Model-based deconstruction of cortical evoked potentials generated by subthalamic nucleus deep brain stimulation

Area of Science:

• Neuroscience
• Computational Neuroscience
• Systems Neuroscience

Background:

• Parkinson's disease (PD) involves altered motor cortex activity, often treated with subthalamic nucleus (STN) deep brain stimulation (DBS).
• STN DBS effectively suppresses motor symptoms and modulates cortical activity, but the precise anatomical pathways involved remain unclear.
• Cortical evoked potentials (cEPs) generated by STN DBS offer a window into cortical responses to subcortical stimulation.

Purpose of the Study:

• To elucidate the neural origins of STN DBS-generated cortical evoked potentials (cEPs).
• To determine the specific anatomical pathways mediating cortical modulation by STN DBS.
• To investigate the role of antidromic versus orthodromic pathways in STN DBS-induced cortical activity.

Main Methods:

• In vivo electrophysiology: Recorded cEPs over the rat motor cortex during STN DBS at varying frequencies in healthy and parkinsonian models.
• Computational modeling: Utilized a biophysically detailed thalamocortical network model to simulate STN DBS and analyze cEP generation.
• Two-step approach combining in vivo recordings with in silico modeling to deconstruct neural origins of cEPs.

Main Results:

• In vivo cEPs exhibited short (R1), intermediate (R2), and long (R3) latency responses.
• Computational model accurately reproduced in vivo cEPs, identifying neural generators for each latency.
• Short-latency (R1) responses originated from antidromic activation of layer 5 pyramidal neurons; intermediate (R2) from recurrent layer 5 activation; long-latency (R3) from polysynaptic layer 2/3 activation via the cortico-thalamic-cortical pathway.

Conclusions:

• Antidromic activation of the hyperdirect pathway and subsequent cortico-thalamic-cortical interactions are sufficient to generate STN DBS-evoked cortical potentials.
• Orthodromic activation through basal ganglia-thalamus-cortex pathways is not required for generating these cortical responses.
• cEP analysis is a valuable tool for identifying neural elements modulated by STN DBS, potentially explaining its therapeutic effects in Parkinson's disease.