title: Considering total intracranial volume and other nuisance variables in brain voxel based morphometry in idiopathic PD.
abstract: 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.
authors.affiliation: Department of Clinical and Health Psychology, University of Florida, 1225 Center Drive, Gainesville, FL, 32611, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Crowley
authors.affiliation: Department of Biomedical Engineering, University of Florida, 1275 Center Drive, Gainesville, FL, 32611, USA.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Clinical and Health Psychology, University of Florida, 1225 Center Drive, Gainesville, FL, 32611, USA.
authors.forename: Jared
authors.initials: J
authors.lastname: Tanner
authors.affiliation: Department of Biomedical Engineering, University of Florida, 1275 Center Drive, Gainesville, FL, 32611, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Clinical and Health Psychology, University of Florida, 1225 Center Drive, Gainesville, FL, 32611, USA.
authors.forename: Nadine A
authors.initials: NA
authors.lastname: Schwab
authors.affiliation: Department of Clinical and Health Psychology, University of Florida, 1225 Center Drive, Gainesville, FL, 32611, USA.
authors.forename: Loren
authors.initials: L
authors.lastname: Hizel
authors.affiliation: Department of Clinical and Health Psychology, University of Florida, 1225 Center Drive, Gainesville, FL, 32611, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ramon
authors.affiliation: Department of Biostatistics, University of Florida, 2004 Mowry Road, 5th Floor CTRB, Gainesville, FL, 32611, USA.
authors.forename: Babette
authors.initials: B
authors.lastname: Brumback
authors.affiliation: Department of Biomedical Engineering, University of Florida, 1275 Center Drive, Gainesville, FL, 32611, USA.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Ding
authors.affiliation: Department of Clinical and Health Psychology, University of Florida, 1225 Center Drive, Gainesville, FL, 32611, USA. cep23@phhp.ufl.edu.|Clinical and Health Psychology, University of Florida, 101 S. Newell Drive, PO Box 100165, Gainesville, FL, 32610, USA. cep23@phhp.ufl.edu.
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Price
mesh_terms: D000367:Age Factors; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000000981:diagnostic imaging; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009929:Organ Size; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D012189:Retrospective Studies; D012737:Sex Factors; D012886:Skull / Q000000981:diagnostic imaging / Q000473:pathology; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology
keywords: Parkinson’s disease; Structural MRI; TICV; TIV; Total intracranial volume; VBM; Voxel-based morphometry