Longitudinal change in fine motor skills after brain radiotherapy and in vivo imaging biomarkers associated with decline.
BACKGROUND We explored fine motor skills (FMS) before and after brain radiotherapy (RT), analyzing associations between longitudinal FMS and imaging biomarkers of cortical and white matter (WM) integrity in motor regions of interest (ROIs). METHODS On a prospective trial, 52 primary brain tumor patients receiving fractionated brain RT underwent volumetric brain MRI, diffusion tensor imaging, and FMS assessments (Delis-Kaplan Executive Function System Trail Making Test Motor Speed [DKEFS-MS], Grooved Pegboard Dominant [PDH] and Non-dominant [PNDH] Hands) at baseline and 3, 6, and 12 months post-RT. Motor ROIs autosegmented included: sensorimotor cortices and superficial WM, corticospinal tracts, cerebellar cortices and WM, and basal ganglia. Volume (cc) was measured in all ROIs at each timepoint. Diffusion biomarkers (FA and MD) were additionally measured in WM ROIs. Linear mixed-effects models assessed biomarkers as predictors of FMS scores. P-values were corrected for multiple comparisons. RESULTS Higher RT dose was associated with right paracentral cortical thinning (β=-2.42 Gy/(month*mm), p=0.03) and higher right precentral WM MD (β=0.69 Gy/(month*µm 2/ms), p=0.04). Higher left (β=38.7 points/(month*µm 2/ms), p=0.004) and right (β=42.4 points/(month*µm 2/ms), p=0.01) cerebellar WM MD, left precentral cortical atrophy (β=-8.67 points/(month*mm), p=0.02), and reduced right cerebral peduncle FA (β=-0.50 points/month, p=0.01) were associated with worse DKEFS-MS performance. Left precentral cortex thinning was associated with worse PDH scores (β=-17.3 points/(month*mm), p=0.02). Left (β=-0.87 points/(month*cm 3), p=0.001) and right (β=-0.64 points/(month*cm 3), p=0.02) cerebellar cortex, left pons (β=-19.8 points/(month*cm 3), p=0.02), and right pallidum (β=-10.8 points/(month*cm 3), p=0.02) atrophy and reduced right internal capsule FA (β=-1.02 points/month, p=0.03, p=0.03) were associated with worse PNDH performance. CONCLUSIONS Biomarkers of microstructural injury in motor-associated brain regions were associated with worse FMS. Dose avoidance in these areas may preserve FMS.