Origin of the secondary increase in firing probability of human motor neurons following transcranial magnetic stimulation. Studies in healthy subjects, type I hereditary motor and sensory neuropathy and multiple sclerosis.

In tonically active human motor neurons serving upper limb muscles there is a late rise in firing probability following transcranial magnetic stimulation termed the secondary peak (SP). The aim was to study the mechanism of SP and the pathway that mediates it. For this purpose, the response to transcranial magnetic stimulation of 62 repetitively firing low threshold single motor units from upper limb muscles was studied with peri-stimulus time histograms in 8 healthy subjects and in 13 patients with either Type I hereditary motor and sensory neuropathy (HMSN) or multiple sclerosis (MS). Separate peri-stimulus time histograms, constructed for trials in which the motor unit fired in the primary peak (PP) and those in which it fired in SP, showed that SP was not caused by a resumption of firing after the preceding PP. In the first dorsal interosseous muscle, the observed increase in the interval between PP and SP in patients with either HMSN or MS, when compared with healthy subjects, suggested that the pathway mediating SP had both peripheral and central components. Evidence for a peripheral component was substantiated by the observed slope of the line relating the latency of SP in different upper limb muscles to peripheral conduction distance, which was more than 3 times greater than that for PP, and by comparisons in the same motor unit made between the latency of responses to finger taps and to transcranial magnetic stimulation. Evidence for the origin of SP was consistent with a long loop reflex, or with collateral activation of gamma motor neurons and subsequent motor neuron firing from muscle afferent inputs. SP discharges were found to occur earlier than expected on the basis of the spontaneous motor unit firing rate, suggesting that SP was caused by the rising phase of an excitatory post-synaptic potential, rather than by the decay of an inhibitory postsynaptic potential.