Increased repulsion of working memory representations in schizophrenia

Abstract

Computational neuroscience models propose that working memory (WM) involves recurrent excitatory feedback loops that maintain firing over time along with lateral inhibition that prevents the spreading of activity to other feature values. In behavioral paradigms, this lateral inhibition appears to cause a repulsion of WM representations away from each other and from other strong sources of input. Recent computational models of schizophrenia have proposed that reduction in the strength of inhibition relative to strength of excitation may underlie impaired cognition, and this leads to the prediction that repulsion effects should be reduced in people with schizophrenia spectrum disorders (PSZ) relative to healthy control subjects (HCS). We tested this hypothesis in 2 experiments measuring WM repulsion effects. In Experiment 1, 45 PSZ and 32 HCS remembered the location of a single object relative to a centrally presented visual landmark and reported this location after a short delay. The reported location was repelled away from the landmark in both groups, but this repulsion effect was increased rather than decreased in PSZ relative to HCS. In Experiment 2, 41 PSZ and 34 HCS remembered 2 sequentially presented orientations and reported each orientation after a short delay. The reported orientations were biased away from each other in both groups, and this repulsion effect was again more pronounced in PSZ than in HCS. Contrary to the widespread hypothesis of reduced inhibition in schizophrenia, we provide robust evidence from 2 experiments showing that the behavioral performance of PSZ exhibited an exaggeration rather than a reduction of competitive inhibition. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Figure 1.

Predictions of bump attractor models with tuned inhibition. (A) Basic model. Neurons (circles) that are selective for similar feature values (e.g., similar locations) are connected via recurrent excitation (green lines), and they also inhibit neurons that code adjacent feature values (red lines). This leads to a pattern of activity (blue line) with a positive peak (bump) near the true feature value and inhibition at surrounding values. Note that the X axis represents the space of feature values (e.g., locations) and the height of the curve represents the activity level of neurons coding that feature value. (B) Pattern of activity for two objects with similar feature values presented individually (top two curves) and presented simultaneously (bottom curve). The black vertical lines represent the true feature values. Note that the peaks of activity are shifted slightly outward from the true values when the two features are presented simultaneously. (C) Pattern of activity for a visible landmark and a weaker working memory representation. The peak for the working memory activity is repelled quite far from the true value. (D) Same as (C), but for objects with very different feature values. The peak of activity is now very close to the true value. (E) Same as (C), but with weaker inhibition. Note that the peak of activation exhibits less repulsion than in (C).

Figure 2.

Landmark Task. (A) Example of a trial in Experiment 1. A visual landmark, a white vertical line appearing at the top half of the display was continuously visible. Each trial began with a red fixation cross appearing at the center, followed by a white target circle appearing at one of 16 horizontal locations (displayed in the callout box), evenly spaced on a log scale, either to the right or the left of the middle of the display. The target circle was visible for 200 ms, followed by a retention period of 3000 ms during which only the visual landmark and fixation cross were present. At the end of this period, a response cue in the form of a white crosshair atop the fixation cross appeared, prompting participants to indicate the remembered location of the target circle by using the mouse to move the crosshair until it matched the remembered target location and clicking to finalize the response. (B)Response Bias Quantification. Response Bias was quantified as the horizontal displacement of the reported location away from the actual target location on each trial (in degrees of visual angle) and was given a positive sign if the reported location was away from the landmark (repulsion), and it was given a negative sign if the reported error was toward the landmark (attraction). The data were collapsed for mirror-image target locations, producing eight different distances (relative to the landmark). (C)Response Bias results. Mean response bias as a function of target location (horizontal distance from the visual landmark), separated by group. Asterisks indicate significant difference between the groups and hashtags indicate distances at which the bias as significantly different from zero in each group respectively. (black for HCS, red for PSZ) (D) Absolute Response Error. Mean unsigned error was derived as a precision measure, as quantified as the absolute horizontal displacement of the reported location from the actual target location on each trial (in degrees of visual angle). Mean response error is displayed as a function of target location (horizontal distance from the visual landmark), separated by group (Red, PSZ, Black, HCS). In the inlay, the bars indicate the mean slopes of the regression lines between response error and distance(which was on a log scale) for each group.

Figure 3.

Relative Orientation Task. (A) Example of a single trial. Participants remembered two serially presented target orientations and reproduced each orientation in a cued order. The cues (“1^st orientation” and “2^nd orientation”) indicate that second target should be reported first in this example, but the order of report varied unpredictably across trials. (B) Mean response bias as a function of the orientation difference between the two items, collapsed across order of presentation and response order. The variable of interest is the angular deviation between reported orientation and actual orientation of the target being reported. To determine whether the response to one target was attracted toward or repelled away from the other target, the sign of the response error for the target being reported at a given moment was designated relative to the orientation of the target that was not being reported at that moment. The response error was given a positive sign if the reported orientation was away from the orientation of the other target, and it was given a negative sign if the reported error was toward the orientation of the other target. Positive error indicates bias away from the other target, and negative error represents bias toward the other target; the zero line indicates no bias. Asterisks indicate significant difference between the groups and hashtags indicate that the mean is significantly different from zero (black for HCS, red for PSZ). (C) Absolute Response Error. Mean absolute response error, quantified as the absolute value of the angular difference between the reported orientation and the actual target orientation on each trial, is displayed as a function of the difference between the two orientations for each group. Absolute error was greater in PSZ (red) than HCS (black). In both groups, the absolute error was also lower at the 0 and 180° orientation differences.