You are in: eMedicine Specialties > Neurology > Electroencephalography and Evoked Potentials Motor Evoked PotentialsArticle Last Updated: Apr 24, 2006AUTHOR AND EDITOR INFORMATION
Author: Jasvinder Chawla, MD, Assistant Professor of Neurology, Director of Neurology Residency Training Program, Assistant Director of Neurology Clerkship Program, Department of Neurology, Loyola University of Chicago Stritch School of Medicine Jasvinder Chawla is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, and American Medical Association Editors: Sydney Louis, MD, Emeritus Professor, Department of Neurology, Brown University School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Norberto Alvarez, MD, Assistant Professor, Department of Neurology, Harvard Medical School; Consulting Staff, Department of Neurology, Boston Children's Hospital; Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital; Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants Author and Editor Disclosure Synonyms and related keywords: motor evoked potentials, MEPs, electrical stimulation of motor cortex, corticospinal connections, transcranial electrical stimulation, TES, transcranial magnetic stimulation, TMS, pyramidal tract, stimulation of the central nervous system, stimulation of the CNS, magnetic stimulation, electrical stimulation, electrophysiology of motor evoked potentials, electrophysiology of MEPs, clinical applications of motor evoked potentials, clinical applications of MEPs INTRODUCTION
Significant studies and landmarks on the effects of electricity on animals and human brains have been described in the past. The most famous pioneers were Penfield and Boldrey, who made direct observations by stimulating the human brain with weak electrical shocks in conscious patients who were undergoing surgery. They constructed the homunculus, a caricature of the human form with body parts drawn in sizes that are proportional to the presumed extent of their representations. From 1950-1970, several other studies of electrical stimulation of the exposed motor cortex (ie, during neurosurgical procedures) were performed in animals and humans to study the pyramidal pathway and other corticospinal connections. This technique was possible only in a surgical setting and not practical in a standard clinical environment. Noninvasive elicitation of motor evoked potentials (MEPs) was made possible by Merton and Morton in 1980. They designed a high-voltage transcranial electrical stimulator that excited the motor cortex using cutaneous electrodes, which were placed over the scalp. After transcranial electrical stimulation (TES), a contraction of contralateral muscles is recorded in a conscious subject. The usefulness of this method has remained limited by the local discomfort of the electrical currents that are applied over the scalp. An exception to this limitation is its use for intraoperative monitoring. The development of transcranial magnetic stimulation (TMS) in 1985 opened new possibilities for MEP studies. Barker et al created a new type of cortical magnetic stimulator, based on the principle of electromagnetic induction. The device was composed of a main unit, which contains a bank of heavy-duty capacitors; the hand-held part was freely movable so that it could be placed over any part of the body. The investigator holds the stimulating coil tangentially over the motor cortex and a technician holds a digitizing pen over the stimulating coil to record its 3-dimensional position, which allows stereotactic mapping of the motor cortex. Motor evoked potentials are recorded with surface electrodes, which are placed over small hand muscles. Although magnetic stimulation was first used to stimulate the peripheral nervous system (PNS) and muscles, cortical stimulation has become the focus of many studies. ANATOMICAL/FUNCTIONAL ORGANIZATION OF CORTICOSPINAL CONNECTIONS
Motor cortex The main motor cortical area is located on the anterior wall of the central sulcus and the adjacent portion of the precentral gyrus. This area corresponds to area 4 of Brodmann. It is rich in pyramidal neurons, which provide the anatomical substrates for the motor output function of area 4. Electrical stimuli over area 4 produce activation of contralateral muscles; the face, mouth, and hand muscles occupy about two thirds of the primary motor area. The size of cortical representation of muscles is less a function of the muscle mass than of precision of the muscle movements. Secondary and tertiary areas of motor function can be mapped roughly around the primary motor cortex. The primary motor cortex contributes more fibers to the corticospinal tract than any other region. Numerous observations support contributions from several other areas, including the frontal and parietal cortices. Ipsilateral projections are far less numerous than contralateral, estimated between 1.8-5.9% of corticospinal connections. Pyramidal tract Fibers of the corticospinal tract and corticobulbar tract originate from the sensorimotor cortex around the central sulcus. The human pyramidal