Visual dysfunction is commonplace in schizophrenia and occurs alongside cognitive, psychotic and affective symptoms of the disorder. Evidence from psychophysical paradigms suggests that this dysfunction results from impairment in integrating low-level neural signals into complex cortical representations. Despite the symptoms of schizophrenia occurring in a range of disorders, the integration deficit has not been tested in broader patient populations, nor whether the deficits generalise across visual and auditory modalities. We assessed patients with a range of psychotic and non-psychotic disorders and healthy controls on visual and auditory detection and integration tasks. The sample included 249 participants with a range of psychiatric diagnosis. Compared with non-psychotic patients and healthy controls, psychotic patients trans-diagnostically were impaired on both visual and auditory tasks requiring sensory integration, but unimpaired in simple visual or auditory detection. Impairment in sensory integration was correlated with the severity of positive psychotic symptoms. Our results demonstrate that impaired functional integration is not specific to schizophrenia, as has previously been assumed. Instead, sensory deficits are closely related to the presence of psychotic symptoms independent of diagnosis. The finding that equivalent integrative sensory processing is impaired in audition is consistent with hypotheses that propose a generalised deficit of neural integration in psychotic disorders.

Recent models of schizophrenia suggest that high-level cognitive symptoms are due to alterations at the earliest stages of sensory processing. Here, I present functional and behavioural evidence for a perturbation of early sensory mechanisms involved in the visual processing of orientation. Using functional magnetic resonance imaging (fMRI), our data show that orientation-specific contextual modulation of neural responses in primary visual cortex (V1) is dramatically reduced in patients with schizophrenia. Our psychophysical data also reveal abnormalities in contextual processing of orientation, but suggest a more pervasive deficit in sensory integration might link perceptual disturbance with clinical symptoms.

I will briefly review the range of phenomena demonstrating that schizophrenia (SZ) is associated with poor processing of sensory information, and with a reduced influence of visual context. I will then go on to describe some new work from lab that probes the neural basis of this deficit using functional MRI (fMRI) and population receptive field (pRF) mapping to infer properties of populations of visually responsive neurons in people with SZ. Our analysis reveals that SZ is associated with smaller pRFs throughout the visual pathway. Using a difference-of Gaussian (DoG) model to capture the centre-surround configuration we find this reduction in pRF size is largely due to reduced (smaller and shallower) inhibitory surrounds. Such a finding likely reflects differences in neurons at the single-unit level and population-level. I’ll discuss how reduced inhibition, within and across receptive fields, might contribute to the diverse range of sensory deficits reported in SZ.

Rhythmical high-frequency “gamma” oscillations in the central nervous system are thought to reflect the balance of excitation and inhibition in neuronal networks and are disturbed in patients with schizophrenia. Gamma-band activity can be recorded throughout the central nervous at microscopic and macroscopic levels but the interpretation of data across levels represents a major challenge. In this talk I will describe our attempts to integrate these levels of analysis using pharmacological techniques to modify stimulus-induced gamma oscillations in the visual cortex. Consistent with in vivo and in vitro animal work our human studies demonstrate elevation of visual gamma amplitude and reduction of frequency with both GABAergic drugs and the NMDA antagonist ketamine whilst reductions in gamma amplitude occur with the AMPA antagonist perampanel. These results suggest that similar generator mechanisms underlie both microscopic and macroscopically recorded gamma-band activity. Using the same approach with healthy participants we also demonstrate that the frequency of gamma-band activity can serve as a predictor of performance in an orientation discrimination task. In patients with schizophrenia, both stimulus-induced peak gamma frequency and stimulus-induced gamma amplitude are reduced in comparison to matched controls. Neural mass modelling suggests that these abnormalities are driven by alterations in underlying GABAergic signalling, and can be related to the impairments in psychophysical performance seen in patients performing orientation discrimination. Overall, these data suggest that simple visual tasks can be used to probe GABAergic dysfunction in schizophrenia but complexities remain in terms of both methodology and interpretation and these will be highlighted.