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Induction Of Plasticity In The Human Motor Cortex By Paired Associative Stimulation.
K. Stefan, E. Kunesch, L. Cohen, R. Benecke, J. Classen
Published 2000 · Psychology, Medicine
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Current models of motor cortical plasticity, developed in studies on experimental animals, emphasize the importance of the conjoint activity of somatosensory afferents and intrinsic motor cortical circuits. The hypothesis that an enduring change in excitability in the cortical output circuitry can be induced in the human motor cortex by a paired-stimulation protocol was tested. Low-frequency median nerve stimulation was paired with transcranial magnetic stimulation (TMS) over the optimal cranial site for stimulating the abductor pollicis brevis muscle (APB). This protocol induced an increase in the amplitudes of the motor evoked potentials (MEPs) in the resting APB as well as a prolongation of the silent period measured in the precontracted APB following TMS; amplitudes of MEPs measured in voluntary contraction remained unchanged. Experiments testing the excitability of spinal motoneurons using F-wave studies and electrical stimulation of the brainstem suggested that the site of the plastic changes was within the motor cortex. The increases in resting amplitudes and silent period duration were conditionally dependent on the timing between the afferent and the magnetic stimulation in that they were present when events elicited by afferent and magnetic stimulation were synchronous at the level of the motor cortex. Plasticity induced by paired stimulation evolved rapidly (within 30 min), was persistent (minimum duration 30-60 min) yet reversible, and was topographically specific. This combination of features and the similarity to properties of induced enduring changes in synaptic efficacy, as elucidated in animal studies, leads us to propose that the induced plasticity may represent a signature of associative long-term potentiation of cortical synapses or closely related neuronal mechanisms in the human cortex.
This paper references
Effects Rothwell JC . Techniques and mechanisms of action of transcranialof diphenylhydantoin on motor potentials evoked with magnetic stimulation of the human motor cortex
N Mavroudakis (1994)
Techniques and mechanisms of action of transcranial stimulation of the human motor cortex
J. Rothwell (1997)
of preand postsynaptic activity regulates functional connectivity in the visual cortex
E Kunesch (1994)
Long-lasting potentiation of synaptic transmission requires postnaptic modifications in the neocortex
A. Baranyi (1987)
Fusimotor control of proprioceptive feedback during locomotion and balancing: can simple lessons be learned for artificial control of gait?
M. Hulliger (1993)
Unpredictable and dependent alterations of movement representations in primary motor uncontrollable stress impairs neuronal plasticity in the rat cortex of adult squirrel monkeys
RJ Nudo (1996)
Acquisition of motor behavior in vertebrates. Cambridge (MA)
New York: adult auditory cortex induced by Hebbian covariance
E G Jones (1986)
Dendritic spine changes associated with during motor skill learning
F Engert (1995)
Modulation of muscle responses evoked by transcranial magnetic stimulation during the acquisition of new fine motor skills.
A. Pascual-Leone (1995)
Parallel augmentation of hippocampal long - term potentiation , theta of the monkey motor cortex : input - output relations
PM Rossini (1972)
Regulation of Synaptic Efficacy by Coincidence of Postsynaptic APs and EPSPs
H. Markram (1997)
Fusimotor control of proprioceptive feedback during locomotion and balancing: can simple lessons be learned for artificial Chang FL, Hawrylak N, Greenough WT. Astrocytic and synaptic control of gait?
M Hulliger (1993)
Receptive-field plasticity in the adult auditory cortex induced by Hebbian covariance
S. Cruikshank (1996)
Hebbian synapses in visual cortex
A. Kirkwood (1994)
Increases in excitability of neurons of the motor cortex of cats after rapid acquisition of eye blink conditioning
S. Aou (1992)
Common forms of synaptic plasticity in the hippocampus and Fregnac Y ,
A Kirkwood (1987)
Shared neural substrates controlling hand movements in human motor cortex.
J. Sanes (1995)
Information processing within the motor cortex. II. Intracortical connections between neurons receiving somatosensory cortical input and motor output neurons of the cortex
T. Kaneko (1994)
Long-term reorganization of human motor cortex driven by short-term sensory stimulation
S. Hamdy (1998)
Long-term potentiation of thalamic input to the motor cortex induced by coactivation of thalamocortical and corticocortical afferents.
A. Iriki (1991)
Long-term potentiation in the motor cortex.
