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Motor Evoked Potential
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Motor Evoked Potential
Motor Evoked Potential G Abbruzzese, University of Genoa, Italy ã 2010 Elsevier Ltd. All rights reserved.
Definition and History The term ‘motor evoked potential’ (MEP) most commonly refers to the action potential elicited by noninvasive stimulation of the motor cortex through the scalp. MEPs were originally reported following electrical stimulation (high voltage: 1000/1500 V, and short duration: 50/100 ms, pulses) of the motor cortex, first introduced by Merton and Morton. Subsequently, magnetic stimuli (rapidly transient fields with variable flow direction and intensity up to 1.5/2.5 Tesla) were introduced by Barker and collaborators to evoke MEPs. The latter method, transcranial magnetic stimulation (TMS), is largely preferred since magnetic fields pass unattenuated through the skull and scalp, without nociceptive activation, and penetrate easily into the brain generating an electrical current that activates the neural tissue.
Origin of MEPs In humans, MEPs can be recorded using surface electromyography from all skeletal muscles. They are characterized by a preferential contralateral distribution, short latency with proximo-distal progression, a variable amplitude (larger in distal muscles), and sensitivity to voluntary contraction. Such features support the notion that MEPs are mainly mediated by fast-conducting corticomotoneuronal connections projecting monosynaptically to the alpha-motoneurons in the contralateral spinal cord. It has been suggested that MEPs probably reflect the transynaptic activation of corticospinal neurons (including large pyramidal neurons and intracortical interneurons). Indeed, the recorded MEP is the sum of multiple descending volleys produced by a single high-intensity TMS pulse: a shorter latency direct D-wave (reflecting the direct excitation of the corticospinal axon) is followed by several later indirect I-waves (reflecting the indirect excitation of tangentially oriented axons in the deep cortical layers).
MEP Parameters MEP recordings are largely used in clinical practice as well as in experimental research and several parameters can be considered. The threshold refers to the lowest intensity of the magnetic stimulus able to evoke a MEP of minimal size during either muscle relaxation or contraction.
MEP threshold reflects the excitability of the corticospinal connections. The latency of the response, expressed in milliseconds, indicates the time taken by descending impulses to reach the target muscle. MEP latencies, therefore, vary as a function of the muscle distance (or subject height) and may be used to assess conduction along the central motor pathways (central motor conduction time, CMCT) by subtracting the peripheral conduction time. The peak-to-peak amplitude of the response is usually expressed as a percentage of the amplitude of the maximum response (direct M-wave) recorded in the same muscle on supramaximal electrical stimulation of the corresponding peripheral nerve. MEP size provides a measure of the portion of the spinal motoneurons discharged by TMS. This is clearly demonstrated by the observation that the MEP amplitude can be differently modulated by various motor tasks (reach, grasp, locomotion) and even by motor imagery and observation. When TMS is delivered during a voluntary contraction of the target muscle, the MEP is followed by a pause of the ongoing electromyogram (EMG) activity lasting up to 200–300 ms. This period of inhibition is defined ‘cortical silent period’ and depends on GABA-mediated mechanisms controlling cortical excitability. Finally, when a focal coil is used for TMS, MEP recordings can be used for noninvasive and painless mapping of the somatotopic representation of muscles within the motor cortex. The cortical maps are constructed by stimulating different points on the scalp at a constant intensity and analyzing the number of sites from which MEPs can be elicited in the target muscle.
