Motor Evoked Potentials (MEP)

Introduction

Motor evoked potentials (MEPs) are electrical signals recorded from muscle tissue in response to stimulation of the motor cortex. The stimulation may be magnetic or electrical and applied directly to the motor cortex or applied transcranially through the skull.

Motor Pathways

MEPs are used to monitor the functional integrity of the descending motor pathways, which mediate voluntary movement of the face, limbs, and torso, respectively. The descending motor pathways can be divided into a lateral system and a medial system. The lateral system includes the corticospinal tract and a smaller rubrospinal tract. The corticospinal pathway originates mainly in the primary motor cortex (Brodmann’s area 4), but fibers from other regions, such as the premotor, the supplemental motor, and somatosensory cortices contribute as well. The descending motor pathways consist of upper and lower motor neurons, as well as interneurons at the level of the spinal cord. The cell bodies of the upper motor neurons lie in the motor cortices, whereas the cell bodies of lower motor neurons lie in the brain stem and spinal cord. Each lower motor neuron gives rise to one axon that exits the spinal cord and passes through a ventral nerve root. The ventral nerve roots form a fiber bundle with the dorsal nerve roots, which together form a peripheral nerve bundle. Each lower motor axon passes through through the peripheral nerve bundle and then arborizes to innervate multiple muscle fibers. Each synaptic connection forms an excitatory synapse. One lower motor neuron and the muscle fibers that it innervates is known as a motor unit. There are hundreds of motor units within a single muscle each of which occupying a space of approximately 5 to 11 mm in diameter (Leppanen et al., 2005).

The corticospinal system. The corticospinal pathway is composed primarily of a lateral system and a smaller anterior system, and these innervates the distal limbs. The axons of the lateral tract descend through the internal capsule and project to the lower medulla. The upper motor neurons of the lateral tract cross the midline to the contralateral side and descend to the lateral column of the dorsal horn. After reaching the ventral horn of the spinal cord, these motor neuron axons form synaptic connections with lower motor neurons, often via local interneurons. The axons of the anterior tract do not appear to cross the midline.

The medial system. The medial system innervates the trunk and proximal limb muscles. Fibers in the motor cortices descend bilaterally and do not cross the midline.

The corticobulbar system. The upper motor neurons of the corticobulbar tract descend to the brain stem and innervate several nuclei for cranial nerves that control the facial muscles, including cranial nerves V, VII, IX, X, and XII. In most cases, the corticobulbar tract innervates the facial motor nuclei, bilaterally, including those nuclei involved in swallowing, speech, chewing and tongue movement. In contrast, upper motor neurons innervate the nuclei the lower facial nuclei and the hypoglossal nerves on the contralateral side of the body.

The basal ganglia. The basal ganglia is a set of subcortical structures that help to control movement. Many now view the basal ganglia as part of the upper motor systems because the basal ganglia modulates these systems. The structures of the basal ganglia typically include the caudate/putamen (striatum), globus pallidus internal (GPi) and external (GPe) segments, subthalamic nucleus, substantia nigra pars compacta (SNc) and reticulata (SNr). The cortical motor areas and SNc provide input to the striatum. The projection neurons of the striatum are connected to the GPi and the SNr via the direct and indirect pathways. The projection neurons of the direct pathway predominantly express dopamine D1 receptors, whereas those of the indirect pathway predominantly expresses dopamine D2 receptors. The indirect pathway includes the GPe and the subthalamic nucleus. The GPi and the SNr provide tonic inhibitory feedback to the motor cortex via the thalamocortical pathway.

Stimulation

1. Transcranial electrical stimulation (tES). tES is a commonly used, non-invasive technique for generating MEPs. Stimulating electrodes for tES are placed on the scalp or subcutaneously above the primary motor cortex. Electrical current is then applied to the head to alter neuronal activity in the brain. However, due to the thickness and high resistance of the skull bone, only a small percentage of current reaches the brain tissue. Therefore, to record MEPs from muscle tissue, the stimulus strength must be set high enough to overcome that resistance and activate the underlying motor pathways. We call this type of stimulation supra-maximal, as the stimulus is higher than that required for the recruitment of all muscle fibers around the recording electrode. Train stimulation is required to elicit reliable MEPs under anesthesia, requiring the use of a multi-pulse stimulator.

