Overview

REM sleep behavior disorder is a parasomnia that reflects the presence of alpha-synucleinopathy in the brain and is highly predictive of eventual phenoconversion to Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy over the course of years to decades. Neuroplastic adaptations in the brain during the prodromal stage of disease are thought to mask the expression of motor and non-motor signs and may substantially delay diagnosis during a potentially critical time window. This study will examine the state and progression (over 30 to 36 months) of neuroplastic changes in the excitability of the motor and prefrontal cortex (using transcranial magnetic stimulation), the structural and functional connectivity of the brain (using highfield, 7T, magnetic resonance imaging), and the relationship of these changes to the expression of motor and neuropsychological signs, in a cohort of individuals with REM sleep behavior disorder and matched controls.

Eligibility

Inclusion Criteria for the iRBD Group:

• Diagnosis of polysomnogram-confirmed isolated iRBD.
• Able to ambulate independently without the use of an assistive device (e.g., cane) for 50 meters.
• Age: 21-75 years.

Inclusion Criteria For Control Subject Group:

• Age: 21-75 years.
• Able to ambulate independently without the use of an assistive device (e.g., cane or walker for 50 meters.

Exclusion criteria for iRBD group:

• Dementia diagnosis and/or a University of California Brief Assessment of Capacity to Consent (UBACC) score and MacCAT-CR score indicating impaired capacity to consent.
• History of musculoskeletal disorders that significant affect movement of lower or upper limbs as determined at the time of enrollment.
• Other significant neurological disorders that may affect participation or performance in the study.
• Anti-depressant associated RBD. Individuals will be excluded if their dream enactment emerged or clearly worsened after initiating an antidepressant medication.
• Meet criteria for overt Parkinson's disease, dementia with Lewy bodies, Multiple Systems Atrophy, Alzheimer's disease, or other neurodegenerative disorder, or other known cause of RBD (e.g., narcolepsy and drug induced RBD).
• Untreated sleep-disordered breathing
• History of musculoskeletal disorders that significantly affect movement of lower or upper limbs as determined at the time of enrollment.
• Pregnant women
• Additional exclusion criteria for TMS experiments (note that individuals who are excluded from the TMS experiment still have the opportunity to participate in the other data collection sessions):
  • History of seizures, epilepsy, stroke, multiple sclerosis, or traumatic brain injury
  • Intracranial metallic or magnetic devices (e.g. cochlear implant, deep brain stimulator)
  • Pacemaker or any implanted device
  • History of surgery on blood vessels, brain, or heart
  • Unexplained, recurring headaches or concussion within the last six months
  • Severe hearing impairment
  • If participant is taking one of the following medications that affects neuroplasticity testing, they will be excluded from the TMS experiment: haloperidol (dopamine antagonist), prazosin (norepinephrine antagonist), biperiden (acetylcholine antagonist), dopamine modulators, NMDA receptor and calcium channel modulators, GABAergic drugs (benzodiazepines), lithium, lovastatin, and cannabis.

Exclusion Criteria for Control subject Group:

• Same as exclusion criteria as the iRBD group
• History of dream enactment from either patient report or from a bed partner witness that may suggest iRBD.
• History of untreated sleep-disordered breathing.
• Presence of parkinsonism or cognitive impairment (including dementia or mild cognitive impairment).
• Active central nervous system, systemic, psychiatric conditions or use of psychoactive medication that would adversely affect cognitive, neuropsychiatric, motor, or autonomic functioning