E009 Investigating altered reward system in Huntington’s disease: implications for apathy

<h3>Background</h3> Reward processing and motivation are known to be affected in Huntington’s Disease (HD). However, the potential relationship between these impairments at both behavioral and neuronal levels is not fully understood. <h3>Aims</h3> Our study aimed to evaluate the reward processing system in Huntington’s Disease gene expansion carriers (HDGEC) and investigate whether amotivated behavior, manifested by apathy, modulates neural responses associated with gain and loss valuation. <h3>Methods</h3> Thirty-nine HDGEC and twenty-six non-apathetic control participants underwent functional magnetic resonance imaging (fMRI) during a gambling task. The short-Lille Apathy Rating Scale was used to assess apathy, characterizing its three subdimensions namely emotional, executive, and initiation. <h3>Results</h3> Whole-brain analysis revealed a significant reduction in activity within the left ventral striatum (VS) in HDGEC group compared to controls, during the gain processing. This effect was driven by lower levels of activation in the clinically apathetic subgroup. Furthermore, higher levels of global, emotional, and initiation apathy (but not executive apathy) were linked to decreased activity related to gain processing in the VS. <h3>Conclusions</h3> Our findings highlight the vulnerability of the left VS in HD and its association with the altered processing of gains, while loss valuation remains unaffected. We propose insensitivity to positive outcomes, underpinned by functional deficits in VS, as a potential mechanism of emotional and initiation apathy in HD. This insight could contribute to the development of incentivisation-based behavioral strategies to address amotivation.