Sensorimotor integration is abnormal in asymptomatic Parkin mutation carriers: a TMS study

Area of Science:

• Neuroscience
• Genetics
• Neurology

Background:

• Parkinson disease (PD) is linked to reduced sensorimotor cortex inhibition.
• It's unclear if this inhibition deficit is due to motor symptoms or compensatory changes from dopaminergic neuron degeneration.
• This study investigates subclinical changes in asymptomatic Parkin mutation carriers.

Purpose of the Study:

• To probe intracortical sensorimotor excitability in asymptomatic carriers of a single mutant Parkin allele.
• To determine if reduced sensorimotor inhibition is present before the onset of motor symptoms in PD.
• To differentiate between adaptive changes and direct effects of the Parkin mutation on cortical excitability.

Main Methods:

• Used short-interval afferent inhibition (dSAI) and paired-pulse transcranial magnetic stimulation (TMS).
• Investigated nine heterozygous Parkin mutation carriers and nine healthy controls.
• Tested sensorimotor inhibition at specific interstimulus intervals (ISIs) for dSAI and paired-pulse TMS.

Main Results:

• Reduced dSAI was observed at a 25 msec ISI in Parkin mutation carriers.
• Intracortical paired-pulse TMS measures of inhibition and facilitation remained normal.
• These findings indicate a specific deficit in sensorimotor inhibition in preclinical PD.

Conclusions:

• The observed decrease in sensorimotor inhibition may stem directly from the Parkin mutation.
• Alternatively, it could represent adaptive cortical changes in response to subcortical dopaminergic dysfunction.
• This reduced inhibition is not attributable to motor symptoms, highlighting its preclinical nature.