The stimulating electrodes for MEPs are placed at C1 (for right extremities) and C2 (for left extremities) using the 10-20 system. Unlike the cathodal stimulation used for SSEPs, clinicians use anodal (+) stimulation to elicit MEPs. Electrical current flow from the anode to the cathode is more effective at depolarizing the pyramidal neurons of the primary motor cortex due to the more vertical organization of these cells.[1] Typical tES parameters used to elicit myogenic MEPs include intensities ranging from ~400-600 V, a train of 4-9 pulses, an inter-pulse interval ranging from 2-4 ms, and a pulse width between 50-75 μs (but higher values are used in other countries).

2. Transcranial magnetic stimulation (TMS). TMS is another non-invasive technique for generating MEPs. By applying a magnetic field over the scalp, TMS can induce electrical currents in brain tissue in awake patients. One disadvantage of TMS, however, is that TMS-induced MEPs are suppressed under anesthesia.

3. Direct cortical stimulation. For some brain surgeries, such as tumor resections, the surgeon will directly stimulate the motor cortex or adjacent subcortical tissue to elicit a MEP. Direct cortical stimulation requires a much lower stimulation intensity because of the absence of the skull. In most cases, it is necessary to find the lowest stimulation threshold for MEPs, which provides important information on the proximity of the neural probe to the motor pathways. The lower the stimulation intensity, the closer the probe is to the motor pathways. The position of the neural probe relative to the homunculus will normally dictate which muscle groups are activated.

4. Spinal cord stimulation. Also called neurogenic motor evoked potentials, these signals are evoked in the rostral spinal cord and often recorded from electrodes on peripheral nerves in the legs. However, this technique is not widely used for monitoring the motor pathways because the recordings are not easy to interpret. Neurogenic MEPs likely arise from retrograde activation of the sensory pathways [2], in addition to the corticospinal tract. Other forms of spinal cord stimulation are used to test the efficacy of spinal cord stimulators during implantation. Spinal cord stimulators are typically placed in the thoracic spine and used for the treatment of neuropathic pain and other chronic pain disorders.

Recording Techniques

1. Recording Sites and Parameters. MEPs are typically recorded from muscles (myogenic MEPs), as compound muscle action potentials, following tES of the primary motor cortex. Myogenic MEPs are recorded on different muscle groups associated with the myotome. The myotome is a set of muscle groups innervated by a single motor neuron, which together is known as a motor unit. Myogenic MEPs are recorded with needle or surface electrodes on bilateral muscle groups of the upper and lower extremities. The placement of the electrodes on specific muscles depends on the surgical procedure and which motor unit is potentially at risk. For an anterior cervical discectomy involving C6-7, for example, electrodes would be placed on the biceps and triceps, bilaterally, as these muscle groups are innervated by lower motor neurons that exit the spinal cord at C6-7.

MEPs are large amplitude signals that do not require averaging, as SSEPs do. The signals are filtered at the high and low frequency range to eliminate electrical artifacts (e.g., 10 Hz for the low-cut filter and 2000-3000 Hz for the high cut filter). The resistance of the recording electrodes in the muscle tissue should be low (< 5 kOhms). Myogenic MEPs can be repeated at a rate of 0.5-2 Hz.

2. Surgical and medical considerations. Some considerations for recording MEPs include the use of anesthetics and neuromuscular blocking agents. For example, myogenic MEPS are very sensitive to inhalation anesthetics, which limits the use of these anesthetics during IONM. Gas anesthesia strongly influences synaptic transmission. Inhalation anesthetics reduce the amplitude and prolong the latency of MEPs, and this affect becomes more pronounced when multiple synapses are involved, as is the case for myogenic MEPs, which involve the upper and lower motor neurons as well as interneurons in the spinal column. Intravenous anesthetics have a similar effect on MEPs but to a lesser degree. Total intravenous anesthesia (TIVA) - e.g., propofol and narcotic cocktails - is preferred in most cases, particularly those involving the spinal cord at L2 vertebrae and above. Propofol acts as a positive allosteric modulator of the GABA-A receptor, and it may also act directly as an agonist. For cases involving L3 and below, corresponding to the cauda equina, it is acceptable to supplement the TIVA with gas anesthesia, also known as half MAC (Monitored Anesthesia Care).

