Advertisement
Research Article

Crowding Deficits in the Visual Periphery of Schizophrenia Patients

  • Rainer Kraehenmann,

    Affiliations: Neuropsychopharmacology and Brain Imaging & Heffter Research Center, Clinic of Affective Disorders and General Psychiatry, Psychiatric University Hospital, University of Zurich, Zurich, Switzerland, Clinic of Affective Disorders and General Psychiatry, Psychiatric University Hospital, University of Zurich, Zurich, Switzerland

    X
  • Franz X. Vollenweider,

    Affiliations: Neuropsychopharmacology and Brain Imaging & Heffter Research Center, Clinic of Affective Disorders and General Psychiatry, Psychiatric University Hospital, University of Zurich, Zurich, Switzerland, Clinic of Affective Disorders and General Psychiatry, Psychiatric University Hospital, University of Zurich, Zurich, Switzerland

    X
  • Erich Seifritz,

    Affiliation: Clinic of Affective Disorders and General Psychiatry, Psychiatric University Hospital, University of Zurich, Zurich, Switzerland

    X
  • Michael Kometer mail

    michael.kometer@bli.uzh.ch

    Affiliation: Neuropsychopharmacology and Brain Imaging & Heffter Research Center, Clinic of Affective Disorders and General Psychiatry, Psychiatric University Hospital, University of Zurich, Zurich, Switzerland

    X
  • Published: September 26, 2012
  • DOI: 10.1371/journal.pone.0045884

Abstract

Accumulating evidence suggests that basic visual information processing is impaired in schizophrenia. However, deficits in peripheral vision remain largely unexplored. Here we hypothesized that sensory processing of information in the visual periphery would be impaired in schizophrenia patients and, as a result, crowding – the breakdown in target recognition that occurs in cluttered visual environments – would be stronger. Therefore, we assessed visual crowding in the peripheral vision of schizophrenia patients and healthy controls. Subjects were asked to identify a target letter that was surrounded by distracter letters of similar appearance. Targets and distracters were displayed at 8° and 10° of visual angle from the fixation point (eccentricity), and target-distracter spacing was 2°, 3°, 4°, 5°, 6°, 7° or 8° of visual angle. Eccentricity and target-distracter spacing were randomly varied. Accuracy was defined as the proportion of correctly identified targets. Critical spacing was defined as the spacing at which target identification accuracy began to deteriorate, and was assessed at viewing eccentricities of 8° and 10°. Schizophrenia patients were less accurate and showed a larger critical spacing than healthy individuals. These results indicate that crowding is stronger and sensory processing of information in the visual periphery is impaired in schizophrenia. This is in line with previous reports of preferential magnocellular dysfunction in schizophrenia. Thus, deficits in peripheral vision may account for perceptual alterations and contribute to cognitive dysfunction in schizophrenia.

Introduction

Deficits in basic visual information processing are a key impairment in schizophrenia. They are related to higher-order neurocognitive dysfunctions and functional outcomes [1][3] and are evident at incipient stages of schizophrenia before any psychotic symptoms occur [4]. However, the conditions under which dysfunctional visual processing occurs are unclear [5], [6]. Under natural viewing conditions, information from the visual periphery is essential for object and scene gist recognition, as well as for guiding eye movements to context-relevant locations [7], [8]. Previous studies on visual information processing in schizophrenia have largely neglected peripheral vision, and information regarding the presence, extent and nature of peripheral visual dysfunction in schizophrenia is incomplete and inconsistent [9][15]. For example, although Miller et al. [14] found no difference between central and peripheral visual processing in schizophrenia patients, Elahipanah et al. [10] found disproportionately large deficits when target stimuli were located peripherally, and Granholm et al. [11] identified peripheral deficits in schizophrenia patients that were most prominent when object density in the visual field was high. It therefore appears as though peripheral vision may be impaired in schizophrenia.

Crowding is a breakdown in object perception whereby one's ability to recognize a peripheral target is severely impaired by the presence of flanking objects [16]. Crowding in peripheral vision reduces the ability to recognize objects because they are too close together, and leads to a phenomenon whereby a single object in the periphery (“target”) becomes indistinct from nearby objects (“distracters”). As such, it is object spacing (target-distracter distance), and not object size (spatial resolution), that critically limits target-distracter discrimination in the periphery [16], [17]. Crowding is closely related to input processing in low-level visual cortices, where target and distracter signals are “compulsorily pooled” [18], [19]. Although this has the advantage of information compression, it comes at the cost of target-distracter discriminability [19][22]. In healthy individuals, crowding occurs when spacing falls below a critical value (critical spacing). This critical value of spacing increases as the visual angle between the fixation point and target (eccentricity) increases, and the approximately linear relationship between the two is been termed “Bouma's rule” [21].

It is suggested that peripheral visual stimuli are preferentially processed via the magnocellular pathway [23][26], which is disrupted in schizophrenia [27][29]. This is consistent with reports of peripheral vision deficits in schizophrenia patients [9][11], [15]. Therefore, we hypothesized that sensory processing of information from the visual periphery would be impaired in schizophrenia patients and, as a result, crowding would be stronger than in healthy individuals. To test this hypothesis we studied crowding in the visual periphery of both schizophrenic patients and healthy controls. We expected that accuracy in the crowding task would be lower, and the critical spacing larger, in schizophrenia patients than in healthy individuals.

Materials and Methods

Ethics statement

This study was approved by the Ethics Committee of the Canton of Zurich and was carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki, 2008 version). A clinician who was experienced in the evaluation of mental illness assessed by a direct examination of participants, their understanding of all the procedures and capacity to consent [30]. The participants were included in the study only if they had the full capacity to consent.

Subjects

Twenty patients meeting the DSM-IV criteria for schizophrenia and 20 healthy subjects participated in the study. Schizophrenia patients comprised inpatients (n = 5) and outpatients (n = 15). Schizophrenia patients were recruited from the Psychiatric University Hospital Zurich and healthy controls were recruited by advertisement from the University of Zurich and the Zurich urban area. Diagnoses were obtained using the Mini International Neuropsychiatric Interview (MINI) [31] and available clinical information. Controls with a history of DSM-IV Axis I psychiatric disorder or substance dependence within the last year, as assessed by the MINI, were excluded. Patients and controls were excluded if they had a history of neurological or ophthalmologic disorders. All subjects were between 19 and 54 years old and had a corrected visual acuity of at least 0.6 according to the Freiburg Visual Acuity Test [32]. Groups were matched for age (t(38) = −1.51, p = 0.139), gender (Fisher's exact test, odds ratio = 0.63, 95% confidence interval = [0.12, 2.96], p = 0.731), IQ (t(38) = 1.76, p = 0.087) and visual acuity (t(37) = 0.48, p = 0.631). All patients were receiving antipsychotic medication at the time of testing. Chlorpromazine equivalents were calculated using conversion factors described elsewhere [33], [34]. The chlorpromazine equivalent dose of paliperidone is not adequately defined in the literature; therefore, the chlorpromazine equivalent dose was calculated from the defined daily dose set out in the WHO Collaborating Center for Drug Statistics Methodology Index 2011 (http://www.whocc.no/atc_ddd_index). A certified Positive and Negative Syndrome Scale (PANSS) rater (RK; The PANSS Institute LLC, NY) obtained PANSS ratings from patients. Demographics and clinical characteristics of subjects are presented in Table 1.

thumbnail

Table 1. Demographic and clinical characteristics of schizophrenia patients and healthy controls.

doi:10.1371/journal.pone.0045884.t001

Apparatus

Subjects were tested in a dimly lit room (ambient illumination, 11 lux). Stimuli were presented using E-Prime software (Psychology Software Tools Inc., Pittsburgh, PA) and displayed on a liquid crystal display (Hewlett-Packard LP2065, resolution 1600×1200 pixels; Radeon HD4350 graphics card) placed 0.75 m in front of the subject. Head movement was constrained by a head-chin rest. During administration of the examination, the experimenter (RK) sat behind the computer screen and monitored eye movements and eye gaze direction in real time with an infrared eye camera. All participants reliably maintained central eye fixation. Furthermore, we reduced processing time by backward-masking and presented the stimuli in a randomized order on the left and the right sight of the screen to reduce the amount of eye movements towards the target stimuli.

