Study Rationale:
People affected by Parkinson’s experience a range of sleep problems such as excessive daytime sleeping and difficulty sleeping at night. These issues can make daily life more challenging but may also worsen the condition itself. For example, sleep disruption is thought to accelerate the loss of the brain cells that are the primary cause of Parkinson’s. In a healthy brain, the different stages of sleep and wakefulness are carefully coordinated by oscillatory activity that synchronizes nerve cells across the brain (brain oscillations). Whilst we know that this precise coordination is disrupted in Parkinson’s, we don’t know exactly how this causes specific sleep problems.
Hypothesis:
We think that different sleep problems in PD are caused by specific disruptions to distinct brain oscillations and we will test whether restoring these activities to their healthy state will improve these specific aspects of sleep and slow down the progression of nerve cell loss.
Study Design:
We will record electrical activity from the brains of people with Parkinson’s using non-invasive approaches, to establish how brain oscillations in sleep relate to clinical symptoms. In preclinical models of Parkinson’s, we will identify changes in the activity of large populations of nerve cells that cause these changes in patients. In humans and preclinical models, we will then restore brain activities associated with sleep disturbance to normal levels using closed-loop modulation, whereby stimulating the brain with sound or electricity at specific times in relation to ongoing brain oscillations can make them stronger or weaker. We will quantify the effects of this stimulation at the level of symptom improvement (people with Parkinson’s) and on neurodegeneration (preclinical models).
Impact on Diagnosis/Treatment of Parkinson’s disease:
This project will identify and validate approaches for measurement and manipulation of brain-wide sleep networks to diagnose and treat specific sleep issues. We will employ techniques that are affordable and scalable to quickly and widely have an impact on patients’ lives.
Next Steps for Development:
The next steps would be expand our approaches to larger populations (100-1000s) of people with Parkinson’s to establish their effectiveness in identifying the signatures of sleep disorders in brain activity, reducing symptoms and slowing the progression of cell loss.