cuing on luminance detectability: psychophysical and electrophysiological evidence for early selection. J Exp Psychol Hum Percept Perform. 1994;20887- 904
Link to Article
Butler  PBSchechter  IZemon  VSchwartz  SGGreenstein  VCGordon  JSchroeder  CEJavitt  DC Dysfunction of early stage visual processing in schizophrenia. Am J Psychiatry. 2001;1581126- 1133
Link to Article
Martinez  AAnllo-Vento  LSereno  MIFrank  LRBuxton  RBDubowitz  DJWong  ECHinrichs  HHeinze  HJHillyard  SA Involvement of striate and extrastriate visual cortical areas in spatial attention. Nat Neurosci. 1999;2364- 369
Link to Article
Gomez Gonzalez  CMClark  VPFan  SLuck  SJHillyard  SA Sources of attention-sensitive visual event-related potentials. Brain Topogr. 1994;741- 51
Link to Article
Merigan  WHMaunsell  JH How parallel are the primate visual pathways? Annu Rev Neurosci. 1993;16369- 402
Link to Article
Foxe  JJSimpson  GVAhlfors  SP Parieto-occipital approximately 10 Hz activity reflects anticipatory state of visual attention mechanisms. Neuroreport. 1998;93929- 3933
Link to Article
Nowak  LGBullier  J The timing of information transfer in the visual system. Rockland  KKaas  JPeters  Aeds.Cerebral Cortex, Vol. 12: Extrastriate Cortex New York, NY Plenum Press1997;205- 241
Vidyasagar  TR A neuronal model of attentional spotlight: parietal guiding the temporal. Brain Res Brain Res Rev. 1999;3066- 76
Link to Article
Han  SFan  SChen  LZhuo  Y Modulation of brain activities by hierarchical processing: a high-density ERP study. Brain Topogr. 1999;11171- 183
Link to Article
Han  SHe  XWoods  DL Hierarchical processing and level-repetition effect as indexed by early brain potentials. Psychophysiology. 2000;37817- 830
Link to Article
Han  SLiu  WYund  EWWoods  DL Interactions between spatial attention and global/local feature selection: an ERP study. Neuroreport. 2000;112753- 2758
Link to Article
Robertson  LCLamb  MRKnight  RT Normal global-local analysis in patients with dorsolateral frontal lobe lesions. Neuropsychologia. 1991;29959- 967
Link to Article
Granholm  EPerry  WFiloteo  JVBraff  D Hemispheric and attentional contributions to perceptual organization deficits on the global-local task in schizophrenia. Neuropsychology. 1999;13271- 281
Link to Article
Carter  CSRobertson  LCNordahl  TEChaderjian  MOshora-Celaya  L Perceptual and attentional asymmetries in schizophrenia: further evidence for a left hemisphere deficit. Psychiatry Res. 1996;62111- 119
Link to Article
Weinberger  DRBerman  KF Prefrontal function in schizophrenia: confounds and controversies. Philos Trans R Soc Lond B Biol Sci. 1996;3511495- 1503
Link to Article
Carter  CSPerlstein  WGanguli  RBrar  JMintun  MCohen  JD Functional hypofrontality and working memory dysfunction in schizophrenia. Am J Psychiatry. 1998;1551285- 1287
Andreasen  NCRezai  KAlliger  RSwayze  VW  IIFlaum  MKirchner  PCohen  GO'Leary  DS Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia: assessment with xenon 133 single-photon emission computed tomography and the Tower of London. Arch Gen Psychiatry. 1992;49943- 958
Link to Article
Goldman-Rakic  PSSelemon  LD Functional and anatomical aspects of prefrontal pathology in schizophrenia. Schizophr Bull. 1997;23437- 458
Link to Article
Bar  MTootell  RBSchacter  DLGreve  DNFischl  BMendola  JDRosen  BRDale  AM Cortical mechanisms specific to explicit visual object recognition. Neuron. 2001;29529- 535
Link to Article
Spohn  HELacoursiere  RBThompson  KCoyne  L Phenothiazine effects on psychological and psychophysiological dysfunction in chronic schizophrenics. Arch Gen Psychiatry. 1977;34633- 644
Link to Article

Figures

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Figure 1.