Visual stimuli

The visual stimuli comprised uppercase letters from the Roman alphabet. All letters were presented in a dark gray color on a white background (background illumination, 63 lux) and were of identical height and width (0.8° of visual angle). Four variables were manipulated: target, target-distracter spacing, the side of stimulus presentation, and the stimulus presentation eccentricity.

Target.

The target letters were upright or 90° tilted uppercase “T”s, which appeared alone or flanked by uppercase distracter letters (“I” or “H”) above and below. The target and distracter letters were similar in appearance to increase the crowding effect [39].

Spacing.

Distracters appeared at one of seven equidistant locations on the vertical meridian of the targets. The target-distracter spacings (center-to-center) were 2°, 3°, 4°, 5°, 6°, 7° and 8° of visual angle (Figure 1).

thumbnail

Figure 1. Schematic showing the crowding experiment and selected examples of stimuli used in the experiment.

Panel A: A fixation point was first presented for 1500 ms, followed by a target/distracter array (4° spacing/10° eccentricity condition shown here) for 60 ms. Then, a mask appeared for 200 ms. Finally, a response screen displaying a fixation point was shown and the subjects were required to register whether they saw an upright or 90° tilted target “T” by pressing a key. Panel B: 2° spacing/10° eccentricity condition (top left); 8° spacing/10° eccentricity condition (top right); target-only/10° eccentricity condition, 90° tilted target “T” (bottom left); 8° spacing/8° eccentricity condition (bottom right).

doi:10.1371/journal.pone.0045884.g001
Side.

Targets and distracters appeared on either the left or right side of the central fixation point to ensure reliable central fixation, since selectively fixating at the left or right side of the central fixation point would be counterproductive for the subjects' accuracy performance.

Eccentricity.

Targets and distracters appeared at either 8° or 10° of visual angle from the horizontal meridian.

Experimental procedures

The crowding task has been previously described [40]. Figure 1 depicts a trial sequence in this crowding task. Subjects were instructed to fixate on a central point before stimulus onset, and to maintain central fixation during the trials. They were then asked to press the space key on the computer keyboard to initiate the trial. Initially, a fixation point (with a diameter of 0.2° of visual angle) appeared for 1500 ms. Next, target and distracter letters were displayed for 60 ms. This short interval between the stimuli interval precluded any eye movement [41]. Subsequently, masks appeared at the same target/distracter locations for 200 ms. Finally, a response screen displaying a fixation point was shown. At this time, the subjects were required to indicate whether they saw an upright or 90° tilted “T” by pressing the appropriate key on the computer keyboard. Following the response, a new trial was started. No feedback was given. The experiment consisted of six blocks of 64 trials each, giving a total of 384 trials. Within each block, all variables (target, spacing, side and eccentricity) were randomly intermixed. Spacing conditions appeared with equal probability (including a “target-only” condition where the target appeared without distracters). Between blocks, the subjects received a short break to avoid fatigue. Test blocks of 16 trials with visual feedback were performed before the experiment, and were repeated until the experimenter was sure that the subject understood the procedure.

Calculation of critical spacing

Crowding occurs when target-distracter spacing falls below a critical value and recognition of the target letter is reduced. We computed the critical spacing value using a two-step algorithm. First, a logistic function (equation 1) was modeled to the data obtained from each individual subject, where y is the probability of correct target recognition and x is the corresponding target-distracter spacing:

(1)

The constants a, b and c were used for standardization. Critical spacing was then computed from the fitted logistic function (equation 2) as the point of the curve where accuracy began to deteriorate [18], [40], [42]. We defined critical spacing according to Scolari et al. [40] and Yeshurun and Rashal [43], i.e., the point at which accuracy reached 90% of asymptotic performance:

(2)

Statistical analyses

All data were first tested for normality by means of a Shapiro-Wilk test. Accuracy was calculated as the proportion of correctly identified targets. Accuracy was then analyzed using a 2×7×2×6 mixed model analysis of variance (ANOVA) with group (schizophrenia, control) as a between-group factor, and spacing (2°, 3°, 4°, 5°, 6°, 7°, 8°), eccentricity (8°, 10°) and block (1, 2, 3, 4, 5, 6) as within-group factors. To control for group differences due to differential feature detection, attention, or task engagement effects, the effect of group on accuracy during the target-only condition was assessed using an unpaired t test for accuracy at each eccentricity (8°, 10°). Critical spacing was analyzed using a 2×2 mixed model ANOVA with group (schizophrenia, control) as a between-group factor and eccentricity (8°, 10°) as a within-group factor. When the ANOVA assumption of sphericity was violated, the Greenhouse-Geisser correction [44] was applied. Bonferroni-corrected post-hoc t tests were performed when ANOVA identified significant group main effects or interactions. Generalized eta squared (ηG2) [45] or Cohen's d [46] were reported as measures of effect size. Pearson's product moment correlation was used to examine correlations between critical spacing and demographic/clinical variables. All significance levels were two-tailed with a preset α<0.05. If not stated otherwise, all values represent the mean (± standard deviation). The open source statistical software R, version 2.14.2 [47] was used for statistical analyses.

Results

Accuracy

Figure 2 shows target identification accuracy as a function of spacing at 8° and 10° eccentricity in the patient and the control groups. Accuracy was significantly lower in the schizophrenia group than in the control group [F(1, 38) = 10.4, p = 0.003, ηG2 = 0.09]. A significant main effect was found for spacing [F(2.17, 82.5) = 129, p<0.001, ηG2 = 0.57] demonstrating increased accuracy with increased spacing. The main effect of target eccentricity was also significant [F(1, 38) = 8.38, p = 0.006, ηG2 = 0.01] – accuracy decreased as target eccentricity increased. There was also a spacing × eccentricity interaction [F(3.78, 144) = 5.15, p<0.001, ηG2 = 0.024]. At 8° eccentricity, accuracy was significantly lower in the schizophrenia group than in the control group at spacings of 3° [t(38) = 4.95, p<0.001, d = 1.56], 4° [t(38) = 3.13, p = 0.024, d = 0.99] and 6° [t(38) = 3.17, p = 0.021, d = 1.00]. At 10° eccentricity, accuracy was significantly lower in the schizophrenia group than in the control group at spacings of 4° [t(38) = 3.20, p = 0.019, d = 1.01], 5° [t(38) = 3.43, p = 0.010, d = 1.08] and 8° [t(38) = 3.84, p = 0.003, d = 1.22].

thumbnail

Figure 2. Accuracy and fitted logistic curves as a function of spacing at 8° eccentricity (panel A) and 10° eccentricity (panel B) in schizophrenia patients and healthy controls.

Vertical dotted lines indicate critical spacing. Values represent the mean ± standard error of mean.

doi:10.1371/journal.pone.0045884.g002

Accuracy during the target-only condition at 8° eccentricity was similar for both groups [t(38) = 1.64, p = 0.110, d = 0.52]. There was a tendency for schizophrenia patients to perform worse than controls at 10° eccentricity (accuracy of 0.96 (0.072) and 0.99 (0.023) respectively; t(38) = 1.97, p = 0.056, d = 0.62), but this was not significant. There were no differences of performance between groups due to vigilance decrements or training effects, as evidenced by a lack of a significant group × block, group × block × eccentricity, group × block × spacing and group × block × eccentricity × spacing interaction (all F≤1.45, p≥0.139, ηG2≤0.010).

