Decision cost hypersensitivity underlies Huntington's disease apathy

Area of Science:

• Neuroscience
• Behavioral Science

Background:

• Apathy is a common and disabling neuropsychiatric symptom in Huntington's disease (HD).
• The underlying mechanisms of apathy in HD are poorly understood.
• Understanding apathy requires examining breakdowns in normal motivated behavior, particularly cost-benefit analysis.

Purpose of the Study:

• To investigate whether apathy in Huntington's disease is associated with increased sensitivity to action costs (physical effort, time delay) or decreased sensitivity to rewards.
• To test the hypothesis that a general hypersensitivity to costs underlies apathy in HD, given the known pathology.

Main Methods:

• Compared genetically confirmed HD gene carriers (n=53) with healthy controls (n=38).
• Utilized the Apple Gathering Task (physical effort) and Money Choice Questionnaire (delay discounting).
• Analyzed choice data using linear regression and drift diffusion models, accounting for decision time.

Main Results:

• Apathetic HD participants showed increased sensitivity to physical effort costs on the Apple Gathering Task.
• Drift diffusion modeling indicated a faster drift towards rejecting offers as effort increased in apathetic HD individuals.
• Increased sensitivity to time delay (delay discounting) was also associated with apathy in HD, with a faster drift towards immediate options.
• Effort and delay sensitivity parameters were positively correlated.

Conclusions:

• Apathy in Huntington's disease is mechanistically linked to hypersensitivity to both effort and time costs.
• This cost hypersensitivity suggests a domain-general disruption of cost processing in HD pathology.
• These findings may inform distinct therapeutic strategies for apathy in HD compared to other neurological disorders.