Subcortical visual dysfunction in schizophrenia drives secondary cortical impairments

Abstract

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.

What's in a face? Effects of stimulus duration and inversion on face processing in schizophrenia

“…Deficits in contrast sensitivity have also been seen in other studies of schizophrenia Keri et al, 2002;Slaghuis, 1998). The contrast sensitivity findings as well as prolonged duration for same/different discrmination of objects confirm earlier findings of impaired early visual processing in schizophrenia (Butler et al, 2007;Butler et al, 2005;Cadenhead et al, 1998;Green et al, 1994;Keri et al, 2004;Kim et al, 2005;O'Donnell et al, 2002;Slaghuis and Thompson, 2003).…”

“…These subcortical pathways are differentiated based upon their anatomy and responsiveness to specific physical features such as contrast or spatial frequency (Kaplan, 2003). Deficits in early visual processing in patients with schizophrenia have been extensively documented over recent years (Dakin et al, 2005;Doniger et al, 2002;Krishnan et al, 2005;Spencer et al, 2003), particularly with regard to magnocellular processing (Butler et al, 2007;Butler et al, 2005;Keri et al, 2004;Slaghuis and Bishop, 2001). …”

“…Significant deficits in schizophrenia have been observed on tasks that tap dorsal stream function, like motion detection (Brenner et al, 2003;Chen et al, 1999), as well as ventral stream processing, such as perceptual closure (Doniger et al, 2002). It has yet to be determined, however, whether visual cortical processing is impaired because of intrinsic dysfunction within dorsal or ventral stream cortical regions, or because of impaired input from subcortical visual systems (Butler et al, 2007).…”

Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia

“…Because recurrent inhibition is a fundamental feature of cortical circuitry, blockade of NMDARs will likely cause disinhibition in many brain regions. Consistent with this, in schizophrenia there are abnormalities in sensory processes mediated by sensory cortex [95][96][97], as well as in highlevel functions (working memory) carried out in prefrontal cortex [98]. However, there appears to be a special role of disinhibition in the hippocampal region in stimulating the hyperdopaminergic state (and the consequent psychosis).…”

Visual sensory processing deficits in Schizophrenia and their relationship to disease state

“…An association between the reduced P1 amplitude and impairment in the magnocellular (M) pathway has also been drawn [7,9,23] and evidence from behavioural studies has also pointed to impairments in this system [33,45,57). The M pathway is the part of the visual system responsible for the rapid conduction of low-resolution visual information to the cortex and is involved in processing of overall stimulus organization [46,62,66].…”