A. Iriki (1989)
Large-scale reorganization at multiple levels synaptic enhancement in hippocampal brain slices
S L Florence (1986)
Information processing within the motor cortex Substrates and mechanisms for receiving somatosensory cortical input and motor output neurons learning in motor cortex of the cortex
T Kaneko (1994)
Long‐term changes in synaptic strength along specific intrinsic pathways in the cat visual cortex.
J. Hirsch (1993)
Synaptic plasticity in rat hippocampal slice cultures: local "Hebbian" conjunction of pre- and postsynaptic stimulation leads to distributed synaptic enhancement.
T. Bonhoeffer (1989)
Large-scale reorganization at multiple levels of the somatosensory pathway follows therapeutic amputation of the hand in monkeys
Sherre L. Florence (1995)
Long - term potentiation of horizontal connections provides a mechanism to reorganize cortical motorBrasilNeto JP , VallsSole J , PascualLeone A , Cammarota A , maps
G Hess (1989)
Adaptive mechanisms in cortical networks underlying cortical contributions to learning and nondeclarative memory.
M. Merzenich (1990)
Differential conditioning of associative synaptic enhancement in hippocampal brain slices.
S. Kelso (1986)
Connectivity of the Primate Sensory-Motor Cortex
E. Jones (1986)
Common forms of synaptic plasticity in the hippocampus and neocortex in vitro.
A. Kirkwood (1993)
Substrates and mechanisms for learning in motor cortex
JP Donoghue (1996)
Temporal covariance neocortex in vitro
JP Burke (1993)
Cranial nerve modulation of human cortical swallowing motor pathways.
S. Hamdy (1997)
Potential Circuit Mechanisms Underlying Concurrent Thalamic and Cortical Plasticity
M. Nicolelis (1998)
Pyramidal tract control overOldfield RC . The assessment and analysis of handedness : the cutaneous and kinesthetic sensory transmission in the cat thalamus . Edinburgh inventory
T Tsumoto (1990)
Long-term potentiation of horizontal connections provides a mechanism to reorganize cortical motor maps.
Grzegorz Hess (1994)
Mechanisms of deafferentationinduced plasticity in human motor cortex
U Ziemann (1998)
Shared neural substrates controlling hand movements in human Nicolelis MA, Katz D, Krupa DJ. Potential circuit mechanisms motor cortex
M. Castro-Alamancos (1997)
Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee.
P. Rossini (1994)
Non - invasive electrical and magnetic stimulationMarkram H ,
Strengthening of horizontal cortical connections following skill learning
Mengia -S. Rioult-Pedotti (1998)
Associative induction of posttetanicRev Neurosci 1998 ; 9 : 213 – 24 . and long - term potentiation in CA 1 neurons of rat hippocampus
BR Sastry (1995)
motor cortex output to target muscles in adult rats. II. Rapid 282: 1121-5. reorganization following motor nerve lesions
the hand in monkeys
The assessment and analysis of handedness: the Edinburgh inventory.
R. Oldfield (1971)
A critical period for long-term potentiation at thalamocortical synapses
M. Crair (1995)
Somatosensory input onto pyramidal tract neurons in rodent motor cortex.
L. L. Porter (1996)
Transcranial magnetic stimulation: negative effects. In: microstimulation of afferent nerve fibers
M Hallett (1995)
Negative 12: 476-87. motor phenomena. Philadelphia (PA): Lippincott-Raven
S Fahn (1995)
Dynamic organization of primary scale plasticity of primate somatosensory cortex
J P Donoghue (1998)
Functional MRI evidence for adult motor cortex plasticity Engert F, Bonhoeffer T. Dendritic spine changes associated with during motor skill learning
A Karni (1995)
Associative induction of posttetanic and long-term potentiation in CA1 neurons of rat hippocampus.
B. R. Sastry (1986)
Functional Organization of the Projection From Area 2 to Area 4γ in the Cat
M. Caria (1997)
Reorganization of movement representations in primary motor cortex following focal ischemic infarcts in adult squirrel monkeys.
R. Nudo (1996)
A critical period for long - term potentiation 65 : 1435 – 41 . at thalamocortical synapses
MC Crair (1991)
of the somatosensory pathway follows therapeutic amputation of 232: 85-7. the hand in monkeys
hippocampal long-term synaptic plasticity
Rapid modulation of human cortical motor outputs following ischaemic nerve block.
