Functional Neuroimaging at Different Disease Stages Reveals Distinct Phases of Neuroplastic Changes in Amyotrophic Lateral Sclerosis

Some previous functional magnetic resonance imaging (fMRI) studies have revealed increased activation in amyotrophic lateral sclerosis (ALS) patients but longitudinal data on such activation changes are lacking. To assess the time course of changes in fMRI patterns and their potential contribution to the understanding of ALS pathophysiology, we, therefore, investigated a total of 22 patients with ALS and matched control participants while they performed a blocked motor task. Patients were assigned to three groups according to whether they had no (MRC grade 5), mild (MRC 4), or marked (MRC 3) weakness of the examined right hand. Significant activations were seen in primary motor and premotor cortex, somatosensory cortex, supplementary motor area and subcortical areas in all groups. The size of the activated area in the contralateral sensorimotor cortex was increased to a similar degree in all three ALS groups compared to control participants irrespective of weakness on clinical examination. Whereas movement related signal change and beta weights extracted from the activated cluster were unchanged relative to controls in ALS patients with no weakness, a marked decrease of these parameters was seen in patients with weakness. Two distinct stages of neuroplastic changes could be identified in ALS (first: increase of the activated area in contralateral sensorimotor cortex; second: reduction of signal change and beta weights with increasing weakness). We interpret the increase of the activated area as a result of decreased intracortical inhibition and the reduction of movement related signal change and beta weights as a consequence of loss of upper motor neurons. Hum Brain Mapp 32: 750-758, 2011. (C) 2010 Wiley-Liss, Inc.