Objective: To analyze differences in functional connectivity (FC) between Parkinson’s disease (PD) patients with and without premotor REM behavior disorder (pRBD), by means of high-density EEG.

Background: RBD is highly associated with PD [1], and may precede the motor onset by years. According to recent hypothesis, isolated RBD before parkinsonism (premotor RBD or pRBD) is a marker of PD body-first subtype, where synucleopathy originates from enteric or autonomic system and then spreads to the brain, in contrast to a brain-first subtype, in which α-synuclein pathology initially arises in limbic areas [2]. FC, estimating interactions between brain regions, could improve the understanding of clinical and pathophysiological features of these PD subtypes.

Method: This study involved 39 early-stage PD patients, divided into 28 RBD-negative (PD^RDB-) and 11 RBD-positive (PD^RBD+) subjects, and 24 age and sex-matched healthy controls. A 64-channels EEG system was used to record 10 minutes data in resting-state with eyes closed. Source reconstruction method, based on personal brain MRI, was used to identify brain regions activity. Cortical FC in θ-α-β bands was analyzed based on weighted phase-lag index. Disruptions in frequency-specific FC between controls, PD^RDB- and PD^RBD+ groups were assessed using Network based statistics [3].

Results: In line with previous findings [4], FC was lower at α band in PD than controls in a network mainly composed by frontal and sensorimotor areas (t=2.3, p=0.041). Moreover, FC was higher at α band in PD^pRBD- compared to PD^pRBD+ group in a network involving sensorimotor areas (18%) and parieto (20.2%), temporo (19.3%) and occipital (12.5%) lobes (t=2.3, p=0.039). No differences were found in other bands.

Conclusion: iRBD converts quite equally in PD and in dementia with Lewy bodies (DLB) [5]. Based on this observation, Borghammer et al. hypothesized that the body-first subtype, identified by pRBD, rather than the brain-first, could progress to a “dementia-first” phenotype [2]. Our finding of an early dysfunction in parieto-occipital areas in the PD^pRBD+ group, regions typically involved in PD dementia, seems to support this hypothesis. The mechanisms underlying this apparent contradiction are not known but are probably related to a widespread involvement of subcortical modulatory structures in the body-first subtype.

References: [1] E. K. St Louis, A. R. Boeve, and B. F. Boeve, “REM Sleep Behavior Disorder in Parkinson’s Disease and Other Synucleinopathies,” Movement Disorders, vol. 32, no. 5. 2017, doi: 10.1002/mds.27018.
[2] J. Horsager et al., “Brain-first versus body-first Parkinson’s disease: A multimodal imaging case-control study,” Brain, vol. 143, no. 10, pp. 3077–3088, 2020, doi: 10.1093/brain/awaa238.
[3] A. Zalesky, A. Fornito, and E. T. Bullmore, “Network-based statistic: Identifying differences in brain networks,” Neuroimage, vol. 53, no. 4, 2010, doi: 10.1016/j.neuroimage.2010.06.041.
[4] M. Conti et al., “Brain Functional Connectivity in de novo Parkinson’s Disease Patients Based on Clinical EEG,” Front. Neurol., vol. 13, no. March, 2022, doi: 10.3389/fneur.2022.844745.
[5] R. B. Postuma et al., “Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: A multicentre study,” Brain, vol. 142, no. 3, 2019, doi: 10.1093/brain/awz030.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/early-functional-disruption-in-body-first-compared-to-brain-first-parkinsons-disease/