Critical spacing

Logistic regression model fitting was very good for both patients (mean R2 = 0.97) and controls (mean R2 = 0.99). Critical spacing was significantly larger in the schizophrenia group than in the control group [F(1, 38) = 4.51, p = 0.040, ηG2 = 0.08] (Figure 3). No main effect of eccentricity and no group × eccentricity interaction (all F≤3.15, p≥0.084, ηG2≤0.022) were found.

thumbnail

Figure 3. Mean critical spacing for schizophrenia patients (Sz) and healthy controls (Hc) by eccentricity.

Critical spacing was larger in the schizophrenia group than in the control group. Error bars represent the standard error of the mean.

doi:10.1371/journal.pone.0045884.g003

Relationship between critical spacing and demographic/clinical variables

There were no significant correlations between critical spacing and PANSS score (total, positive, negative, and disorganization), Revised Hallucination Scale (RHS) score, medication (chlorpromazine equivalents), visual acuity, intelligence quotient, age, or gender for the schizophrenia group (all Bonferroni-corrected p>0.100).

Discussion

The results of this study provide the first evidence that visual crowding, a fundamental process in the visual periphery, is dysfunctional in schizophrenia patients. Visual crowding was greater in schizophrenia patients than in healthy controls, as evidenced by lower target identification accuracy and larger critical spacing. These results indicate that schizophrenia patients need more space between a target and distracters than healthy controls to correctly identify the target. This is consistent with our hypothesis of stronger crowding in schizophrenia, and indicates impaired sensory processing of information in the visual periphery.

Magnocellular system

Converging lines of evidence indicate that information processing in the visual periphery is mediated by magnocellular neurons, whereas foveal processing is mediated by parvocellular neurons [26], [48]. Interestingly, Omtzigt et al. [49] compared the identification of parafoveally-presented flanked and unflanked target letters in healthy subjects, and found that the magnocellular system was specifically involved in the identification of flanked letters. This underpins the role of the magnocellular system in tasks where target and distracters are closely spaced, such as the crowding task in the present study. The finding that schizophrenia patients have deficits in the crowding task is consistent with previous studies showing robust magnocellular deficits in schizophrenia patients [27][29], [50]. N-methyl-D-aspartate (NMDA) receptor dysfunction may underlie these magnocellular deficits [28] and may therefore be a critical pathogenetic mechanism of crowding deficits in schizophrenia. It has been demonstrated [51][54] that, in schizophrenia, magnocellular dysfunction leads to increased intrinsic neural activity, which in turn elevates noise levels during signal processing in early visual cortex. According to signal detection theory, increased internal noise at the sensory level reduces target-distracter discriminability, which may in turn increase critical spacing [18], [55]. Therefore, the larger critical spacing in schizophrenic patients observed here might be a result of increased intrinsic noise due to magnocellular dysfunction. One might argue that increased noise at higher-level processing stages, including attention and decision making, might also reduce accuracy and therefore lead to a larger critical spacing. However, it is important to keep in mind that critical spacing is a relative measure of accuracy and is calculated as 90% accuracy relative to asymptotic performance. Therefore, although increased noise levels at higher-level processing stages may indeed reduce accuracy levels, the critical spacing effect will still be evident.

Interestingly, it has been shown that noisy sensory processing in subcortical areas may lead to secondary cortical processing impairments in schizophrenia [56][58]. Indeed, crowding deficits may themselves lead to downstream cognitive dysfunctions such as impaired perceptual decision making. Baldassi et al. [59] showed that intrinsic noise may account for perceptual decision errors under crowding conditions. Such perceptual decision errors are usually made with high confidence, and the underlying cortical activity in the sensory visual cortex strongly correlates with the subjective percept [60]. This may have implications for the understanding of bottom-up contributions to hallucination and delusion formation in schizophrenia, as several lines of evidence indicate that fixed, false beliefs may arise from erroneous sensory processing [54], [61][64]. Our finding of larger critical spacing in schizophrenia implies a smaller uncrowded window and a more corrupted visual field, compromising the quality of visual input to thalamic nuclei [61]. This, in turn, may damage coherent thalamocortical oscillations, which are critical to normal cognitive functioning. Moreover, deficits in synchronized neural oscillations have been related to disconnectivity between and within cortical areas and thus may underlie the fragmentation of mind and behavior in schizophrenia [65]. Indeed, patients report impressions such as “If I look at my watch, I see a watch, watchstrap, face, hands and so on, then I have got to put them together to get it into one piece” [66].

Perceptual organization

In crowding, the perception of a peripherally viewed target is impaired by adjacent distracters, leading to a cluttered percept. As described in the introduction, crowding is usually considered to result from spatial pooling of information that yields the perception of a textural representation of the visual periphery. Although the neuronal correlates and computations that result in crowding are still undetermined, it is assumed that the underlying mechanisms comprise contour integration [67], feature binding [68], [69] and spatial attention [70]. Converging lines of evidence indicate that schizophrenia patients are impaired in their ability to organize low-level visual information into coherent patterns such as groups, contours, perceptual wholes and object representations [71][75]. For example, Silverstein et al. [74] used a psychophysically well-controlled contour integration paradigm and found that schizophrenia patients performed poorly if they had to detect a smooth contour among discrete but aligned elements embedded in a background of random distracters. In addition, Must et al. [71] reported that, in schizophrenia patients, the detection of an oriented target is less facilitated by the presence of collinear flankers than in healthy individuals and Dakin et al. [72] showed that suppression of visual context is weaker in schizophrenia patients than in healthy subjects. Such perceptual organization deficits have been related to abnormal lateral interactions of local processing units in early visual cortex [76].

It has been shown [69], [77] in healthy subjects that target-distracter similarity, or good continuation between target and distracters, leads to perceptual grouping and thus increases crowding, whereas target-distracter dissimilarity or “wiggle” of target and distracter elements alleviates crowding. Therefore, perceptual organization deficits in schizophrenia patients may be expected to result in weaker crowding. However, our finding of stronger crowding in schizophrenia is contrary to this expectation. There are several possible explanations for this inconsistency. First, previous studies using perceptual organization tasks in schizophrenia patients may have favored central over peripheral visual processing because stimuli were presented centrally rather than peripherally. Perceptual organization deficits observed in central vision might differ from those observed in peripheral vision, a view corroborated by May et al. [78], who showed that contour integration may be strongly impaired by crowding effects at extreme eccentricity. Second, Hess et al. [79] reported that contour linking due to long-range horizontal interactions is absent in the visual periphery. Therefore, it is conceivable that the neural mechanisms underlying perceptual organization may differ between the fovea and the visual periphery. Third, it has been shown [74], [80] that perceptual organization deficits strongly correlate with the disorganized syndrome of schizophrenia and that clinically stabilized outpatients may lack perceptual organization deficits. In fact, we found no significant correlations between crowding measures and the PANSS disorganization score, and 75% of the patients in our study were stabilized outpatients. Therefore, it seems plausible that perceptual organization deficits do not account for the crowding deficits that we observed.

Spatial attention

Dysfunctional spatial attention might better explain increased crowding in schizophrenia patients. Several studies [70], [81], [82] have shown that visual crowding may result from limitations set by spatial attention, and accumulating evidence [83][85] indicates that spatial attention is impaired in schizophrenia. Moreover, deficits in spatial attention in peripheral vision may be related to deficits in the magnocellular system, also termed the “where” pathway, because this is the system that mediates the perception of spatial relationships in the visual periphery [23], [24], [86]. Increased crowding in schizophrenia would be in line with a more limited peripheral visual system due to dysfunctional spatial attention. The interaction between crowding and spatial attention may be better understood in light of the findings of Zhang et al. [87]. They showed that in order to improve localized visual discrimination, the primary visual cortex constructs a bottom-up saliency map of visual space, which then guides attentional shifts by reporting local attentional attraction. Saliency maps are important processing interfaces in crowding [88] and visual search [89]. Results from electrophysiological and neuroimaging studies [82], [90][93] also indicate that the interaction between spatial attention, magnocellular processing and crowding may be mediated by sensory visual cortical areas, which is in line with the evidence of impairments at the earliest stages of visual processing in schizophrenia patients [76].

