Peristimulus time histograms (PSTHs) – a marker for upper motor neuron involvement in ALS?

Upper motor neuron involvement in ALS has been widely studied by means of transcranial magnetic stimulation and various imaging methods, such as magnetic resonance imaging, proton emission tomography, single photon emission computer tomography and magnetic resonance spectroscopy. Although almost all of these methods have detected 'abnormalities' of the motor cortex, no method has yet proven to be capable of monitoring disease progression. We and others have used peristimulus time histograms (PSTH) to evaluate corticomotoneuronal dysfunction. The primary peak (PP) in the PSTH reflects the initial rising phase of the excitatory post-synaptic potential evoked at the anterior horn cell by converging corticomotoneurons. In ALS, the PP is delayed in onset, increased in duration, and desynchronized. These abnormalities become more pronounced over time. Delayed PPs also occur more frequently in non-hereditary ALS (nHALS) with disease progression and are a hallmark of the autosomal recessively inherited D90A Cu-Zn SOD mutation. Evidence indicates that in this particular mutation, as well as in nHALS, the fast-conducting monosynaptic pathway originating from large pyramidal Betz cells is preferentially lost, whereas a slow-conducting pathway seems to be spared. This is most likely due to the enormous metabolic demand of the large pyramidal cells, which may explain the selective vulnerability of the most recent phylogenetic system to develop in the human nervous system.