Abnormal activity in the brainstem affects gait in a neuromusculoskeletal model

Area of Science:

• Neuroscience
• Biomechanics
• Computational modeling

Background:

• Mammalian locomotion is vital for survival and controlled by spinal cord central pattern generators modulated by the midbrain locomotor region.
• The midbrain locomotor region includes the pedunculopontine nucleus (PPN) and cuneiform nucleus (CnF), with distinct roles in locomotion.
• Neurological disorders like Parkinson's disease impair locomotion, causing freezing of gait (FOG), a phenomenon with unclear mechanisms.

Purpose of the Study:

• To elucidate the mechanisms underlying freezing of gait (FOG).
• To investigate the roles of the pedunculopontine nucleus (PPN) and cuneiform nucleus (CnF) in FOG.
• To develop and utilize a neuromusculoskeletal model to simulate FOG events.

Main Methods:

• A two-dimensional neuromusculoskeletal model with seven links, 18 muscles, and a brainstem-spinal cord neural system was developed.
• A normal locomotion model was created and then modified to simulate abnormal brainstem activity by altering PPN and CnF parameters.
• Genetic algorithms and a FOG-identifying algorithm were used for model optimization and event detection.

Main Results:

• The normal model successfully simulated walking.
• In the abnormal model, 156 freezing of gait events were identified out of 40,000 parameter sets.
• Hierarchical cluster analysis revealed four distinct clusters of parameters associated with PPN and CnF activity, correlating with clinical FOG subtypes.

Conclusions:

• Pedunculopontine nucleus (PPN) and cuneiform nucleus (CnF) activities are linked to freezing of gait (FOG).
• Differential modulation of PPN and CnF activity can generate observed FOG subtypes.
• The developed models offer insights into FOG pathophysiology and aid in classifying FOG subtypes.