Real-time simultaneous recording of electrophysiological activities and dopamine overflow in the deep brain nuclei of a non-human primate with Parkinson's disease using nano-based microelectrode arrays

Parkinson's disease (PD) is characterized by a progressive degeneration of nigrostriatal dopaminergic neurons. The precise mechanisms are still unknown. Since the neuronal communications are inherently electrical and chemical in nature, dual-mode detection of PD-related neuroelectrical and neurochemical information is essential for PD research. Subthalamic nucleus (STN) high-frequency stimulation (HFS) can improve most symptoms of PD patients and decrease the dosage of antiparkinsonian drugs. The mechanism of STN-HFS for PD still remains elusive. In this study, a silicon-based dual-mode microelectrode array (MEA) probe was designed and fabricated, and systematic dual-mode detection methods were established. The recording sites were modified using Pt nanoparticles and Nafion to improve the signal-to-noise (SNR) ratio. To evaluate its applicability to PD research, in vivo electrophysiological and electrochemical detection was performed in normal and hemiparkinsonian models, respectively. Through comparison of the dual-mode signals, we demonstrated the following in a PD monkey: (1) the maximum dopamine concentration in the striatum decreased by 90%; (2) the spike firing frequency increased significantly, especially in the region of the cortex; (3) the spectrogram analysis showed that much power existed in the 0-10 Hz frequency band; and (4) following repeated subthalamic nucleus high-frequency stimulation trials, the level of DA in the striatum increased by 16.5 mu M, which led to a better elucidation of the mechanism of HFS. The dual-mode MEA probe was demonstrated to be an effective tool for the study of neurological disorders.