Correlates of movement initiation and velocity in Parkinson's disease: A longitudinal PET study

Abstract

Limited data exist concerning the mechanisms that underlie the different motor features of Parkinson's disease (PD) and their course over time. Our aims were (1) to identify longitudinal changes in PD patients and (2) to determine the neural correlates of the changes in movement initiation and velocity that occur in the course the disease. Thirteen early stage PD patients were scanned twice off antiparkinsonian medication with H(2)15O PET. Imaging was performed at baseline and again after 2 years while the subjects performed a motor task that was kinematically controlled across time. Paced reaching movements were made towards targets that were presented in a predictable order. Measures of movement onset time (OT) and mean velocity (MV) were recorded during PET. OT and MV decreased significantly from baseline to follow-up. With advancing disease, increasing subcortical activation was detected in the pallidum bilaterally and in the left putamen. In the cortex, motor-related activation increased in the right pre-SMA, anterior cingulate cortex and the left postcentral gyrus. Progressive delays in movement initiation (OT) correlated with increases in the right dorsal premotor cortex (dPMC). Slowing of movement (MV) was associated with declining activation in the left dorsolateral prefrontal cortex and dPMC. Our data suggest that with advancing PD, motor performance is associated with the recruitment of brain regions normally involved in the execution of more complex tasks.

Fig. 1

Significant (p_corr <0.05) activation responses during the execution of an externally cued repetitive reaching task (see text). The surface rendering of the statistical map (SPM 99 canonical template) reflects the main effect of the task in 13 early stage PD patients scanned at baseline and at 2 years follow-up. The motor activation response was localized to the primary (sensorimotor cortex, SMC) and secondary motor areas (premotor cortex, PMC; and supplementary motor area, SMA) and to parietal (PAR) and occipital association cortices (OCC). Significant cerebellar and basal ganglia activation responses were also present.

Fig. 2

Significant increases in motor-related brain activation with disease progression in early stage PD (see text). SPM{t} maps were superimposed on a single-subject MRI T1 template (left panel: axial slices; right panel: sagittal slices). Relatively increased activation at follow-up was localized to the globus pallidus bilaterally, extending into the left putamen. Longitudinal motor activation increases were also noted in the right anterior cingulate, pre-SMA and in the inferior brainstem [the color scale represents T values thresholded at 4.55; p=0.05, corrected for multiple comparisons].

Fig. 3

Significant declines in motor-related brain activation with disease progression in early stage PD (see text). SPM{t} maps were superimposed on a single-subject MRI T1 template (overlay as in Fig. 2: axial slice). At follow-up, a significant decline was present in the right inferior parietal region (BA 40) [the color scale represents T values thresholded at 3.55; p<0.001, uncorrected for multiple comparisons].

Fig. 4

Relationship between progressive slowing in movement initiation and longitudinal changes in motor activation. (A) A significant correlation between these variables was identified in the right dorsal premotor cortex (dPMC) [the color stripe represents T values thresholded at 3.23; p<0.001, uncorrected]. (B) Scatterplot of individual subject rCBF values extracted from the cluster displayed in panel A (arrow; gray diamonds=R-Hemi; black diamonds=L-Hemi; see text). A significant correlation was present between worsening OT measures at follow-up and increasing activation within the right dPMC.

Fig. 5

Relationship between changes in movement velocity and longitudinal changes in motor activation (positive values indicate increases in speed and negative values indicating movement slowing). (A) Significant correlations between these variables were identified in the left premotor cortex (dPMC; top) and in the dorsolateral prefrontal cortex (DLPFC; bottom) [the color stripe represents T values thresholded at 3.23; p<0.001, uncorrected]. (B) Scatterplots of individual subject rCBF values extracted from the clusters displayed in panel A (arrows; gray diamonds=R-Hemi; black diamonds=L-Hemi; see text). Significant correlations were present between the reduction in mean velocity at follow-up and declining activation within the left dPMC and DLPFC.