Abstract
Apathy is a common neurobehavioural disturbance in Huntington’s disease (HD) and Parkinson’s disease (PD). However, the mechanisms leading to this reduction in goal-directed behaviour are poorly understood. A core process underlying goal-directed behaviour is value-based decision-making. By examining how changing rewards and costs influence decisions about actions for rewards, it is possible to disentangle whether apathy is driven by reduced sensitivity to rewards, increased sensitivity to costs, or both.
Firstly, using a hypothesis-driven approach, I examined the structural and functional integrity of neural networks subserving value-based decision-making in PD apathy. I examined their association with the development of apathy and with existing apathy using longitudinal MRI data. I found that network reorganisation was evident in PD prior to the development of apathy, with structural change in those with existing apathy.
Secondly, I examined the cognitive signature of HD apathy using carefully controlled decision-making tasks that dissociated the effects of changing rewards and costs on choice. In contrast to other brain disorders, apathetic people with HD showed increased sensitivity to physical effort and time delay costs - a cost-general hypersensitivity. This, rather than reward insensitivity, was the key mechanistic disruption leading to reduced goal pursuit. Cost hypersensitivity was evident for people with apathy in both choice behaviour and modelled drift rate – a parameter derived from drift diffusion modeling - which showed faster evidence accumulation towards rejecting offers as effort costs increased, and towards immediately available options on delay discounting. This same signature was not evident when examining these decision variables in another decision context – foraging patch-leaving decisions (in which optimal behaviour requires comparison of foreground reward rates and the average background reward available in the environment). Whilst effort and delay costs modulated patch-leaving times, performance did not differ as a function of HD apathy. Thus the context of a decision seemed paramount for the relationship between cost sensitivity and apathy.
Given that time is a crucial denominator for estimating the reward rates underlying many goal-directed decisions, I examined whether time perception varied in people with HD as a function of apathy as well as impulsivity – another common behavioural change in HD. Both behavioural disturbances were associated with thinking more time had passed than really had, a plausible mechanism that could contribute to both apathy and impulsivity. Lastly, I examined the relationship between apathy and impulsivity in HD. I found them to be positively associated, but despite this, the signature of each on value-based decision-making tasks differed.
Overall, I demonstrate that alterations in neural networks underpinning value-based decision-making precede and accompany apathy in one neurodegenerative condition - PD, whilst identifying the key cognitive drivers of apathy in another - HD. Hypersensitivity to the costs of actions is a core mechanism leading to reduced goal-directed behaviour in HD apathy, crucially dependent on decision context, with this same signature not shared by HD impulsivity despite a clear relationship between the two. This work deepens our understanding of the neural and cognitive mechanisms underlying apathy in PD and HD.