Stimulus configuration. A, Images displayed from least complete to most complete (4 of 8 levels shown). B, Onset of the most fragmented image (level 8) at 0 milliseconds (duration, 750 milliseconds), followed by a yes/no response prompt (R) (duration, 200 milliseconds) at 1550 milliseconds. A no response resulted in presentation of the next-level image 2.2 seconds after the response prompt. A yes response terminated the sequence for the subject's verbal response.

Graphic Jump Location
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Figure 2.

Behavioral performance: mean level of fragmentation at which object recognition was achieved for patients (n= 16) and controls (n = 16). For patients, P<.005. Error bars indicate SEM.

Graphic Jump Location
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Figure 3.

Closure negativity (Ncl)effect. A, Group-averaged (n = 16) voltage waveforms for controls (left plot) and patients with schizophrenia (right plot) at a right-hemisphere parieto-occipital electrode (P6) at the level of object identification (ID) and at 3 prior levels. B, Topographic voltage maps of the difference waveform between levels ID and 1-prior at 290 milliseconds after stimulus onset for controls (top row) and patients with schizophrenia (bottom row). Different scales were used for patients and controls to equate for overall amplitude reduction in patients. Each isocontour line represents a division. Red isocontour lines indicate positive values; purple lines, negative values. A light-blue disk indicates the location of electrode P6 shown in A. Robust bilateral negative foci characteristic of Ncl are evident over the occipitotemporal scalp for control subjects but are markedly decreased in patients with schizophrenia, even at a reduced scale.

Graphic Jump Location
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Figure 4.

Positive (P1) effect. A, Group-averaged waveforms at dorsal (PO5) and ventral (T5) left-hemisphere electrodes for controls (n = 16) and patients with schizophrenia (n = 16). Although patients showed comparable P1 amplitude at dorsal and ventral sites, control subjects showed greater amplitude at the dorsal relative to the ventral site. B, Topographic voltage maps at 100 milliseconds for the object identification level (ID) waveform for controls (top row) and patients with schizophrenia (middle row) and for the difference waveform for level ID for controls and patients (bottom row). Red isocontour lines indicate positive values; purple lines, negative values. Patients with schizophenia show a marked decrease in P1 amplitude relative to controls that can be attributed to dysfunction in dorsal P1 generators.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 5.

Frontal activity. Group-averaged(n = 16) voltage waveforms for controls (left plot) and patients with schizophrenia(right plot) at a left-hemisphere frontal electrode (F3) at the level of object identification (ID) and at 3 prior levels.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Demographic and Clinical Characteristics of Patients With Schizophrenia*
Table Graphic Jump LocationTable 2. Event-Related Potential Mean Area Measurements in Control Subjects and Patients With Schizophrenia*