Muscle relaxants are normally needed for the intubation and for exposure of the surgical site. As expected, neuromuscular blockers, such as Rocuronium and Succinylcholine, strongly suppress myogenic MEPs. Rocuronium (ROC) is a commonly used, non‐depolarizing neuromuscular blocker. ROC is a nicotinic receptor antagonist that has a duration of ~30-60 min at standard doses. In contrast, succinylcholine is a depolarizing neuromuscular blocker with a rapid onset and elimination, which can be used as an alternative to ROC.

MEPs are also influenced by neurological disorders, such as myasthenia gravis, botulinum toxin treatments for dystonia, and muscular dystrophy. Therefore, it is important to understand the patient's medical history when preparing for cases that involve MEPs.

Waveform

The MEP waveform arises from direct and indirect activation of the pyramidal cells in the motor cortex.[3] Electrical and magnetic stimulation directly activate the pyramidal cells. MEPs from these upper motor neurons can be recorded directly in the spinal cord as near-field potentials called ‘D-waves,’ as there are no synaptic connections between the activated neurons in the cortex and the recording site, or far-field potentials from muscles of the upper and lower extremities. Indirect synaptic activation of the pyramidal neurons from activated local interneurons also contributes to the MEP. These components of the MEP are called ‘I-waves.’ The number of I-waves in the MEP waveform, and the interval between each I-wave, depend on the number of synapses or synaptic delays in the circuit between the cortical interneurons and the activated pyramidal cell.

MEPs recorded from muscle tissue also involve another level of synaptic integration at the ventral horn, where upper motor neurons form synaptic connections with lower motor neurons. As a result, pulse-train stimulation tends to produce a multi-phasic waveform, which reflects greater complexity of the far-field potentials recorded from muscles.

Intraoperative Monitoring

1. Data acquisition: Baseline MEP responses should be established shortly after the patient is sedated, but the exact timing depends on the type of surgery being monitored. For example, for anterior cervical spinal surgeries, it is ideal to record baseline responses prior to neck and shoulder positioning because these manipulations could adversely affect spinal cord function and exacerbate the patient's condition. For posterior lumbar spinal surgeries, the baseline responses can be recorded after the patient has been flipped to the prone position. In this case, patient positioning is less likely to cause neurological damage because the nerve roots are mainly at risk, not the spinal cord. MEP tests should be run throughout the surgical procedure and should correspond to surgical events such as the incision, insertion of hardware, decompression, closure, etc.

2. Alarm criteria: Similar to the criterion used for SSEPs, a 50% decrease in MEP amplitude is cause for concern. The amplitude of the myogenic MEP is measured from the most positive peak to the most negative peak in the waveform. The MEP amplitude and waveform shape can vary over time, even in the absence of changes in corticospinal tract function. Therefore, some clinicians have argued that the criterion of 50% decrease in amplitude is not always reliable and can lead to false alarms.[4] However, an 80-100% drop in the MEP signal would certainly constitute an alarm and should be reported to the surgeon.

References

1. Vogel RW (2017). Understanding Anodal and Cathodal Stimulation. The ASNM Monitor, The American Society of Neurophysiological Monitoring. https://www.asnm.org/blogpost/1635804/290597/Understanding-Anodal-and-Cathodal-Stimulation

2. MacDonald DB (2006). Intraoperative motor evoked potential monitoring: overview and update. J Clin Monit Comput 20:347–377.

3. Legatt AD, Emerson RG, Epstein CM, MacDonald DB, Deletis V, Bravo RJ, López JR (2016). ACNS Guideline: Transcranial Electrical Stimulation Motor Evoked Potential Monitoring. J Clin Neurophysiol 33(1):42-50.

4. Langeloo DD, Journée HL, de Kleuver M, et al. (2007). Criteria for transcranial electrical motor evoked potential monitoring during spinal deformity surgery: A review and discussion of the literature. Neurophysiol Clin 37:431–439.