Objective:To study whether the motor cortex excitability and the sensorimotor integration function are differentially affected in patients with Parkinson’s disease（PD）in early stage in relative to mid-late stage. Methods :Sixteen patients with PD were divided into early course group（PD-E

n=10） and middle-late course（PD-L

n=6） according to Hoen/Yahr scale;10 normal healthy volunteers were included as the normal control group. Transcranial magnetic stimulation（TMS）was applied on the hand area of the cerebral motor cortex

and motor evoked potentials（MEPs）on the contralateral were recorded by surface electrodes. The resting motor threshold（RMT）

silent period（SP）and intensity-response of MEP were measured in each group to assess the background excitability of motor cortex. Paired associative stimulation（PAS）

which comprised of electrical stimulation of contralateral median nerve and TMS at defined interstimulus interval（ISI）

was used to analyze the influence of sensory input to motor cortex output and the sensorimotor integration function.PAS at serial ISI（16

20

24

28

100

200 ms）were delivered at contralateral median nerve and motor cortex and the amplitudes of MEPs on abductor pollicis brevis were measured as the conditioned-stimulus MEPs

and the amplitudes of MEPs induced by TMS without associative sensory input were also measured as the unconditioned-stimulus MEPs. The ratio of MEPs of conditioned-stimulus and unconditioned-stimulus

defined as MEP’

was used to analyze the effects of sensory input to motor cortex excitability and sensorimotor integration. Results:Both PD-E group and PD-L group showed lower RTMs than the control group（P <0.05）

while the RTMs between PD-E group and PD-L group were not significantly different（P>0.05）. The SP of PD-L group

not PD-E group was significantly shorter than that of the control group（P<0.05）;SP between PD-E group and PD-L group was not significantly different（P>0.05）. In intensity-response study of TMS-MEP

the MEP amplitudes were increased with the escalation of the magnetic stimulation intensity in all the groups

however

the TMS-MEP amplitude was significantly less in PD-L group than in PD-E group and normal control group when the TMS intensity increased from 130% RMT to 150% RMT（P<0.05）. In PAS test

the MEP’fluctuated in response to PAS of various ISI（MEP’>1 or<1）. PAS with ISI of 24 ms has no obvious effect in normal control group[MEP’:（0.98±0.40）]

slight inhibitory effect in PD-E group[MEP’:（0.75±0.44）]

facilitative effect in PD-L group [MEP’:（1.71±0.67）];MEP’of PD-L group was significantly higher than that of the other two groups（both P<0.05）

suggesting that the inhibitory effect of sensory input on motor cortex was reduced and even reversed in late stage PD patients. PAS with ISI of 200 ms showed facilitative effects on amplitude of MEP in both normal control group[MEP’:（1.37±0.66）] and PD-E group[MEP’:（1.35±0.64）] and inhibitory effects on amplitude of MEP in PD-L group [MEP’:（0.84 ±0.35）]

however

the differences of MEP’were not statistically significant among the three groups（P>0.05）. Effects of PAS on the amplitudes of MEP were similar between PD-E group and normal control group

the MEP’related to serial ISI PAS was not statistically different between the two groups（P>0.05）. Conclusion:PAS with various ISI may have facilitative or inhibitory effects on the amplitudes of MEP. The impacts of peripheral sensory input on motor cortex excitability are not significantly affected in early stage PD patients compared to normal controls

the short latency afferent inhibition at ISI of 24 ms observed in early stage PD patients was remarkably reduced and even reversed in mid-late stage PD patients

indicating that the sensorimotor integration function is disrupted in mid-late stage PD.