References

Andreasen  NC Schizophrenia: the fundamental questions. Brain Res Brain Res Rev. 2000;31106- 112
Link to Article
Javitt  DCLiederman  ECienfuegos  AShelley  AM Panmodal processing imprecision as a basis for dysfunction of transient memory storage systems in schizophrenia. Schizophr Bull. 1999;25763- 775
Link to Article
Chen  YLevy  DLNakayama  KMatthysse  SPalafox  GHolzman  PS Dependence of impaired eye tracking on deficient velocity discrimination in schizophrenia. Arch Gen Psychiatry. 1999;56155- 161
Link to Article
Chen  YNakayama  KLevy  DLMatthysse  SHolzman  PS Psychophysical isolation of a motion-processing deficit in schizophrenics and their relatives and its association with impaired smooth pursuit. Proc Natl Acad Sci U S A. 1999;964724- 4729
Link to Article
Cornblatt  BAKeilp  JG Impaired attention, genetics, and the pathophysiology of schizophrenia. Schizophr Bull. 1994;2031- 46
Link to Article
Braff  DLSaccuzzo  DP Effect of antipsychotic medication on speed of information processing in schizophrenic patients. Am J Psychiatry. 1982;1391127- 1130
Butler  PBHarkavy-Friedman  JMAmador  XFGorman  JM Backward masking in schizophrenia: relationship to medication status, neuropsychological functioning, and dopamine metabolism. Biol Psychiatry. 1996;40295- 298
Link to Article
Green  MFNuechterlein  KHBreitmeyer  BMintz  J Backward masking in unmedicated schizophrenic patients in psychotic remission: possible reflection of aberrant cortical oscillation. Am J Psychiatry. 1999;1561367- 1373
Kee  KSKern  RSGreen  MF Perception of emotion and neurocognitive functioning in schizophrenia: what's the link? Psychiatry Res. 1998;8157- 65
Link to Article
Doniger  GMSilipo  GRabinowicz  ESnodgrass  JGJavitt  DC Impaired sensory processing as a basis for object recognition deficits in schizophrenia. Am J Psychiatry. 2001;1581818- 1826
Link to Article
Bartlett  FC An experimental study of some problems of perceiving and imagining. Br J Psychol. 1916;8222- 266
Snodgrass  JGFeenan  K Priming effects in picture fragment completion: support for the perceptual closure hypothesis. J Exp Psychol Gen. 1990;119276- 296
Link to Article
Doniger  GMFoxe  JJMurray  MMHiggins  BASnodgrass  JGSchroeder  CEJavitt  DC Activation timecourse of ventral visual stream object-recognition areas: high density electrical mapping of perceptual closure processes. J Cogn Neurosci. 2000;12615- 621
Link to Article
Doniger  GMFoxe  JJSchroeder  CEMurray  MMHiggins  BAJavitt  DC Visual perceptual learning in human object recognition areas: a repetition priming study using high-density electrical mapping. Neuroimage. 2001;13305- 313
Link to Article
Ungerleider  LGMishkin  M Two cortical visual systems. Ingle  DJMansfield  RJWGoodale  MSeds.The Analysis of Visual Behavior Cambridge, Mass MIT Press1982;549- 586
Callaway  EM Local circuits in primary visual cortex of the macaque monkey. Annu Rev Neurosci. 1998;2147- 74
Link to Article
Schroeder  CEMehta  ADFoxe  JJ Determinants and mechanisms of attentional modulation of neural processing. Front Biosci. 2001;6D672- D684
Link to Article
Schroeder  CEMehta  ADGivre  SJ A spatiotemporal profile of visual system activation revealed by current source density analysis in the awake macaque. Cereb Cortex. 1998;8575- 592
Link to Article
Schmolesky  MTWang  YHanes  DPThompson  KGLeutgeb  SSchall  JDLeventhal  AG Signal timing across the macaque visual system. J Neurophysiol. 1998;793272- 3278
Heinze  HJMangun  GRBurchert  WHinrichs  HScholz  MMunte  TFGos  AScherg  MJohannes  SHundeshagen  HGazzaniga  MSHillyard  SA Combined spatial and temporal imaging of brain activity during visual selective attention in humans. Nature. 1994;372543- 546
Link to Article
Mangun  GRHopfinger  JBKussmaul  CLFletcher  EMHeinze  HJ Covariations in ERP and PET measures of spatial selective attention in human extrastriate visual cortex. Hum Brain Mapp. 1997;5273- 279
Link to Article
Murray  MMFoxe  JJHiggins  BAJavitt  DCSchroeder  CE Visuo-spatial neural response interactions in early cortical processing during a simple reaction time task: a high-density electrical mapping study. Neuropsychologia. 2001;39828- 844
Link to Article
Murray  MMFoxe  JJHiggins  BASchroeder  CEJavitt  DC Intact illusory contour processing despite diminished early visual cortical responses in schizophrenia. J Cogn Neurosci Suppl. 2001;104
