Shake it out: Arousing Brain States drive Parkinson’s Tremor

Many people with Parkinson’s disease have tremor, which waxes and wanes during the day, but particularly increases during stress and arousal. This makes tremor a visible “stress barometer” for Parkinson’s disease, but the brain mechanisms underlying this effect are unclear.

Researchers Michiel Dirkx and Rick Helmich set out to investigate the reasons behind this phenomenon, in the hopes of eventually developing treatments to reduce tremor. The research group, led by Rick Helmich from the department of Neurology and the Donders Institute, in collaboration with researchers from the University of Sydney, published the results in Movement Disorders on 26 June.

Previous work has shown that during arousal, the brain functions more in an “integrative mode”. This means that there is enhanced communication between different brain regions, which can be measured as increased functional connectivity with functional MRI. We tested whether spontaneous fluctuations in integrative brain states drive spontaneous fluctuations in Parkinson’s rest tremor. In 40 tremor-dominant PD patients, we performed functional MRI (to measure whole-brain functional connectivity), together with tremor recordings (to measure fluctuations in tremor), and proxy measures of the ascending arousal system (pupil diameter, heart rate). We calculated a moment-by-moment measure of cerebral integration, which we related to spontaneous onsets of tremor episodes during scanning. We found that fluctuations in cerebral integration were time-locked to spontaneous changes in tremor amplitude: cerebral integration increased already 13 seconds before tremor onset and predicted the amplitude of subsequent increases in tremor amplitude. This shows that integrative brain states are an important cerebral environment in which pathological tremor-related activity emerges, which is then amplified by the ascending arousal system. New treatments focused on attenuating enhanced cerebral integration in PD may reduce tremor.

Publication in Movement Disorders

Integrative Brain States Facilitate the Expression of Parkinson's Tremor

Michiel F. Dirkx MD, PhD, James M. Shine MD, PhD, Rick C. Helmich MD, PhD