Altered cortical activation during a motor task in ALS - Evidence for involvement of central pathways

Objective To test the hypothesis that patients with amyotrophic lateral sclerosis (ALS) show increased cortical activation during a motor task compared to both healthy controls and patients with muscle weakness due to peripheral lesions. Methods Functional magnetic resonance imaging (fMRI) was used to measure activation during a block design paradigm contrasting right hand movements against rest in sixteen patients with ALS, seventeen healthy controls and nine patients with peripheral lesions. The groups were matched for age and gender and the two patient groups were matched for their degree of upper limb weakness. Analysis used a non-parametric approach to perform a 3 way hypothesis-driven comparison between the groups. Results During the motor task, patients with ALS showed increased cortical activation bilaterally, extending from the sensorimotor cortex [Brodmann areas (BA) 1, 2, 4] posteriorly into the inferior parietal lobule (BA 40) and inferiorly to the superior temporal gyrus (BA 22) when compared to peripheral lesion patients and controls. In addition, ALS patients showed reduced activation in the dorsolateral prefrontal cortex (DLPFC) extending to anterior and medial frontal cortex (BA 8, 9, 10, 32). Conclusions We conclude that alterations in cortical function in ALS differ in sensorimotor and prefrontal regions. Importantly, we have shown that these changes do not reflect confounding by weakness or task difficulty, but are likely to be related to upper motor neuron pathology in ALS.