Structural Brain Alterations Associated with Rapid Eye Movement Sleep Behavior Disorder in Parkinson’s Disease

Abstract

Characterized by dream-enactment motor manifestations arising from rapid eye movement (REM) sleep, REM sleep behavior disorder (RBD) is frequently encountered in Parkinson’s disease (PD). Yet the specific neurostructural changes associated with RBD in PD patients remain to be revealed by neuroimaging. Here we identified such neurostructural alterations by comparing large samples of magnetic resonance imaging (MRI) scans in 69 PD patients with probable RBD, 240 patients without RBD and 138 healthy controls, using deformation-based morphometry (p < 0.05 corrected for multiple comparisons). All data were extracted from the Parkinson’s Progression Markers Initiative. PD patients with probable RBD showed smaller volumes than patients without RBD and than healthy controls in the pontomesencephalic tegmentum, medullary reticular formation, hypothalamus, thalamus, putamen, amygdala and anterior cingulate cortex. These results demonstrate that RBD is associated with a prominent loss of volume in the pontomesencephalic tegmentum, where cholinergic, GABAergic and glutamatergic neurons are located and implicated in the promotion of REM sleep and muscle atonia. It is additionally associated with more widespread atrophy in other subcortical and cortical regions whose loss also likely contributes to the altered regulation of sleep-wake states and motor activity underlying RBD in PD patients.

A clinical-anatomical signature of Parkinson’s Disease identified with partial least squares and magnetic resonance imaging

“…We used our standard image analysis pipeline to calculate DBM as a measure of brain alterations. This pipeline (Aubert-Broche et al, 2013) has been previously used for several multicenter and multi-scanner studies and it has been shown to produce robust results by removing site-specific biases (Boucetta et al, 2016;Sanford et al, 2017;Zeighami et al, 2015). Also, in an earlier study, we provided evidence that DBM was a more sensitive measure of atrophy than VBM, especially for subcortical areas (Zeighami et al, 2015).…”

The Sleeping Cerebellum

“…Likewise, patients with REM sleep behavior disorder, which generates dream-enacting motor activity during REM, show a volumetric decrement in the anterior lobes of the cerebellar cortex and cerebellar nuclei [67,68]. Vice versa, patients suffering from primary malfunctions of the cerebellum can show a variety of sleep disorders (for a detailed review, see [11,[69][70][71][72][73]).…”

Imaging in Parkinson's Disease

“…PD patients who experienced visual hallucinations had significant loss of GM volume in the lingual gyrus and superior parietal lobe compared to healthy controls and PD patients without visual hallucinations (Ramírez-Ruiz et al, 2007). PD patients with probable RBD showed volume loss in the pontomesencephalic tegmentum, medullary reticular formation, hypothalamus, thalamus, putamen, amygdala, and anterior cingulate cortex compared to healthy controls and PD patients without RBD (Boucetta et al, 2016). Structural cortical and subcortical changes in mesocortical and limbic reward-related areas have been observed in PD patients with ICDs.…”