BackgroundThe human subcortical visual system is divided into distinct magnocellular, parvocellular and koniocellular pathways, which contribute differentially to specific aspects of early visual processing. Schizophrenia is associated with deficits in early-visual processing, especially involving N-methyl-D-aspartate receptor (NMDAR)-mediated non-linear gain within the subcortical magnocellular visual system. Nevertheless, methods for investigating the pathophysiological consequences remain limited. Flash-VEP can be obtained using either transient (tVEP) or steady-state (ssVEP) approaches. Flash stimuli also induce sustained reduction (“blocking”) of the posterior alpha rhythm. Red (vs. white) flash stimuli selectively suppress activity in magnocellular-recipient layers of primary visual cortex. Here, we investigated flash-VEP responses in schizophrenia, with emphasis on the potential utility for assessing selective pathophysiological involvement of the magnocellular and koniocellular pathways.MethodsWe obtained flash-VEP from 28 healthy control and 27 schizophrenia participants to white and red stimuli across a range of stimulation rates, and pattern-VEP from 29 control and 22 schizophrenia participants. A subset (17 control/15 schizophrenia) participated in both studies. We also obtained fMRI to 6-Hz white and red stimuli in an additional sample of 14 control and 14 schizophrenia participants. fMRI analyses focused on both visual cortex and inferior pulvinar nucleus.ResultsSchizophrenia participants showed increased flash-tVEP responses (d = 0.99, p < 0.001) despite significantly reduced pattern-tVEP (d = −0.99, p < 0.001). In addition, the ssVEP (photic driving) response was significantly reduced in schizophrenia, as reflected by reduced intertrial trial coherence (ITC) within the alpha frequency band (d = −0.78, p < 0.001). Alpha blocking was induced equivalently by white and red stimuli in HC, suggesting magnocellular involvement via the retinotectal system. The degree of blocking was significantly reduced in schizophrenia (d = −0.83, p = 0.003) and correlated significantly with neurocognitive impairment (rp = 0.65, p < 0.001). fMRI studies showed reduced pulvinar activation (d = −1.1, p = 0.008), along with aberrantly increased dorsal cortical activation (d = 0.98, p = 0.019).ConclusionThe findings reinforce the importance of subcortical visual dysfunction as a driver of impaired neurocognition in schizophrenia and provide a scalable mechanism for assessment of early-visual dysfunction within the clinical setting. Deficit patterns are consistent with concepts of impaired magnocellular and koniocellular visual function affecting both thalamocortical and retinotectal system function in schizophrenia.