A category of stimuli of great importance for primates, humans in particular, is that formed by actions done by other individuals. If we want to survive, we must understand the actions of others. Furthermore, without action understanding, social organization is impossible. In the case of humans, there is another faculty that depends on the observation of others' actions: imitation learning. Unlike most species, we are able to learn by imitation, and this faculty is at the basis of human culture. In this review we present data on a neurophysiological mechanism--the mirror-neuron mechanism--that appears to play a fundamental role in both action understanding and imitation. We describe first the functional properties of mirror neurons in monkeys. We review next the characteristics of the mirror-neuron system in humans. We stress, in particular, those properties specific to the human mirror-neuron system that might explain the human capacity to learn by imitation. We conclude by discussing the relationship between the mirror-neuron system and language.

The mirror-neuron system.

The approach taken in this study to produce localised changes of cerebral excitability in the intact human was modulation of neuronal excitability by weak electric currents applied transcranially. So far, this technique has mainly been used in animal research, primarily through modulation of the resting membrane potential (Terzuolo & Bullock, 1956; Creutzfeld et al. 1962; Eccles et al. 1962; Bindman et al. 1964; Purpura & McMurtry, 1965; Artola et al. 1990; Malenka & Nicoll, 1999). In general, cerebral excitability was diminished by cathodal stimulation, which hyperpolarises neurones. Anodal stimulation caused neuronal depolarisation, leading to an increase in excitability (Bindman et al. 1962; Purpura & McMurtry, 1965), as was shown by spontaneous neuronal discharges and the amplitudes of evoked potentials (Landau et al. 1964; Purpura & McMurtry, 1965; Gorman, 1966). However, in single cortical layers opposite effects were seen (Purpura & McMurtry, 1965), underlining the fact that the effects of DC stimulation depend on the interaction of electric flow direction and neuronal geometry. Enduring effects of 5 h and longer have been described if the stimulation itself lasts sufficiently long, about 10–30 min. These prolonged effects are not simply due to prolonged membrane potential shifts or recurrent excitation, because intermittent complete cancellation of electrical brain activity by hypothermia does not abolish them (Gartside, 1968a,b). Long-term potentiation (LTP) and long-term depression (LTD) have been proposed as the likely candidates for this phenomenon (Hattori et al. 1990; Moriwaki, 1991; Islam et al. 1995; Malenka & Nicoll, 1999).

The concept described here was an attempt to induce neuronal excitability changes in man by application of weak DC stimulation through the intact skull. It has already been demonstrated within invasive presurgical epilepsy diagnostics that intracranial currents of sufficient strength can be achieved in humans by stimulation with surface electrodes at intensities of up to 1.5 mA (Dymond et al. 1975). A suitable candidate for evaluating cortical excitability changes is transcranial magnetic stimulation (TMS), because it allows the quantification of motor-cortical neurone responses in a painless and non-invasive manner. The amplitude of the resulting motor-evoked potential (MEP) represents the excitability of the motor system. In the following, we confirm the principal possibility of altering cortical excitability by applying weak DC. Furthermore we show that systematic DC stimulation with minimum stimulation duration and intensity is necessary for an effective application of weak current in humans. This is of particular importance for inducing effects which outlast the duration of stimulation.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1469-7793.2000.t01-1-00633.x

Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation.

The organization of behavior: A neuropsychological theory

Theta Burst Stimulation of the Human Motor Cortex

Muscle fatigue is an exercise-induced reduction in maximal voluntary muscle force. It may arise not only because of peripheral changes at the level of the muscle, but also because the central nervous system fails to drive the motoneurons adequately. Evidence for “central” fatigue and the neural mechanisms underlying it are reviewed, together with its terminology and the methods used to reveal it. Much data suggest that voluntary activation of human motoneurons and muscle fibers is suboptimal and thus maximal voluntary force is commonly less than true maximal force. Hence, maximal voluntary strength can often be below true maximal muscle force. The technique of twitch interpolation has helped to reveal the changes in drive to motoneurons during fatigue. Voluntary activation usually diminishes during maximal voluntary isometric tasks, that is central fatigue develops, and motor unit firing rates decline. Transcranial magnetic stimulation over the motor cortex during fatiguing exercise has revealed focal cha...

Spinal and Supraspinal Factors in Human Muscle Fatigue

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.

http://www.tmslab.org/tms%20articles%20research/022.pdf

Induction of plasticity in the human motor cortex by paired associative stimulation.

