Transsaccadic Perception Deficits in Schizophrenia Reflect the Improper Internal Monitoring of Eye Movement Rather Than Abnormal Sensory Processing

Abstract

Background: Symptoms of psychosis in schizophrenia reflect disturbances in sense of agency-difficulty distinguishing internally from externally generated sensory and perceptual experiences. One theory attributes these anomalies to a disruption in corollary discharge (CD), an internal copy of generated motor commands used to distinguish self-movement-generated sensations from externally generated stimulation.

Methods: We used a transsaccadic shift detection paradigm to examine possible deficits in CD and sense of agency based on the ability to perceive visual changes in 31 schizophrenia patients (SZPs) and 31 healthy control subjects. We derived perceptual measures based on manual responses indicating the transsaccadic target shift direction. We also developed a distance-from-unity-line measure to quantify use of CD versus purely sensory (visual) information in evaluating visual changes in the environment after an eye movement.

Results: SZPs had higher perceptual thresholds in detecting shift of target location than healthy control subjects, regardless of movement direction or amplitude. Despite producing similar hypometric saccades, healthy control subjects overestimated target location, whereas SZPs relied more on the experienced visual error and consequently underestimated the target position. We show that in SZPs the postsaccadic judgment of the initial target location was largely aligned with the measure based only on visual error, suggesting a deficit in the use of CD. This CD deficit also correlated with positive schizophrenia symptoms and disturbances in sense of agency.

Conclusions: These results provide a novel approach in quantifying abnormal use of CD in SZPs and provide a framework to distinguish deficits in sensory processing versus defects in the internal CD-based monitoring of movement.

Keywords: Corollary discharge; Positive symptoms; Saccade; Schizophrenia; Sense of agency; Visual perception.

Figure 1. Trans-saccadic shift-detection task

(A) Task procedure. Each trial began with a central fixation cross (0.3^o in extent) appearing for a variable period (random duration between 1200 and 1800 ms), followed by the appearance of an initial target that could appear randomly at any one of the two amplitudes (4° or 8°) and two directions (leftward or rightward). Subjects were required to make a saccadic eye movement toward this initial target, and upon online detection (when eye position exceeded a virtual window, 3.2° in extent) the target was displaced during the saccade, reappearing at a new location after a 250 ms blank period. This blank period was used to measure properties of the saccade CD rather than the effect of saccadic suppression on perception—an effect studied when the target immediately reappears at the shifted location. Previous results suggest that differences in perception due to CD are observable during this blank target condition (32,57). The displaced target, T2, appeared randomly at shifted positions according the illustrated Gaussian distribution ranging from -3.5° to 3.5° shifts. After the reappearance of the target a t the shifted location, subjects were required to indicate the direction of the displacement (backward or forward) using the left or right mouse buttons. A successful trial required a response to occur within 3000 ms of the shifted target’s reappearance, but no instructions or feedback were given regarding reaction time and accuracy. (B) The percentage of forward responses on the y-axis is plotted as a function of target displacement on the abscissa. The manual response data were fitted with a cumulative Gaussian distribution to determine the psychometric function and measures of perceptual bias and threshold. Two example psychometric curves are shown with different slopes. Two perceptual measures are derived: perceptual threshold and bias. The threshold, top right, is computed as the difference in target displacement between the 50% and the 75% points of the sample psychometric curves. The perceptual bias, bottom right, was taken as the displacement from 0 (x-axis) at the point where the forward and backward responses were equal to 50% (y-axis). Each example curve yields a different threshold and bias. (C)The visual error was quantified by taking the vector magnitude, in visual angle degrees, between the eye position at the time when the shifted target appeared and the location of the shifted target. The examples show rightward saccades that undershoot the target, and leftward target shifts. Upon presaccadic target appearance the corollary discharge (CD) vector is used to predict the saccadic landing position. In this example, the saccade falls short of the target and the postsaccadic target is to the left of the presaccadic target, efficient CD-driven remapping would predict that subjects will perceive the shift as backward. In the left panel the large target shift and visual error are aligned, resulting in the correct ‘backward’ response. In the right panel the small target shift is in the opposite direction of the resulting visual error since the landing site is ‘behind’ the shifted target, with no CD vector information, it would result in an incorrect ‘forward’ response. These visual errors were used to derive hypothetical responses for target localization and psychometric curves based solely on the experienced sensory information.

Figure 2. Percent gain of saccade amplitude and percent error estimation of target location

We plot the percent error of the estimated target location per amplitude and direction as a function of percent gain in the mean saccade amplitude. Percent gain is the saccade amplitude as a percentage of the required movement amplitude. A percentage above 100 signifies that the mean saccade amplitude exceeded the target amplitude (overshoot); a percentage below 100 signifies that the mean saccade amplitude fell short of the target amplitude (undershoot). Percent error was perceptual bias as a percentage of the target amplitude. A percentage above 0 signified that the perceptual estimate exceeded the target amplitude (overestimation); a negative percentage signified that the perceptual estimate was lower than the target amplitude (underestimation). Each filled circle represents the mean values for each subject (Red: SZP, Blue:HC). Each panel shows the result for the respective saccade amplitude and direction. The larger solid circles represent the respective mean percent gains in saccade amplitude and mean percent errors in target location estimation, with the corresponding ellipses representing the 95% confidence interval. The histograms to the right and above each panel are the respective distributions of the percent error and the percent gain.

Figure 3. Example psychometric curves for leftward 4° saccades

Eye positions of an example subject from each group for saccades to a leftward target at 4°. Eye position at the time the target reappeared are displayed as filled red (A, SZP) and blue (B, HC) circles, respectively. The initial target is marked by a white circle with a black outline, and the solid ellipses represent the spatial extent of the 1 SD confidence interval of eye position variability. (Note that we could not depict the shifted target because this displacement varied on each trial.) Purple and green squares represent the perceptual (Visual Error + CD-based) and hyopothetical Visual Error-based estimates of the target location, respectively. Visual Error-based and Visual Error + CD-based psychometric functions of perceived target shift are shown next to the corresponding eye movements. The corresponding values for bias and threshold are given in each plot.

Figure 4. Clinical correaltions to behavioral measures

(A) Individual data points (light circles, red for SZP and blue for HC) for perceptual bias. Estimates for visual error-based (ordinate) vs. visual error + CD-based (abscissa) are plotted for each target amplitude and direction. Square symbols with the thick black outline represent the mean values across the respective groups. We obtain a distance from the unity line measure as an assay of how closely the two estimates of perceptual bias matched. Points along the unity line designate subjects for whom the two biases are closely related, thus indicating the lack of CD utilization in the estimate of the pre-saccadic target location and an incorrect reliance on post-saccade sensory information. The distance of points lying above or below the line indicate the magnitude of misalignment between the two measures. The bar charts show mean absolute values indicating the magnitude of the distance from the unity line across the respective group. (B) Scatter plot showing correlations between mean distance from the unity line (across the two directions and movement amplitudes) and “Mental” SoA for SZP (Red circles) and HC (Blue circles), respectively with Spearman’s R and p-values displayed, as well as the R² value for the regression line over the entire sample (SZP and HC combined). The grey shaded area shows overlap between HC and SZP subjects—across groups these subjects had similar mean distance-from-unity-line values. The HC within this range demonstarted perceptual judgments that were closely related to the hypothetical judgments derived from the experienced visual error, similar to most SZP. Thus, these HC had lower values for distance-from-unity-line measure and also demonstrated a disturbed subjective sense of mental agency. (C) Scatter plots showing significant correlation between mean distance from the unity line and Hallucinations, Delusions and Total PANSS score.