By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College
SYNOPSIS: The presence or absence of F-waves is an important observation during the electrophysiological investigation of a patient with acute, progressive weakness. But the underlying physiological basis of F-waves has been elusive. This ex vivo animal study showed that F-waves are solely generated by motor nerves arising from the ventral horn of the spinal cord and require intact synapses.
SOURCE: Görkem Özyurt M, Nascimento F, Brownstone RM, Beato M. On the origin of F-wave: Involvement of central synaptic mechanisms. Brain 2023; Oct 5. doi: 10.1093/brain/awad342. [Online ahead of print].
Varying in amplitude, latency, and configuration, and obtained by supramaximal stimulation of virtually any motor or mixed peripheral nerve, F-waves, first described in 1950 and so named because they were originally recorded in foot muscles, are late responses originally considered reflex in nature.
Abundant discussion regarding their origin was followed by a consensus that they were antidromic responses produced by a pool of motor neurons activated by peripheral nerve stimulation. Somatic depolarization in a variable minority of motor axons, produced by antidromic spikes elicited by peripheral motor nerve electrical stimulation, generated a second orthodromically propagated spike resulting in a low amplitude motor response, the F-wave. Yet, inactivation of sodium channel kinetics should inhibit the development of a second spike. Hence, the underlying mechanism remains incompletely understood.
To address this problem, ex vivo experiments with a nerve attached were performed on tissue obtained from seven female and four male mice on postnatal days 1-3, with patch clamp experiments performed on dorsal horn ablated spinal cords in four female and six male wild-type mice. Stimulation of ventral roots and recording motor neurons innervating either the lateral gastrocnemius or tibialis anterior muscle in dorsal horn ablated spinal cords produced an antidromic spike following same segment stimulation.
Hyperpolarization of the motor neuron prevented an antidromic spike in 14 of 25 recorded motor neurons with antidromic spikes, but when held at its resting membrane potential, the occurrence of the antidromic spike prevented the occurrence of the orthodromic spike. When the whole sciatic nerve was stimulated, an early, large, direct response at a more proximal sciatic site was seen, followed by a subsequent response whose latency was consistent with an ex vivo analogue of the F-wave.
Having recorded F-wave analogues, the next step was to determine if F-waves could be abolished by manipulating either pre- or post-synaptic transmission. Removing calcium from the extracellular solution did not reduce the direct response but did abolish the F-wave, which was reversible by re-equilibrating the extracellular calcium, indicating that blocking pre-synaptic transmitter release by removing Ca2+ can prevent F-wave generation. Blocking post-synaptic receptors had a similar effect, as demonstrated when exogenous NBQX, a glutamate antagonist, also suppressed F-wave generation, indicating that F-waves are generated by recurrent synaptic connections, but not by rebound spikes.
Reproduction of these findings was demonstrated by tibial branch stimulation, where manipulation of synaptic transmission by either removal of extracellular calcium or block of post-synaptic glutamate receptors abolished F-waves, supporting the notion that F-waves are mediated by spinal microcircuits activated by recurrent motor axon collaterals via glutamatergic synapses.
COMMENTARY
Routinely obtained by peripheral nerve stimulation (PNS), F-waves also may be obtained by motor point stimulation (MPS) over the muscle belly. In 13 individuals, applying monopolar double-pulse MPS and PNS to the left soleus muscle elicited an H-reflex, which diminished in size following the second stimulus, whereas the motor response at the F-wave latency did not drop, indicating that the motor response at the F-wave latency was indeed an F-wave.
Furthermore, the MPS-induced F-wave increased in amplitude, was more persistent, and was less painful to elicit compared to PNS-elicited F-waves. MPS appears to produce F-waves more consistently than PNS.1
REFERENCE
- Kaneko N, Fok KL, Nakazawa K, Masani K. Motor point stimulation induces more robust F-waves than peripheral nerve stimulation. Eur J Neurosci 2022;55:1614-1628.
