Functional and free-water imaging in rapid eye movement behaviour disorder and Parkinson's disease

Abstract

It is established that one of the best predictors of a future diagnosis of Parkinson's disease is a current diagnosis of rapid eye movement behaviour disorder (RBD). In such patients, this provides a unique opportunity to study brain physiology and behavioural motor features of RBD that may precede early-stage Parkinson's disease. Based on prior work in early-stage Parkinson's disease, we aim to determine if the function of corticostriatal and cerebellar regions are impaired in RBD using task-based functional MRI and if structural changes can be detected within the caudate, putamen and substantia nigra in RBD using free-water imaging. To assess motor function, we measured performance on the Purdue Pegboard Test, which is affected in patients with RBD and Parkinson's disease. A cohort of 24 RBD, 39 early-stage Parkinson's disease and 25 controls were investigated. All participants were imaged at 3 Telsa. Individuals performed a unimanual grip force task during functional imaging. Participants also completed scales to assess cognition, sleep and motor symptoms. We found decreased functional activity in both RBD and Parkinson's disease within the motor cortex, caudate, putamen and thalamus compared with controls. There was elevated free-water-corrected fractional anisotropy in the putamen in RBD and Parkinson's disease and elevated free-water in the putamen and posterior substantia nigra in Parkinson's disease compared with controls. Participants with RBD and Parkinson's disease performed significantly worse on all tasks of the Purdue Pegboard Test compared with controls. The both hands task of the Purdue Pegboard Test was most sensitive in distinguishing between groups. A subgroup analysis of early-stage RBD (<2 years diagnosis) confirmed similar findings as those in the larger RBD group. These findings provide new evidence that the putamen is affected in early-stage RBD using both functional and free-water imaging. We also found evidence that the striatum, thalamus and motor cortex have reduced functional activity in early-stage RBD and Parkinson's disease. While the substantia nigra shows elevated free-water in Parkinson's disease, we did not observe this effect in early-stage RBD. These findings point to the corticostriatal and thalamocortical circuits being impaired in RBD patients.

Keywords: Parkinson’s disease; Purdue Pegboard Test; REM sleep behaviour disorder; fMRI; free-water.

Graphical Abstract

Figure 1

fMRI task. (A) Participant set-up inside the scanner. All participants were positioned lying on their back inside the scanner with the force sensor placed in their right hand, a pulse oximeter positioned on the index finger of the left hand and a respiratory belt monitor placed across the subject’s chest. (B) fMRI block task design. One scan consists of a 30-s rest block followed by a 30-s task block. This sequence will be repeated four times, and then an additional 30-s rest block will be added on at the end. (C) Force task. Position and grip of the right-hand during rest condition and force production part of the task. One bar is a white stationary/target bar, which marks 15% of the individuals MVC and does not move during the task. The other bar changes from light blue to navy blue and represents the force bar. When the bar is light blue, this indicates that the participant should relax their hand and stop producing force. During the force production part of the task, when the bar turned to navy blue, participants are instructed to press on the sensor, moving the bar vertical to align and hold it on the top of the white target bar. The navy blue force bar also instructs participants to generate and maintain 15% MVC force for 2 s, and the light blue force bar instructs the participants to release force for 1 s.

Figure 2

BOLD imaging post hoc. (A) Group means (± 1 SEM) for controls versus RBD and controls versus Parkinson’s disease for significant BOLD ROIs. (B) Group means (± 1 SEM) for only controls versus Parkinson’s disease for significant BOLD ROIs. Significance indicated by *P_FDR < 0.05 and **P_FDR < 0.01. Note: Repeated measures MANCOVA was used covarying for age, sex and handedness. Controls (n = 25). RBD (n = 24). Parkinson’s disease (n = 39). FDR, false discovery rate; MANCOVA, multivariate analysis of covariance; M1, primary motor cortex; PD, Parkinson’s disease; RBD, rapid eye movement behaviour disorder; SEM, standard error of the mean.

Figure 3

Free-water imaging post hoc. (A) Free-water group means (± 1 SEM) for the putamen and pSN. (B) Free-water-corrected fractional anisotropy group mean (± 1 SEM) for the putamen. Significance indicated by *P_FDR < 0.05 and **P_FDR < 0.01. Note: MANCOVA was used covarying for age and sex. Controls (n = 25). RBD (n = 24). Parkinson’s disease (n = 39). FDR, false discovery rate; MANCOVA, multivariate analysis of covariance; PD, Parkinson’s disease; pSN, posterior substantia nigra; RBD, rapid eye movement behaviour disorder; SEM, standard error of the mean.

Figure 4

PPT tasks. Group mean (± 1 SEM) for the dominant hand task, non-dominant hand task, both hands task and assembly task. Significance indicated by *P_FDR < 0.05, **P_FDR < 0.01 and ***P_FDR < 0.001. Note: MANCOVA was used covarying for age and sex. Controls (n = 25). RBD (n = 24). Parkinson’s disease (n = 39). FDR, false discovery rate; MANCOVA, multivariate analysis of covariance; PD, Parkinson’s disease; RBD, rapid eye movement behaviour disorder; SEM, standard error of the mean.