Pallidal stimulation modifies after-effects of paired associative stimulation on motor cortex excitability in primary generalised dystonia

Abstract

Objective To determine the effect of globus pallidus internus (GPi) deep brain stimulation (DBS) on motor cortex plasticity in patients with primary generalised dystonia. Methods We studied 10 patients with primary generalised dystonia (5 DYT1+, 5 idiopathic, 5 female, mean age 42) following GPi DBS and 10 healthy subjects. Motor cortex plasticity was assessed using transcranial magnetic stimulation (TMS) paired associative stimulation (PAS) of motor cortex and median nerve, a method which has been shown in healthy subjects to produce LTP-like effects. Thresholds and TMS intensity to produce a resting motor evoked potential (MEP) of 1 mV were determined. Resting MEP amplitude and stimulus response curves were recorded before and after PAS. Patients were recorded ON and OFF DBS in separate sessions. Results The mean TMS intensity to produce a resting MEP of 1 mV was 54% of maximum stimulator output when OFF and 52% ON DBS. Fifteen minutes after PAS the resting MEP amplitude increased in patients OFF DBS and in control subjects whereas it decreased in patients ON DBS. Similarly, after PAS, the mean amplitude of the stimulus response curve increased OFF DBS, but this effect was abolished with DBS ON. Furthermore, patients who had the largest clinical response to chronic DBS also had the largest difference in the effect of PAS with DBS ON vs. OFF. Conclusions After PAS, patients with primary generalised dystonia showed a similar pattern of increased motor cortex excitability as healthy subjects when GPi DBS was OFF but not with GPi DBS ON. These results suggest that GPi DBS may reduce LTP-like motor cortex plasticity, which could contribute to its mechanism of action in dystonia.