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

Abstract

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. © 2021 International Parkinson and Movement Disorder Society.

Keywords: Parkinson disease; cerebellum; functional connectivity; gait impairment; vermis.

FIG. 1.

FC differences of the cerebellar vermis between controls and PD participants in cohort of 42 PD and 35 control participants. (A) FC [z(r) maps] with vermis seed region averaged over participants in the control (top row) and PD group (middle row). Warm and cool colors represent positive and negative correlations. The underlying image is the study-specific atlas template. The Talairach atlas plane of the section is indicated under each column; z, x and y correspond to the axial, sagittal and coronal sections respectively. Random effects analysis contrasting PD and control groups (bottom row). The mapped quantity is the Gaussianized t-statistic (Z-score) thresholded at |Z| >3.5; all clusters are significant at the P ≤ 0.05 level. Cool colors indicate more positive correlations in the PD group. Significant clusters reported here include those in: right lateral sensorimotor cortex (R_SMC (a), cluster size: 169, Talairach coordinates: x=33; y=−30; z=53), left lateral sensorimotor cortex (L_SMC (b), cluster size: 67, Talairach coordinates: x=−38; y=−28; z=47), bilateral medial sensorimotor cortices including paracentral lobules and SMA (b/l_PCL (c), cluster size: 196, Talairach coordinates: x=2; y=−33; z=62) and right peristriate visual association cortex ((d), cluster size: 66, Talairach coordinates: x=16; y=−87; z=25). (B-D) Boxplots (with median value and interquartile range) and scatterplots demonstrate the more positive FC in (B) vermis:bilateral paracentral lobules (b/l_PCL), (C) vermis:right sensorimotor cortex (R_SMC) and (D) vermis:left sensorimotor cortex (L_SMC) in the PD (red triangles) cohort compared to controls (blue circles). Abbreviations: a = right lateral sensorimotor cortex (R_SMC); b = left lateral sensorimotor cortex (L_SMC); c = bilateral medial sensorimotor cortex including paracentral lobules and SMA; d = peristriate visual association cortex; SMC = sensorimotor cortex; PCL = paracentral lobules; FC = resting-state functional connectivity; PD = Parkinson disease; SMA = supplementary motor area.

FIG. 2.

Behavioral correlation of significantly altered vermal FC with the sensorimotor cortex in PD participants. Scatter plots for only the significant correlations (p<0.05) that satisfied correction for multiple comparisons are shown here. Correlation of vermis:L_SMC significant cortical cluster FC (Fisher z(r) correlation coefficients) in PD with (A) stride length and (B) coefficient of variation in stride length. Correlation of vermis:b/l_PCL significant cortical cluster FC with the coefficient of variation of (C) stride length, (D) single support time, and (E) step time in PD participants. The FC and gait measures were both acquired OFF dopaminergics. Abbreviations: R_SMC = right lateral sensorimotor cortex; L_SMC = left lateral sensorimotor cortex; b/l_PCL = bilateral medial sensorimotor cortex including paracentral lobules and SMA; CV = coefficient of variation.