Intraoperative neural firing correlates with motor and cognitive features in Parkinson's disease

During deep brain stimulation (DBS) surgery for Parkinson's disease (PD), intraoperative microelectrode recordings (MERs) are frequently used to determine electrode positioning within the subthalamic nucleus (STN) and globus pallidus internus (GPi). Various patient characteristics might be associated with abnormal STN and GPi firing activity and thus influence electrode placement. In this study, the authors aimed to elucidate the relationship between preoperative dopamine responsiveness or changes in cognitive status and STN or GPi multiunit activity.

This retrospective cohort study included patients with PD undergoing awake STN (n = 74) or GPi (n = 63) DBS surgery with intraoperative MER at a single institution from 2013 to 2021. To control for the lead position, contralateral motor outcomes of each lead were graded using 1-year neurological follow-up notes. Multiunit neural firing activity for each lead was recorded from MER at the location corresponding to lead active contact at the 1-year follow-up assessment. Linear regression models, controlling for disease duration and age, were used to identify associations between multiunit neural firing rates and preoperative dopamine responsiveness, determined by the difference between preoperative motor scores when on medication minus preoperative motor scores when off medication, and between multiunit activity and the pre- to postoperative change in Mini-Mental State Examination scores.

Seventy-four patients with 130 STN leads (mean age 61.2 ± 10.4 years) and 63 patients with 110 GPi leads (mean age 62.8 ± 8.6 years) were included. In STN leads with maximum contralateral motor improvement, increased dopamine responsiveness was associated with both the intraoperative firing rate (p = 0.01) and disease duration (p = 0.01). These relationships were not significant in the GPi leads or when looking at leads for which patients experienced suboptimal motor improvement (p > 0.05). In the GPi leads, an increased intraoperative firing rate in electrodes with maximum symptom improvement was associated with declining cognitive status (p = 0.045).

These findings suggest patient characteristics that correlate with neural firing rates and influence intraoperative MER, final electrode placement, and patient outcomes, while improving understanding of STN and GPi pathophysiologic mechanisms in PD. Future investigations into other characteristics that might affect STN and GPi intraoperative neurophysiology are warranted.