Stimulation at the cervicomedullary junction in human subjects
Introduction
Movement is brought about through the contraction of muscle fibres which are controlled by the firing of motoneurones in the spinal cord. Thus, knowledge of the responses of the motoneurones to synaptic input under different conditions is essential to understanding motor control. In humans, it is difficult to test the responses of motoneurones in a controlled way. The tests that are commonly used are: H-reflexes, the largely monosynaptic muscle response to activation of Ia afferents (primary muscle spindle afferents); F-waves, the muscle response to antidromic activation of motoneurones; and transcranial electrical stimulation, the short-latency muscle response to activation of corticospinal neurones by anodal stimulation over the motor cortex. Transcranial magnetic stimulation over the motor cortex (TMS) also evokes a short-latency excitatory response in muscle (motor evoked potential, MEP) through stimulation of corticospinal neurones but depends on the excitability of both cortical and spinal neurones and so cannot alone define changes in responsiveness at either level.
Although each of these responses can help describe motoneurone behaviour, each has characteristics that limits its effectiveness as a test of motoneurone excitability. The H-reflex, which is widely used, has well-described effects that can alter the afferent volley. Under many conditions there are changes in the presynaptic inhibition which acts on the Ia terminals via afferent and descending axons [39]. The Ia terminal is also affected by homosynaptic post-activation depression whereby release of transmitter from a terminal results in decreased efficacy of subsequent action potentials [19]. Finally, in conditions where there is repetitive firing of the Ia afferents, the excitability of the axons to electrical stimulation can diminish so that the same intensity stimulation no longer evokes the same afferent volley [5]. Each of these changes can alter the H-reflex response with no alteration of the motoneurones. Furthermore, the H-reflex can be evoked in a limited number of muscles, particularly at rest. The F-wave depends on reactivation of motoneurones after antidromic activation of the cell body. The mechanism of reactivation is poorly understood and changes in F-waves may not reflect the way the motoneurones would respond to synaptic input [21]. F-waves test a fraction of the motoneurone pool which may not include the smaller, slower motoneurones [12]. Practically, F-waves are small and multiple responses are needed to demonstrate a change in motoneurone excitability. Testing of proximal muscles is difficult because of the overlap of the large muscle response to orthodromic stimulation (M-wave) with the small F-wave. Transcranial electrical stimulation (TES) activates corticospinal neurones at the motor cortex. Low intensity stimuli activate the axons of the corticospinal neurones so that responses are unaffected by changes in cortical excitability. However, higher intensity stimuli also activate other neurones within the cortex which act synaptically on corticospinal neurones to evoke additional firing. Thus, except at very low intensities, muscle responses to TES can be affected by intracortical changes [8], [24]. This limits the use of this test to small motor units and makes its use in resting muscles problematic.
Stimulation of the descending tracts at the cervicomedullary junction also evokes a short-latency excitatory response in the muscle (cervicomedullary motor evoked potential; CMEP) and can also be used as a test of motoneurone excitability in awake humans. It has some advantages over other tests, as well as its own disadvantages. The use of cervicomedullary junction stimulation, and its advantages and problems are presented below. Findings on the behaviour of motoneurones and the operation of corticospinal input revealed by cervicomedullary stimulation are also presented.
Section snippets
Electrical cervicomedullary junction stimulation
Electrical stimulation between electrodes fixed over the mastoid processes can evoke CMEPs in the muscles of the upper and, in some subjects, the lower limb [48], [49]. A high-voltage electrical pulse (50–100 μs duration, up to 750 V) is passed across the spinal cord between electrodes fixed over the back of each mastoid (see Fig. 1A). Responses with the same latency are evoked with electrodes at levels between 2 cm above to 4 cm below the bottom of the mastoids. In the arms, this latency is ∼2 ms
Magnetic cervicomedullary junction stimulation
Magnetic stimulation over the back of the head using a double-cone coil (Fig. 1B) can evoke muscle responses with the same latencies as those evoked by electrical stimulation of the cervicomedullary junction [51]. This implies that it also activates descending axons at the pyramidal decussation. The centre portion of the coil is placed upright over the inion with the current going downwards in it (Fig. 3A). The coil can then be moved laterally and caudally to find the optimal site for
What does cervicomedullary junction stimulation activate?
