Elsevier

Cortex

Volume 48, Issue 7, July–August 2012, Pages 936-944
Cortex

Special issue: Viewpoint
What wires together dies together: Verbs, actions and neurodegeneration in motor neuron disease

https://doi.org/10.1016/j.cortex.2011.07.008Get rights and content

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.

Section snippets

The two faces of Motor Neuron Disease (MND)

From the very beginning of the systematic study of MND in late 19th Century up to the present day clinicians and researchers have been confronted with a fundamental dilemma. On one hand, the most striking and characteristic feature of the disease is its apparent selectivity, affecting motor neurons from the cerebral cortex down to the lumbar spine. Indeed, the classical manifestations of the disease can be explained by the dysfunction of upper (spasticity, brisk reflexes) as well as lower

The relationship between MND, FTD and aphasia

The clinical descriptions of MND/Dementia show a remarkable degree of consistency. Most symptoms can be accommodated within three broad categories: behavioural/psychiatric, cognitive and linguistic. Behavioural symptoms, such as apathy, mental rigidity, tendency to hoard, socially inappropriate comments and actions etc are considered to be highly characteristic of FTD (Neary et al., 1998). The same can be said about cognitive symptoms, such as a prominent reduction in verbal fluency and

MND/Dementia/Aphasia: the sequence of events

What is typical for MND/Dementia/Aphasia is not only the pattern of symptoms but also the order of their appearance (Bak, 2010). In the majority of cases the disease begins with rapidly progressive behavioural and cognitive symptoms, sometimes associated with psychotic features (Lillo et al., 2010), followed within a year or two by the occurrence of the classical amyotrophic features of MND (weakness, fasciculations, brisk reflexes) with a predominantly bulbar distribution. The involvement of

The spread of neurodegeneration in MND

The discussion of the typical sequence of symptoms in MND/Dementia/Aphasia brings us to one of the most important characteristics of neurodegenerative processes, namely the continuous and often systematic progression of symptoms. The vast majority of diseases begin focally, affecting circumscribed, often small areas of the nervous system and then progress systematically to encompass more and more anatomical regions. However, only rarely, and then usually only in the late stages, will a disease

Neurodegeneration and functional networks

In the early days of functional neuroimaging its findings were often interpreted in terms of particular areas being “dedicated” to specific cognitive functions. Regions such as “fusiform face area” (Kanwisher et al., 1997) or “parahippocampal place area” (Epstein and Kanwisher, 1998) have been identified, with a more or less explicit underlying assumption that these are the places where the processing of the relevant information takes place. Indeed, attempts have been made to localise within

Verbs, actions and embodied cognition

The evidence in favour of distributed, interactive and interdependent functional networks is particularly compelling in the domain of language (Pulvermüller and Fadiga, 2010). Functional neuroimaging studies suggest that the brain regions involved in language processing extend well beyond the classical Broca and Wernicke areas (Hickok and Peoppel, 2007) and involve, importantly, areas traditionally considered as parts of the motor system. An event-related fMRI study conducted on healthy

Conclusions: E pluribus unum

Drawing on several lines of evidence, from clinical studies of the natural course of MND, through current models of neurodegeneration as network vulnerability to the theories of embodied cognition we propose a unified concept of MND, which includes motor as well cognitive features. Specifically, we suggest that the cognitive symptoms in MND should be viewed as different manifestations of the same underlying pathological process, extending into different parts of the nervous system.

In our view,

Acknowledgements

This work integrates insights won in many years of work with patients with MND and MND/Dementia and we would like to express particular thanks to our collaborators, particularly John Hodges (formerly Cambridge, now Sydney) and Sharon Abrahams (Edinburgh) as well as to our patients and their families and carers. Our theoretical understanding has been greatly enhanced by discussions with experts in different fields, especially Albert Ludolph (neurology), Stefano Cappa and Argye Hillis (cognitive

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