Motor reserve and novel area recruitment: amplitude and spatial characteristics of compensation in Parkinson’s disease

Abstract

Motor symptoms of Parkinson's disease (PD) do not appear until the majority of dopaminergic cells in the substantia nigra pars compacta are lost, suggesting significant redundancy or compensation in the motor systems affected by PD. Using functional magnetic resonance imaging, we examined whether compensation in PD is manifested by changes in amplitude and/or spatial extent of activity within normal networks (active motor reserve) and/or newly recruited regions [novel area recruitment (NAR)]. Ten PD subjects off and on medication and 10 age-matched controls performed a visually guided sinusoidal force task at 0.25, 0.5 and 0.75 Hz. Regression was used to determine the combination of regions where activation amplitude scaled linearly with movement speed in controls. We then determined the activation of PD subjects in this network, as well as the corresponding PD network. To measure the spatial variance of activation, we used an invariant spatial feature approach. Control subjects monotonically increased activity within striato-thalamo-cortical and cerebello-thalamo-cortical regions with increasing movement speed. In PD subjects, the activity of this network at low speeds was similar to that in controls at higher speeds. Additionally, PD subjects off medication demonstrated NARs of the bilateral cerebellum and primary motor cortex, which were incompletely normalized by levodopa. Our results suggest that PD subjects tap into motor reserve, increase the spatial extent of activation and demonstrate NAR to maintain near-normal motor output.

Compensatory fronto-parietal hyperactivation during set-shifting in unmedicated patients with Parkinson's disease

“…We hypothesize that patients with PD recruited these areas more extensively in order to compensate for the decreased activation in the VLPFC. These results fit with previous task-related fMRI studies in PD patients that reported increased, and presumably compensatory, neural activation (Au et al, 2012;Palmer et al, 2009;Rottschy et al, 2013). The interpretation is also in accordance with a recently postulated hypothesis (Brittain and Brown, 2013) stating that brain areas become less synchronized due to the dopamine depletion and therefore exchange less information.…”

Cortical and motor responses to acute forced exercise in Parkinson's disease

“…In general, levodopa therapy has produced patterns of activation which typically show a normalization and or return to an activation pattern seen more commonly in control subjects. [11, 13, 28] These findings may reflect both direct motor effects, as well as the potential effects of attention.…”

Cortico-basal ganglia and cortico-cerebellar circuits in Parkinson's disease: Pathophysiology or compensation?

“…A shift in this balance, however, could still simply be due the pathophysiological imbalance. Palmer et al (2009) were driven to similar conclusions using a sinusoidal force task of varying frequencies to demonstrate that, as movement frequency (and therefore difficulty) increases, PD patients first increasingly recruit the CBG and CC circuits, and then recruit additional areas in the bilateral cerebellum and primary motor cortex. In this study, the authors worked with the assumption that disease-related activation changes are constant, whereas compensatory changes are not.…”