Functional magnetic resonance imaging (fMRI) clinical studies in ALS - paradigms, problems and promises

Functional magnetic resonance imaging (fMRI) provides high-resolution, non- invasive estimates of neural activity detected by a blood oxygen level depe ndant signal by assessing the increase in blood flow to the local vasculatu re that accompanies neural activity in the brain, fMRI studies with standar d hand motor test (index-thumb opposition, ITO, or pinch) in ALS patients s how good test-retest reliability and similar amplitude of signals in ALS pa tients compared with control subjects. Isometric force can be performed wit h careful control for the force exerted, recruitment of other muscles and m otion artefact. The volume (number of voxels above threshold) of sensorimot or and cerebellar cortex activated by ITO is reproducibly larger in ALS pat ients compared with control subjects. Imagined movements in ALS have been s tudied, as in amputees, and larger volumes are activated in ALS patients wi th imagined movements as well, compared with control subjects. fMRI studies in ALS patients evaluating cortical activation during pure somatosensory s timulation cutaneous stimulation of the hand to elicit the palmomental resp onse and cutaneous stimulation of the sole to elicit the plantar response - indicate that ALS patients activate a significantly smaller volume of the contralateral sensorimotor cortex compared to control subjects. No statisti cally significant difference was seen in other areas, including the ipsilat eral cerebellum and the contralateral thalamus. An anterior shift in the vo lume of cortex activated by these paradigms occurs in ALS patients, with a volume of activation, anteriorly, not activated in control subjects. fMRI s tudies will complement other clinical neurophysiological and neuroimaging t echniques in our future attempts to solve the riddle of ALS and other motor neuron diseases.