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Research paper
Gyrification abnormalities in presymptomatic c9orf72 expansion carriers
  1. Eduardo Caverzasi1,
  2. Giovanni Battistella1,
  3. Stephanie A Chu2,
  4. Howie Rosen2,
  5. Theodore P Zanto1,
  6. Anna Karydas1,
  7. Wendy Shwe2,
  8. Giovanni Coppola3,
  9. Daniel H Geschwind4,
  10. Rosa Rademakers5,
  11. Bruce L Miller2,6,
  12. Maria Luisa Gorno-Tempini2,
  13. Suzee E Lee1
  1. 1 Neurology, University of California, San Francisco, San Francisco, California, USA
  2. 2 Neurology, Memory and Aging Center University of California, San Francisco, San Francisco, California, USA
  3. 3 Neurology, UCLA, Los Angeles, California, USA
  4. 4 Psychiatry and Neurology, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, USA
  5. 5 Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA
  6. 6 University of California, San Francisco, San Francisco, California, USA
  1. Correspondence to Dr Eduardo Caverzasi, Neurology, University of California, San Francisco, San Francisco, California, USA; eduardo.caverzasi{at}


Objective To investigate in-vivo cortical gyrification patterns measured by the local gyrification index (lGI) in presymptomatic c9orf72 expansion carriers compared with healthy controls, and investigate relationships between lGI and cortical thickness, an established morphometric measure of neurodegeneration.

Methods We assessed cortical gyrification and thickness patterns in a cohort of 15 presymptomatic c9orf72 expansion carriers (age 43.7 ± 10.2 years, 9 females) compared with 67 (age 42.4 ± 12.4 years, 36 females) age and sex matched healthy controls using the dedicated Freesurfer pipeline.

Results Compared with controls, presymptomatic carriers showed significantly lower lGI in left frontal and right parieto-occipital regions. Interestingly, those areas with abnormal gyrification in presymptomatic carriers showed no concomitant cortical thickness abnormality. Overall, for both presymptomatic carriers and healthy controls, gyrification and cortical thickness measures were not correlated, suggesting that gyrification captures a feature distinct from cortical thickness.

Conclusions Presymptomatic c9orf72 expansion carriers show regions of abnormally low gyrification as early as their 30s, decades before expected symptom onset. Cortical gyrification represents a novel grey matter metric distinctive from grey matter thickness or volume and detects differences in presymptomatic carriers at an early age.

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  • EC and GB contributed equally.

  • MLG-T and SEL contributed equally.

  • Contributors EC and GB designed and conceptualised the study. They processed the data,

    performed the statistical analysis of the data and drafted the manuscript for intellectual content. SAC, AMK and WS were involved in the data collection. HLR, TPZ, GC, DHG and RR were involved in the data collection and revision of the manuscript for intellectual content. BLM revised the manuscript for intellectual content. MLG-T and SEL were involved in the design and conceptualisation of the study and revision of the manuscript for intellectual content.

  • Funding This work was supported by the National Institutes of Health [SEL: R01 AG058233, K23AG039414; TPZ: F32AG030249,R01MH096861; MGT: R01NS050915, K24DC015544; GC: AG035610; RR: R35NS097261; BLM:P01AG019724, P50AG23501]. The John Douglas French Alzheimer's Foundation[GC]. State of California DHS04-35516[MGT]. Samples from the National Cell Repository for Alzheimer's Disease(NCRAD), which receives government support under a cooperative agreement grant(U24AG21886) awarded by the National Institute on Aging (NIA), were used in this study.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Researchers may obtain imaging code used for preprocessing and statistical analysis in this study from the corresponding author on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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