Cervicomedullary stimulation elicits a single volley in descending axons. This activates motoneurones synaptically and evokes a short-latency excitatory response that can be recorded from muscle. The antidromic volley from a supramaximal peripheral nerve stimulus can collide with the evoked response and annihilate it. This demonstrates that motoneurones fire only once in response to the descending volley [2]. The stimulus primarily activates axons in the corticospinal tract. When
During voluntary contractions
CMEPs can be used to test motoneurone excitability in a wide variety of tasks. A basic observation made with CMEPs is that the response increases in size with voluntary contraction (Fig. 2). That is, the response of the motoneurone pool to the same descending input becomes greater. The size of this increase depends on the muscle, on the size of the response at rest and on the level of activation [28], [44], [50]. Although this may seem obvious, other tests of motoneurone excitability are
Cervicomedullary stimulation as a control for TMS
Transcranial magnetic stimulation activates corticospinal neurones in the motor cortex both directly and through synapses from other cortical neurones. This direct and indirect activation produces multiple descending volleys which arrive at the motoneurones over some 3–8 ms. Some corticospinal neurones can fire more than once in response to a single magnetic pulse and some motoneurones can fire more than once in the same MEP. Because the pathway involves synapses at both a cortical and spinal
Conclusion
Cervicomedullary stimulation allows the actions of corticospinal input on motoneurones in human subjects to be examined during a variety of tasks. Repetitive activation is likely to result in presynaptic changes which may alter the efficacy of the descending volley in some circumstances. Despite this, CMEPs provide the most direct assessment of the response to synaptic input of motoneurones in awake human subjects. They can reveal aspects of motoneurone behaviour that cannot be studied in other
Acknowledgements
I am grateful to Prof. S.C. Gandevia for comments on the manuscript. Much of the work described here was performed together with Prof. Gandevia and Drs. J.E. Butler and N.T. Petersen.
Janet Taylor is a Senior Research Fellow at the Prince of Wales Medical Research Institute and a conjoint Senior Lecturer in the Faculty of Medicine at the University of New South Wales, Sydney, Australia. She received her MD for research in neurophysiology from the University of New South Wales and was a postdoctoral fellow at the University of Alberta, Edmonton and at the Institute for Neurology, Queens Square, London. Her interests include the neural control of human movement, particularly
References (57)
- et al.
Modelling magnetic coil excitation of human cerebral cortex with a peripheral nerve immersed in a brain-shaped volume conductor: the significance of fiber bending in excitation
Electroencephalogr. Clin. Neurophysiol.
(1992) - et al.
Multiple firing of motoneurones is produced by cortical stimulation but not by direct activation of descending motor tracts
Electroencephalogr. Clin. Neurophysiol.
(1991) - et al.
Properties of human peripheral nerves: implication for studies of human motor control
Prog. Brain. Res.
(1999) - et al.
Control of forelimb muscle activity by populations of corticomotoneuronal and rubromotoneuronal cells
Prog. Brain Res.
(1989) - et al.
Electrical stimulation over the human vertebral column: which neural elements are excited?
Electroencephalogr. Clin. Neurophysiol.
(1986) - et al.
Changes in motor cortex excitability during ipsilateral hand muscle activation in humans
Clin. Neurophysiol.
(2000) - et al.
The monosynaptic reflex: a tool to investigate motor control in humans. Interest and limits
Neurophysiol. Clin.
(2000) - et al.
Nerve impulse propagation along central and peripheral fast conducting motor and sensory pathways in man
Electroencephalogr. Clin. Neurophysiol.
(1985) - et al.