J. Brasil-Neto (1993)
Effects of diphenylhydantoin on motor potentials evoked with magnetic stimulation.
N. Mavroudakis (1994)
Thalamic and brainstem contributions to large-scale plasticity of primate somatosensory cortex.
E. Jones (1998)
Neurobiological basis of motor learning in mammals.
H. Asanuma (1997)
Changes in unit activity and thresholds to electrical microstimulation at coronal-pericruciate cortex of cat with classical conditioning of different facial movements.
C. Woody (1972)
Therefore , of convergent pathways in the neocortex
Common forms of synaptic plasticity in the hippocampus and Fregnac Y Temporal covariance neocortex in vitro
A Kirkwood (1993)
Parallel augmentation of hippocampal long-term potentiation, theta of the monkey motor cortex: input-output relations
Corticospinal Function and Voluntary Movement
R. Porter (1993)
motor output maps during development of implicit and explicit Percutaneous electrical stimulation of corticospinal pathways at the knowledge level of the pyramidal decussation in humans
A Pascual-Leone (1991)
Behavioral stress impairs long-term potentiation in rodent hippocampus.
M. Foy (1987)
Somatosensory evoked potentials elicited by intraneural Hallett M . Transcranial magnetic stimulation : negative effects . In : microstimulation of afferent nerve fibers
M Hallett (1995)
reorganization following motor nerve lesions
Edited by Physiological Society of Great Britain Mechanisms of deafferentation- Clarendon Press; 1995. induced plasticity in human motor cortex
U Ziemann (1998)
Dendritic spine changes associated with hippocampal long-term synaptic plasticity
F. Engert (1999)
Synaptic facilitation requires paired activation of convergent pathways in the neocortex
A. Baranyi (1981)
Percutaneous electrical stimulation of corticospinal pathways at the level of the pyramidal decussation in humans
Y. Ugawa (1991)
Projection from the sensory to the motor cortex is important in learning motor skills in the monkey.
C. Pavlides (1993)
Cortical plasticity: from synapses to maps.
D. Buonomano (1998)
magnetic stimulation during the acquisition of new fine motor skills . Differential effects on motorcortical inhibition induced by blockade
A Pascual-Leone (1991)
Functional MRI evidence for adult motor cortex plasticityEngert F , Bonhoeffer T . Dendritic spine changes associated with during motor skill learning
Mechanisms of deafferentation-Clarendon Press; 1995. induced plasticity in human motor cortex
M Hallett (1998)
Parallel augmentation of hippocampal long-term potentiation, theta rhythm, and contextual fear conditioning in water-deprived rats
Stephen Maren (1994)
Somatosensory evoked potentials elicited by intraneural microstimulation of afferent nerve fibers.
E. Kunesch (1995)
Unpredictable and uncontrollable stress impairs neuronal plasticity in the rat hippocampus
T. Shors (1990)
Temporal covariance of pre- and postsynaptic activity regulates functional connectivity in the visual cortex.
Y. Frégnac (1994)
Transcranial magnetic stimulation. Negative effects.
M. Hallett (1995)
Changes in unit activity and thresholds to to the motor cortex is important in learning motor skills in the electrical microstimulation at coronal-pericruciate cortex of cat with monkey
C Pavlides (1972)
Differential conditioning of associativeFlorence SL , Kaas JH . Large - scale reorganization at multiple levels synaptic enhancement in hippocampal brain slices
Techniques and mechanisms of action of transcranial of diphenylhydantoin on motor potentials evoked with magnetic stimulation of the human motor cortex
N Mavroudakis (1994)
Jn Spring Harb Symp Sanes (1990)
Modulation of cortical motor output maps during development of implicit and explicit knowledge.
A. Pascual-Leone (1994)
Conditions for the induction of long-term potentiation in layer II/III horizontal connections of the rat motor cortex.
Grzegorz Hess (1996)
Thalamic and brainstem contributions to largeDonoghue JP , Suner S , Sanes JN . Dynamic organization of primary scale plasticity of primate somatosensory cortex
EG Jones (1998)
hippocampal long-term synaptic plasticity Differential conditioning of associative Florence SL, Kaas JH. Large-scale reorganization at multiple levels synaptic enhancement in hippocampal brain slices
Sr Kelso (1986)
Long-term potentiation of horizontal connections provides a mechanism to reorganize cortical motor Brasil-Neto JP, Valls-Sole J, Pascual-Leone A, Cammarota A, maps
G Hess (1994)
neocortical synapses in slices of rat brain Cranial nerve modulation of human cortical swallowing motor 60
S Hamdy (1988)
Negative Motor Phenomena
S. Fahn (1995)
Immediate and delayed changes of rat motor cortical output representation with new forelimb configurations.
