View source for Motor Evoked Potentials (MEP)

Motor evoked potentials (MEP) are signals recorded from muscles following stimulation of motor cortex. The stimulation may be applied to exposed motor cortex or applied transcranially through the skull. The stimulator may be magnetic or electrical.

== Motor Pathways==
MEPs are used to monitor the functional integrity of the corticospinal motor pathway. 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 corticospinal pathway can be subdivided into the lateral and anterior tracts, which mediate voluntary movement. 

These motor pathways consist of upper and lower motor neurons. The axons of the upper motor neurons originate in the primary motor cortex, 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, the upper motor neuron axons form synaptic connections with lower motor neurons, the peripheral neurons that innervate the skeletal muscles. The axons of the anterior tract do not cross the midline in the medulla. These axons typically cross the midline as they approach their target area and synapse with lower motor neurons that innervate the trunk muscles.

==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 5-9 pulses, an inter-pulse interval ranging from 2-4 ms, and a pulse width of 50 or 500 μs.

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 craniotomies, MEPs can also be induced by direct stimulation of the primary motor cortex. Without the resistance of the skull, direct cortical stimulation involves the use of much lower stimulation levels.  

4. Spinal cord stimulation. Also called neurogenic motor evoked potentials, these signals are generated in the rostral spinal cord and often recorded from electrodes place in the leg muscles. 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 multiple circuits, including 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==
MEPs are typically recorded from muscles (myogenic MEPs), as compound muscle action potentials, following tES of the primary motor cortex. The 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, often on upper and lower extremity muscle groups bilaterally. 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 3000 Hz for the high cut filter). The resistance of the recording electrodes in the muscle tissue should be low (< 5 kOhms). 

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. Therefore, total intravenous anesthesia (TIVA) - e.g., propofol - 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 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.

==Waveform==
The MEP waveform arises from direct and indirect activation of the pyramidal cells in the motor cortex.[3] Electrical or magnetic stimulation directly activates 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. 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 in muscle tissue involve synaptic transmission at the ventral horn, where upper motor neurons form synaptic connections with lower motor neurons.  Train stimulation produces multiple I-waves.

==Intraoperative monitoring==

==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.