Levodopa boosts brain connections to ease Parkinson’s resting tremor
Supplementary motor area, primary motor cortex work together in movement
Taking levodopa, the mainstay of treatment for Parkinson’s disease, results in two key brain regions for movement strongly connecting and easing resting tremor, a study finds.
The study led by Ann-Maree Vallence, PhD, of Murdoch University’s Centre for Healthy Ageing in Australia, offers an avenue to target the neural connections that form networks in the brain and identify new interventions to treat Parkinson’s motor symptoms.
“Levodopa medication is already commonly used in Parkinson’s, but this research helps us to understand the neural connections altered by the medication, and how this relates to tremor,” Vallence said in a university press release. “In [the] future, this could provide the evidence we need to develop new interventions.”
The study, “Cortico-cortical connectivity is influenced by levodopa in tremor-dominant Parkinson’s disease,” was published in Neurobiology of Disease.
Like resting tremor, that is, shaking when muscles are at rest, other motor symptoms of Parkinson’s occur when dopaminergic neurons in the brain gradually stop functioning and die. Dopaminergic neurons are nerve cells that produce dopamine, a chemical involved in movement control.
How SMA, M1 work together
Vallence’s team focused on two brain regions and how low dopamine levels affect how they connect, or work together. The supplementary motor area (SMA) helps plan and initiate movement and communicates with the primary motor cortex (M1), which then sends signals to muscles to make them move.
“These regions communicate with each other to enable our skilled and controlled movements,” Vallence said.
The study measured how the connection between SMA and M1 changed in 18 patients with a diagnosis of idiopathic Parkinson’s an hour after taking levodopa (on) and 12 hours after its overnight withdrawal (off). Idiopathic Parkinson’s refers to when the cause of disease is unknown.
Using dual-site transcranial magnetic stimulation, a noninvasive technique that applies magnetic pulses at two locations on the scalp to study the connection between different regions of the brain, the researchers found that when patients were off levodopa, stimulating the SMA made M1 less active.
But when they were tested within an hour of taking levodopa, the researchers saw that the SMA connected more strongly with the M1 and muscle activity increased. Stronger SMA-M1 connectivity while on the medication was linked to less resting tremor.
“When people with Parkinson’s disease took levodopa, a dopamine medication, the connectivity between brain regions — the pathways for neural communication — was strengthened,” Vallence said. “This strengthened connectivity was associated with the severity of their tremor.”
“Once on the medication, there was an association between tremor severity and supplementary motor area and primary motor cortex connectivity, resulting in reduced tremors,” said Brittany Rurak, PhD, also of Murdoch University’s Center for Healthy Ageing.
The researchers said the findings add to their understanding of the “neural networks” involved in Parkinson’s that are altered by levodopa and “provide a neurophysiological basis for the development of interventions to treat resting tremor.”
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