Motivational Deficits in Schizophrenia Are Associated With Reduced Differentiation Between Gain and Loss-Avoidance Feedback in the Striatum

Abstract

Background: The current study was designed to test the hypothesis that motivational deficits in schizophrenia (SZ) are tied to a reduced ability to differentially signal gains and instances of loss-avoidance in the brain, leading to reduced ability to form adaptive representations of expected value.

Methods: We administered a reinforcement learning paradigm to 27 medicated SZ patients and 27 control subjects in which participants learned three probabilistic discriminations. In regions of interest in reward networks identified a priori, we examined contrasts between trial types with different expected values (e.g., expected gain-nonmonetary) and between outcomes with the same prediction error valence but different experienced values (e.g., gain-loss-avoidance outcome, miss-loss outcome).

Results: Both whole-brain and region of interest analyses revealed that SZ patients showed reduced differentiation between gain and loss-avoidance outcomes in the dorsal anterior cingulate cortex and bilateral anterior insula. That is, SZ patients showed reduced contrasts between positive prediction errors of different objective values in these areas. In addition, we observed significant correlations between gain-loss-avoidance outcome contrasts in the ventral striatum and ratings for avolition/anhedonia and between expected gain-nonmonetary contrasts in the ventral striatum and ventromedial prefrontal cortex.

Conclusions: These results provide further evidence for intact prediction error signaling in medicated SZ patients, especially with regard to loss-avoidance. By contrast, components of frontostriatal circuits appear to show reduced sensitivity to the absolute valence of expected and experienced outcomes, suggesting a mechanism by which motivational deficits may emerge.

Keywords: Anterior insula; Avolition; Reinforcement learning; Reward; Ventral striatum; fMRI.

Figure 1

Trial structure and task outcome contingencies. A. On each trial, participants were presented with one of three pairs of landscapes, and had 2 s to choose either the left or right image, after which, their choice was indicated by a red border around the image. Stimuli were shown on the screen for a total of 3 seconds, with the choice highlighted, and the feedback presented centrally, for the remainder of the trial, following the response (for 3 seconds - the response time). A running tally of their total earned points was shown at the end of each trial, for the duration of the inter-trial interval. B. Trials belonged to one of three conditions: potential gain (“Gain-Miss”, or “GM”), non-monetary (“Correct-Incorrect”, or “CI”), and potential loss (“Loss-Avoid”, or “LA”). In a “Gain-Miss” pair, possible outcomes were a 25-cent gain or a neutral outcome, and thus, the expected values of those choices were positive. In a “Loss-Avoid” pair, outcomes were either neutral or a 25-cent loss, and thus, the expected values of those choices were negative. In the non-monetary pair, subjects received only verbal feedback (“Correct” or “Incorrect”), and thus, the expected values of those choices were neutral. In all three conditions, the better item was reinforced 70% of the time. For example, 70% of the time the better item was chosen on potential gain trials, the word “Win!” along with an image of a quarter was presented, while “Not a winner” was displayed 70% of the time the worse item was selected. On potential loss trials, the better choice prompted the feedback “Keep your money” 70% of the time, while choices of the worse item resulted in the image of a crossed out quarter 70% of the time.

Figure 2

Whole-brain analyses of RPE-evoked MRI activity based on trial-by-trial estimates produced by RL modeling. Brain viewed from the front. Top row cut at y=10, to display striatal activations in both healthy volunteers and patients. Bottom row cut at y=19 and z=10, to display deactivations in dorsomedial prefrontal cortex and anterior insula. Whole-brain analyses revealed no between-group differences in these regions (Table S4).

Figure 3

Regions-of-interest (ROI) analyses of effects of obtained outcome valence on positive RPE signals. A. The ventral striatum (VS) ROI consisted of two spheres of 5-mm radius, centered on (±10, 8, −4). Cut at y=8. B. The ventromedial prefrontal cortex (vmPFC) ROI consisted of a sphere of 10-mm radius, centered on 3, 32, −7), while the dorsal anterior cingulate (dACC) ROI consisted of a sphere of 10-mm radius, centered on (5, 22, 27). Brain image cut at x=4. C. The right anterior insula (RAI) ROI consisted of a sphere of 10-mm radius, centered on (32, 18, 2), while the left anterior insula (LAI) ROI consisted of a sphere of 10-mm radius, centered on (−33, 19, 3). Brain image cut at y=19. For Panels A–C, Brains viewed from the front, with right side of brain on left side of figure. D. Healthy volunteers, as a group, showed significant contrasts between gain outcomes and loss-avoidance outcomes in all a priori ROIs. E. Schizophrenia patients, as a group, showed significant contrasts between gain outcomes and loss-avoidance outcomes in none of the a priori ROIs. F. In healthy volunteers, differences in learning rates associated with positive and negative RPEs correlated significantly with [Experienced Gain – Loss-avoidance] contrasts in the right anterior insula ROI. G. In schizophrenia patients, avolition/anhedonia scores correlate significantly (inversely) with [Experienced Gain – Loss-avoidance] contrasts in the VS ROI. Error bars represent 1 standard error in either direction. * represents paired t-test significant at p<0.05.