Abstract
Objective: (1) To determine the brain connectivity pattern associated with clinical rigidity scores in Parkinson’s disease (PD) and (2) to determine the relation between clinically assessed rigidity and quantitative metrics of motor performance.Background: Rigidity, the resistance to passive movement, is exacerbated in PD by asking the subject to move the contralateral limb, implying that rigidity involves a distributed brain network. Rigidity mainly affects subjects when they attempt to move; yet the relation between clinical rigidity scores and quantitative aspects of motor performance are unknown.Methods: Ten clinically diagnosed PD patients (off-medication) and 10 controls were recruited to perform an fMRI squeeze-bulb tracking task that included both visually guided and internally guided features. The direct functional connectivity between anatomically defined regions of interest was assessed with Dynamic Bayesian Networks (DBNs). Tracking performance was assessed by fitting Linear Dynamical System (LDS) models to the motor performance, and was compared to the clinical rigidity scores. A cross-validated Least Absolute Shrinkage and Selection Operator (LASSO) regression method was used to determine the brain connectivity network that best predicted clinical rigidity scores.Results: The damping ratio of the LDS models significantly correlated with clinical rigidity scores (p = 0.014). An fMRI connectivity network in subcortical and primary and premotor cortical regions accurately predicted clinical rigidity scores (p < 10−5).Conclusion: A widely distributed cortical/subcortical network is associated with rigidity observed in PD patients, which reinforces the importance of altered functional connectivity in the pathophysiology of PD. PD subjects with higher rigidity scores tend to have less overshoot in their tracking performance, and damping ratio may represent a robust, quantitative marker of the motoric effects of increasing rigidity.
Highlights
Rigidity is defined by increased resistance during passive mobilization of an extremity, independent of direction and velocity of movement (Delwaide, 2001), and is one of the cardinal diagnostic features of Parkinson’s disease (PD), along with tremor, bradykinesia, and postural instability (Tolosa et al, 2006; Shapiro et al, 2007)
The damping ratio of the Linear Dynamical System (LDS) models significantly correlated with clinical rigidity scores (p = 0.014)
A widely distributed cortical/subcortical network is associated with rigidity observed in PD patients, which reinforces the importance of altered functional connectivity in the pathophysiology of PD
Summary
Rigidity is defined by increased resistance during passive mobilization of an extremity, independent of direction and velocity of movement (Delwaide, 2001), and is one of the cardinal diagnostic features of Parkinson’s disease (PD), along with tremor, bradykinesia, and postural instability (Tolosa et al, 2006; Shapiro et al, 2007). The underlying mechanism of rigidity in PD is poorly understood, and no direct relationship exists between dopamine deficiency and rigidity, making it difficult to explain through the classic model of basal ganglia pathophysiology (Rodriguez-Oroz et al, 2009). The classic description of basal ganglia activity in PD predicts that increased neuronal activity in the subthalamic nucleus (STN) and internal globus pallidus (GPi), and its resultant inhibition of thalamocortical projections, should result in decreased muscle activation and reduced response to stretching when, the opposite is observed (Bezard and Przedborski, 2011). The resistance to passive movement, is exacerbated in PD by asking the subject to move the contralateral limb, implying that rigidity involves a distributed brain network. Rigidity mainly affects subjects when they attempt to move; yet the relation between clinical rigidity scores and quantitative aspects of motor performance are unknown
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