tract contains over 1 million fibers. Most fibers are myelinated and have a small diameter (1-4 mm); only a small portion (3-5%) are large-diameter fibers (10-22 mm) that originate in Betz cells from area 4. In humans, only 5% of the fibers of the corticospinal tract originate from Betz cells in area 4. The concept of pyramidal pathways with fibers originating only from Betz cells in the primary motor cortex has been invalidated. A large part of the corticospinal neurons have nonmotor function, especially those originating in sensory or associative areas. Subcortical projections of the pyramidal pathway Pyramidal fibers converge into the corona radiata toward the posterior arm of the internal capsule. In the pons, they divide into multiple longitudinal pathways, which merge in the medulla oblongata to form the pyramidal tract after branching out efferences to motor nuclei of cranial nerves. At the junction between the medulla oblongata and the spinal cord, 75-90% of the fibers cross through the midline to constitute the crossed (ie, indirect) pyramidal pathway. The remaining fibers comprise the uncrossed (ie, direct) pyramidal pathway. A large part of direct pyramidal tract fibers actually cross the midline at the spinal cord level (ie, through the white anterior commissura), so that its projections are bilateral. BASIC PRINCIPLES OF STIMULATION OF THE CNS
Magnetic stimulation Magnetic stimulation of the nervous system can occur only in the setting of a rapidly changing magnetic field. Subjects exposed to a constant field strength (eg, magnetic resonance imaging [MRI]) do not experience stimulation of nervous tissue. The intensity of the secondarily produced electrical field in nervous tissue (and of the stimulation) is related to the speed of change in magnetic field strength. Formation of the magnetic pulse starts within the main unit of the stimulator, where a large bank of heavy-duty capacitors is electrically charged. When triggered, these capacitors rapidly discharge through a cable into the hand-held coil, producing a brief burst of high current (up to 4000 volts [V] or several 1000 amperes [A]). The current that moves through the hand-held coil produces a large magnetic field (1-3 T) that lasts only 50-200 milliseconds. The stimulating coil consists of tightly wound and well-insulated copper coil. As a result of the brief magnetic field induced from the coil, a secondary electric field that circulates in the opposite direction to the magnetic field is produced. The strength of the electric field is related in part to the first derivative of the magnetic flux over time: the more rapid the change in magnetic field, the stronger the intensity of the secondary electric field and nervous stimulation. Most commercially available stimulators can produce stimulations at a rate as high as 5 Hz, although some can produce repetitive stimulations as high as 50 Hz. A big advantage of magnetic stimulation over electrical stimulation is its ability to penetrate tissues regardless of electrical resistance. The drop-off is essentially the same for air, bone, fat, muscle, and saline. The magnitude, waveform, and rise time of the magnetic field are important parameters of the stimulation. The diameter, shape, and thickness of the coil are also important. Because of these multiple variables, the measurement of intensity of stimulation usually is expressed as a percentage of the maximal output of the stimulator. In choosing coils, the trade-off is between strength and focality of stimulation. Coil diameter may vary between 5 cm and 15 cm. Large-diameter coils stimulate over a wider area but are less focal than small-diameter coils. With the round coils, the highest intensity electric field is measured at the edges of the coil with lower intensities in the center. To obtain more focality, use of a butterfly (also called "figure of 8" coil) is recommended. Their focality makes them particularly suitable for the performance of mapping out the upper limb and hand musculature. Electrical stimulation Electrical stimulators have a simpler design than magnetic stimulators. The stimulation is transmitted through cutaneous electrodes. The main advantage is a better depth of penetration, allowing direct spinal cord stimulation. The main limitation is the local discomfort that is created by the stimulation. Electrical stimulators contain a capacitor that produces constant current, high-voltage pulses of brief duration for percutaneous stimulation. The output current range is 0-1000 milliamperes, from a source voltage as high as 400 V. The pulse width range can be varied from 50 milliseconds to 2 milliseconds. The voltage is kept constant during the stimulation, but the intensity of stimulation depends on the skin impedance. Some electrical stimulators can deliver repetitive (2-9) pulses, which have been shown to facilitate induction of motor responses. These stimulators can be particularly useful for monitoring the spinal cord during surgical procedures. ELECTROPHYSIOLOGY OF MOTOR EVOKED POTENTIALS
