The Subthalamic Nucleus and Tremor in Parkinson's Disease *M. C. Rodriguez. MD, *Oroz J. Guridi, MD, $L. Alvarez, MD, "K. Mewes, PhD, $R. Macias, MD, "J. Vitek, MD. 'IM. R. DeLong, MD, and VJ. zyxw A. Obeso, MD Summary: The role of the subthalamic nucleus (STN) in the origin of parkinsonian tremor is discussed. Previous studies in monkeys madc parkinsonian by MPTP zyxwvutsrq ( I -methyl-4-phenyl- 1.~.3.6-trtrahydropyridine) administration suggested a direct participation of the STN in the pathophysiology of tremor. We recorded tremor-related activity in the STN in 12 patients with Parkinson's disease (PD) and found that microstimulation of the sensorimotor region of the nucleus, where these neurons are present. stopped the zyxwvutsrq tremor with a very short latency. Long- term treatment by means of bilateral deep-brain stimulation (DBS) in the same I? patients led to a significant reduction of tremor as well as other cardinal features of PD. This effect was The origin of tremor in Parkinson's disease (PD) is still a matter of debate. Until recently, the ventralis in- termedialis nucleus (Vim) of the thalamus was the only structure closely associated with tremor in PD.' The de- velopment of the I -methyl-4-phenyl- 1,2,3,6-tetrahydro- pyridine (MPTP) model of PD in monkeys allowed us to ~. carry out new physiologic observations in animals show- ing resting and postural tremors (see Bergmann et al. in this supplement, pp. 29-34). These studies indicate that fairly selective dopamine deficiency, as induced by long- term MPTP administration, may provoke tremor in mon- keys that share the characteristics present in PD.' In such animals, it was shown that tremor in the limbs is associated with oscillatory neuronal discharges in the external globus pallidum (GPe), internal globus pallidum (GPi), and subthalamic nucleus (STN) rhythmically fir- ing in phase with the tremor in the limbs3 Neurons with oscillatory discharges in the STN and GPi were found in - zy 111 Address correspondence and reprint requests to J. A. Obeso at Neu- rology and Neurosurgery. HOSPITEN Rambla 1 15. Tenerife. Spain. blindly assessed at 3 months after implantation. In another group of seven patients, a unilateral lesion of the STN was performed. Both postural and resting tremor were significantly improved on the limbs contralateral to the lesion side. In three patients, tremor disappeared completely after I2 months of follow up. The electrophysiologic data and therapeutic effect of inactivating the STN strongly indicated that this structure is directly involved in the origin of parkinsonian tremor. as sug- gested by the MPTP model. Key Words: Subthalamic nucleus-Parkinsonian tremor-Deep-brain stimulation- Subthalamotomy. normal monkeys, but their presence increased dramati- cally (-90%) in parkinsonian animals.3 The degree of synchrony between the electromyographic (EMG) activ- ity underlying the tremor and the neuronal discharges was high, but the analysis could not determine whether the tremor-related neuronal activity in the STN was in- duced (peripherally driven) by the tremor or causally provoking it. Tremor cells were found mainly in the dor- solateral two thirds of the STN, but precise data about their somatotopic organization was not provided. Lesion of the STN reduced4 or even abolished"' the tremor in MPTP monkeys, although there was no effect on the 4- to 8-Hz oscillatory neuronal activity recorded in the GPL4 In our experience, tremor arrest was indeed the earliest and most reliable sign of a therapeutically effec- tive lesion of the STN in MPTP monkeys.' Long-term stimulation of the STN in parkinsonian monkeys also was accompanied by suppression of t r e m ~ r . ~ Thus both recording and inactivation studies in parkinsonian mon- keys indicate that the STN could be included in the cir- cuits mediating tremor. Despite such experimental evi-