The effect of Huntington's disease on cognitive and physical motivation.

Abstract

Apathy is one of the most common neuropsychiatric features of Huntington's disease. A hallmark of apathy is diminished goal-directed behaviour, which is characterized by a lower motivation to engage in cognitively or physically effortful actions. However, it remains unclear whether this reduction in goal-directed behaviour is driven primarily by a motivational deficit and/or is secondary to the progressive cognitive and physical deficits that accompany more advanced disease. We addressed this question by testing 17 individuals with manifest Huntington's disease and 22 age-matched controls on an effort-based decision-making paradigm. Participants were first trained on separate cognitively and physically effortful tasks and provided explicit feedback about their performance. Next, they chose on separate trials how much effort they were willing to exert in each domain in return for varying reward. At the conclusion of the experiment, participants were asked to rate their subjective perception of task load. In the cognitive task, the Huntington's disease group were more averse to cognitive effort than controls. Although the Huntington's disease group were more impaired than controls on the task itself, their greater aversion to cognitive effort persisted even after controlling for task performance. This suggests that the lower levels of cognitive motivation in the Huntington's disease group relative to controls was most likely driven by a primary motivational deficit. In contrast, both groups expressed a similar preference for physical effort. Importantly, the similar levels of physical motivation across both groups occurred even though participants with Huntington's disease performed objectively worse than controls on the physical effort task, and were aware of their performance through explicit feedback on each trial. This indicates that the seemingly preserved level of physical motivation in Huntington's disease was driven by a willingness to engage in physically effortful actions despite a reduced capacity to do so. Finally, the Huntington's disease group provided higher ratings of subjective task demand than controls for the cognitive (but not physical) effort task and when assessing the mental (but not the physical) load of each task. Together, these results revealed a dissociation in cognitive and physical motivation deficits between Huntington's disease and controls, which were accompanied by differences in how effort was subjectively perceived by the two groups. This highlights that motivation is the final manifestation of a complex set of mechanisms involved in effort processing, which are separable across different domains of behaviour. These findings have important clinical implications for the day-to-day management of apathy in Huntington's disease.