The significance of oscillations that characterize the subthalamic nucleus in Parkinson's disease is still under debate. Here, we analysed the spectral and spatial characteristics of 314 microelectrode trajectories from 128 patients undergoing subthalamic nucleus deep brain stimulation surgery for Parkinson's disease. We correlated the subthalamic nucleus pathophysiology with the outcome of surgery, as evaluated by the third section of the Unified Parkinson's Disease Rating Scale (motor score), which was subdivided into tremor, rigidity, limb-bradykinesia and axial-bradykinesia subscores. β-oscillatory activity (13-30 Hz) comprised a continuous stretch within the subthalamic nucleus, and was limited to a distinctly-bounded dorsolateral oscillatory region. Although less consistent and more sporadic, low-frequency (3-7 Hz) power was also increased in the dorsolateral oscillatory region. In contrast, the more ventral subthalamic nucleus was characterized by consistently reduced β and increased gamma (30-100 Hz) activity. Neuronal responses to passive arm movement (analysed by their alignment to goniometer tracing of the joints' angular displacement) were significantly more common in the dorsolateral oscillatory region than the ventral subthalamic nucleus region (62 versus 25 of sites tested respectively, P < 0.01). The length of the dorsolateral oscillatory region recorded in the macroelectrode-implanted trajectory predicted a favourable response to subthalamic nucleus deep brain stimulation (R = 0.67, P < 0.0001). This correlation was also evident for improvement in the specific symptom subscores of rigidity, limb-bradykinesia and axial-bradykinesia (P < 0.05). Similarly, increased subthalamic nucleus β power was associated with postoperative improvement. In contrast, the preoperative response to levodopa did not correlate with dorsolateral oscillatory region length (P = 0.33), however, it did tend to be associated with increased β (and decreased low frequency) subthalamic nucleus power. Finally, the active macroelectrode contact, independently selected by optimal clinical outcome, coincided with the dorsolateral oscillatory region centre. On average, the location of the active contact was not significantly different from the dorsolateral oscillatory region centre (P = 0.10), but was significantly different from the subthalamic nucleus centre (P < 0.0001). We conclude that the spatial extent of the dorsolateral oscillatory region, which overlaps the motor territories of the subthalamic nucleus, predicts the outcome of subthalamic nucleus deep brain stimulation. Thus the frequency and spatial characteristics of the subthalamic nucleus trajectory may be used for deep brain stimulation outcome optimization.
Bibliographical noteFunding Information:
This work was supported by the ‘Fighting against Parkinson’ and the Max Vorst Family Foundations of the Hebrew University Netherlands Association (HUNA) to H.B., and the Parkinson at the Hadassah (PATH) committee of London to Z.I.
- Parkinson's disease
- basal ganglia
- beta oscillations
- power spectral density
- subthalamic nucleus