Functional neuroimaging at different disease stages reveals distinct phases of neuroplastic changes in amyotrophic lateral sclerosis

Introduction:

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder involving upper and lower motor neurons with a progressive limb and/or bulbar muscular weakness and wasting. A suitable method to gain insight to the dynamics of neurodegeneration and possible compensatory processes is functional imaging. Previous functional magnetic resonance imaging (fMRI) studies have revealed increased activation in ALS patients but have not analyzed fMRI changes in relation to disease stage. To assess the time course of changes in fMRI patterns and their potential contribution to the understanding of ALS pathophysiology,

Methods:

Two groups were investigated using BOLD-fMRI, while they performed a blocked motor task (finger flexion and extension of fingers in the right hand against rest). Imaging was performed in a 3T system. fMRI data were analyzed with Brain Voyager QX. We investigated a total of 22 patients with ALS, who fulfilled the diagnostic criteria for probable or definite ALS according to the revised El Escorial criteria of the World Federation of Neurology and matched control participants while they performed a blocked motor task. Medical Research Council (MRC) scale was used for evaluation of muscle strength. Grip strength of the right hand was evaluated using Martin-Type Squeeze Dynamometer (Vigorimeter, Martin, Tüblingen, Germany). 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.

Results:

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.

Conclusion:

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). In light of the pertinent neuropathological and electrophysiological literature, the increase of the activated brain areas appears to reflect a decreased intracortical inhibition early in the disease. Over the course of the disease and with increasing weakness, the signal change in the activated areas is reduced which might be related to cell loss of pyramidal cells. In addition, increased activation of ipsilateral sensorimotor cortex likely reflects reduced transcallosal inhibition.