Using point process models to compare neural spiking activity in the subthalamic nucleus of Parkinson's patients and a healthy primate

Abstract

Placement of deep brain stimulating electrodes in the subthalamic nucleus (STN) to treat Parkinson's disease (PD) also allows the recording of single neuron spiking activity. Analyses of these unique data offer an important opportunity to better understand the pathophysiology of PD. Despite the point process nature of PD neural spiking activity, point process methods are rarely used to analyze these recordings. We develop a point process representation of PD neural spiking activity using a generalized linear model to describe long- and short-term temporal dependencies in the spiking activity of 28 STN neurons from seven PD patients and 35 neurons from one healthy primate (surrogate control) recorded, while the subjects executed a directed-hand movement task. We used the point process model to characterize each neuron's bursting, oscillatory, and directional tuning properties during key periods in the task trial. Relative to the control neurons, the PD neurons showed increased bursting, increased 10-30 Hz oscillations, and increased fluctuations in directional tuning. These features, which traditional methods failed to capture accurately, were efficiently summarized in a single model in the point process analysis of each neuron. The point process framework suggests a useful approach for developing quantitative neural correlates that may be related directly to the movement and behavioral disorders characteristic of PD.

Fig. 1

Schematic of behavioral task trial.

Fig. 2

Time periods, over which the CIF denoted by (3) is estimated, are shaded.

Fig. 3

Optimal model parameters for an STN neuron during MV– and MV+ periods of a (left) PD patient and (right) healthy primate. [Top row (movement direction modulation)] Optimal extrinsic factors e^αd for d = 1,2,3,4(11, R, D, L) are plotted in black lines from left to right and corresponding 95% confidence intervals are shaded around each black line in a gray. [Middle row (short-term history modulation)] Optimal short-term history factors e^β_i for i = 1,2,…,10 are plotted in black from right to left and the corresponding 95% confidence intervals are shaded in gray. [Bottom row (long-term history modulation)] Optimal long-term history factors e^γ_i for j = 1, 2,…, 14 are plotted in black from right to left and corresponding 95% confidence intervals are shaded in gray.

Fig. 4

STN population summary using point process model parameters. Dashed line: bursting, dotted line: 10–30 Hz oscillations, and solid line: directional tuning.

Fig. 5

STN population summary using traditional statistics. Dashed line: bursting, dotted line: 10–30 Hz oscillations, and solid line: directional tuning.