Discharge properties of human subthalamic nucleus neurons in Parkinson's disease

Based on recordings in the MPTP monkey model of Parkinson's disease it has been proposed, that Parkinsonian symptoms are associated with characteristic changes in the spontaneous firing pattern of basal ganglia neurons. One pathophysiological hallmark is the increased firing rate of neurons in globus pallidus internus (GPi) and subthalamic nucleus (STN). Other characteristic features of the Parkinsonian state include abnormal oscillatory discharge patterns and increased synchrony between pairs of basal ganglia neurons. Microelectrode guided implantations of deep brain stimulation (DBS) electrodes in the nucleus subthalamicus (STN) for treating advanced Parkinson's disease allow to compare the predictions of the animal model to the spontaneous discharge behavior of basal ganglia neurons in humans.

We used a Ben-Gun approach to simultaneously collect neuronal activity along 5 parallel microelectrode trajectories during the implantation of STN-DBS electrodes. Recordings of 71 patients were screened and only recordings with stable spiking activity over a period of at least 30 seconds and without signs of injury potentials were further processed. A threshold detection and template matching procedure in combination with a principle component analysis were used to isolate single unit activity (SUA) offline (CED spike 2 software). SUA of 280 STN neurons could be isolated from 51 patients.

The firing pattern of each neuron was classified according to the shape of the inter-spike interval histogram. About 60% of STN neurons exhibited a burst-like positively skewed firing pattern, 10% a burst-like bimodal, 9% a bursting narrow positively skewed pattern, 4% an irregular and 18% a tonic firing pattern. The mean firing rates ranged between 43 and 60Hz within the group of burst-like neurons. Tonic neurons discharged at around 40Hz and irregular neurons at around 12Hz. Oscillatory discharge behavior was identified by significant peaks in the power spectra (4–40Hz) of the autocorrelations of SUA in one third of the neurons. Likewise, synchronous discharge behavior was identified by significant peaks in the power spectra of crosscorrelations in 49% of simultaneously recorded pairs of neurons.

These findings are in agreement with previous reports on changes of STN firing properties in the MPTP monkey. They emphasize the potential importance of abnormal neuronal synchronisation and oscillations in the pathophysiology of Parkinson's disease.