Dissociable Motivational Deficits in Pre-manifest Huntington's Disease

Cell Rep Med. 2020 Nov 30;1(9):100152. doi: 10.1016/j.xcrm.2020.100152. eCollection 2020 Dec 22.

Abstract

Motivation is characterized by a willingness to overcome both cognitive and physical effort costs. Impairments in motivation are common in striatal disorders, such as Huntington's disease (HD), but whether these impairments are isolated to particular domains of behavior is controversial. We ask whether HD differentially affects the willingness of individuals to overcome cognitive versus physical effort. We tested 20 individuals with pre-manifest HD and compared their behavior to 20 controls. Across separate trials, participants made choices about how much cognitive or physical effort they were willing to invest for reward. Our key results were that individuals with pre-manifest HD were less willing than controls to invest cognitive effort but were no different in their overall preference for physical effort. These results cannot be explained by group differences in neuropsychological or psychiatric profiles. This dissociation of cognitive- and physical-effort-based decisions provides important evidence for separable, domain-specific mechanisms of motivation.

Keywords: Huntington’s disease; apathy; cognitive effort; decision making; effort discounting; motivation; physical effort; reward; striatum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apathy*
  • Asymptomatic Diseases
  • Case-Control Studies
  • Cognition / physiology
  • Corpus Striatum / metabolism
  • Corpus Striatum / physiopathology
  • Decision Making
  • Dopamine / metabolism
  • Female
  • Gene Expression
  • Humans
  • Huntingtin Protein / deficiency
  • Huntingtin Protein / genetics*
  • Huntington Disease / genetics
  • Huntington Disease / physiopathology*
  • Huntington Disease / psychology
  • Male
  • Middle Aged
  • Motivation*
  • Mutation
  • Neuropsychological Tests
  • Physical Exertion*
  • Reward

Substances

  • HTT protein, human
  • Huntingtin Protein
  • Dopamine