Simpson  GVFoxe  JJVaughan  HG  JrMehta  ADSchroeder  CE Integration of electrophysiological source analyses, MRI and animal models in the study of visual processing and attention. Electroencephalogr Clin Neurophysiol Suppl. 1995;4476- 92
Woldorff  MGFox  PTMatzke  MLancaster  JL Retinotopic organization of early visual spatial attention effects as revealed by PET and ERPs. Hum Brain Mapp. 1997;5280- 286
Link to Article
Allison  TPuce  ASpencer  DDMcCarthy  G Electrophysiological studies of human face perception, I: potentials generated in occipitotemporal cortex by face and non-face stimuli. Cereb Cortex. 1999;9415- 430
Link to Article
Mouchetant-Rostaing  YGiard  MHBentin  SAguera  PEPernier  J Neurophysiological correlates of face gender processing in humans. Eur J Neurosci. 2000;12303- 310
Link to Article
Vogel  EKLuck  SJ The visual N1 component as an index of a discrimination process. Psychophysiology. 2000;37190- 203
Link to Article
Schwartz  BDMaron  BAEvans  WJWinstead  DK High velocity transient visual processing deficits diminish ability of patients with schizophrenia to recognize objects. Neuropsychiatry Neuropsychol Behav Neurol. 1999;12170- 177
Schwartz  BDMaron  BAEvans  WJWinstead  DK Smooth pursuit tracking deficits of patients with schizophrenia at specific within-sine wave bins. Neuropsychiatry Neuropsychol Behav Neurol. 1999;12221- 229
Spitzer  RLWilliams  JBWGibbon  MFirst  MB Structured Clinical Interview for DSM-III-R–Non-Patient Edition (SCID-NP, Version 1.0).  Washington, DC American Psychiatric Press1990;
White  LHarvey  PDOpler  LLindenmayer  JP Empirical assessment of the factorial structure of clinical symptoms in schizophrenia: a multisite, multimodel evaluation of the factorial structure of the Positive and Negative Syndrome Scale: the PANSS Study Group. Psychopathology. 1997;30263- 274
Link to Article
Snodgrass  JGVanderwart  M A standardized set of 260 pictures: norms for name agreement, image agreement, familiarity, and visual complexity. J Exp Psychol [Hum Learn]. 1980;6174- 215
Link to Article
Cycowicz  YMFriedman  DRothstein  MSnodgrass  JG Picture naming by young children: norms for name agreement, familiarity, and visual complexity. J Exp Child Psychol. 1997;65171- 237
Link to Article
Snodgrass  JGCorwin  J Perceptual identification thresholds for 150 fragmented pictures from the Snodgrass and Vanderwart picture set. Percept Mot Skills. 1988;673- 36
Link to Article
Saccuzzo  DPBraff  DL Information-processing abnormalities: trait- and state-dependent components. Schizophr Bull. 1986;12447- 459
Link to Article
Slaghuis  WLBakker  VJ Forward and backward visual masking of contour by light in positive- and negative-symptom schizophrenia. J Abnorm Psychol. 1995;10441- 54
Link to Article
Weiner  RUOpler  LAKay  SRMerriam  AEPapouchis  N Visual information processing in positive, mixed, and negative schizophrenic syndromes. J Nerv Ment Dis. 1990;178616- 626
Link to Article
Bentin  SAllison  TPuce  APerez  EMcCarthy  G Electrophysiological studies of face perception in humans. J Cogn Neurosci. 1996;8551- 565
Link to Article
Eimer  M Effects of face inversion on the structural encoding and recognition of faces: evidence from event-related brain potentials. Brain Res Cogn Brain Res. 2000;10145- 158
Link to Article
Rossion  BGauthier  ITarr  MJDespland  PBruyer  RLinotte  SCrommelinck  M The N170 occipito-temporal component is delayed and enhanced to inverted faces but not to inverted objects: an electrophysiological account of face-specific processes in the human brain. Neuroreport. 2000;1169- 74
Link to Article
Shelley  AMGrochowski  SLieberman  JAJavitt  DC Premature disinhibition of P3 generation in schizophrenia. Biol Psychiatry. 1996;39714- 719
Link to Article
Shelley  AMSilipo  GJavitt  DC Diminished responsiveness of ERPs in schizophrenic subjects to changes in auditory stimulation parameters: implications for theories of cortical dysfunction. Schizophr Res. 1999;3765- 79
Link to Article
Mangun  GRHillyard  SA Modulations of sensory-evoked brain potentials indicate changes in perceptual processing during visual-spatial priming. J Exp Psychol Hum Percept Perform. 1991;171057- 1074
Link to Article