Applications of MEPs Immediately after the introduction of the techniques of single-pulse TMS, it became evident that recording the MEP represented a reliable method to detect abnormalities of impulse propagation along the corticospinal tract. Afterwards, new techniques of paired-pulse or repetitive TMS have been progressively introduced to test the excitability of motor cortical areas. TMS, therefore, represents a noninvasive neurophysiological technique that allows studying both ‘conductivity’ and ‘excitability’ of the corticospinal system in man and may be regarded as an important new tool in clinical and experimental neurology. Several abnormalities of standard MEP parameters can be documented in clinical studies. The MEP can be
Motor Fluctuations
absent, the onset-latency can be delayed, and the amplitude can be decreased together with a raised threshold. Different mechanisms may underlie such changes: failure of conduction due to damage to the corticospinal tract, dispersion of multiple descending volleys causing desynchronization of alpha-motoneurons discharges, depression of cortico-motoneuronal excitability, or intracortical conduction block. MEP recordings are currently used in routine clinical practice in order to document the functional impairment (even subclinical) of central motor conduction in various neurological conditions such as demyelinating syndromes, amyotrophic lateral sclerosis, myelopathies, stroke, and cerebrovascular disorders. On the other hand, central conduction is usually normal in neurodegenerative disorders not involving the corticospinal tracts. Changes of the MEP size may reflect the efficiency of inhibitory systems within the human motor cortex. Using paired-pulse stimulation, it has been shown that the test MEP can be suppressed by subthreshold or suprathreshold conditioning stimuli delivered respectively a few milliseconds or 50–200 ms before (short- or long-interval intracortical inhibition – SICI or LICI). All these inhibitory phenomena are thought to depend on the activation of intracortical circuits, which are able to suppress the corticospinal output. The modulation of MEP amplitude by conditioning-test paradigms has been largely used to investigate motor cortical excitability in movement disorders (Parkinsonism, dystonia, chorea, dyskinesias). See also: Basal Ganglia, Functional Organization; Blepharospasm; Botulinum Toxin; Dystonia; Multiple System Atrophy; Paired Pulse TMS; rTMS; Single Pulse TMS; Theta Burst TMS.
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Further Reading Abbruzzese G and Trompetto C (2002) Clinical and research methods for evaluating cortical excitability. Journal of Clinical Neurophysiology 19: 307–321. Barker AJ, Jalinous R, and Freeston IL (1985) Non-invasive stimulation of human motor cortex. Lancet 2: 1106–1107. Berardelli A, Abbruzzese G, Chen R, et al. (2008) Consensus paper on short-interval intracortical inhibition and other transcranial magnetic stimulation intracortical paradigms in movement disorders. Brain Stimulation 1: 183–191. Curra` A, Modugno N, Inghilleri M, Manfredi M, Hallett M, and Berardelli A (2002) Transcranial magnetic stimulation techniques in clinical investigation. Neurology 59: 1851–1859. Day BL, Dressler D, Maertens de Noordhout A, et al. (1989) Electric and magnetic stimulation of human motor cortex: Surface EMG and single motor unit responses. The Journal of Physiology 412: 449–473. Di Lazzaro V, Oliviero A, Profice P, et al. (1999) Direct recordings of descending volleys after transcranial magnetic and electric motor cortex stimulation in conscious humans. Electroencephalography and Clinical Neurophysiology Supplement 51: 120–126. Hallett M (2000) Transcranial magnetic stimulation and the human brain. Nature 406: 147–150. Kujirai T, Caramia MD, Rothwell JC, et al. (1993) Corticocortical inhibition in human motor cortex. The Journal of Physiology 471: 501–519. Merton PA, Hill DK, Morton HB, and Marsden CD (1982) Scope of a technique for electrical stimulation of human brain, spinal cord, and muscle. Lancet 2: 597–600. Rothwell JC (1997) Techniques and mechanisms of action of transcranial stimulation of the human motor cortex. Journal of Neuroscience Methods 74: 113–122. Rothwell JC, Hallett M, Berardelli A, Eisen A, Rossini P, and Paulus W (1999) Magnetic stimulation: Motor evoked potentials. The International Federation of Clinical Neurophysiology. Electroencephalography and Clinical Neurophysiology Supplement 52: 97–103. Talelli P, Greenwood RJ, and Rothwell JC (2006) Arm function after stroke: Neurophysiological correlates and recovery mechanisms assessed by transcranial magnetic stimulation. Clinical Neurophysiology 117: 1641–1659.
Motor Fluctuations K A Chung and J G Nutt, Oregon Health & Science University, Portland, OR, USA ã 2010 Elsevier Ltd. All rights reserved.
Glossary COMT – An enzyme that catalyzes the degradation of catecholamines, including the neurotransmitters dopamine, epinephrine, and norepinephrine. MAOI – The brain and liver enzyme that normally breaks down the catecholamines norepinephrine, serotonin, and dopamine. Pharmacodynamics – The study of how drugs act at target sites of action in the body.
Pharmacokinetics – The study of the uptake, distribution, metabolism, biotransformation, and elimination of drugs by the body.
