Brain Imaging and Behavior

, Volume 12, Issue 1, pp 1–12 | Cite as

Considering total intracranial volume and other nuisance variables in brain voxel based morphometry in idiopathic PD

  • Samuel Crowley
  • Haiqing Huang
  • Jared Tanner
  • Qing Zhao
  • Nadine A. Schwab
  • Loren Hizel
  • Daniel Ramon
  • Babette Brumback
  • Mingzhou Ding
  • Catherine C. PriceEmail author
Original Research


Voxel-based morphometry (VBM) studies of Parkinson’s disease (PD), have yielded mixed results, possibly due to several studies not accounting for common nuisance variables (age, sex, and total intracranial volume [TICV]). TICV is particularly important because there is evidence for larger TICV in PD. We explored the influence of these covariates on VBM by 1) comparing PD patients and controls before adding covariates, after adding age and sex, and after adding age, sex and TICV, and 2) by comparing controls split into large and small TICV before and after controlling for TICV, with age and sex accounted for in both analyses. Experiment 1 consisted of 40 PD participants and 40 controls. Experiment 2 consisted of 88 controls median split by TICV. All participants completed an MRI on a 3 T scanner. TICV was calculated as gray + white + CSF from Freesurfer. VBM was performed on T1 images using an optimized VBM protocol. Volume differences were assessed using a voxel-wise GLM analysis. Clusters were considered significant at >10 voxels and p < .05 corrected for familywise error. Before controlling for covariates, PD showed reduced GM in temporal, occipital, and cerebellar regions. Controlling for age and sex did not affect the pattern of significance. Controlling for TICV reduced the size of the significant region although it still contained portions of bilateral temporal lobes, occipital lobes and cerebellum. The large TICV group showed reduced volume in temporal, parietal, and cerebellar areas. None of these differences survived controlling for TICV. This demonstrates that TICV influences VBM results independently from other factors. Controlling for TICV in VBM studies is recommended.


Voxel-based morphometry VBM Parkinson’s disease Structural MRI Total intracranial volume TICV TIV 


Compliance with ethical standards

Conflict of interest

Samuel Crowley, Haiqing Huang, Jared Tanner, Qing Zho, Nadine Schwab, Loren Hizel, Daniel Ramon, Babette Brumback, Mingzhou Ding and Catherine Price declare that they have no conflict of interest.

Informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

Supplementary material

11682_2016_9656_MOESM1_ESM.docx (590 kb)
Electronic supplementary Table 1 (DOCX 589 kb)
11682_2016_9656_MOESM2_ESM.docx (590 kb)
Electronic supplementary Fig. 1 (DOCX 589 kb)


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Samuel Crowley
    • 1
  • Haiqing Huang
    • 2
  • Jared Tanner
    • 1
  • Qing Zhao
    • 2
  • Nadine A. Schwab
    • 1
  • Loren Hizel
    • 1
  • Daniel Ramon
    • 1
  • Babette Brumback
    • 3
  • Mingzhou Ding
    • 2
  • Catherine C. Price
    • 1
    • 4
    Email author
  1. 1.Department of Clinical and Health PsychologyUniversity of FloridaGainesvilleUSA
  2. 2.Department of Biomedical EngineeringUniversity of FloridaGainesvilleUSA
  3. 3.Department of BiostatisticsUniversity of FloridaGainesvilleUSA
  4. 4.Clinical and Health PsychologyUniversity of FloridaGainesvilleUSA

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