Visual search and span of apprehension

Our findings may help to explain the conflicting results reported by previous studies on visual search in schizophrenia [9][15]. There is increasing evidence that crowding critically modulates the performance of visual tasks requiring detection of a target amidst multiple distracters [41], [94][97]. Vlaskamp and Hooge [98] showed that crowding reduces target-distracter discriminability and slows visual search times by up to 76%. In addition, crowding has been closely associated with the “functional visual field” or “span of apprehension”, i.e., the radial area around the fixation point from which information can be extracted at a glimpse [99]. The boundary of this area is defined as the eccentricity beyond which crowding occurs. Target and distracters inside this boundary appear uncrowded; thus, it is termed the “uncrowded window” [16]. Our finding of larger critical spacing in schizophrenia patients indicates a smaller functional visual field, and this is supported by a number of studies that reported a smaller functional visual field in schizophrenic patients [9], [10], [100], [101].

Developmental dyslexia

A smaller functional visual field as a result of increased crowding has also been reported in dyslexic subjects, where, due to the detrimental effect on letter discriminability, it is interpreted as an important constitutive factor for reading deficits [102], [103]. Although a direct link between schizophrenia and dyslexia remains to be established, substantial evidence [104], [105] indicates that a variety of characteristics, including visual processing deficits, visual anomalies of perception, mixed handedness and reading impairment, are common to both disorders and may be a consequence of a shared underlying pathogenetic mechanism. This shared mechanism may also underlie deficits in other perceptual domains, such as auditory processing [106] and multimodal integration [107]. Structural and functional brain abnormalities of cortical regions surrounding the temporoparietal junction have regularly been found in dyslexia and schizophrenia and may be candidate loci of visual dysfunction in these disorders, as they are closely linked to auditory processing, orienting of spatiotemporal attention, and reading acquisition [108]. However, converging lines of evidence [104], [105], [109], [110] indicate that it may be subcortical magnocellular dysfunction that underlies both schizophrenia and dyslexia, in particular with regard to visual processing and associated cognitive abnormalities. This is supported by the finding that, in both disorders, structural and functional lateralization is reduced, as evidenced by abnormal symmetry of the planum temporale and a high rate of mixed handedness [110], [111], and reduced lateralization [106] has been attributed to magnocellular dysfunction. Thus, magnocellular dysfunction may be an important pathophysiologic mechanism underlying visual processing deficits in both schizophrenia and developmental dyslexia.

Face recognition

A similar mechanism may also contribute to face recognition deficits in schizophrenia, although current evidence to support this hypothesis is equivocal [28]. On the one hand, there is evidence that abnormal structural and functional deficits of the fusiform face area, a temporal cortical region relevant to processing of faces, may primarily mediate the well-documented face recognition deficits in schizophrenia [112]. On the other hand, it has been suggested that activity of the fusiform face area is preserved when processing faces [113] and that basic visual processing deficits related to magnocellular dysfunction, along with their amplified modulatory effect on the fusiform face area, might better account for previous findings [114], [115]. We therefore suggest that crowding dysfunctions may substantially contribute to face recognition deficits in schizophrenia. This hypothesis is supported by Shin et al. [116], who reported that schizophrenic patients exhibited extremely poor facial recognition when they had to discriminate faces with different spacing between facial features. Additionally, Martelli et al. [117] showed that, in healthy subjects, crowding occurs among facial features within a single face and thus may severely impair face recognition. However, whether or not the crowding of facial features affects face recognition in schizophrenic patients remains to be tested in future studies.

Compensatory mechanisms

As discussed above, dysfunctional crowding in schizophrenia may be related to perceptual alterations and cognitive disturbances. However, in this study, we did not find any significant correlations between crowding measures and clinical symptoms, perhaps because our clinical sample consisted primarily of clinically stabilized outpatients. The absence of any correlation indicates that the observed crowding deficits were not related to symptoms, and thus may be considered permanent and stable. It is therefore conceivable that the patients' brain may have adapted to, at least in part, compensate for crowding deficits. A global compensatory mechanism was reported in brain-damaged patients with spatial neglect after they wore an optical prism and was attributed to a recalibration of internal spatial maps by fronto-parietal networks [118]. The poor quality of sensory data in schizophrenic patients may likewise necessitate increased top-down control to enable them to make sense of their visual world. On a neural level, top-down control of sensory perception is implemented by frontal and parietal cortical areas through modulation of visual cortex activity [119]. Indeed, compensation of low-level visual deficits through increased recruitment of higher-level cortical areas has consistently been reported in schizophrenic patients [120][123]. For example, Knebel et al. [120] used visual evoked potentials to show that, in parafoveal vision of schizophrenic patients, deficits of early visual processing are compensated for later in the visual hierarchy.

In addition to top-down control strategies, patients may also adapt under natural conditions their eye and/or head movement pattern to compensate for crowding deficits. Because they have a smaller uncrowded window, the amount of information they can extract at a glance is reduced. Consequently, they would need to increase the number of fixations to compensate for this deficit. However, evidence to support this prediction is inconclusive, perhaps because low- and high-level deficits in cortical processing may lead to different eye scanning abnormalities in schizophrenia. Abnormal smooth pursuit and antisaccades, for example, are well documented in schizophrenia and probably reflect deficits in prefrontal cortex, specifically in the frontal eye fields [124]. On the other hand, compensatory eye and/or head movement patterns due to a smaller functional visual field may also be plausible in schizophrenia. Olevitch et al. [125] registered spontaneous head movements of schizophrenic patients during a reading task and found that patients initiated head movements at a smaller visual angle than controls, and Roberts et al. [109] used a psychophysically well-controlled reading paradigm and found that the number of saccades was increased and the observed eye movement patterns were closely related to reduced sensitivity to parafoveal information in schizophrenia patients.

One may think that another strategy to compensate for a smaller functional visual field would be to increase the viewing distance. However, if fixation is maintained on a point in the scene while viewing distance is increased, target size and eccentricity both decrease in proportion to the spacing of target and distracters. Although this “zooming out” will broaden the focus of the scene, the stimulus input at the retina leaves the critical spacing unchanged [16]. Therefore, increasing viewing distance might not be a viable strategy for schizophrenic patients to compensate for a smaller functional visual field. However, as far we are aware, no studies to date have systematically examined visual performance of schizophrenic patients in relation to viewing distance. It would be informative to test this relationship in a future study.

Limitations

All targets and distracters were masked with overlapping high-energy backward masks to minimize the processing time for the stimuli. This reduces eye movements towards target stimuli and therefore ensures peripheral processing. However, backward-masking deficits have been documented in schizophrenia [126], [127] and thus may have confounded the observed crowding effects. Although we cannot exclude this possibility entirely, we consider it unlikely for two reasons. First, all stimuli in the crowding task were equally masked across all conditions, which is contrary to the condition-specific deficits observed, and second, although target detection is differentially modulated by masking and crowding, feature detection is impaired in masking but spared in crowding [18]. Our results show that feature detection was equal in both groups, as evidenced by similar accuracy levels during the target-only condition. We therefore conclude that the crowding effects are specific and not confounded by masking effects.

