What wires together dies together: verbs, actions and neurodegeneration in motor neuron disease

Abstract

For more than a century the research on Motor Neuron Disease (MND) has been dominated by a tension between the concept of a selective, purely motor degeneration and a growing realisation of the high frequency and importance of cognitive symptoms that can culminate in dementia. The present paper aims at integrating these two, seemingly mutually exclusive interpretations of the disease. It is proposed that the cognitive and motor symptoms in MND are due to the same selective neurodegenerative process, spreading along the lines of functional connections in the nervous system. Accordingly, the most impaired aspects of cognitive function are those with the closest functional links to the motor system, a pattern explaining a disproportionate impairment of verb and action processing in this disease. The dementia associated with MND can be interpreted as the fifth major clinical presentation of MND, alongside bulbar, thoracic, upper and lower limb presentation. It follows the same rules of disease progression as other presentations, spreading contiguously from region to region, with a predominantly caudal direction. Accordingly, dementia tends to precede other presentations and is often followed by bulbar symptoms. We believe that the presented model contributes to a more accurate concept of MND, integrating cognitive and motor features within the same disease mechanism. At the same time it highlights the importance of MND for cognitive neuroscience and, in particular, for theories of embodied cognition.