Stimulation of the Subthalamic Nucleus Changes the Firing Pattern of Pallidal Neurons

TLDR

The study aimed to elucidate how high‑frequency subthalamic nucleus stimulation improves parkinsonian symptoms by examining its effects on GPi and GPe neuronal activity in parkinsonian rhesus monkeys. The authors implanted a scaled‑down chronic STN electrode with four 0.5‑mm contacts into two parkinsonian rhesus monkeys and recorded extracellular activity from 110 pallidal neurons during STN stimulation. STN stimulation produced short‑latency excitatory and inhibitory responses in both GPe and GPi neurons, increased mean discharge rates, and synchronized firing patterns, supporting that changes in temporal firing underlie the therapeutic benefit of STN HFS in Parkinson’s disease.

Abstract

To clarify the mechanism underlying improvement of parkinsonian signs by high-frequency electrical stimulation (HFS) of the subthalamic nucleus (STN), we investigated the effects of STN HFS on neuronal activity of the internal and external segment of the globus pallidus (GPi and GPe, respectively) in two rhesus monkeys rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. A scaled-down version of the chronic stimulating electrode used in humans, consisting of four metal contacts 0.50 mm in length each separated by 0.50 mm, was implanted through a cephalic chamber targeting the STN. Histological reconstruction revealed that the cathode was located in the STN in both monkeys. Extracellular recordings from a total of 110 pallidal neurons during STN stimulation were performed. Poststimulus time histograms of single neurons triggered by 2 Hz STN stimulation pulses at 2.4–3.0 V revealed short-latency excitations at 2.5–4.5 and 5.5–7.0 msec after stimulation onset and inhibitions at 1.0–2.5, 4.5–5.5, and 7.0–9.0 msec for both GPe and GPi neurons. These short-latency responses were present with 136 Hz stimulation, at voltages effective for alleviation of parkinsonian signs, resulting in a significant increase in mean discharge rate and a stimulus-synchronized regular firing pattern. These results indicate that activation of the STN efferent fibers and resultant changes in the temporal firing pattern of neurons in GPe and GPi underlie the beneficial effect of HFS in the STN in Parkinson's disease and further support the role of temporal firing patterns in the basal ganglia in the development of Parkinson's disease and other movement disorders.