Definition and History Motor fluctuations are defined as variations in motor ability or performance over time, typically measured in
Motor Evoked Potential
Motor Evoked Potential G Abbruzzese, University of Genoa, Italy ã 2010 Elsevier Ltd. All rights reserved.
Definition and History The term ‘motor evoked potential’ (MEP) most commonly refers to the action potential elicited by noninvasive stimulation of the motor cortex through the scalp. MEPs were originally reported following electrical stimulation (high voltage: 1000/1500 V, and short duration: 50/100 ms, pulses) of the motor cortex, first introduced by Merton and Morton. Subsequently, magnetic stimuli (rapidly transient fields with variable flow direction and intensity up to 1.5/2.5 Tesla) were introduced by Barker and collaborators to evoke MEPs. The latter method, transcranial magnetic stimulation (TMS), is largely preferred since magnetic fields pass unattenuated through the skull and scalp, without nociceptive activation, and penetrate easily into the brain generating an electrical current that activates the neural tissue.
Origin of MEPs In humans, MEPs can be recorded using surface electromyography from all skeletal muscles. They are characterized by a preferential contralateral distribution, short latency with proximo-distal progression, a variable amplitude (larger in distal muscles), and sensitivity to voluntary contraction. Such features support the notion that MEPs are mainly mediated by fast-conducting corticomotoneuronal connections projecting monosynaptically to the alpha-motoneurons in the contralateral spinal cord. It has been suggested that MEPs probably reflect the transynaptic activation of corticospinal neurons (including large pyramidal neurons and intracortical interneurons). Indeed, the recorded MEP is the sum of multiple descending volleys produced by a single high-intensity TMS pulse: a shorter latency direct D-wave (reflecting the direct excitation of the corticospinal axon) is followed by several later indirect I-waves (reflecting the indirect excitation of tangentially oriented axons in the deep cortical layers).
MEP Parameters MEP recordings are largely used in clinical practice as well as in experimental research and several parameters can be considered. The threshold refers to the lowest intensity of the magnetic stimulus able to evoke a MEP of minimal size during either muscle relaxation or contraction.
MEP threshold reflects the excitability of the corticospinal connections. The latency of the response, expressed in milliseconds, indicates the time taken by descending impulses to reach the target muscle. MEP latencies, therefore, vary as a function of the muscle distance (or subject height) and may be used to assess conduction along the central motor pathways (central motor conduction time, CMCT) by subtracting the peripheral conduction time. The peak-to-peak amplitude of the response is usually expressed as a percentage of the amplitude of the maximum response (direct M-wave) recorded in the same muscle on supramaximal electrical stimulation of the corresponding peripheral nerve. MEP size provides a measure of the portion of the spinal motoneurons discharged by TMS. This is clearly demonstrated by the observation that the MEP amplitude can be differently modulated by various motor tasks (reach, grasp, locomotion) and even by motor imagery and observation. When TMS is delivered during a voluntary contraction of the target muscle, the MEP is followed by a pause of the ongoing electromyogram (EMG) activity lasting up to 200–300 ms. This period of inhibition is defined ‘cortical silent period’ and depends on GABA-mediated mechanisms controlling cortical excitability. Finally, when a focal coil is used for TMS, MEP recordings can be used for noninvasive and painless mapping of the somatotopic representation of muscles within the motor cortex. The cortical maps are constructed by stimulating different points on the scalp at a constant intensity and analyzing the number of sites from which MEPs can be elicited in the target muscle.