J. Sanes (1992)
Modulation of Plasticity in Human Motor Cortex after Forearm Ischemic Nerve Block
U. Ziemann (1998)
Properties of associative long-lasting potentiation induced by cellular conditioning in the motor cortex of conscious cats
A. Baranyi (1991)
Long - in the dentate area of the anaesthetized rabbit following stimulation term reorganization of human motor cortex driven by shorttermof the perforant path
S Hamdy (1973)
Effects of antiepileptic drugs on motor cortex excitability in humans : a Porter LL , Sakamoto T , Asanuma H . Morphological and transcranial magnetic stimulation study
U Ziemann (1996)
Substrates and mechanisms for receiving somatosensory cortical input and motor output neurons learning in motor cortex
T Kaneko (1994)
The Acquisition of Motor Behavior in Vertebrates
J. Bloedel (1996)
Somatosensory evoked potentials elicited by intraneural Hallett M. Transcranial magnetic stimulation: negative effects. In: microstimulation of afferent nerve fibers
E Kunesch (1995)
The organization of behavior
D. Hebb (1988)
Receptive - field plasticity in the Jones EG , Peters A ( editors )
NM Weinberger (1986)
Regulation of of the brain, spinal cord and roots: basic principles and procedures synaptic efficacy by coincidence of postsynaptic APs and EPSPs. for routine clinical application
P M Rossini (1997)
Long‐lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path
T. Bliss (1973)
Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans
K. Werhahn (1999)
The organization of behavior: A neuropsychological theory
J. Knott (1951)
Corticospinal function and voluntary movement, Vol. 45. Edited by Physiological Society of Great Britain
R Porter (1995)
Electroencephalogr Clin Neurophysiol
Dynamic organization of primary scale plasticity of primate somatosensory cortex
Eg Jones (1998)
Longin the dentate area of the anaesthetized rabbit following stimulation term reorganization of human motor cortex driven by short-term of the perforant path
Tv Bliss (1973)
Pyramidal tract control over Oldfield RC. The assessment and analysis of handedness: the cutaneous and kinesthetic sensory transmission in the cat thalamus. Edinburgh inventory
T Tsumoto (1971)
Effects of antiepileptic drugs on motor cortex excitability in humans: A transcranial magnetic stimulation study
U. Ziemann (1996)
Rapid plasticity of human cortical movement representation induced by practice.
J. Classen (1998)
Adaptive of rat motor cortical output representation with new forelimb mechanisms in cortical networks underlying cortical contributions configurations
JN Sanes (1994)
Cranial nerve modulation of human cortical swallowing motor 60 : 1053 – 65 . pathways
S Hamdy (1997)
a kinematic memory trace in movements evoked by TMS in the resting thumb following training
motor phenomena. Philadelphia (PA): Lippincott-Raven
motor output maps during development of implicit and explicit Percutaneous electrical stimulation of corticospinal pathways at theknowledge
A Pascual-Leone (1975)
Functional MRI evidence for adult motor cortex plasticity during motor skill learning
A. Kami (1995)
Postsynaptic control of the induction of long-term changes in efficacy of transmission at neocortical synapses in slices of rat brain.
L. Bindman (1988)
Synaptic plasticity in rat Hebb DO. The organization of behavior. A neuropsychological hippocampal slice cultures: local 'Hebbian' conjunction of pre-and theory
T Bonhoeffer (1949)
Mechanisms of Deafferentation-Induced Plasticity in Human Motor Cortex
U. Ziemann (1998)
Use-dependent alterations of movement representations in primary motor cortex of adult squirrel monkeys
R. Nudo (1996)
Locally distributed synaptic potentiation in the hippocampus.
