Subcortical visual dysfunction in schizophrenia drives secondary cortical impairments

Albert Einstein College of Medicine, New York, New York, United States
Brain (Impact Factor: 9.2). 03/2007; 130(Pt 2):417-30. DOI: 10.1093/brain/awl233
Source: PubMed


Visual processing deficits are an integral component of schizophrenia and are sensitive predictors of schizophrenic decompensation in healthy adults. The primate visual system consists of discrete subcortical magnocellular and parvocellular pathways, which project preferentially to dorsal and ventral cortical streams. Subcortical systems show differential stimulus sensitivity, while cortical systems, in turn, can be differentiated using surface potential analysis. The present study examined contributions of subcortical dysfunction to cortical processing deficits using high-density event-related potentials. Event-related potentials were recorded to stimuli biased towards the magnocellular system using low-contrast isolated checks in Experiment 1 and towards the magnocellular or parvocellular system using low versus high spatial frequency (HSF) sinusoidal gratings, respectively, in Experiment 2. The sample consisted of 23 patients with schizophrenia or schizoaffective disorder and 19 non-psychiatric volunteers of similar age. In Experiment 1, a large decrease in the P1 component of the visual event-related potential in response to magnocellular-biased isolated check stimuli was seen in patients compared with controls (F = 13.2, P = 0.001). Patients also showed decreased slope of the contrast response function over the magnocellular-selective contrast range compared with controls (t = 9.2, P = 0.04) indicating decreased signal amplification. In Experiment 2, C1 (F = 8.5, P = 0.007), P1 (F = 33.1, P < 0.001) and N1 (F = 60.8, P < 0.001) were reduced in amplitude to magnocellular-biased low spatial frequency (LSF) stimuli in patients with schizophrenia, but were intact to parvocellular-biased HSF stimuli, regardless of generator location. Source waveforms derived from inverse dipole modelling showed reduced P1 in Experiment 1 and reduced C1, P1 and N1 to LSF stimuli in Experiment 2, consistent with surface waveforms. These results indicate pervasive magnocellular dysfunction at the subcortical level that leads to secondary impairment in activation of cortical visual structures within dorsal and ventral stream visual pathways. Our finding of early visual dysfunction is consistent with and explanatory of classic literature showing subjective complaints of visual distortions and is consistent with early visual processing deficits reported in schizophrenia. Although deficits in visual processing have frequently been construed as resulting from failures of top-down processing, the present findings argue strongly for bottom-up rather than top-down dysfunction at least within the early visual pathway. Deficits in magnocellular processing in this task may reflect more general impairments in neuronal systems functioning, such as deficits in non-linear amplification and may thus represent an organizing principle for predicting neurocognitive dysfunction in schizophrenia.