Applications of MEPs Immediately after the introduction of the techniques of single-pulse TMS, it became evident that recording the MEP represented a reliable method to detect abnormalities of impulse propagation along the corticospinal tract. Afterwards, new techniques of paired-pulse or repetitive TMS have been progressively introduced to test the excitability of motor cortical areas. TMS, therefore, represents a noninvasive neurophysiological technique that allows studying both ‘conductivity’ and ‘excitability’ of the corticospinal system in man and may be regarded as an important new tool in clinical and experimental neurology. Several abnormalities of standard MEP parameters can be documented in clinical studies. The MEP can be
Motor Fluctuations
absent, the onset-latency can be delayed, and the amplitude can be decreased together with a raised threshold. Different mechanisms may underlie such changes: failure of conduction due to damage to the corticospinal tract, dispersion of multiple descending volleys causing desynchronization of alpha-motoneurons discharges, depression of cortico-motoneuronal excitability, or intracortical conduction block. MEP recordings are currently used in routine clinical practice in order to document the functional impairment (even subclinical) of central motor conduction in various neurological conditions such as demyelinating syndromes, amyotrophic lateral sclerosis, myelopathies, stroke, and cerebrovascular disorders. On the other hand, central conduction is usually normal in neurodegenerative disorders not involving the corticospinal tracts. Changes of the MEP size may reflect the efficiency of inhibitory systems within the human motor cortex. Using paired-pulse stimulation, it has been shown that the test MEP can be suppressed by subthreshold or suprathreshold conditioning stimuli delivered respectively a few milliseconds or 50–200 ms before (short- or long-interval intracortical inhibition – SICI or LICI). All these inhibitory phenomena are thought to depend on the activation of intracortical circuits, which are able to suppress the corticospinal output. The modulation of MEP amplitude by conditioning-test paradigms has been largely used to investigate motor cortical excitability in movement disorders (Parkinsonism, dystonia, chorea, dyskinesias). See also: Basal Ganglia, Functional Organization; Blepharospasm; Botulinum Toxin; Dystonia; Multiple System Atrophy; Paired Pulse TMS; rTMS; Single Pulse TMS; Theta Burst TMS.
195
Further Reading Abbruzzese G and Trompetto C (2002) Clinical and research methods for evaluating cortical excitability. Journal of Clinical Neurophysiology 19: 307–321. Barker AJ, Jalinous R, and Freeston IL (1985) Non-invasive stimulation of human motor cortex. Lancet 2: 1106–1107. Berardelli A, Abbruzzese G, Chen R, et al. (2008) Consensus paper on short-interval intracortical inhibition and other transcranial magnetic stimulation intracortical paradigms in movement disorders. Brain Stimulation 1: 183–191. Curra` A, Modugno N, Inghilleri M, Manfredi M, Hallett M, and Berardelli A (2002) Transcranial magnetic stimulation techniques in clinical investigation. Neurology 59: 1851–1859. Day BL, Dressler D, Maertens de Noordhout A, et al. (1989) Electric and magnetic stimulation of human motor cortex: Surface EMG and single motor unit responses. The Journal of Physiology 412: 449–473. Di Lazzaro V, Oliviero A, Profice P, et al. (1999) Direct recordings of descending volleys after transcranial magnetic and electric motor cortex stimulation in conscious humans. Electroencephalography and Clinical Neurophysiology Supplement 51: 120–126. Hallett M (2000) Transcranial magnetic stimulation and the human brain. Nature 406: 147–150. Kujirai T, Caramia MD, Rothwell JC, et al. (1993) Corticocortical inhibition in human motor cortex. The Journal of Physiology 471: 501–519. Merton PA, Hill DK, Morton HB, and Marsden CD (1982) Scope of a technique for electrical stimulation of human brain, spinal cord, and muscle. Lancet 2: 597–600. Rothwell JC (1997) Techniques and mechanisms of action of transcranial stimulation of the human motor cortex. Journal of Neuroscience Methods 74: 113–122. Rothwell JC, Hallett M, Berardelli A, Eisen A, Rossini P, and Paulus W (1999) Magnetic stimulation: Motor evoked potentials. The International Federation of Clinical Neurophysiology. Electroencephalography and Clinical Neurophysiology Supplement 52: 97–103. Talelli P, Greenwood RJ, and Rothwell JC (2006) Arm function after stroke: Neurophysiological correlates and recovery mechanisms assessed by transcranial magnetic stimulation. Clinical Neurophysiology 117: 1641–1659.
Motor Fluctuations K A Chung and J G Nutt, Oregon Health & Science University, Portland, OR, USA ã 2010 Elsevier Ltd. All rights reserved.
Glossary COMT – An enzyme that catalyzes the degradation of catecholamines, including the neurotransmitters dopamine, epinephrine, and norepinephrine. MAOI – The brain and liver enzyme that normally breaks down the catecholamines norepinephrine, serotonin, and dopamine. Pharmacodynamics – The study of how drugs act at target sites of action in the body.
Pharmacokinetics – The study of the uptake, distribution, metabolism, biotransformation, and elimination of drugs by the body.
Definition and History Motor fluctuations are defined as variations in motor ability or performance over time, typically measured in