Murray  MMWylie  GRHiggins  BAJavitt  DCSchroeder  CEFoxe  JJ A spatio-temporal dynamics of illusory contour processing: combined high-density electrical mapping, source analysis, and functional magnetic resonance imaging. J Neurosci. 2002;225055- 5073
Murray  MMWylie  GRHiggins  BAJavitt  DCSchroeder  CEFoxe  JJ Spatio-temporal analysis of illusory contour processing: combined high-density electrical mapping, source analysis, and functional magnetic resonance imaging. J Neurosci. 2002;225055- 5073
Luck  SJHillyard  SA The role of attention in feature detection and conjunction discrimination: an electrophysiological analysis. Int J Neurosci. 1995;80281- 297
Link to Article
Luck  SJHillyard  SAMouloua  MWoldorff  MGClark  VPHawkins  HL Effects of spatial cuing on luminance detectability: psychophysical and electrophysiological evidence for early selection. J Exp Psychol Hum Percept Perform. 1994;20887- 904
Link to Article
Butler  PBSchechter  IZemon  VSchwartz  SGGreenstein  VCGordon  JSchroeder  CEJavitt  DC Dysfunction of early stage visual processing in schizophrenia. Am J Psychiatry. 2001;1581126- 1133
Link to Article
Martinez  AAnllo-Vento  LSereno  MIFrank  LRBuxton  RBDubowitz  DJWong  ECHinrichs  HHeinze  HJHillyard  SA Involvement of striate and extrastriate visual cortical areas in spatial attention. Nat Neurosci. 1999;2364- 369
Link to Article
Gomez Gonzalez  CMClark  VPFan  SLuck  SJHillyard  SA Sources of attention-sensitive visual event-related potentials. Brain Topogr. 1994;741- 51
Link to Article
Merigan  WHMaunsell  JH How parallel are the primate visual pathways? Annu Rev Neurosci. 1993;16369- 402
Link to Article
Foxe  JJSimpson  GVAhlfors  SP Parieto-occipital approximately 10 Hz activity reflects anticipatory state of visual attention mechanisms. Neuroreport. 1998;93929- 3933
Link to Article
Nowak  LGBullier  J The timing of information transfer in the visual system. Rockland  KKaas  JPeters  Aeds.Cerebral Cortex, Vol. 12: Extrastriate Cortex New York, NY Plenum Press1997;205- 241
Vidyasagar  TR A neuronal model of attentional spotlight: parietal guiding the temporal. Brain Res Brain Res Rev. 1999;3066- 76
Link to Article
Han  SFan  SChen  LZhuo  Y Modulation of brain activities by hierarchical processing: a high-density ERP study. Brain Topogr. 1999;11171- 183
Link to Article
Han  SHe  XWoods  DL Hierarchical processing and level-repetition effect as indexed by early brain potentials. Psychophysiology. 2000;37817- 830
Link to Article
Han  SLiu  WYund  EWWoods  DL Interactions between spatial attention and global/local feature selection: an ERP study. Neuroreport. 2000;112753- 2758
Link to Article
Robertson  LCLamb  MRKnight  RT Normal global-local analysis in patients with dorsolateral frontal lobe lesions. Neuropsychologia. 1991;29959- 967
Link to Article
Granholm  EPerry  WFiloteo  JVBraff  D Hemispheric and attentional contributions to perceptual organization deficits on the global-local task in schizophrenia. Neuropsychology. 1999;13271- 281
Link to Article
Carter  CSRobertson  LCNordahl  TEChaderjian  MOshora-Celaya  L Perceptual and attentional asymmetries in schizophrenia: further evidence for a left hemisphere deficit. Psychiatry Res. 1996;62111- 119
Link to Article
Weinberger  DRBerman  KF Prefrontal function in schizophrenia: confounds and controversies. Philos Trans R Soc Lond B Biol Sci. 1996;3511495- 1503
Link to Article
Carter  CSPerlstein  WGanguli  RBrar  JMintun  MCohen  JD Functional hypofrontality and working memory dysfunction in schizophrenia. Am J Psychiatry. 1998;1551285- 1287
Andreasen  NCRezai  KAlliger  RSwayze  VW  IIFlaum  MKirchner  PCohen  GO'Leary  DS Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia: assessment with xenon 133 single-photon emission computed tomography and the Tower of London. Arch Gen Psychiatry. 1992;49943- 958
Link to Article
Goldman-Rakic  PSSelemon  LD Functional and anatomical aspects of prefrontal pathology in schizophrenia. Schizophr Bull. 1997;23437- 458
Link to Article
Bar  MTootell  RBSchacter  DLGreve  DNFischl  BMendola  JDRosen  BRDale  AM Cortical mechanisms specific to explicit visual object recognition. Neuron. 2001;29529- 535
Link to Article
Spohn  HELacoursiere  RBThompson  KCoyne  L Phenothiazine effects on psychological and psychophysiological dysfunction in chronic schizophrenics. Arch Gen Psychiatry. 1977;34633- 644
Link to Article

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