Facilitatory effect of tonic voluntary contraction on responses to motor cortex stimulation
Electroencephalogr. Clin. Neurophysiol.
(1995) - et al.
Magnetic stimulation of the descending and ascending tracts at the foramen magnum level
Electroencephalogr. Clin. Neurophysiol.
(1997)
Clinical utility of magnetic corticospinal tract stimulation at the foramen magnum level
Electroencephalogr. Clin. Neurophysiol.
Presynaptic inhibition of elicited neurotransmitter release
Trends Neurosci.
Reflex origin for the slowing of motoneurone firing rates in fatigue of human voluntary contractions
J. Physiol. (Lond.)
Tonic vibration reflexes elicited during fatigue from maximal voluntary contractions in man
J. Physiol. (Lond.)
Non-monosynaptic transmission of the cortical command for voluntary movement in man
J. Physiol. (Lond.)
Responses of human motoneurons to corticospinal stimulation during maximal voluntary contractions and ischemia
J. Neurosci.
Motor cortex stimulation in intact man. II. Multiple descending volleys
Brain
Direct demonstration of the ouput of the human motor cortex induced by a fatiguing muscle contraction
Exp. Brain Res.
Methodological implication of the post-activation depression of the soleus H-reflex in man
Exp. Brain Res.
Comparison of activation of corticospinal neurons and spinal motor neurons by magnetic and electrical transcranial stimulation in the lumbosacral cord of the anaesthetized monkey
Brain
Motoneuron excitability and the F wave
Muscle Nerve
Supraspinal factors in human muscle fatigue: Evidence for suboptimal output from the motor cortex
J. Physiol. (Lond.)
Impaired response of human motoneurones to corticospinal stimulation after voluntary exercise
J. Physiol. (Lond.)
Role of small diameter afferents in reflex inhibition during human muscle fatigue
J. Physiol. (Lond.)
Reflex inhibition of human soleus muscle during fatigue
J. Physiol. (Lond.)
Changes in segmental and motor cortical output with contralateral muscle contractions and altered sensory inputs in humans
J. Neurophysiol.
On the mechanism of the post-activation depression of the H-reflex in human subjects
Exp. Brain Res.
Changes in presynaptic inhibition of Ia fibres at the onset of voluntary contraction in man
J. Physiol.
Cited by (105)
Corticospinal and spinal excitability during peripheral or central cooling in humans
2023, Journal of Thermal BiologyCortical and Subcortical Neural Interactions Between Trunk and Upper-limb Muscles in Humans
2020, NeuroscienceCitation Excerpt :Moreover, our results showed that subcortical (CMEP) responses of upper-limb muscles were modulated by trunk muscles contractions (Fig. 5D–F), contrary to our hypothesis, while corticospinal (MEP) response of upper-limb muscle during trunk muscles contractions were modulated (Fig. 4D–F), as we hypothesized. CMEP responses can be modulated by voluntary muscle contractions (Ugawa et al., 1994; Taylor et al., 2002; Taylor, 2006), similar to MEP responses (Hallett, 2007), which implies that background EMG activity affects both MEP as well as CMEP as our results confirmed during “active” conditions, ie., Trunk condition for the ES muscles and Hands condition for the FCR muscle (Figs. 4 and 5). However, since background EMG activity was not significantly different between the “remote effect” conditions and the rest state (Rest), i.e., ES muscle during Hands task and FCR muscle during Trunk task for both CMEP and MEP responses (Fig. 3), it can be considered that the observed modulation was an effect of remote muscle contraction.
Janet Taylor is a Senior Research Fellow at the Prince of Wales Medical Research Institute and a conjoint Senior Lecturer in the Faculty of Medicine at the University of New South Wales, Sydney, Australia. She received her MD for research in neurophysiology from the University of New South Wales and was a postdoctoral fellow at the University of Alberta, Edmonton and at the Institute for Neurology, Queens Square, London. Her interests include the neural control of human movement, particularly during muscle fatigue.