The motor deficit of ALS reflects failure to generate muscle synergies for complex motor tasks, not just muscle strength

Customarily the motor deficits that develop in ALS are considered in terms of muscle weakness. Functional rating scales used to assess ALS in terms of functional decline do not measure the deficits when performing complex motor tasks, that make up the human skilled motor repertoire, best exemplified by tasks requiring skilled hand and finger movement. This repertoire depends primarily upon the strength of direct corticomotoneuronal (CM) connectivity from primary motor cortex to the motor units subserving skilled movements. Our review prompts the question: if accumulating evidence suggests involvement of the CM system in the early stages of ALS, what kinds of motor deficit might be expected to result, and is current methodology able to identify such deficits? We point out that the CM system is organized not in "commands" to individual muscles, but rather encodes the building blocks of complex and intricate movements, which depend upon synergy between not only the prime mover muscles, but other muscles that stabilize the limb during skilled movement. Our knowledge of the functional organization of the CM system has come both from invasive studies in non-human primates and from advanced imaging and neurophysiological techniques in humans, some of which are now being applied in ALS. CM pathology in ALS has consequences not only for muscle strength, but importantly in the failure to generate complex motor tasks, often involving elaborate muscle synergies. Our aim is to encourage innovative methodology specifically directed to assessing complex motor tasks, failure of which is likely a very early clinical deficit in ALS.