White matter cortico-striatal tracts predict apathy subtypes in Huntington's disease

Audrey E. De Paepe, Joanna Sierpowska, C. Garcia-Gorro, Saül Martinez-Horta, J. Perez-Perez, J. Kulisevsky, N. Rodriguez-Dechicha, I. Vaquer, Susana Subira, Matilde Calopa, Esteban Muñoz, P. Santacruz, J. Ruiz-Idiago, C. Mareca, Ruth de Diego-Balaguer, Estela Camara

Research output: Contribution to journalArticleResearch

15 Citations (Scopus)


© 2019 Background: Apathy is the neuropsychiatric syndrome that correlates most highly with Huntington's disease progression, and, like early patterns of neurodegeneration, is associated with lesions to cortico-striatal connections. However, due to its multidimensional nature and elusive etiology, treatment options are limited. Objectives: To disentangle underlying white matter microstructural correlates across the apathy spectrum in Huntington's disease. Methods: Forty-six Huntington's disease individuals (premanifest (N = 22) and manifest (N = 24)) and 35 healthy controls were scanned at 3-tesla and underwent apathy evaluation using the short-Problem Behavior Assessment and short-Lille Apathy Rating Scale, with the latter being characterized into three apathy domains, namely emotional, cognitive, and auto-activation deficit. Diffusion tensor imaging was used to study whether individual differences in specific cortico-striatal tracts predicted global apathy and its subdomains. Results: We elucidate that apathy profiles may develop along differential timelines, with the auto-activation deficit domain manifesting prior to motor onset. Furthermore, diffusion tensor imaging revealed that inter-individual variability in the disruption of discrete cortico-striatal tracts might explain the heterogeneous severity of apathy profiles. Specifically, higher levels of auto-activation deficit symptoms significantly correlated with increased mean diffusivity in the right uncinate fasciculus. Conversely, those with severe cognitive apathy demonstrated increased mean diffusivity in the right frontostriatal tract and left dorsolateral prefrontal cortex to caudate nucleus tract. Conclusions: The current study provides evidence that white matter correlates associated with emotional, cognitive, and auto-activation subtypes may elucidate the heterogeneous nature of apathy in Huntington's disease, as such opening a door for individualized pharmacological management of apathy as a multidimensional syndrome in other neurodegenerative disorders.
Original languageEnglish
Article number101965
JournalNeuroImage: Clinical
Publication statusPublished - 1 Jan 2019


  • Apathy
  • Diffusion MRI
  • Huntington's disease
  • Individual differences
  • Neurodegeneration
  • White matter microstructure


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