Cerebral Activations Related to Ballistic, Stepwise Interrupted and Gradually Modulated Movements in Parkinson Patients

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.

Dysfunctional putamen modulation during bimanual finger-to-thumb movement in patients with Parkinson's disease

“…The activity of the frontal area is related with the shift of the attention and the executive control, which are the crucial pre-movement processes (Wu et al, 2010 ; Disbrow et al, 2013 ). There is evidence indicating the hemodynamic responses in the mesiofrontal and sensorimotor cortex, putamen/pallidum, thalamus, and cerebellum and the participation of frontal area in the network for motor preparation (Riecker et al, 2005 ), movement initiation (Toxopeus et al, 2012 ), amplitude adjustment (Fabbri et al, 2012 ; Davare et al, 2015 ), and speed adjustment (Michely et al, 2015 ). It is noted that the executive functions of the PD patients may be affected even at early stages of the disease which would result in impaired motor planning, response preparation, and inhibition (Obeso et al, 2011 ; Toxopeus et al, 2012 ; Michely et al, 2015 ).…”

Topographic organization of the human and non-human primate subthalamic nucleus

“…Despite the current interest, still very little is known about the STN’s normal function in relation to movement. Movement is closely correlated with STN and pallidal activations (Toxopeus et al 2012 ). The impact of STN dysfunction on movement is illustrated by the striking effects of STN lesions, which cause involuntary movements in contralateral extremities (Crossman et al 1984 ).…”

“…A very recent study has investigated brain activation in healthy participants in relation to different aspects of movement. Ballistic movement initiation, stepwise interrupted movement, step track, and continuous circle movements were compared (Toxopeus et al 2012 ). Movement initiation was related to activations in a number of areas including contralateral SN, caudate head, bilateral putamen, and the posterior thalamus.…”

Muscle co-activity tuning in Parkinsonian hand movement: disease-specific changes at behavioral and cerebral level

“…(B) Movement in 0° direction, corresponding to extension. (C) Movement in 90° direction, corresponding to radial deviation (Toxopeus et al, 2012 ).…”