Structural Brain Alterations in Motor Subtypes of Parkinson's Disease: Evidence from Probabilistic Tractography and Shape Analysis.
OBJECTIVE
The postural instability and gait disorder (PIGD) and tremor dominant (TD) subtypes of Parkinson's disease (PD) show different patterns of alterations in functional connectivity (FC) between specific brain regions. This study aimed to investigate the relation between symptomatic heterogeneity in PD and structural alterations underlying these FC changes.


METHODS
68 PD patients classified as PIGD (n = 41) or TD (n = 19) and 19 age-matched controls underwent Magnetic Resonance Imaging (MRI). Diffusion-weighted images were used to assess fractional anisotropy (FA) and mean diffusivity (MD) at the whole-brain level using tract-based spatial statistics (TBSS). In addition, structural connectivity was assessed between regions that previously showed altered FC using probabilistic tractography. Anatomical images were used to determine shape and volume of the putamen, caudate and pallidum.


RESULTS
TBSS revealed widespread FA reductions in PIGD compared to controls involving the superior longitudinal fasciculi and corpus callosum. No such differences were found in TD. Both PD subgroups had increased MD compared to controls in tracts connecting the left caudate with the bilateral ventral putamen. TD patients additionally showed increased MD compared to PIGD and controls in tracts connecting the right inferior parietal lobule with the right premotor and primary motor cortex, which previously showed altered FC. We also found grey matter atrophy in the rostrodorsal head of the caudate in PIGD compared to controls.


CONCLUSIONS
Microstructural changes in white matter tracts, particularly in those connecting striatal sub-areas, partly underlie FC alterations in PD subtypes. Caudate shape alterations further implicate the striatum in PIGD pathophysiology.
KU Leuven, Department of Rehabilitation Sciences, Tervuursevest 101/1501, 3001, Leuven, Belgium.
Griet
G
Vervoort
KU Leuven, Department of Kinesiology, Tervuursevest 101/1501, 3001, Leuven, Belgium.
Inge
I
Leunissen
Institute of Neuroscience and Newcastle University Institute for Ageing, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, NE4 5PL, United Kingdom.
Michael
M
Firbank
KU Leuven, Department of Rehabilitation Sciences, Tervuursevest 101/1501, 3001, Leuven, Belgium.
Elke
E
Heremans
KU Leuven, Department of Rehabilitation Sciences, Tervuursevest 101/1501, 3001, Leuven, Belgium.
Evelien
E
Nackaerts
University Hospitals Leuven, Department of Neurology, Herestraat 49, 3000 Leuven, Belgium; KU Leuven, Department of Neurosciences, Herestraat 49, 3000, Leuven, Belgium.
Wim
W
Vandenberghe
KU Leuven, Department of Rehabilitation Sciences, Tervuursevest 101/1501, 3001, Leuven, Belgium.
Alice
A
Nieuwboer
D000368:Aged; D002490:Central Nervous System / Q000000981:diagnostic imaging / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003337:Corpus Callosum / Q000000981:diagnostic imaging / Q000503:physiopathology*; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D005260:Female; D020233:Gait Disorders, Neurologic / Q000000981:diagnostic imaging / Q000503:physiopathology*; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010296:Parietal Lobe / Q000000981:diagnostic imaging / Q000503:physiopathology; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011187:Posture / Q000502:physiology; D014202:Tremor / Q000188:drug therapy / Q000503:physiopathology; D066127:White Matter / Q000000981:diagnostic imaging / Q000503:physiopathology