Visually guided movements suppress subthalamic oscillations in Parkinson's disease patients

Abstract

There is considerable evidence that abnormal oscillatory activity in the basal ganglia contributes to the pathogenesis of Parkinson's disease. However, little is known regarding the relationship of oscillations to volitional movements. Our goal was to evaluate the dynamics of oscillatory activity at rest and during movement. We performed microelectrode recordings from the subthalamic nucleus (STN) of patients undergoing deep brain stimulation surgery. During recordings, the patients used a joystick to guide a cursor to one of four targets on a monitor. We recorded 184 cells and 47 pairs of cells in 11 patients. At rest, 26 cells (14%) demonstrated significant oscillatory activity, with a mean frequency of 18 Hz. During movement, this oscillatory activity was either reduced or completely abolished in all of the cells. At rest, 18 pairs (38%) of cells in five patients exhibited synchronized oscillatory activity, with a mean frequency of 15 Hz. In 17 of the 18 pairs, both of the cells exhibited oscillations, and, in one pair, only one of the cells was oscillatory. These synchronized oscillations were also significantly decreased with movement. There was a strong inverse correlation between firing rates and oscillatory activity. As the firing rates increased with movement, there was a decrease in oscillatory activity. These findings suggest that visually guided movements are associated with a dampening and desynchronization of oscillatory activity in STN neurons. One possible explanation for these observations is that the increased cortical drive associated with movement preparation and execution leads to a transient dampening of STN oscillations, hence facilitating movement.

Figure 1.

A, Behavioral task. B, Neuronal recordings from the STN with subjects' respective joystick movements at rest and during movement. The top traces in each panel represent deflection of the joystick along one axis. C, D, Representative action potentials (top), autocorrelogram (middle), and interspike interval histogram (bottom) for a relatively well isolated unit and a multiunit recording.

Figure 2.

A-D, Representative autocorrelograms (A) and cross-correlograms (B) during movement and at rest with their respective power spectra from a relatively well isolated unit and from a multiunit recording (C, D). Note the presence of a slope at the edges of the correlograms, caused by a slow drift in the recorded firing rates. The frequency (F, Freq) of the statistically significant peaks and their SNRs (S) are shown in the top right corners of the power spectra. Cond Rate, Conditional rate, the rate at which the firing from one cell relates to itself (autocorrelogram) or another cell (CC).

Figure 3.

A, Scatter plot of mean power during movement versus at rest. The diagonal line represents the null hypothesis of no change in oscillations during movement. B, Mean power of autocorrelograms and cross-correlograms at rest and during movement. Error bars indicate SEM. C, The maximum SNR of the power spectrums and the average neuronal firing rates aligned to the start of movement (0 msec). ^*p < 0.05, statistically significant changes of neuronal firing rate from baseline (paired t test). D, Correlation of firing rates and the power of oscillatory activity.