Cerebellar sensory processing alterations impact motor cortical plasticity in Parkinson's disease: clues from dyskinetic patients.

The plasticity of primary motor cortex (M1) in patients with Parkinson's disease (PD) and levodopa-induced dyskinesias (LIDs) is severely impaired. We recently reported in young healthy subjects that inhibitory cerebellar stimulation enhanced the sensorimotor plasticity of M1 that was induced by paired associative stimulation (PAS). This study demonstrates that the deficient sensorimotor M1 plasticity in 16 patients with LIDs could be reinstated by a single session of real inhibitory cerebellar stimulation but not sham stimulation. This was evident only when a sensory component was involved in the induction of plasticity, indicating that cerebellar sensory processing function is involved in the resurgence of M1 plasticity. The benefit of inhibitory cerebellar stimulation on LIDs is known. To explore whether this benefit is linked to the restoration of sensorimotor plasticity of M1, we conducted an additional study looking at changes in LIDs and PAS-induced plasticity after 10 sessions of either bilateral, real inhibitory cerebellar stimulation or sham stimulation. Only real and not sham stimulation had an antidyskinetic effect and it was paralleled by a resurgence in the sensorimotor plasticity of M1. These results suggest that alterations in cerebellar sensory processing function, occurring secondary to abnormal basal ganglia signals reaching it, may be an important element contributing to the maladaptive sensorimotor plasticity of M1 and the emergence of abnormal involuntary movements.

Age-related decline in the responsiveness of motor cortex to plastic forces reverses with levodopa or cerebellar stimulation.

The plasticity of motor cortex is integral for motor memory and skills acquisition but it declines with aging. Forty healthy volunteers, across 6 decades, were tested to examine the (a) age-dependency of motor cortex responsiveness to plasticity induction, as measured from the response to paired associative stimulation (PAS) and the (b) effect of aging on the cerebellar modulation of motor cortex response to PAS. We examined if reduced dopaminergic transmission was involved in the age-related decline of response to PAS by retesting 10 of the older subjects after a single dose of levodopa. There was a substantial decline in the motor cortex response to PAS with aging, which was restored by levodopa in the older subjects. The cerebellar modulation of motor cortex response to PAS was less vulnerable to aging and a single session of cerebellar inhibition reinstated the cortical responsiveness in older subjects. Both levodopa and cerebellar inhibition can be tested for their ability to enhance motor skills acquisition and motor performance in the elderly individuals.