Circuits and mechanisms for TMS-induced corticospinal waves: Connecting sensitivity analysis to the network graph

Area of Science:

• Neuroscience
• Computational modeling
• Biophysics

Background:

• Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique used for neuropsychiatric disorders.
• The precise neural circuits activated by TMS, particularly within the motor cortex, remain incompletely understood.
• Corticospinal tract recordings offer a direct measure of motor cortex response to TMS, enabling circuit dynamics modeling.

Purpose of the Study:

• To develop a computational model of a motor cortical macrocolumn using human epidural recordings.
• To investigate the mechanisms underlying TMS-induced direct and indirect corticospinal waves.
• To identify key neural pathways and neuron types involved in TMS responses.

Main Methods:

• Epidural recordings from the cervical spine in human subjects.
• Development of a computational model of the motor cortical macrocolumn.
• In-depth sensitivity analysis to identify critical pathways and neuron types.
• Machine learning to identify common circuit features among sensitive pathways.
• Analysis of connection probability and conduction delays.

Main Results:

• Sensitivity analysis identified specific neuron types contributing preferentially to single corticospinal waves.
• Prediction of single wave preference based on average connection probability to L5 pyramidal tract neurons (PTNs).
• Conduction delay of the shortest path to L5 PTNs determined corticospinal wave latency.
• Multiple neuron type activations were found to preferentially modulate specific corticospinal waves.
• Results support the hypothesis that distinct activation pathways generate different I-waves, involving excitatory and inhibitory neurons.

Conclusions:

• Different neural pathways and neuron types within the motor cortex differentially contribute to TMS-evoked corticospinal waves (I-waves).
• The computational model and sensitivity analysis provide a framework for understanding TMS mechanisms.
• Proposed cortical origins for afferents contributing to specific I-waves.
• Methodology offers a workflow for analyzing complex models and understanding stimulation responses.