The impact of motivation on cognitive performance in an animal model of the negative and cognitive symptoms of schizophrenia

Abstract

Interactions between motivation and cognition are implicated in producing functional impairments and poor quality of life in psychiatric patients. This interaction, however, is not well understood at either the behavioral or neural level. We developed a procedure for mice in which a cognitive measure, sustained attention, is modulated by a motivationally relevant signal that predicts reward probability on a trial-by-trial basis. Using this paradigm, we tested the interaction between motivation and cognition in mice that model the increased striatal D2 receptor activity observed in schizophrenia patients (D2R-OE mice). In control mice, attention was modulated by signaled-reward probability. In D2R-OE mice, however, attention was not modulated by reward-related cues. This impairment was not due to any global deficits in attention or maintenance of the trial-specific information in working memory. Turning off the transgene in D2R-OE mice rescued the motivational modulation of attention. These results indicate that deficits in motivation impair the ability to use reward-related cues to recruit attention and that improving motivation improves functional cognitive performance. These results further suggest that addressing motivational impairments in patients is critical to achieving substantive cognitive and functional gains.

Figure 1

Schematic of the sustained-attention task. Trials began with both response levers retracted and a variable-duration inter-trial interval (mean = 45 s). Following the ITI, a cue light was lit above the position of either the left or right lever (p=0.5). Following cue presentation, choice levers were inserted, and a response on the lever that had been cued at the beginning of the trial resulted in a presentation of a drop of condensed milk via the dipper. Incorrect responses had no programmed consequences.

Figure 2

A. Proportion correct during the sustained attention task as a function of decreasing cue duration. Cue duration was decreased across sessions. X-axis is on a logarithmic scale. B. Proportion correct as a function of decreasing cue duration and signaled-reward probability. C. Latency to make a choice response as a function of decreasing cue duration and signaled-reward probability. (N=7). *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

Figure 3

A. Proportion correct during the sustained-attention task as a function of decreasing cue duration for control and D2R-OE mice. Cue duration was decreased across sessions. X-axis is on a logarithmic scale. Control N=10, D2R-OE N=10. B. Proportion correct as a function of decreasing cue duration (within session) for control and D2R-OE mice. Control N=11, D2R-OE N=10. C. Proportion correct as a function of increasing delay between cue presentation and presentation of the choice levers for control and D2R-OE mice. Delay duration was increased across sessions. Control N=10, D2R-OE N=10. Other details as in Figure 2.

Figure 4

A. Proportion correct as a function of signaled-reward probability for control and D2R-OE mice. B. Proportion correct as a function of signaled-reward probability for control and D2R-OE mice following doxycycline treatment (see text for details). Control N=17, D2R-OE N=15. Other details as in Figure 2.