Objective: To investigate the electrophysiological interplay between the human cortex and the subthalamic nucleus (STN) by comparing STN responses to direct cortical electrical stimulation and spontaneous cortical discharges in Parkinson’s disease (PD) patients undergoing deep brain stimulation (DBS) surgery, with a focus on medication-dependent differences.

Background: The frontal cortex interacts with the basal ganglia via multiple pathways, including the hyperdirect pathway, a monosynaptic projection from the cortex to the STN. While cortical stimulation studies in non-human primates have demonstrated these pathways, their functional dynamics in humans remain unclear. Beyond connectivity, neural transmission within these pathways may depend on time-domain features of oscillatory activity. Recent evidence suggests that the nonsinusoidal features of oscillatory waveforms encode physiologically relevant information, particularly in the beta band, where waveform sharpness has been linked to cortical excitatory input synchrony.

Method: We recorded simultaneous invasive electrocorticography (ECoG) and subthalamic local field potentials (LFPs) in PD patients undergoing DBS surgery. Subthalamic responses to direct cortical stimulation were analyzed and compared to spontaneous cortical discharges, identified using the cycle-by-cycle toolbox. Additionally, we examined medication-dependent differences.

Results: We observed distinct short- and long-latency STN responses to cortical stimulation, with the earliest at 2.5 ± 0.4 ms, followed by responses at 6.3 ± 2.3 ms, 23.1 ± 0.9 ms, 38.6 ± 6.6 ms, and 56 ± 5.5 ms. STN responses differed significantly between medication ON and OFF states, with greater amplitudes in the OFF state for both cortical stimulation and spontaneous discharges, indicating medication-dependent modulation of cortico-subthalamic dynamics.

Conclusion: These findings highlight the role of dopamine in cortico-subthalamic interactions and suggest that waveform dynamics of spontaneous cortical discharges and evoked STN responses provide novel insights into circuit-level mechanisms in PD. Understanding these features could refine our analytic toolkit for investigating basal ganglia physiology and inform future adaptive DBS strategies, shifting from oscillatory activity-based approaches to network response-based interventions leveraging intrinsic neural dynamics.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/investigation-of-cortex-basal-ganglia-pathways-with-cortical-stimulation-and-subthalamic-evoked-responses-in-patients-with-parkinsons-disease/