Stimulation at the cervicomedullary junction in human subjects

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Abstract

In awake human subjects, corticospinal axons can be activated at the level of the cervicomedullary junction by electrical or magnetic stimulation. Such stimuli evoke single descending volleys which activate motoneurones and elicit responses in muscles of the upper limb. These responses (cervicomedullary motor evoked potentials, CMEPs) have a large monosynaptic component and can be used to test motoneurone excitability in a variety of tasks. CMEPs can be elicited in resting muscle and during all strengths of voluntary contraction. Examination of CMEPs during and after voluntary contractions reveals changes in motoneurone excitability but also suggests activity-dependent changes in the efficacy of the corticospinal pathway. Because they test the same subcortical pathway as transcranial magnetic stimulation, but are unaffected by altered excitability at a cortical level, CMEPs often offer the most appropriate comparison to allow interpretation of changes in motor evoked potentials. The advantages and disadvantages of stimulation at the cervicomedullary junction as a test of motoneurone excitability are reviewed.

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

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    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.

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