Effects of anterior cingulate cortex lesions on a continuous performance task for mice

Abstract

Important tools in the study of prefrontal cortical-dependent executive functions are cross-species behavioural tasks with translational validity. A widely used test of executive function and attention in humans is the continuous performance task (CPT). Optimal performance in variations of this task is associated with activity along the medial wall of the prefrontal cortex, including the anterior cingulate cortex (ACC), for its essential components such as response control, target detection and processing of false alarm errors. We assess the validity of a recently developed rodent touchscreen continuous performance task (rCPT) that is analogous to typical human CPT procedures. Here we evaluate the performance of mice with quinolinic acid-induced lesions centred on the ACC in the rCPT following a range of task parameter manipulations designed to challenge attention and impulse control. Lesioned mice showed a disinhibited response profile expressed as a decreased response criterion and increased false alarm rates. ACC lesions also resulted in a milder increase in inter-trial interval responses ('ITI touches') and hit rate. Lesions did not affect discriminative sensitivity d'. The disinhibited behaviour of ACC lesioned animals was stable and not affected by the manipulation of variable task parameter manipulations designed to increase task difficulty. The results are in general agreement with human studies implicating the ACC in the processing of inappropriate responses. We conclude that the rCPT may be useful for studying prefrontal cortex function in mice and has the capability of providing meaningful links between animal and human cognitive tasks.

Keywords: animal model; anterior cingulate cortex; continuous performance task; executive function; mouse; prefrontal cortex; touchscreen.

Figure 1.

Schematic drawings (a) and representative photomicrographs (b) of the lesions and sham controls. (a) Light shading represents the largest damage observed at that coronal section (measured as distance in millimetre from bregma), black shading represents minimum damage and dark grey represents an animal with typical damage. Drawings adapted from Paxinos and Franklin (2007). (b) Photographs of coronal sections of a representative lesion (left side) and sham animal (right side). The white arrows indicate lesions.

Figure 2.

Performance of ACC-lesioned and sham controls in the rCPT when challenged with tests of variable stimulus durations (vSD; a, b), target probabilities (c, d), inter-trial intervals (e, f) and session length (g, h). Data are presented as mean ± SEM values. ACC-lesioned animals showed significantly reduced response criterion c and significantly increased false alarm rates compared to sham mice in tests of vSD, target probabilities and inter-trial intervals. ACC-lesioned animals also tended to show reduced c and increased FAR in tests of session length. Asterisks denote significant main effect of group at p < 0.05. c: response criterion; d′: discrimination sensitivity; SD: stimulus duration; vSD: variable stimulus durations; ITIs: inter-trial intervals.

Figure 3.

Performance of ACC-lesioned and sham controls in the rCPT when challenged with flanking congruent or incongruent distractors. Data are presented as mean ± SEM values. ACC-lesioned animals showed significantly higher hit rate and a general tendency for increased false alarm rate and lower response criterion compared to sham mice. The presence of distractors significantly reduced the hit rate and false alarm rate in both groups. Asterisks denote significant main effect of group at p < 0.05. c: response criterion; d′: discrimination sensitivity.