Using neuroimaging to understand brain–behaviour relationships in the context of motor neurone disease

Sandra E. Black and Yana Yunusova

in Amyotrophic Lateral Sclerosis and the Frontotemporal Dementias

Published on behalf of Oxford University Press

Published in print October 2012 | ISBN: 9780199590674
Published online November 2012 | e-ISBN: 9780191753466 | DOI:
Using neuroimaging to understand brain–behaviour relationships in the context of motor neurone disease

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Traditionally, amyotrophic lateral sclerosis (ALS) was considered a lethal single-system disease that destroyed upper (UMN) and lower motor neurones (LMN). However, it is very clinically heterogeneous in the motor signs first manifested, the extent of extramotor involvement, and progression rate. Cognitive-behavioural syndromes such as behavioural variant frontotemporal lobar degeneration (bvFTLD), or primary progressive aphasia, may initiate, predominate, or emerge as the disease progresses. Rapid motor decline, including severe dysarthria can make cognitive assessment difficult, when motor symptoms manifest first, and the shortened lifespan may prevent expression of cognitive deficits. Now recognized to be a multisystem disease, its variety of endophenotypes are being elucidated through genetic, biochemical, neuroimaging, and pathological studies.

Advances in neuroimaging, including computational analysis, are increasingly important in capturing in vivo patterns of brain degeneration not readily apparent by qualitative interpretation of structural scans. In particular, functional imaging using single-photon emission computerized tomography (SPECT) or 18fluorodeoxy glucose positron emission tomography (PET), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and quantitative structural magnetic resonance imaging (MRI) analysis, can be used to quantify distribution and severity of neuropathology in life. DTI provides a means to map microstructural change in motor projections and association tracts that may prove useful not only in correlation with symptomatology but also in predicting progression patterns and guiding treatment.

An important landmark study of 42 patients with sporadic ALS demonstrated that neuropathology was more widespread than the motor neurone system in the 27 post-mortem cases, eight of whom had parkinsonism–ALS dementia, seven had substantia nigra degeneration, and one had Alzheimer's disease (AD). Many had vacuolation in specific areas of the frontal cortices. The multisystem nature of ALS has been validated in subsequent studies. Subsequent studies have also confirmed cognitive deficits in about 30% of patients with sporadic ALS and 15% of familial ALS cases. Moreover, new insights have been gained into the molecular neuropathology within the family of frontotemporal lobar degeneration with transactive response DNA-binding protein of 43 kDa and fused in sarcoma proteinopathies accounting for many cases of FTLD-ubiquitin/ALS.

This chapter will summarize neuroimaging advances pioneered in the study of AD exemplified by the Alzheimer's Disease Neuroimaging Initiative (ADNI) and show how different imaging modalities can be applied to ALS, such as SPECT and PET, with new ligands on the horizon, and multimodal MRI, ranging from tissue volumetrics, DTI, MEG to resting-state and activation functional (MRI) fMRI. We will show how clinical imaging can help diagnosis in a case example. We will review how neuroimaging can provide diagnostic biomarkers to detect early disease and document heterogeneity, follow course and monitor therapy and understand the brain–behaviour relationship in neurodegenerative disorders using different MR modalities, with an emphasis on DTI, which has been the most widely applied advance technique in ALS.

Chapter.  8461 words.  Illustrated.

Subjects: Neurology

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