Functional Connectivity of Vermis Correlates with Future Gait Impairments in Parkinson's Disease

Background Dysfunction of cerebellar vermis contributes to gait abnormalities in multiple conditions and may play a key role in gait impairment in Parkinson's disease (PD). Objective The purpose of this study was to investigate whether altered resting-state functional connectivity of the vermis relates to subsequent impairment of specific domains of gait in PD. Methods We conducted morphometric and resting-state functional connectivity MRI analyses contrasting 45 PD and 32 age-matched healthy participants. Quantitative gait measures were acquired with a GAITRite walkway at varying intervals after functional connectivity data acquisition. Results At baseline, PD participants had significantly altered functional connectivity between vermis and sensorimotor cortex compared with controls. Altered vermal functional connectivity with bilateral paracentral lobules correlated with subsequent measures of variability in stride length, step time, and single support time after controlling for confounding variables including the interval between imaging and gait measures. Similarly, altered functional connectivity between vermis and left sensorimotor cortex correlated with mean stride length and its variability. Vermis volume did not relate to any gait measure. PD participants did not differ from controls in vermis volume or cortical thickness at the site of significant regional clusters. Only altered lobule V:sensorimotor cortex functional connectivity correlated with subsequent gait measures in exploratory analyses involving all the other cerebellar lobules. Conclusions These results demonstrate that abnormal vermal functional connectivity with sensorimotor cortex, in the absence of relevant vermal or cortical atrophy, correlates with subsequent gait impairment in PD. Our data reflect the potential of vermal functional connectivity as a novel imaging biomarker of gait impairment in PD. (c) 2021 International Parkinson and Movement Disorder Society