Associative stimulation has been shown to enhance excitability in the human motor cortex (Stefan et al. 2000); however, little is known about the underlying mechanisms. An interventional paired associative stimulation (IPAS) was employed consisting of repetitive application of single afferent electric stimuli, delivered to the right median nerve, paired with single pulse transcranial magnetic stimulation (TMS) over the optimal site for activation of the abductor pollicis brevis muscle (APB) to generate approximately synchronous events in the primary motor cortex. Compared to baseline, motor evoked potentials (MEPs) induced by unconditioned, single TMS pulses increased after IPAS. By contrast, intracortical inhibition, assessed using (i) a suprathreshold test TMS pulse conditioned by a subthreshold TMS pulse delivered 3 ms before the test pulse, and (ii) a suprathreshold test TMS pulse conditioned by afferent median nerve stimulation delivered 25 ms before the TMS pulse, remained unchanged when assessed with appropriately matching test stimulus intensities. The increase of single-pulse TMS-evoked MEP amplitudes was blocked when IPAS was performed under the influence of dextromethorphan, an N-methyl-d-aspartate (NMDA) receptor antagonist known to block long-term potentiation (LTP). Further experiments employing the double-shock TMS protocol suggested that the afferent pulse, as one component of the IPAS protocol, induced disinhibition of the primary motor cortex at the time when the TMS pulse, as the other component of IPAS, was delivered. Together, these findings support the view that LTP-like mechanisms may underlie the cortical plasticity induced by IPAS.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.2002.023317

Mechanisms of enhancement of human motor cortex excitability induced by interventional paired associative stimulation.

Synaptic plasticity is conspicuously dependent on the temporal order of the pre- and postsynaptic activity. Human motor cortical excitability can be increased by a paired associative stimulation (P...

https://www.physiology.org/doi/pdf/10.1152/jn.00900.2002

A temporally asymmetric Hebbian rule governing plasticity in the human motor cortex.

The role of attention in generating motor memories remains controversial principally because it is difficult to separate the effects of attention from changes in kinematics of motor performance. We attempted to disentangle attention from performance effects by varying attention while plasticity was induced in human primary motor cortex by external stimulation in the absence of voluntary movement. A paired associative stimulation (PAS) protocol was employed consisting of repetitive application of single afferent electric stimuli, delivered to the right median nerve, paired with single-pulse transcranial magnetic stimulation (TMS) over the optimal site for activation of the right abductor pollicis brevis muscle (APB) to generate near-synchronous events in the left primary motor cortex. In experiment 1, the spatial location of attention was varied. PAS failed to induce plasticity when the subject's attention was directed to their left hand, away from the right target hand the cortical representation of which was being stimulated by PAS. In experiment 2, the grade of attention to the target hand was manipulated. PAS-induced plasticity was maximal when the subject viewed their target hand, and its magnitude was slightly reduced when the subject could only feel their hand. Conversely, plasticity was completely blocked when the subject's attention was diverted from the target hand by a competing cognitive task. A similar modulation by attention was observed for PAS-induced changes in the duration of the silent period evoked by TMS in voluntarily contracted muscle. Associative plasticity in the human motor cortex depends decisively on attention.

https://www.physiology.org/doi/pdf/10.1152/jn.00383.2003

Modulation of Associative Human Motor Cortical Plasticity by Attention

Mirror neurons discharge with both action observation and action execution. It has been proposed that the mirror neuron system is instrumental in motor learning. The human primary motor cortex (M1) displays mirror activity in response to movement observation, is capable of forming motor memories, and is involved in motor learning. However, it is not known whether movement observation can lead directly to the formation of motor memories in the M1, which is considered a likely physiological step in motor learning. Here, we used transcranial magnetic stimulation (TMS) to show that observation of another individual performing simple repetitive thumb movements gives rise to a kinematically specific memory trace of the observed motions in M1. An extended period of observation of thumb movements that were oriented oppositely to the previously determined habitual directional bias increased the probability of TMS-evoked thumb movements to fall within the observed direction. Furthermore, the acceleration of TMS-evoked thumb movements along the principal movement axis and the balance of excitability of muscle representations active in the observed movements were altered in favor of the observed movement direction. These findings support a role for the mirror neuron system in memory formation and possibly human motor learning.

https://www.jneurosci.org/content/jneuro/25/41/9339.full.pdf

Katja Stefan

Papers

Induction of plasticity in the human motor cortex by paired associative stimulation.

Mechanisms of enhancement of human motor cortex excitability induced by interventional paired associative stimulation.

A temporally asymmetric Hebbian rule governing plasticity in the human motor cortex.

Modulation of Associative Human Motor Cortical Plasticity by Attention

Formation of a motor memory by action observation.