Side of symptom onset affects motor dysfunction in Parkinson's disease.

The healthy brain appears to have an asymmetric dopamine distribution, with higher levels of dopamine in the left than in the right striatum. Here, we test the hypothesis that this neurochemical asymmetry renders the right striatum relatively more vulnerable to the effects of dopaminergic denervation in Parkinson's disease (PD). Using the pegboard dexterity test, we compared motor performance of both hands between healthy subjects (n=48), PD patients with predominantly right-hemispheric dopamine depletion (PD-RIGHT; n=83) and PD patients with more severe left-hemispheric dopamine depletion (PD-LEFT; n=103). All subjects were right-handed. After adjusting for hand-dominance effects, we found that PD-RIGHT patients exhibited a 55% larger difference between right and left dexterity scores than PD-LEFT patients. This effect could be attributed to greater motor dysfunction of the more-affected hand in PD-RIGHT patients, while the less-affected hand performed similarly in both groups. We conclude that the side of symptom onset affects motor dysfunction in PD, and suggest that the non-dominant right hemisphere may be more susceptible to dopaminergic denervation than the dominant left hemisphere.

Hemispheric asymmetry and somatotopy of afferent inhibition in healthy humans.

A conditioning electrical stimulus to a digital nerve can inhibit the motor-evoked potentials (MEPs) in adjacent hand muscles elicited by transcranial magnetic stimulation (TMS) to the contralateral primary motor cortex (M1) when given 25-50 ms before the TMS pulse. This is referred to as short-latency afferent inhibition (SAI). We studied inter-hemispheric differences (Experiment 1) and within-limb somatotopy (Experiment 2) of SAI in healthy right-handers. In Experiment 1, conditioning electrical pulses were applied to the right or left index finger (D2) and MEPs were recorded from relaxed first dorsal interosseus (FDI) and abductor digiti minimi (ADM) muscles ipsilateral to the conditioning stimulus. We found that SAI was more pronounced in right hand muscles. In Experiment 2, electrical stimulation was applied to the right D2 and MEPs were recorded from ipsilateral FDI, extensor digitorum communis (EDC) and biceps brachii (BB) muscles. The amount of SAI did not differ between FDI, EDC and BB muscles. These data demonstrate inter-hemispheric differences in the processing of cutaneous input from the hand, with stronger SAI in the dominant left hemisphere. We also found that SAI occurred not only in hand muscles adjacent to electrical digital stimulation, but also in distant hand and forearm and also proximal arm muscles. This suggests that SAI induced by electrical D2 stimulation is not focal and somatotopically specific, but a more widespread inhibitory phenomenon.