Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for medically refractory Parkinson's disease. Although it has recognized clinical utility, its biologic mechanisms are not fully understood, and dopamine release as a potential factor in those mechanisms is in dispute. Here, we tested the hypothesis that STN DBS-evoked dopamine release depends on the precise location of the stimulation site in the STN and site of recording in the caudate and putamen.
Methods: We conducted DBS with miniature, scaled-to-animal size, multi-contact electrodes and used fMRI to identify the optimal dopamine recording site in the brains of three non-human primates, which are highly representative of human brain anatomy and circuitry. Real-time stimulation- evoked dopamine release was monitored at carbon fiber microelectrodes using in vivo fast scan cyclic voltammetry.
Results: This study of STN DBS-evoked dopamine modulation in intact nonhuman primates used fMRI to identify the optimal recording site in the putamen and caudate and found a relationship between dopamine release in those structures and site of stimulation in the STN.
Conclusions: This study demonstrates that STN DBS-evoked dopamine release can be minimized or maximized through subtle changes in the STN stimulation site.
Patient Care: Here we show that dopamine release in the caudate and putamen is dependent on the site of stimulation within the STN, which may have behavioral implications and explain potential side effects with STN DBS in Parkinson's disease.
Learning Objectives: The objective of this study was to characterize STN DBS-evoked dopamine release as a function of the location of the DBS electrode in the STN and of the neurochemical sensing electrode in the caudate and putamen.