The small sample size and the higher variance of critical spacing in the schizophrenia group compared with the control group means that this study was underpowered for detecting critical spacing deficits at both eccentricities. This might explain the lack of an eccentricity effect and a group by eccentricity interaction on critical spacing in the ANOVA's. In addition, to ensure that the length of the testing session was tolerable to the participants, we only tested visual crowding at two eccentricities. Therefore, we cannot make direct conclusions about the full extent of the visual periphery. It would be very interesting to examine critical spacing in schizophrenia patients across a broader range of eccentricities in future studies.

Conclusions

This study provides evidence that processing in the visual periphery of schizophrenic patients is impaired. Most notably, we report for the first time that crowding, a critical and ubiquitous process of peripheral vision, is impaired in schizophrenia. Our findings indicate that it is important to consider object spacing in relation to eccentricity in future studies of visual processing in schizophrenia, and that studying crowding might help us better understand visuospatial deficits associated with this illness. In particular, our findings imply that crowding deficits in schizophrenia might underlie perceptual alterations and cognitive dysfunction. For future studies, it would be enlightening to examine the relationship between visual crowding and magnocellular-biased processing, as well as cognitive, emotional and social functioning in a large sample of schizophrenia patients, preferably using multi-sensory modalities.

Acknowledgments

We would like to thank the subjects who participated in the study. We thank Prof. Hans H. Stassen, who assisted with the proofreading of the manuscript.

Author Contributions

Conceived and designed the experiments: RK MK ES FXV. Performed the experiments: RK. Analyzed the data: RK MK ES FXV. Contributed reagents/materials/analysis tools: RK MK ES FXV. Wrote the paper: RK MK ES FXV.

