Brief monocular deprivation as an assay of short-term visual sensory plasticity in schizophrenia - "the binocular effect"

Abstract

Background: Visual sensory processing deficits are consistently observed in schizophrenia, with clear amplitude reduction of the visual evoked potential (VEP) during the initial 50-150 ms of processing. Similar deficits are seen in unaffected first-degree relatives and drug-naïve first-episode patients, pointing to these deficits as potential endophenotypic markers. Schizophrenia is also associated with deficits in neural plasticity, implicating dysfunction of both glutamatergic and GABAergic systems. Here, we sought to understand the intersection of these two domains, asking whether short-term plasticity during early visual processing is specifically affected in schizophrenia.

Methods: Brief periods of monocular deprivation (MD) induce relatively rapid changes in the amplitude of the early VEP - i.e., short-term plasticity. Twenty patients and 20 non-psychiatric controls participated. VEPs were recorded during binocular viewing, and were compared to the sum of VEP responses during brief monocular viewing periods (i.e., Left-eye + Right-eye viewing).

Results: Under monocular conditions, neurotypical controls exhibited an effect that patients failed to demonstrate. That is, the amplitude of the summed monocular VEPs was robustly greater than the amplitude elicited binocularly during the initial sensory processing period. In patients, this "binocular effect" was absent.

Limitations: Patients were all medicated. Ideally, this study would also include first-episode unmedicated patients.

Conclusion: These results suggest that short-term compensatory mechanisms that allow healthy individuals to generate robust VEPs in the context of MD are not effectively activated in patients with schizophrenia. This simple assay may provide a useful biomarker of short-term plasticity in the psychotic disorders and a target endophenotype for therapeutic interventions.

Keywords: EEG; biomarker; endophenotype; event-related potential; genetic liability; psychosis; vision; visual evoked potential.

Figure 1

Waveforms from two representative parieto-occipital scalp sites (PO3 and PO4) are shown for neurotypical control participants and patients with schizophrenia. (A) Data from 20 control subjects are displayed in pink and blue; (B) data from 20 patients are displayed in red and green.

Figure 2

Modulation index for the binocular effect: each point in the scatter plot represents the data for one participant. Values were derived by subtracting Binocular (BASE) from SUM conditions. Controls are shown in blue, patients in red. Using Cohen’s d, the effect size of the difference is 0.67.

Figure 3

The binocular effect is characterized with difference waveforms (SUM minus BASE) for controls (red) and patients (green) at two representative electrodes (PO3 and PO4). The yellow shading denotes the early “binocular effect” period.

Figure 4

Scatter plot is displayed showing correlations for each subject of P1 amplitude to modulation index. The x-axis displays values for P1 amplitudes; y-axis displays binocular modulation indices. The P1 values used here are collapsed averages of left and right hemiscalp amplitudes. Controls are depicted by blue points (n = 16), patients by pink (n = 16).

Figure 5

Statistical cluster plots depict point-wise running t-tests comparing the amplitudes of participants’ VEPs in Binocular vs. SUM conditions. Time with respect to stimulus onset is presented on the x-axis and the general topographic regions of 72 electrode positions are displayed on the y-axis. Color corresponds to t values. Periods of significant difference are only plotted if a strict alpha criterion of <0.05 was exceeded for at least 10 consecutive data points. The early “binocular effect” period has been outlined with a black box for each group.