The Corticospinal System and Amyotrophic Lateral Sclerosis: IFCN handbook chapter

Area of Science:

• Neuroscience
• Motor Control
• Primate Neuroanatomy

Background:

• The corticospinal system originates in the motor cortex, projecting to spinal networks.
• A parallel corticobulbar system targets cranial motor networks and brainstem pathways.
• Primate corticospinal tracts feature diverse fiber diameters, including fast-conducting axons.

Purpose of the Study:

• To elucidate the organization and function of the primate corticospinal and cortico-motoneuronal (CM) systems.
• To highlight evolutionary differences between primate and non-primate corticospinal pathways.
• To inform the selection of appropriate animal models for studying neurodegenerative disorders like ALS.

Main Methods:

• Comparative analysis of corticospinal and CM system organization in primates versus non-primates.
• Review of literature on the functional roles of these systems in motor control.
• Examination of how system dysfunction relates to neurodegenerative diseases.

Main Results:

• Direct CM projections to alpha motoneurons are a key feature in dexterous primates, originating from 'new' M1.
• The CM system is involved in fine motor control, particularly fractionation of distal extremities.
• Significant differences exist in corticospinal system organization and function between primates and rodents.

Conclusions:

• Recognizing primate-specific corticospinal and CM system features is essential for accurate animal model selection in neurodegenerative disease research.
• Selective loss of fast-conducting corticospinal axons and CM connections contributes to ALS pathology, including the 'split-hand' phenotype and impaired skilled hand function.
• Validated tests of skilled hand function can serve as biomarkers for ALS progression.