References

  1. 1. Butler PD, Schechter I, Revheim N, Silipo G, Javitt DC (2010) Has an important test been overlooked? Closure flexibility in schizophrenia. Schizophrenia Research 118: 20–25. doi: 10.1016/j.schres.2010.01.005
  2. 2. Green MF, Butler PD, Chen Y, Geyer MA, Silverstein S, et al. (2009) Perception measurement in clinical trials of schizophrenia: promising paradigms from CNTRICS. Schizophrenia Bulletin 35: 163–181. doi: 10.1093/schbul/sbn156
  3. 3. Rassovsky Y, Horan WP, Lee J, Sergi MJ, Green MF (2011) Pathways between early visual processing and functional outcome in schizophrenia. Psychological Medicine 41: 487–497. doi: 10.1017/s0033291710001054
  4. 4. Klosterkotter J, Hellmich M, Steinmeyer EM, Schultze-Lutter F (2001) Diagnosing schizophrenia in the initial prodromal phase. Archives of General Psychiatry 58: 158–164. doi: 10.1001/archpsyc.58.2.158
  5. 5. Sehatpour P, Dias EC, Butler PD, Revheim N, Guilfoyle DN, et al. (2010) Impaired visual object processing across an occipital-frontal-hippocampal brain network in schizophrenia: an integrated neuroimaging study. Archives of General Psychiatry 67: 772–782. doi: 10.1001/archgenpsychiatry.2010.85
  6. 6. van Assche M, Giersch A (2011) Visual organization processes in schizophrenia. Schizophrenia Bulletin 37: 394–404. doi: 10.1093/schbul/sbp084
  7. 7. To MPS, Gilchrist ID, Troscianko T, Tolhurst DJ (2011) Discrimination of natural scenes in central and peripheral vision. Vision Research 51: 1686–1698. doi: 10.1016/j.visres.2011.05.010
  8. 8. Torralba A, Oliva A, Castelhano MS, Henderson JM (2006) Contextual guidance of eye movements and attention in real-world scenes: the role of global features in object search. Psychological Review 113: 766–786. doi: 10.1037/0033-295x.113.4.766
  9. 9. Cegalis JA, Deptula D (1981) Attention in schizophrenia – signal-detection in the visual periphery. Journal of Nervous and Mental Disease 169: 751–760. doi: 10.1097/00005053-198112000-00002
  10. 10. Elahipanah A, Christensen BK, Reingold EM (2010) Visual search performance among persons with schizophrenia as a function of target eccentricity. Neuropsychology 24: 192–198. doi: 10.1037/a0017523
  11. 11. Granholm E, Asarnow RF, Marder SR (1996) Display visual angle and attentional scanpaths on the span of apprehension task in schizophrenia. Journal of Abnormal Psychology 105: 17–24. doi: 10.1037/0021-843x.105.1.17
  12. 12. Lieb K, Merklin G, Rieth C, Schuttler R, Hess R (1994) Preattentive information-processing in schizophrenia. Schizophrenia Research 14: 47–56. doi: 10.1016/0920-9964(94)90008-6
  13. 13. Matsuda Y, Matsui M, Tonoya Y, Ebihara N, Kurachi M (2011) Useful visual field in patients with schizophrenia: a choice reaction time study. Perceptual and Motor Skills 112: 369–381. doi: 10.2466/15.19.22.27.pms.112.2.369-381
  14. 14. Miller MB, Chapman LJ, Chapman JP, Barnett EM (1990) Schizophrenic deficit in span of apprehension. Journal of Abnormal Psychology 99: 313–316. doi: 10.1037/0021-843x.99.3.313
  15. 15. Slaghuis WL, Thompson AK (2003) The effect of peripheral visual motion on focal contrast sensitivity in positive- and negative-symptom schizophrenia. Neuropsychologia 41: 968–980. doi: 10.1016/s0028-3932(02)00321-4
  16. 16. Pelli DG, Tillman KA (2008) The uncrowded window of object recognition. Nature Neuroscience 11: 1129–1135. doi: 10.1038/nn.2187
  17. 17. Levi DM (2008) Crowding – an essential bottleneck for object recognition: a mini-review. Vision Research 48: 635–654. doi: 10.1016/j.visres.2007.12.009
  18. 18. Pelli DG, Palomares M, Majaj NJ (2004) Crowding is unlike ordinary masking: distinguishing feature integration from detection. Journal of Vision 4: 1136–1169. doi: 10.1167/4.12.12
  19. 19. Parkes L, Lund J, Angelucci A, Solomon JA, Morgan M (2001) Compulsory averaging of crowded orientation signals in human vision. Nature Neuroscience 4: 739–744. doi: 10.1038/89532
  20. 20. Balas B, Nakano L, Rosenholtz R (2009) A summary-statistic representation in peripheral vision explains visual crowding. Journal of Vision 9: 1–18. doi: 10.1167/9.12.13
  21. 21. Freeman J, Simoncelli EP (2011) Metamers of the ventral stream. Nature Neuroscience 14: 1195–1204. doi: 10.1038/nn.2889
  22. 22. Greenwood JA, Bex PJ, Dakin SC (2009) Positional averaging explains crowding with letter-like stimuli. Proceedings of the National Academy of Sciences of the United States of America 106: 13130–13135. doi: 10.1073/pnas.0901352106
  23. 23. Pandya DN, Yeterian EH (1990) Prefrontal cortex in relation to other cortical areas in rhesus-monkey – architecture and connections. Progress in Brain Research 85: 63–94. doi: 10.1016/s0079-6123(08)62676-x
  24. 24. Yeterian EH, Pandya DN (2010) Fiber pathways and cortical connections of preoccipital areas in rhesus monkeys. Journal of Comparative Neurology 518: 3725–3751. doi: 10.1002/cne.22420
  25. 25. Trevarthen CB (1968) Two mechanisms of vision in primates. Psychologische Forschung 31: 299–337. doi: 10.1007/bf00422717
  26. 26. Connolly M, Vanessen D (1984) The representation of the visual-field in parvicellular and magnocellular layers of the lateral geniculate-nucleuas in the macaque monkey. Journal of Comparative Neurology 226: 544–564. doi: 10.1002/cne.902260408
  27. 27. Butler PD, Zemon V, Schechter I, Saperstein AM, Hoptman MJ, et al. (2005) Early-stage visual processing and cortical amplification deficits in schizophrenia. Archives of General Psychiatry 62: 495–504. doi: 10.1001/archpsyc.62.5.495
  28. 28. Javitt DC (2009) When doors of perception close: bottom-up models of disrupted cognition in schizophrenia. Annual Review of Clinical Psychology 5: 249–275. doi: 10.1146/annurev.clinpsy.032408.153502
  29. 29. Martinez A, Hillyard SA, Dias EC, Hagler DJ Jr, Butler PD, et al. (2008) Magnocellular pathway impairment in schizophrenia: evidence from functional magnetic resonance imaging. Journal of Neuroscience 28: 7492–7500. doi: 10.1523/jneurosci.1852-08.2008
  30. 30. Jeste DV, Palmer BW, Appelbaum PS, Golshan S, Glorioso D, et al. (2007) A new brief instrument for assessing decisional capacity for clinical research. Archives of General Psychiatry 64: 966–974. doi: 10.1001/archpsyc.64.8.966
  31. 31. Sheehan DV, Janavs J, Baker R, Harnett-Sheehan K, Knapp E, et al. (1998) MINI – mini international neuropsychiatric interview – English version 5.0.0 – DSM-IV. Journal of Clinical Psychiatry 59: 34–57. doi: 10.1016/s0924-9338(97)83297-x
  32. 32. Bach M (1996) The Freiburg visual acuity test – automatic measurement of visual acuity. Optometry and Vision Science 73: 49–53. doi: 10.1097/00006324-199601000-00008
  33. 33. Andreasen NC, Pressler M, Nopoulos P, Miller D, Ho BC (2010) Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs. Biological Psychiatry 67: 255–262. doi: 10.1016/j.biopsych.2009.08.040
  34. 34. Kroken RA, Johnsen E, Ruud T, Wentzel-Larsen T, Jorgensen HA (2009) Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study. Bmc Psychiatry 9: 1–9. doi: 10.1186/1471-244x-9-24
  35. 35. Merz J (1975) The multiple selection vocabulary test (MSVT-B) – an accelerated intelligence test. Psychiatr Neurol Med Psychol 27: 423–428.
  36. 36. Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13: 261–276. doi: 10.1093/schbul/13.2.261
  37. 37. Lepine JP, Piron JJ, Chapotot E (1989) Factor analysis of the PANSS in schizophrenic patients. In: Stefanis CN, Soldatos CR, Radavilas AD, editors. Psychiatry today: accomplishments and promises. Amsterdam: Excerpta Medica.
  38. 38. Morrison AP, Wells A, Nothard S (2002) Cognitive and emotional predictors of predisposition to hallucinations in non-patients. British Journal of Clinical Psychology 41: 259–270. doi: 10.1348/014466502760379127
  39. 39. Kooi FL, Toet A, Tripathy SP, Levi DM (1994) The effect of similarity and duration on spatial interaction in peripheral-vision. Spatial Vision 8: 255–279. doi: 10.1163/156856894x00350
  40. 40. Scolari M, Kohnen A, Barton B, Awh E (2007) Spatial attention, preview, and popout: which factors influence critical spacing in crowded displays? Journal of Vision 7: 1–23. doi: 10.1167/7.2.7
  41. 41. Carrasco M, Evert DL, Chang I, Katz SM (1995) The eccentricity effect – target eccentricity affects performance on conjunction searches. Perception & Psychophysics 57: 1241–1261. doi: 10.3758/bf03208380