Generation of motor evoked potentials Electrical stimulation of the exposed cortex has been studied in animal models for several decades. An initial D (ie, direct) wave is followed by several I (ie, indirect) waves, which come at periodic intervals (usually about 1 millisecond). D-waves represent the direct excitation of corticospinal tract neurons, while I-waves reflect indirect depolarization of the same axons via corticocortical connections. This propagation pattern of descending impulses has been confirmed and demonstrated in humans after cortical magnetic stimulation by epidural recordings during surgical procedures. As these multiple volleys descend the corticospinal tracts, they summate at the anterior horn cells in the spinal cord. Although the first D-wave may not bring the alpha motoneuron to fire, summation of subsequent I-waves may reach the threshold and trigger neuronal firing. While this summation may result in a single discharge, the spinal motoneuron also may fire repeatedly after a sufficiently intense, single cortical stimulation. Consequently, the amplitude of an evoked potential after cortical stimulation may be larger than the response produced by supramaximal stimulation of the corresponding peripheral nerve. Facilitation of motor evoked potentials The excitability threshold for eliciting MEPs can be decreased by performing a voluntary contraction of the target muscle. In parallel to such threshold changes, a decrease of latency of the response to stimulation (2-6 ms) can be observed with respect to the MEPs that are obtained with no contraction of the target muscle. The origin of this facilitation remains controversial. Some authors ascribe it, at least partially, to modifications of cortical excitability. Others support a segmental spinal mechanism, which seems to play a major role. The conduction speed as measured in several studies (60-70 m/s) agrees with propagation through fast corticospinal tract axons. Safety issues Heating: Magnetic stimulation creates intense electrical discharges. Repetitive stimuli make the coil hot, and this can be a problem in clinical practice. Commercially available equipment has auto-shutdown systems and temperature monitors that indicate coil overheating; these features protect patients but may prolong the duration of the procedure by 100-200%. This inconvenience may be reduced by using several interchangeable coils or water-cooled coils. Noise: The magnetic stimulator generates a high-intensity noise artifact that lasts about 1-2 milliseconds. Although no acoustic damage has been documented in humans, ear protectors attenuate the sound pressure level and have been recommended. Seizure: Seizures are reported rarely in seizure-prone individuals. Stimulation at a high rate clearly can induce seizures even in healthy subjects, but the effect of low-rate stimulation is controversial. Some recent studies suggest a beneficial role of TMS in decreasing the frequency of epileptic seizures. Patients with epilepsy still are excluded routinely from magnetic stimulation studies. Kindling (ie, induction of permanent seizure focus) has never been induced in animals with stimulation at less than 10 Hz despite prolonged stimulation. PRACTICAL METHODOLOGY OF TRANSCRANIAL MAGNETIC AND ELECTRIC STIMULATION
Transcranial magnetic stimulation Contraindications
Stimulation: For circular coils, the direction of the current in the coil (clockwise or counterclockwise) must be selected first.
Response recording: MEPs usually are recorded with surface electrodes in target muscles.
MEP parameters
Practical methodology of transcranial electrical stimulation After skin preparation with acetone, stimulation is performed using cutaneous electrodes. Specific montages allow preferential stimulation of specific muscle groups. For example, MEPs are induced preferentially in hand muscles if the anode is placed 7 cm away from the vertex on the line joining the vertex to the tragus and the cathode is placed over the vertex. TES cannot stimulate individual muscles selectively. Conversely, TMS can stimulate discrete muscles or muscle groups preferentially. Responses are recorded in target muscles with surface or coaxial electrodes, as in TMS. CLINICAL APPLICATIONS OF MEPS
Multiple sclerosis MEP studies may be useful for 2 applications in multiple sclerosis (MS): as a diagnostic tool and as an index of corticospinal pathway dysfunction. MS diagnosis is based on the detection of multiple inflammatory, demyelinating white matter lesions, which are disseminated in time and space. In many patients, clinical assessment is insufficient, and paraclinical studies must be performed. These tests, such as MRI, cerebrospinal fluid (CSF) studies, visual evoked potentials (VEPs), and somatosensory evoked potentials (SEPs), may be used in conjunction with MEP studies to establish the diagnosis of MS when clinical findings are equivocal. In MS, a prolongation of CMCT may be explained by reduced stimulus conduction in the large-diameter corticospinal fibers; this phenomenon is caused by demyelination or incomplete