Rapid eye movement sleep behavior disorder

Abstract

Rapid eye movement (REM) sleep behavior disorder (RBD) is a failure of the circuitry regulating motor atonia during REM sleep. In REM sleep, neurons of the sublaterodorsal tegmental nucleus (SLD) project to interneurons in the ventromedial medulla (VMM) and spinal cord that in turn inhibit spinal motoneurons. In RBD, degeneration of this circuitry disinhibits phasic motor commands originating from motor generators. The resulting behavior ranges from simple twitches or jerks to complex behavior. Simple behaviors in RBD may originate from cortical, brainstem and spinal cord motor generators, while complex behavior may originate from cortical motor generators, possibly related to dream content in REM sleep. While RBD can occur idiopathically, it is usually comorbid with or a precursor to a synucleinopathy such as Parkinson's disease (PD). RBD can precede the onset of PD by decades, suggesting an underlying pathology that can progressively afflict REM atonia and midbrain dopaminergic centers. The relative recovery of motor function during REM sleep in some of the cases of PD with RBD emphasizes the complexity of motor pathway control during wakefulness and REM sleep.

Figure 1

A simplified model of the interaction of motor function and REM atonia in humans. During wake (A), motor commands from primary (PMC) and premotor cortices (PreMo), with modulatory basal ganglia (BG) input, as well as brainstem motor pattern generators (BrMo), project to spinal motoneurons (SpMO) to drive motor behavior. During REM sleep (B), the SLD projections directly to inhibitory spinal interneurons (SpIN), as well as through the ventromedial medulla, inhibit SpMO and enforce atonia. In RBD (C), degeneration of the SLD and/or VMM releases this inhibition, resulting inappropriate motor activity during REM sleep. Note that in most non-primates, corticospinal projections target spinal pattern generators, rather than spinal motoneurons directly.

Figure 2

A simplified model of the interaction of motor function in Parkinson’s Disease (PD) and REM atonia. During wake in PD (A), dysfunctional BG input to premotor (PreMo) and primary motor cortex (PMC) impairs motor function. During RBD in PD, lesions to the SLD and/or VMM result in disinhibition of descending motor commands, resulting in motor behavior that in some aspects is improved over waking behavior. This may be due to PreMo and PMC bypass of dysfunctional BG modulation during REM sleep (B), or a specific reduction in dysfunctional PreMo influence on PMC motor commands due to different putative topographies of BG loops with PreMo and PMC (C).