  42. 42. Whitney D, Levi DM (2011) Visual crowding: a fundamental limit on conscious perception and object recognition. Trends in Cognitive Sciences 15: 160–168. doi: 10.1016/j.tics.2011.02.005
  43. 43. Yeshurun Y, Rashal E (2010) Precueing attention to the target location diminishes crowding and reduces the critical distance. Journal of Vision 10: 1–12. doi: 10.1167/10.10.16
  44. 44. Greenhouse SW, Geisser S (1959) On methods in the analysis of profile data. Psychometrika 24: 95–112. doi: 10.1007/bf02289823
  45. 45. Bakeman R (2005) Recommended effect size statistics for repeated measures designs. Behavior Research Methods 37: 379–384. doi: 10.3758/bf03192707
  46. 46. Cohen J (1992) A power primer. Psychological Bulletin 112: 155–159. doi: 10.1037//0033-2909.112.1.155
  47. 47. R Development Core Team (2011) R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing.
  48. 48. Livingstone MS, Hubel DH (1988) Do the relative mapping densities of the magnocellular and parvocellular systems vary with eccentricity. Journal of Neuroscience 8: 4334–4339.
  49. 49. Omtzigt D, Hendriks AW, Kolk HHJ (2002) Evidence for magnocellular involvement in the identification of flanked letters. Neuropsychologia 40: 1881–1890. doi: 10.1016/s0028-3932(02)00069-6
  50. 50. Keri S, Benedek G (2007) Visual contrast sensitivity alterations in inferred magnocellular pathways and anomalous perceptual experiences in people at high-risk for psychosis. Visual Neuroscience 24: 183–189. doi: 10.1017/s0952523807070253
  51. 51. Ethridge L, Moratti S, Gao Y, Keil A, Clementz BA (2011) Sustained versus transient brain responses in schizophrenia: the role of intrinsic neural activity. Schizophrenia Research 133: 106–111. doi: 10.1016/j.schres.2011.07.016
  52. 52. Saunders JA, Ganda MJ, Siegel SJ (2012) NMDA antagonists recreate signal-to-noise ratio and timing perturbations present in schizophrenia. Neurobiology of Disease 46: 93–100. doi: 10.1016/j.nbd.2011.12.049
  53. 53. Brenner CA, Krishnan GP, Vohs JL, Ahn W-Y, Hetrick WP, et al. (2009) Steady State Responses: Electrophysiological Assessment of Sensory Function in Schizophrenia. Schizophrenia Bulletin 35: 1065–1077. doi: 10.1093/schbul/sbp091
  54. 54. Spencer KM, Nestor PG, Perlmutter R, Niznikiewicz MA, Klump MC, et al. (2004) Neural synchrony indexes disordered perception and cognition in schizophrenia. Proceedings of the National Academy of Sciences of the United States of America 101: 17288–17293. doi: 10.1073/pnas.0406074101
  55. 55. Verghese P, McKee SP (2004) Visual search in clutter. Vision Research 44: 1217–1225. doi: 10.1016/j.visres.2003.12.006
  56. 56. Butler PD, Martinez A, Foxe JJ, Kim D, Zemon V, et al. (2007) Subcortical visual dysfunction in schizophrenia drives secondary cortical impairments. Brain 130: 417–430. doi: 10.1093/brain/awl233
  57. 57. Tjan BS, Lestou V, Kourtzi Z (2006) Uncertainty and invariance in the human visual cortex. Journal of Neurophysiology 96: 1556–1568. doi: 10.1152/jn.01367.2005
  58. 58. Winterer G (2002) Schizophrenia: Reduced signal-to-noise ratio and impaired phase-locking during information processing. Biological Psychiatry 51: 151S–152S. doi: 10.1016/s1388-2457(99)00322-3
  59. 59. Baldassi S, Megna N, Burr DC (2006) Visual clutter causes high-magnitude errors. Plos Biology 4: 387–394. doi: 10.1371/journal.pbio.0040056
  60. 60. Ress D, Heeger DJ (2003) Neuronal correlates of perception in early visual cortex. Nature Neuroscience 6: 414–420. doi: 10.1038/nn1024
  61. 61. Behrendt RP, Young C (2004) Hallucinations in schizophrenia, sensory impairment, and brain disease: A unifying model. Behavioral and Brain Sciences 27: 771–830. doi: 10.1017/s0140525x04000184
  62. 62. Gross J, Ploner M (2009) Perceptual Decisions: From Sensory Signals to Behavior. Current Biology 19: R847–R849. doi: 10.1016/j.cub.2009.07.023
  63. 63. Maher BA (1974) Delusional thinking and perceptual disorder. Journal of Individual Psychology 30: 98–113.
  64. 64. Rahnev DA, Maniscalco B, Luber B, Lau H, Lisanby SH (2012) Direct injection of noise to the visual cortex decreases accuracy but increases decision confidence. Journal of Neurophysiology 107: 1556–1563. doi: 10.1152/jn.00985.2011
  65. 65. Uhlhaas PJ, Haenschel C, Nikolic D, Singer W (2008) The role of oscillations and synchrony in cortical networks and their putative relevance for the pathophysiology of schizophrenia. Schizophrenia Bulletin 34: 927–943. doi: 10.1093/schbul/sbn062
  66. 66. Chapman J (1966) The early symptoms of schizophrenia. Br J Psychiatry 112: 225–251. doi: 10.1192/bjp.112.484.225
  67. 67. Field DJ, Hayes A, Hess RF (1993) Contour integration by the human visual-system – evidence for a local association field. Vision Research 33: 173–193. doi: 10.1016/0042-6989(93)90156-q
  68. 68. Neri P, Levi DM (2006) Spatial resolution for feature binding is impaired in peripheral and amblyopic vision. Journal of Neurophysiology 96: 142–153. doi: 10.1152/jn.01261.2005
  69. 69. Saarela TP, Sayim B, Westheimer G, Herzog MH (2009) Global stimulus configuration modulates crowding. Journal of Vision 9: 1–11. doi: 10.1167/9.2.5
  70. 70. He S, Cavanagh P, Intriligator J (1996) Attentional resolution and the locus of visual awareness. Nature 383: 334–337. doi: 10.1038/383334a0
  71. 71. Must A, Janka Z, Benedek G, Keri S (2004) Reduced facilitation effect of collinear flankers on contrast detection reveals impaired lateral connectivity in the visual cortex of schizophrenia patients. Neuroscience Letters 357: 131–134. doi: 10.1016/j.neulet.2003.12.046
  72. 72. Dakin S, Carlin P, Hemsley D (2005) Weak suppression of visual context in chronic schizophrenia. Current Biology 15: R822–R824. doi: 10.1016/j.cub.2005.10.015
  73. 73. Kurylo DD, Pasternak R, Silipo G, Javitt DC, Butler PD (2007) Perceptual organization by proximity and similarity in schizophrenia. Schizophrenia Research 95: 205–214. doi: 10.1016/j.schres.2007.07.001
  74. 74. Silverstein SM, Kovacs I, Corry R, Valone C (2000) Perceptual organization, the disorganization syndrome, and context processing in chronic schizophrenia. Schizophrenia Research 43: 11–20. doi: 10.1016/s0920-9964(99)00180-2
  75. 75. Doniger GM, Silipo G, Rabinowicz EF, Snodgrass JG, Javitt DC (2001) Impaired sensory processing as a basis for object-recognition deficits in schizophrenia. American Journal of Psychiatry 158: 1818–1826. doi: 10.1176/appi.ajp.158.11.1818
  76. 76. Butler PD, Silverstein SM, Dakin SC (2008) Visual perception and its impairment in schizophrenia. Biological Psychiatry 64: 40–47. doi: 10.1016/j.biopsych.2008.03.023
  77. 77. Chakravarthi R, Pelli DG (2011) The same binding in contour integration and crowding. Journal of Vision 11: 1–12. doi: 10.1167/11.8.10
  78. 78. May KA, Hess RF (2007) Ladder contours are undetectable in the periphery: A crowding effect? Journal of Vision 7: 1–15. doi: 10.1167/7.13.9
  79. 79. Hess RF, Dakin SC (1997) Absence of contour linking in peripheral vision. Nature 390: 602–604. doi: 10.1038/37593
  80. 80. Silverstein SM, Knight RA, Schwarzkopf SB, West LL, Osborn LM, et al. (1996) Stimulus configuration and context effects in perceptual organization in schizophrenia. Journal of Abnormal Psychology 105: 410–420. doi: 10.1037/0021-843x.105.3.410
  81. 81. Intriligator J, Cavanagh P (2001) The spatial resolution of visual attention. Cognitive Psychology 43: 171–216. doi: 10.1006/cogp.2001.0755
  82. 82. Fang F, He S (2008) Crowding alters the spatial distribution of attention modulation in human primary visual cortex. Journal of Vision 8: 9. doi: 10.1167/8.9.6
  83. 83. Nuechterlein KH, Dawson ME (1984) Information-processing and attentional functioning in the developmental course of schizophrenic disorders. Schizophrenia Bulletin 10: 160–203. doi: 10.1093/schbul/10.2.160
  84. 84. Elahipanah A, Christensen BK, Reingold EM (2011) Controlling the spotlight of attention: Visual span size and flexibility in schizophrenia. Neuropsychologia 49: 3370–3376. doi: 10.1016/j.neuropsychologia.2011.08.011
  85. 85. Granholm E, Verney SP (2004) Pupillary responses and attentional allocation problems on the backward masking task in schizophrenia. International Journal of Psychophysiology 52: 37–51. doi: 10.1016/j.ijpsycho.2003.12.004
  86. 86. Ungerleider LG, Haxby JV (1994) 'What' and 'where' in the human brain. Current Opinion in Neurobiology 4: 157–165. doi: 10.1016/0959-4388(94)90066-3