remyelination. The temporal stimulus summation that is necessary for large motor anterior cells to discharge may be reduced. Dispersion of the conduction velocity of individual axons may be increased. MEPs are more sensitive than SEPs in MS, with an overall incidence of abnormality greater than 70%. In patients with definite MS, prolonged CMCT to lower extremities muscles is observed in 77-89% of patients, while abnormal VEP findings are observed in 74.4% of these patients. Recording MEPs in upper and lower extremities increases the sensitivity of the study, as lesions that are caudal to C8 can be detected. MEP duration is increased in patients with definite MS, which is compatible with increased temporal dispersion of the impulses that arrive at the motoneuron pool. In patients with definite MS, a correlation between CMCT and manual dexterity (but not with muscle strength) has been reported. The lack of correlation between CMCT and isometric muscle strength, hyperreflexia, or spasticity is attributed to the role of fast-conducting pyramidal tract in generating rapid phasic muscle action important for fine motor skills, but not for strength of muscle contraction, which can be carried by different descending tracts. MEP studies can be useful for monitoring the electrophysiological correlates of clinical response to treatment. In patients who show clinical improvement after steroid treatment, CMCT decreases toward normal values and can remain stable if disease activity is controlled. Cervical myelopathy MEP recordings from thenar and tibialis anterior muscles appear to be especially sensitive (84-100%) for detecting cervical myelopathy. MEP studies may be more sensitive than SEPs for detecting cervical myelopathy, possibly because cervical spondylosis (often with prominent bony spurs projecting from the vertebral body) predominantly involves the anterolateral quadrant of the spinal cord. This potentially could affect descending motor tracts in the corticospinal tract, leaving dorsal column pathways relatively unaffected. MEP studies can indicate whether lesions identified on anatomic CT or MRI studies have neurophysiological significance. Spinal cord injury Monitoring MEPs is a significantly reliable technique to assess spinal cord ischemia during thoracoabdominal aortic aneurysm repair. Prognosis of motor recovery is determined by the severity of spinal cord injury (SCI). Patients with complete SCI usually show limited improvement. In cases of incomplete SCI, as many as 74% of patients show significant improvement, and 59% have a complete recovery. The prognostic value of MEP studies in SCI is limited, probably because of the spinal shock in the acute phase. Among 10 patients who presented within 2 weeks after injury, MEPs were absent below the level of the lesion in 7 patients with complete paraplegia; MEPs remained absent 6 months later. In 3 patients with incomplete quadriplegia and subsequent recovery, MEPs were recordable in 2 subjects and absent in 1 subject. Among 25 patients studied within 6 hours after onset and monitored over 6 weeks, MEPs were not obtained in patients without preceding clinical evidence of voluntary contraction. Motor neuron disease Reported abnormalities include absence of response, prolongation of latency, enhanced cortical threshold and, most commonly, low-amplitude polyphasic responses. The degeneration of spinal motoneurons explains the tendency of MEPs to be of short duration. The average survival duration of patients with normal CMCT is not significantly different from those with abnormal CMCT. MEP studies have limited use in the diagnosis of amyotrophic lateral sclerosis. They do not provide significant prognostic information. Stroke motor recovery prognosis Recovery of motor function after a stroke varies. In the first days, motor prognosis is difficult to establish from clinical and even head CT scan data. Clinical application of MEPs in stroke is done mainly to evaluate the prognosis for recovery. Most studies suggest that the early presence of MEPs after stroke indicates a good recovery of daily functions. Absence of MEPs is associated with variable outcomes, usually poor. For patients who do not respond to cortical stimulation at stroke onset, the risk of poor functional recovery at 12 months is high and the probability of stroke-related death during this period greater than for patients who do respond. Prolonged CMCT is found mainly in subcortical lesions. Severe cortical strokes are more likely to result in absent MEPs. MEPs have a better predictive value for functional prognosis than SEPs. OTHER CLINICAL APPLICATIONS OF MEPS