E. Schuman (1994)
Astrocytic and synaptic response to kindling in hippocampal subfield CA1. I. Synaptogenesis in response to kindling in vitro
Fen-Lei F. Chang (1993)
Potential circuit mechanisms motor cortex
D Katz (1990)
Synaptic plasticity in rat Hebb DO . The organization of behavior . A neuropsychologicalhippocampal slice cultures : local ‘ Hebbian ’ conjunction of preand theory
T Bonhoeffer (1998)
Reorganization of movement representations in primary motor cortex following focal ischemic infarcts in Schuman EM , Madison DV . Locally distributed synaptic potentiation adult squirrel monkeys
RJ Nudo (1986)
This paper is referenced by
Volitional muscle activity paired with transcranial magnetic stimulation increases corticospinal excitability
M. A. Edwardson (2015)
Modulatory effect of repetitive peripheral magnetic stimulation on skeletal muscle tone in healthy subjects: stabilization of the elbow joint
A. Struppler (2003)
Exercise-mediated locomotor recovery and lower-limb neuroplasticity after stroke.
L. Forrester (2008)
Cortical thickness in primary sensorimotor cortex influences the effectiveness of paired associative stimulation
V. Conde (2012)
Transcranial magnetic stimulation: new insights into representational cortical plasticity
H. Siebner (2002)
Electrophysiological Markers of Sensory Plasticity and Connectomics in Ageing and Mild Cognitive Impairment
Margaret Spriggs (2018)
Mudanças reorganizacionais nos córtices somatossensorial e motor em amputados
Liliane Fonseca de Almeida (2019)
Effect of Serotonin on Paired Associative Stimulation-Induced Plasticity in the Human Motor Cortex
G. Batsikadze (2013)
Reversed timing-dependent associative plasticity in the human brain through interhemispheric interactions.
V. Conde (2013)
Paired Associative Stimulation as a Tool to Assess Plasticity Enhancers in Chronic Stroke
Joshua Silverstein (2019)
Motor cortical plasticity in basal ganglia disorders or movement disorders
Y. Ugawa (2012)
Paired Associative Electroacupuncture and Transcranial Magnetic Stimulation in Humans
Y. Huang (2019)
A History of Spike-Timing-Dependent Plasticity
H. Markram (2011)
The interindividual variability of transcranial magnetic stimulation effects: Implications for diagnostic use in movement disorders
A. Latorre (2019)
Transcranial Magnetic Stimulation to Investigate Motor Cortical Circuitry and Plasticity in Spinal Cord Injury
A. Z. Bailey (2014)
Retraining and assessing hand movement after stroke using the MusicGlove: comparison with conventional hand therapy and isometric grip training
Nizan Friedman (2013)
P675: Interneuron networks involved in human associative plasticity
G. Strigaro (2014)
Modifying motor learning through gating and homeostatic metaplasticity
U. Ziemann (2008)
Changes in somatosensory-evoked potentials and high-frequency oscillations after paired-associative stimulation
T. Murakami (2007)
Non-invasive brain stimulation as a tool to study cerebellar-M1 interactions in humans
S. Tremblay (2016)
Effects of Cutaneous Digital Nerve Electrical Stimulation and Transcranial Magnetic Stimulation on the Excitability of the Motor Cortex in Humans
Tetsuya Tomaru (2003)
Interhemispheric effects of high and low frequency rTMS in healthy humans
A. Gorsler (2003)
Clinical utility and prospective of TMS–EEG
S. Tremblay (2019)
Long-term plasticity of speech-related auditory functions in professional musicians
C. Ott (2013)
Effects of repetitive paired associative stimulation on brain plasticity and working memory in Alzheimer's disease: a pilot randomized double-blind-controlled trial.
S. Kumar (2020)
Synaptic function as a preclinical and experimental medicine readout for disease-modifying therapy in Alzheimer's Disease
B. Lu (2013)
Combination of Static Magnetic Fields and Peripheral Nerve Stimulation Can Alter Focal Cortical Excitability
I. Nojima (2016)
Extent of Dorsolateral Prefrontal Cortex Plasticity and Its Association With Working Memory in Patients With Alzheimer Disease
S. Kumar (2017)
Effects of patterned peripheral nerve stimulation on soleus spinal motor neuron excitability
S. Jiménez (2018)
Observing and perceiving: A combined approach to induce plasticity in human motor cortex
A. Bisio (2015)
Age-related decline in the responsiveness of motor cortex to plastic forces reverses with levodopa or cerebellar stimulation
A. Kishore (2014)
Relation of Brain Stimulation Induced Changes in MEP Amplitude and BOLD Signal
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