Abstract
Patients with Parkinson’s disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular.
Highlights
Successful motor performance in daily life implies that movements are adequately tuned to external conditions, experienced by visual cues [1,2,3]
Patients with Parkinsonism other than Parkinson’s disease (PD), or the tremor-dominant type of PD were excluded from participation in the study to obtain a maximally homogeneous group of patients; tremor-dominant PD might be regarded as a PD subtype [43]
We modelled the BOLD response by the canonical standard hemodynamic response function (HRF) in SPM5
Summary
Successful motor performance in daily life implies that movements are adequately tuned to external conditions, experienced by visual cues [1,2,3] Such performance requires a well-proportioned balance between initiation and inhibition of movement. In task-related motor control, one may distinguish two levels of ongoing movement adjustments: (i) overall visuomotor control and (ii) co-ordination between various muscle groups to achieve a distinct movement. Regarding the latter, an adequate balance between initiation and inhibition is required to achieve the purpose of the intended movement [4,5,6,7,8]. A fast reach to catch a dropped object mainly involves abrupt initiation of agonist activation, whereas gentle object manipulation or smooth handwriting requires gradual agonistantagonist adjustment achieved by the timed selection of specific muscles [5,9,10]
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