Parkinson disease Basic research findings support a decrease of the excitatory drive from the thalamus, which projects to the cortex in Parkinson disease, and an enhanced cortical excitability. Rapid (5 Hz) repetitive magnetic stimulation (rTMS) over the dominant hemisphere was reported to shorten reaction time and movement time in Parkinson disease. Some report improvement that lasted 20 minutes after rTMS. Other groups reported negative results. The use of rTMS probably will be limited to electrophysiological studies of cortical excitability in Parkinson disease; its therapeutic use remains anecdotal. Writer's cramp Handwriting was reported to be improved after 1 Hz rTMS over the left hemisphere. The decreased intracortical inhibition in individuals with writer's cramp was corrected after 1 Hz rTMS. Epilepsy Some believe that TMS induces seizures when evaluating patients with partial epilepsy. TMS actually appeared poorly epileptogenic at low frequencies of stimulation (induction rate in epileptic patients: 0-92%). To what extent low-rate TMS may induce seizures, even in susceptible individuals, remains questionable. rTMS can provoke seizures, but the effect depends on the individual (epileptic vs nonepileptic), antiepileptic treatment, and stimulus type (intensity-frequency). Therapeutic benefit of rTMS: Intracortical inhibition is reduced in epileptic patients. As low-rate rTMS can increase intracortical inhibition, this paradigm was used as a treatment in patients with intractable epilepsy. A substantial reduction of seizure frequency was reported in an open study. Determination of language dominance before surgical procedures: Induction of speech arrest after stimulation of the dominant hemisphere is possible, but the success rate reported varies between 50% and 100% of subjects. This seems to depend at least partly on the stimulation technique (ie, coil type) used, but remains to be clarified fully in further studies. Surgical monitoring The standard method of surgical spinal monitoring has been SEP studies. Special stimulators that can provide 3-4 short-interval, successive pulses can overcome the reduction in evoked potentials caused by anesthetic agents. Special anesthetic methods using ketamine, etomidate, or propofol are required. Since myogenic MEPs can be affected by most anesthetic agents and muscle relaxants, anesthesiologists are therefore required to properly understand MEPs and to manage anesthesia carefully. Electrical stimulation has been used widely to stimulate motor nerves and the spinal cord during surgery. TES is currently under investigation for this use. RESEARCH APPLICATIONS OF MEPS
Double-pulse studies Intracortical inhibition (ICI) or facilitation (ICF) defines the inhibitory or facilitatory action between areas of the motor strip itself or between cortical areas of the same hemisphere. ICI and ICF can be elicited by using a double-pulse (DP) technique with focal stimulations (see Picture 1). With intervals between 1 and 5 milliseconds, DP studies test the influence of short-range inhibitory GABA-ergic interneurons. With intervals between 7 and 30 milliseconds, DP studies measure the influence of short-range excitatory interneurons. DP studies have been useful in evaluating the effect of rTMS on cortical excitability in several neurological diseases. Interhemispheric conditioning studies Interhemispheric inhibition can be demonstrated in humans by studying transcallosal effects of magnetic stimulation on motor cortical excitability (see Picture 2). Two stimulating coils are positioned at the optimal positions ("hot spots") on both hemispheres. A conditioning stimulus is performed to activate one hemisphere with a preset delay before a test stimulation over the other hemisphere. Previous studies have suggested that in right-handed individuals, the inhibition after stimulation of the "dominant" hemisphere was more marked than after stimulation of the "nondominant hemisphere." Interhemispheric inhibition appears to be decreased significantly in patients with an abnormality of the anterior part of the corpus callosum. Mapping studies Magnetic stimulation studies can address specifically the issue of cortical reorganization by mapping procedures with focal stimulations using "figure-of-8" coils (see Picture 3). Single pulses are used to sequentially stimulate successive positions over the scalp, usually 1 centimeter apart. The intensities or latencies of responses then can be plotted on a 2-dimensional map, which is obtained in reference to the vertex or other anatomical landmarks. A refined technique, which uses frameless stereotactic localization of the stimulating coil and of the subject's head, allows the researcher to project the TMS maps directly onto 3-dimensional brain reconstruction images. TMS mapping has been used successfully in studying the changes of cortical sensorimotor maps in response to experimental injury to the PNS or CNS. TMS mapping provided evidence that changes in cortical motor maps may, in some situations, occur rapidly (ie, during motor learning in healthy volunteers) or much more slowly (eg, after peripheral nerve transposition). Stereotactic TMS mapping can be co-registered to functional MRI, positron emission tomography (PET) scan, or electroencephalogram (EEG) for various assessments of brain function. MULTIMEDIA
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Motor Evoked Potentials excerpt Article Last Updated: Apr 24, 2006 | |||||||||||||||||||||