Apomorphine Induces Changes in GPi Spontaneous Outflow in Patients With Parkinson’s Disease Marcelo Merello, MD, Jorge Balej, PhD, Marina Delfino, PhD, Angel Cammarota, MD, Osvaldo Betti, MD, and Ramo ´ n Leiguarda, MD Movement Disorders Section, Raul Carrea Institute for Neurological Research (FLENI), Buenos Aires, Argentina Summary OBJECTIVE: To determine the effect of a single dose of apomorphine on internal globus pallidus (GPi) neuronal dis- charge in patients with Parkinson’s disease (PD). PATIENTS AND METHODS: Nine PD patients who un- derwent microelectrode-guided posteroventral pallidotomy (PVP) were studied. After identification of a single GPi unit discharge with sufficient spike S/N ratio to allow reliable thresholding, basal recording was followed by a single 3-mg subcutaneous injection. One-minute samples were recorded 10', 30', and 60' after apomorphine. RESULTS: In four patients, recording was lost after 5–10 minutes. In two, changes were observed at peak-of-dose but recording was then lost, whereas three completed recording and returned to baseline, all five showing significant reduction in GPi firing rate (mean ± standard deviation for basal and post- apomorphine were 143 ± 55.6 and 52 ± 19.2, respectively; p <0.002). CONCLUSION: In patients with PD, apomorphine induces changes in GPi spontaneous discharge and modifies firing rates resembling recordings in normal primates. These findings show that clinical improvement as well as induction of dyskinesias following DA administration could be mediated by reduction of GPi outflow. Key Words: Apomorphine—GPi—Basal ganglia. Converging electrophysiological evidence suggests that loss of neurons in the nigrostriatal dopamine path- way leads to increased single-unit activity in the internal globus pallidus (GPi) and decreased single-unit activity in the external globus pallidus (GPe) consistent with ac- tivation of striatal projections to GPe and inhibition of striatal output to the GPi and substantia nigra pars re- ticulata (SNr). Inhibition of GABAergic neurons in the GPe releases the STN from its tonic inhibition by the GPe. Increased activity in the subthalamic nucleus (STN) contributes to the increased output from the GPi and SNr resulting in an excessive inhibition of thalamocortical projections. 1 In this study we investigated the behavior of single neurons in the GPi under the effects of apomorphine in eight patients with advanced PD who underwent unilat- eral pallidotomy. PATIENTS AND METHODS Patients Nine Hoehn and Yahr IV-V patients with PD who underwent microelectrode-guided posteroventral pal- lidotomy (PVP) were studied. Patients belonged to the Movement Disorders Section of our institute with asym- metric akinetorigid Parkinson’s disease (PD), according to the United Kingdom Parkinson’s Disease Society Brain Bank (UKPDS-BB) criteria, 2 and drug-induced in- voluntary movements. Protocol was accepted by the lo- cal ethics committee and patients were informed about the experimental nature of the intraoperative apomor- phine test. Briefly, clinical features of our population were as follows: five patients were men and four were women with ages ranging from 51–62 years (mean ± standard deviation [SD], 57 ± 4.7); all were right-handed and had a disease duration ranging from 7–20 years (mean ± SD, 13.2 ± 6.3). Pallidotomy side was left in Received February 27, 1998; revision received July 17, 1998. Ac- cepted August 26, 1998. Address correspondence and reprint requests to Marcelo Merello, MD, at the Movement Disorders Section, Raul Carrea Institute for Neurological Research, FLENI, Montaneses 2325, 1428 Buenos Aires, Argentina. Movement Disorders Vol. 14, No. 1, 1999, pp. 45–49 © 1999 Movement Disorder Society 45