T49. Motor cortical circuit interactions in Parkinson’s disease

Abstract

Introduction Using transcranial magnetic stimulation (TMS), previous work has established that motor cortical inhibitory and facilitatory circuits are aberrant in patients with Parkinson’s disease (PD). Three such circuits are short interval intracortical inhibition (SICI), short interval intracortical facilitation (SICF) and short latency afferent inhibition (SAI). They assess GABAAergic, glutamatergic and cholinergic function, respectively. Importantly, these circuits interact with each other and their interactions can be tested using a triple-pulse TMS paradigm, which elicits one circuit in the presence of another. However, these interactions have not been studied in PD. Methods 14 right-handed PD patients (10 males; 65.1 ± 8.0 years) were studied ON and OFF dopaminergic medication. Unified Parkinson’s Disease Rating Scale Part III was used to assess disease severity. 14 right-handed, age-matched healthy participants (8 males; 64.4 ± 7.3 years) served as controls. Surface electromyography measured target muscle (first dorsal interosseous) motor evoked potentials generated by TMS of left M1 in controls and of M1 in the more affected hemisphere in PD patients. SICI was tested at an interstimulus interval (ISI) of 2 ms and SICF at an ISI of 1.5 ms. The interactions between SICI and SICF were evaluated by comparing SICF alone to SICF in the presence of SICI. The latency of the median nerve N20 somatosensory evoked potential plus 2 ms was used as the ISI for SAI. The interactions between SAI and SICI were evaluated by comparing SAI alone to SAI in the presence of SICI and by comparing SICI alone to SICI in the presence of SAI. Repeated measures analyses of variance were applied to test the within-subject effect of condition (circuit A alone; circuit A in the presence of circuit B) and the between-subject factor of group (PD ON; PD OFF; control). Results For the comparison between SAI alone and SAI in the presence of SICI, there was a significant effect of condition, but no effect of group. SAI was disinhibited in the presence of SICI. For the comparison between SICI alone and SICI in the presence of SAI, there was a significant effect of condition, but no effect of group. SICI was disinhibited in the presence of SAI. For the comparison between SICF alone and SICF in the presence of SICI, there was no significant effect of condition or group, or interaction between the two. When groups were tested separately, SICF was facilitated in the presence of SICI in controls, but not in PD ON or OFF. Conclusion While previous studies showed that individual cortical circuits of SICI and SAI are abnormal in PD, our findings suggest the interactions between these circuits are preserved in PD. Thus, abnormal SICI and SAI cannot be attributed to abnormal interaction among these circuits. Our results suggest that the facilitatory effect of SICI on SICF is diminished in PD and is not affected by dopaminergic medications. Altered interaction between cortical circuits may contribute to the pathophysiology of PD.