Objective: Given the typical asymmetric onset of motor symptoms in PD, the current study sought to investigate whether patients with iRBD show evidence of asymmetric motor impairments compared to healthy control participants, and also evaluated the neural correlates associated with motor asymmetry.

Background: REM sleep behaviour disorder (RBD) has been closely linked to neurodegenerative disease, and is argued to precede PD and DLB by several years. Since several neural substrates of RBD are located in the brainstem, many researchers have suggested that RBD may represent preclinical stage 2 of Braak’s model [1], and thus represent an early sign of widespread neurodegeneration. In keeping with this notion, there are a number of disease predictors, however quantitative motor tests are argued to have the best sensitivity and specificity up to 3 years prior to diagnosis of PD or DLB [2].

Methods: Eleven healthy older adults, fourteen patients with idiopathic RBD, and fourteen patients with early PD (<4 years diagnosed) participated in the current study. To assess whether iRBD patients had detectable asymmetries in stepping, all participants underwent functional magnetic resonance imaging with a virtual reality gait paradigm. Participants operated foot pedals to navigate a virtual corridor that has been previously shown to produce impairments in step timing akin to that of ‘real’ gait [3]. Stepping parameters were collected and analysed, while blood-oxygen-level dependent (BOLD) responses were recorded. Asymmetry between footsteps was calculated by comparing the absolute value of the difference between the time to step left-right and right-left. To estimate gait asymmetry, a parametric modulator was designed that allowed for the examination of brain regions associated with periods of greater asymmetry.

Results: Behaviourally, patients with iRBD showed significantly greater step asymmetry compared to healthy older adults (p=0.01), but were not different from patients with PD. Results from the parametric modulation analysis (k=5, p<0.05) revealed that when iRBD patients had the greatest asymmetry there was hypoactivation in regions such as the putamen, thalamus, motor cortex and medial prefrontal cortex (mPFC). Similar patterns were observed in the Early PD cohort (i.e. hypoactivation in the thalamus, putamen and motor cortex was associated with asymmetric stepping). Healthy older adults did not show enough variance in asymmetry during the gait paradigm to examine using a parametric modulator.

Conclusions: These findings demonstrate that iRBD patients do indeed have subtle asymmetric motor impairments similar to PD which is linked to abnormalities within the motor control system in the brain.

References: [1] Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E. (2003): Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol. Aging 24(2), 197–211. [2] Postuma RB, Aarsland D, Barone P, Burn DJ, Hawkes CH, Oertel W, Ziemssen T. (2012): Indentifying prodromal Parkinson’s disease: pre-motor disorders in Parkinson’s disesae. Movement Disorders 27(5):617-26. [3] Gilat M, Shine JM, Bolitho SJ, Matar E, Kamsma YPT, Naismith SL, Lewis SJG (2013): Variability of Stepping during a Virtual Reality Paradigm in Parkinson’s Disease Patients with and without Freezing of Gait. PLoS One 8:e66718.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/exploring-the-neural-correlates-of-gait-asymmetry-in-idiopathic-rem-sleep-behaviour-disorder/