Longitudinal monitoring of motor neuron circuitry in FALS rats using in-vivo phMRI.

Abstract

Amyotrophic lateral sclerosis (ALS) presents challenges for diagnosis and objective monitoring of disease progression. We show, using pharmacologic MRI, that alterations in motor circuitry can be characterized using a passive stimulus in a rat model of familial ALS as a function of symptom progression. Presymptomatic familial ALS rats had a pattern of activation to amphetamine that was statistically indistinguishable from the wild-type controls. In contrast, symptomatic rats showed significantly decreased response in sensorimotor cortex and increased response in M2 motor cortex, caudate/putamen, and thalamus. These results are similar to findings in humans of altered response to motor tasks in ALS. It may be plausible to use a passive amphetamine challenge as a biomarker to assess progression of the disease and efficacy of potential treatments.