Research PaperCognitive training modifies disease symptoms in a mouse model of Huntington's disease

- Cognitive training improves HD related behaviour in HD knock-in mice.
- Attentional cognitive training improves cognition in both HD and WT mice.
- Attentional cognitive training can improve cognitive and motor signs in HD mice.

Huntington's disease (HD) is an incurable neurodegenerative disorder which causes a triad of motor, cognitive and psychiatric disturbances. Cognitive disruptions are a core feature of the disease, which significantly affect daily activities and quality of life, therefore cognitive training interventions present an exciting therapeutic intervention possibility for HD. We aimed to determine if specific cognitive training, in an operant task of attention, modifies the subsequent behavioural and neuropathological phenotype of the HdhQ111 mouse model of HD.Three testing groups comprising both HdhQ111 mice and wildtype controls were used. The first group received cognitive training in an operant task of attention at 4 months of age. The second group received cognitive training in a comparable non-attentional operant task at 4 months of age, and the third group were control animals that did not receive cognitive training. All groups were then tested in an operant task of attention at 12 months of age. Relative to naïve untrained mice, both wildtype and HdhQ111 mice that received cognitive training in the operant task of attention demonstrated an increased number of trials initiated, greater accuracy, and fewer 'time out' errors. A specific improvement in response time performance was observed in HdhQ111 mice, relative to naïve untrained HdhQ111 mice. Relative to the group that received comparable training in a non-attentional task, both wildtype and HdhQ111 mice that received attentional training demonstrated superior accuracy in the task and made fewer 'time out' errors. Despite significant behavioural change, in both wildtype and HdhQ111 mice that had received cognitive training, no significant changes in neuropathology were observed between any of the testing groups. These results demonstrate that attentional cognitive training implemented at a young age significantly improves attentional performance, at an older age, in both wildtype and HdhQ111 mice. Attentional cognitive training also improved motor performance in HdhQ111 mice, thus leading to the conclusion that cognitive training can improve disease symptoms in a mouse model of HD.