  87. 87. Zhang XL, Zhaoping L, Zhou TG, Fang F (2012) Neural Activities in V1 Create a Bottom-Up Saliency Map. Neuron 73: 183–192. doi: 10.1016/j.neuron.2011.10.035
  88. 88. Schade U, Meinecke C (2011) Texture segmentation: Do the processing units on the saliency map increase with eccentricity? Vision Research 51: 1–12. doi: 10.1016/j.visres.2010.09.010
  89. 89. Li ZP (1999) Contextual influences in V1 as a basis for pop out and asymmetry in visual search. Proceedings of the National Academy of Sciences of the United States of America 96: 10530–10535. doi: 10.1073/pnas.96.18.10530
  90. 90. Martinez A, Hillyard SA, Bickel S, Dias EC, Butler PD, et al. (2012) Consequences of Magnocellular Dysfunction on Processing Attended Information in Schizophrenia. Cerebral Cortex 22: 1282–1293. doi: 10.1093/cercor/bhr195
  91. 91. Arman AC, Chung STL, Tjan BS (2006) Neural correlates of letter crowding in the periphery. Journal of Vision 6: 804. doi: 10.1167/6.6.804
  92. 92. Anderson EJ, Dakin SC, Schwarzkopf DS, Rees G, Greenwood JA (2012) The Neural Correlates of Crowding-Induced Changes in Appearance. Curr Biol 22: 1–8. doi: 10.1016/j.cub.2012.04.063
  93. 93. Kelly SP, Gomez-Ramirez M, Foxe JJ (2008) Spatial Attention Modulates Initial Afferent Activity in Human Primary Visual Cortex. Cerebral Cortex 18: 2629–2636. doi: 10.1093/cercor/bhn022
  94. 94. Kyllingsbaek S, Valla C, Vanrie J, Bundesen C (2007) Effects of spatial separation between stimuli in whole report from brief visual displays. Perception & Psychophysics 69: 1040–1050. doi: 10.3758/bf03193942
  95. 95. Reddy L, VanRullen R (2007) Spacing affects some but not all visual searches: implications for theories of attention and crowding. Journal of Vision 7: 1–17. doi: 10.1167/7.2.3
  96. 96. Wertheim AH, Hooge ITC, Krikke K, Johnson A (2006) How important is lateral masking in visual search? Experimental Brain Research 170: 387–402. doi: 10.1007/s00221-005-0221-9
  97. 97. Rosenholtz R, Huang J, Raj A, Balas BJ, Ilie L (2012) A summary statistic representation in peripheral vision explains visual search. Journal of vision 12: 1–17. doi: 10.1167/12.4.14
  98. 98. Vlaskamp BNS, Hooge ITC (2006) Crowding degrades saccadic search performance. Vision Research 46: 417–425. doi: 10.1016/j.visres.2005.04.006
  99. 99. Motter BC, Simoni DA (2008) Changes in the functional visual field during search with and without eye movements. Vision Research 48: 2382–2393. doi: 10.1016/j.visres.2008.07.020
  100. 100. Elkins IJ, Cromwell RL, Asarnow RF (1992) Span of apprehension in schizophrenic-patients as a function of distractor masking and laterality. Journal of Abnormal Psychology 101: 53–60. doi: 10.1037/0021-843x.101.1.53
  101. 101. Neale JM (1971) Perceptual span in schizophrenia. Journal of Abnormal Psychology 77: 196–204. doi: 10.1037/h0030751
  102. 102. Martelli M, Di Filippo G, Spinelli D, Zoccolotti P (2009) Crowding, reading, and developmental dyslexia. Journal of Vision 9: 1–18. doi: 10.1167/9.4.14
  103. 103. Prado C, Dubois M, Valdois S (2007) The eye movements of dyslexic children during reading and visual search: impact of the visual attention span. Vision Research 47: 2521–2530. doi: 10.1016/j.visres.2007.06.001
  104. 104. Richardson AJ, Gruzelier J (1994) Visual processing, lateralization and syndromes of schizotypy. International Journal of Psychophysiology 18: 227–239. doi: 10.1016/0167-8760(94)90009-4
  105. 105. Revheim N, Butler PD, Schechter I, Jalbrzikowski M, Silipo G, et al. (2006) Reading impairment and visual processing deficits in schizophrenia. Schizophrenia Research 87: 238–245. doi: 10.1016/j.schres.2006.06.022
  106. 106. Bach DR, Buxtorf K, Strik WK, Neuhoff JG, Seifritz E (2011) Evidence for Impaired Sound Intensity Processing in Schizophrenia. Schizophrenia Bulletin 37: 426–431. doi: 10.1093/schbul/sbp092
  107. 107. Williams LE, Light GA, Braff DL, Ramachandran VS (2010) Reduced multisensory integration in patients with schizophrenia on a target detection task. Neuropsychologia 48: 3128–3136. doi: 10.1016/j.neuropsychologia.2010.06.028
  108. 108. Franceschini S, Gori S, Ruffino M, Pedrolli K, Facoetti A (2012) A Causal Link between Visual Spatial Attention and Reading Acquisition. Current Biology 22: 814–819. doi: 10.1016/j.cub.2012.03.013
  109. 109. Roberts EO, Proudlock FA, Martin K, Reveley MA, Al-Uzri M, et al. (2012) Reading in Schizophrenic Subjects and Their Nonsymptomatic First-Degree Relatives. Schizophr Bull: 1–12 [Epub ahead of print].
  110. 110. Richardson AJ (1994) Dyslexia, handedness and syndromes of psychosis-proneness. International Journal of Psychophysiology 18: 251–263. doi: 10.1016/0167-8760(94)90011-6
  111. 111. Shapleske J, Rossell SL, Woodruff PWR, David AS (1999) The planum temporale: a systematic, quantitative review of its structural, functional and clinical significance. Brain Research Reviews 29: 26–49. doi: 10.1016/s0165-0173(98)00047-2
  112. 112. Chen Y, Norton D, Ongur D, Heckers S (2008) Inefficient face detection in schizophrenia. Schizophrenia Bulletin 34: 367–374. doi: 10.1093/schbul/sbm071
  113. 113. Yoon JH, D'Esposito M, Carter CS (2006) Preserved function of the fusiform face area in schizophrenia as revealed by fMRI. Psychiatry Research-Neuroimaging 148: 205–216. doi: 10.1016/j.pscychresns.2006.06.002
  114. 114. Butler PD, Tambini A, Yovel G, Jalbrzikowski M, Ziwich R, et al. (2008) What's in a face? Effects of stimulus duration and inversion on face processing in schizophrenia. Schizophrenia Research 103: 283–292. doi: 10.1016/j.schres.2008.03.007
  115. 115. Campanella S, Montedoro C, Streel E, Verbanck P, Rosier V (2006) Early visual components (P100, N170) are disrupted in chronic schizophrenic patients: an event-related potentials study. Neurophysiologie Clinique-Clinical Neurophysiology 36: 71–78. doi: 10.1016/j.neucli.2006.04.005
  116. 116. Shin YW, Na MH, Ha TH, Kang DH, Yoo SY, et al. (2008) Dysfunction in configural face processing in patients with schizophrenia. Schizophrenia Bulletin 34: 538–543. doi: 10.1093/schbul/sbm118
  117. 117. Martelli M, Majaj NJ, Pelli DG (2005) Are faces processed like words? A diagnostic test for recognition by parts. Journal of Vision 5: 58–70. doi: 10.1167/5.1.6
  118. 118. Saj A, Cojan Y, Vocat R, Luaute J, Vuilleumier P (2011) Prism adaptation enhances activity of intact fronto-parietal areas in both hemispheres in neglect patients. Cortex: 1–12 [Epub ahead of print].
  119. 119. Corbetta M, Shulman GL (2002) Control of goal-directed and stimulus-driven attention in the brain. Nature Reviews Neuroscience 3: 201–215. doi: 10.1038/nrn755
  120. 120. Knebel JF, Javitt DC, Murray MM (2011) Impaired early visual response modulations to spatial information in chronic schizophrenia. Psychiatry Research-Neuroimaging 193: 168–176. doi: 10.1016/j.pscychresns.2011.02.006
  121. 121. Foxe JJ, Murray MM, Javitt DC (2005) Filling-in in schizophrenia: A high-density electrical mapping and source-analysis investigation of illusory contour processing. Cerebral Cortex 15: 1914–1927. doi: 10.1093/cercor/bhi069
  122. 122. McGhie A, Chapman J (1961) Disorders of attention and perception in early schizophrenia. British Journal of Medical Psychology 34: 103–116. doi: 10.1111/j.2044-8341.1961.tb00936.x
  123. 123. Chen Y, Grossman EA, Bidwell LC, Yurgelun-Todd D, Gruber SA, et al. (2008) Differential activation patterns of occipital and prefrontal cortices during motion processing: Evidence from normal and schizophrenic brains. Cognitive Affective & Behavioral Neuroscience 8: 293–303. doi: 10.3758/cabn.8.3.293
  124. 124. Sereno AB, Holzman PS (1995) Antisaccades and smooth-pursuit eye-movements in schizophrenia. Biological Psychiatry 37: 394–401. doi: 10.1016/0006-3223(94)00127-o
  125. 125. Olevitch BA, Stern JA (1996) Head movements in schizophrenia: New biological marker, critical neurological flaw, or artifact of subvocalization? International Journal of Neuroscience 88: 249–260. doi: 10.3109/00207459609000618
  126. 126. Green MF, Nuechterlein KH, Mintz J (1994) Backward-masking in schizophrenia and mania. 1. Specifying a mechanism. Archives of General Psychiatry 51: 939–944. doi: 10.1001/archpsyc.1994.03950120011003
  127. 127. Chkonia E, Roinishvili M, Makhatadze N, Tsverava L, Stroux A, et al. (2010) The Shine-Through Masking Paradigm Is a Potential Endophenotype of Schizophrenia. Plos One 5: 1–7. doi: 10.1371/journal.pone.0014268