Magnetic Source Imaging of Cortical Dysfunction in Amyotrophic Lateral Sclerosis

Abstract

The goal was to determine whether magnetic source imaging could identify a signature for cortical involvement in patients with amyotrophic lateral sclerosis (ALS), and to determine whether the method might provide insight into functional abnormalities associated with the disease process. Spontaneous brain activity recordings from whole-head 148-channel magnetoencephalography (MEG) were employed to look for localized dipolar sources of focal delta-theta (1-7 Hz) discharges in patients with ALS without dementia. Localized slow wave dipoles were mapped and counted by anatomic brain region, defined by MRI, and correlated against the revised ALS functional rating scale (a functional measure of ALS disability). In a substudy, defects in cortical activations mediating purposeful movement were investigated in an ALS patient with probable motor apraxia of an upper limb. MEG revealed localized slow wave dipole sources in 7/7 ALS patients, including two recently diagnosed patients (0/8 age-similar controls). Systematic brain mapping of dipole source generators was possible in all seven ALS patients. The slow wave bursts were being generated from frontal, temporal, and parietal cortices, but not from occipital areas. The density of slow wave dipoles in cingulate gyrus correlated with the severity of upper-extremity disability as judged by the functional ALS measure. Further magnetic source imaging in the substudy patient with unilateral limb apraxia revealed abnormal central processing of purposeful movement with absent M2 in the contralateral secondary motor areas generating slow waves. This exploratory study documents widespread cortical dysfunction in patients with ALS, including those with recent onset of their disease. MEG is likely to be a powerful new tool for researching the contribution of cortical dysfunction to the motor disability that characterizes the disease process.