Download full-text


Available from: John J Foxe,
  • Source
    • "In healthy subjects, linguistic threat has been shown to modulate limbic/paralimbic (e.g., amygdala, parahippocampus, medial OFC, ACC), semantic processing (vlPFC), and lingual gyrus activations (Isenberg et al., 1999; Lewis et al., 2007; Citron, 2012); negatively valenced pictures commonly increase occipital-temporal ventral visual stream ( " what " pathway) activations (Taylor et al., 2000; Sabatinelli et al., 2005, 2009). Visual processing deficits in schizophrenia have increasingly been characterized as involving predominantly dorsal stream ( " where " pathway) abnormalities (Butler et al., 2001, 2007a; Braus et al., 2002; Chen et al., 2004; Seymour et al., 2013). However, increased ventral stream activations were found in paranoid schizophrenic patients compared to healthy subjects during performance of a dual working memory, affectively valenced face-viewing task (Wolf et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Persecutory delusions are a clinically important symptom in schizophrenia associated with social avoidance and increased violence. Few studies have investigated the neurobiology of persecutory delusions, which is a prerequisite for developing novel treatments. The aim of this two-paradigm functional magnetic resonance imaging (fMRI) study is to characterize social "real world" and linguistic threat brain activations linked to persecutory delusions in schizophrenia (n=26) using instructed-fear/safety and emotional word paradigms. Instructed-fear/safety activations correlated to persecutory delusion severity demonstrated significant increased lateral orbitofrontal cortex and visual association cortex activations for the instructed-fear vs. safety and instructed-fear vs. baseline contrasts; decreased lateral orbitofrontal cortex and ventral occipital-temporal cortex activations were observed for the instructed-safety stimuli vs. baseline contrast. The salience network also showed divergent fear and safety cued activations correlated to persecutory delusions. Emotional word paradigm analyses showed positive correlations between persecutory delusion severity and left-lateralized linguistic and hippocampal-parahippocampal activations for the threat vs. neutral word contrast. Visual word form area activations correlated positively with persecutory delusions for both threat and neutral word vs. baseline contrasts. This study links persecutory delusions to enhanced neural processing of threatening stimuli and decreased processing of safety cues, and helps elucidate systems-level activations associated with persecutory delusions in schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Psychiatry Research: Neuroimaging 06/2015; 233(3). DOI:10.1016/j.pscychresns.2015.06.002 · 2.42 Impact Factor
  • Source
    • "An in-house visual acuity correction kit was used for individuals without appropriate glasses or contacts. Each group had an average binocular acuity of almost exactly $ 20/20 (see Table 1) and no subject had worse than 20/32 binocular acuity, a cut-off similar to previous studies (Butler et al., 2007b; Martinez et al., 2008; Schechter et al., 2005). All subjects completed the three psychometric tasks described below. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Schizophrenia patients poorly perceive Kanizsa figures and integrate co-aligned contour elements (Gabors). They also poorly process low spatial frequencies (SFs), which presumably reflects dysfunction along the dorsal pathway. Can contour grouping deficits be explained in terms of the spatial frequency content of the display elements? To address the question, we tested patients and matched controls on three contour grouping paradigms in which the SF composition was modulated. In the Kanizsa task, subjects discriminated quartets of sectored circles (“pac-men”) that either formed or did not form Kanizsa shapes (illusory and fragmented conditions, respectively). In contour integration, subjects identified the screen quadrant thought to contain a closed chain of co-circular Gabors. In collinear facilitation, subjects attempted to detect a central low-contrast element flanked by collinear or orthogonal high-contrast elements, and facilitation corresponded to the amount by which collinear flankers reduced contrast thresholds. We varied SF by modifying the element features in the Kanizsa task and by scaling the entire stimulus display in the remaining tasks (SFs ranging from 4 to 12 cycles/deg). Irrespective of SF, patients were worse at discriminating illusory, but not fragmented shapes. Contrary to our hypothesis, collinear facilitation and contour integration were abnormal in the clinical group only for the higher SF (>=10 c/deg). Grouping performance correlated with clinical variables, such as conceptual disorganization, general symptoms, and levels of functioning. In schizophrenia, three forms of contour grouping impairments prominently arise and cannot be attributed to poor low SF processing. Neurobiological and clinical implications are discussed.
    Neuropsychologia 11/2014; 65. DOI:10.1016/j.neuropsychologia.2014.10.031 · 3.30 Impact Factor
  • Source
    • "Because locating targets in space is thought to be a dorsal stream function, and because the dorsal stream receives primarily M pathway input, this result has been interpreted as evidence of abnormal M pathway (subcortical) or dorsal stream (cortical) processing in SZ. As noted, there is considerable overlap between the M and P visual channels as early as the primary visual cortex (V1) and this interaction extends into the dorsal and ventral streams occurring thereafter (Kovacs et al., 1995; Sawatari and Callaway, 1996; Keri et al., 2000; Butler et al., 2007; Skottun and Skoyles, 2007) making it difficult to conclude from the VBM paradigm alone whether there are specific subcortical pathway deficits. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Individuals with schizophrenia spectrum diagnoses have deficient visual information processing as assessed by a variety of paradigms including visual backward masking, motion perception and visual contrast sensitivity (VCS). In the present study, the VCS paradigm was used to investigate potential differences in magnocellular (M) vs. parvocellular (P) channel function that might account for the observed information processing deficits of schizophrenia spectrum patients. Specifically, VCS for near threshold luminance (black/white) stimuli is known to be governed primarily by the M channel, while VCS for near threshold chromatic (red/green) stimuli is governed by the P channel. Methods: VCS for luminance and chromatic stimuli (counterphase-reversing sinusoidal gratings, 1.22 c/degree, 8.3 Hz) was assessed in 53 patients with schizophrenia (including 5 off antipsychotic medication), 22 individuals diagnosed with schizotypal personality disorder and 53 healthy comparison subjects. Results: Schizophrenia spectrum groups demonstrated reduced VCS in both conditions relative to normals, and there was no significant group by condition interaction effect. Post-hoc analyses suggest that it was the patients with schizophrenia on antipsychotic medication as well as SPD participants who accounted for the deficits in the luminance condition. Conclusions: These results demonstrate visual information processing deficits in schizophrenia spectrum populations but do not support the notion of selective abnormalities in the function of subcortical channels as suggested by previous studies. Further work is needed in a longitudinal design to further assess VCS as a vulnerability marker for psychosis as well as the effect of antipsychotic agents on performance in schizophrenia spectrum populations.
    Frontiers in Psychology 08/2013; 4:535. DOI:10.3389/fpsyg.2013.00535 · 2.80 Impact Factor
Show more