Reduced motor facilitation during action observation in schizophrenia: a mirror neuron deficit?

Impairments in social cognitive functioning are well documented in schizophrenia, however the neural basis of these deficits is unclear. A recent explanatory model of social cognition centers upon the activity of mirror neurons, which are cortical brain cells that become active during both the performance and observation of behavior. Here, we test for the first time whether mirror neuron functioning is reduced in schizophrenia. Fifteen individuals with schizophrenia or schizoaffective disorder and fifteen healthy controls completed a transcranial magnetic stimulation (TMS) experiment designed to assess mirror neuron activation. While patients demonstrated no abnormalities in cortical excitability, motor facilitation during action observation, putatively reflecting mirror neuron activity, was reduced in schizophrenia. Dysfunction within the mirror neuron system may contribute to the pathophysiology of schizophrenia.     

Motor network activation during human action observation and imagery: Mu rhythm EEG evidence on typical and atypical neurodevelopment

The mental simulation theory suggests activation of the motor network during imagery and observation of human movements, similarly to the activation during action execution and is proposed to be mediated by the mirror neuron system. This activation can be measured by several technologies such as electroencephalography, magnetoencephalography, functional magnetic resonance imaging and positron emission tomography. It is proposed that motor network activation and therefore increased cortical excitability of primary motor cortex occur due to premotor mirror neuron system inputs. This mechanism has been demonstrated as important for planning actions and seems relevant for anticipating others actions and for empathy establishing as well as for language development. In this review we focused on studies relative to electroencephalography data of motor neural network activation during movement observation and imagery in typical and atypical development.     

Spatio-temporal dynamics of the mirror neuron system during social intentions

Previous research has shown that specific goals and intentions influence a person’s allocation of social attention. From a neural viewpoint, a growing body of evidence suggests that the inferior fronto-parietal network, including the mirror neuron system, plays a role in the planning and the understanding of motor intentions. However, it is unclear whether and when the mirror neuron system plays a role in social intentions. Combining a behavioral task with electrical neuroimaging in 22 healthy male participants, the current study investigates whether the temporal brain dynamic of the mirror neuron system differs during two types of social intentions i.e., lust vs. romantic intentions. Our results showed that 62% of the stimuli evoking lustful intentions also evoked romantic intentions, and both intentions were sustained by similar activations of the inferior frontal gyrus and the inferior parietal lobule/angular gyrus for the first 432 ms after stimulus onset. Intentions to not love or not lust, on the other hand, were characterized by earlier differential activations of the inferior fronto-parietal network i.e., as early as 244 ms after stimulus onset. These results suggest that the mirror neuron system may not only code for the motor correlates of intentions, but also for the social meaning of intentions and its valence at both early/automatic and later/more elaborative stages of information processing.     

Understanding mirror neurons: Evidence for enhanced corticospinal excitability during the observation of transitive but not intransitive hand gestures

Putative measures of mirror neuron activity suggest that mirror neurons respond preferentially to biological motion, but it remains unclear whether enhanced cortical activity occurs during the observation of any behaviour, or whether that behaviour needs to be associated with a particular object or goal. Forty-three healthy adults completed a transcranial magnetic stimulation (TMS) experiment that assessed corticospinal excitability while viewing intransitive and transitive hand gestures (compared with the presentation of a static hand). Visual presentations were designed to control for motoric and stimulus properties. A significant increase in corticospinal excitability (putatively reflecting mirror neuron activation) was seen only during the observation of transitive behaviour. These findings are consistent with the notion that human hand-related mirror neurons are sensitive to object- and goal-directed behaviour, rather than biological motion per se.     

Does cortical motor neuron excitability change in peripheral nerve injury?

OBJECTIVE: To investigate changes in cortical motor neuron excitability after peripheral nerve injury, evoked spinal cord potentials (ESCPs) following hemispheric transcranial magnetic stimulation (TMS) were recorded in awake patients with unilateral brachial plexus injury. METHODS: ESCPs following hemispheric TMS were recorded in 6 patients with unilateral complete type brachial plexus injury. Studies were performed within 6 months from the time of injury. ESCPs were recorded from posterior epidural space using catheter electrodes. Hemispheric TMS was applied on the motor cortex using a figure-of-8 coil. The threshold of ESCPs following hemispheric TMS was measured. The number, latency, and amplitude of ESCPs following high stimulus hemispheric TMS were measured and compared. RESULTS: No significant change was observed in the threshold of ESCPs following TMS contra-lateral to the injured upper limb compared to that following TMS contra-lateral to the intact upper limb. Several ESCP components were recorded following high stimulus hemispheric TMS. No significant changes were observed in comparison with number, latency and amplitude of ESCPs following high stimulus TMS contra-lateral to the injured upper limb and those following TMS contra-lateral to the intact upper limb. CONCLUSIONS: From a study of ESCPs following single TMS, no evidence was obtained that cortical motor neuron excitability changes in patients with traumatic unilateral brachial plexus injury at relatively early stages. We investigated the changes of cortical motor neuron excitability in patients with brachial plexus injury from the ESCPs following TMS. In single TMS, our data gave no evidence for cortical excitability changes at relatively early stages.     

Force requirements of observed object lifting are encoded by the observer’s motor system: a TMS study

Several transcranial magnetic stimulation (TMS) studies have reported facilitation of the primary motor cortex (M1) during the mere observation of actions. This facilitation was shown to be highly congruent, in terms of somatotopy, with the observed action, even at the level of single muscles. With the present study, we investigated whether this muscle‐specific facilitation of the observer’s motor system reflects the degree of muscular force that is exerted in an observed action. Two separate TMS experiments are reported in which corticospinal excitability was measured in the hand area of M1 while subjects observed the lifting of objects of different weights. The type of action ‘grasping‐and‐lifting‐the‐object’ was always identical, but the grip force varied according to the object’s weight. In accordance to previous findings, excitability of M1 was shown to modulate in a muscle‐specific way, such that only the cortical representation areas in M1 that control the specific muscles used in the observed lifting action became increasingly facilitated. Moreover, muscle‐specific M1 facilitation was shown to modulate to the force requirements of the observed actions, such that M1 excitability was considerably higher when observing heavy object lifting compared with light object lifting. Overall, these results indicate that different levels of observed grip force are mirrored onto the observer’s motor system in a highly muscle‐specific manner. The measured force‐dependent modulations of corticospinal excitability in M1 are hypothesized to be functionally relevant for scaling the observed grip force in the observer’s own motor system. In turn, this mechanism may contribute, at least partly, to the observer’s ability to infer the weight of the lifted object.     

Seeing touch and pain in a stranger modulates the cortical responses elicited by somatosensory but not auditory stimulation

Viewing other's pain inhibits the excitability of the motor cortex and also modulates the neural activity elicited by a concomitantly delivered nociceptive somatosensory stimulus. As the neural activity elicited by a transient nociceptive stimulus largely reflects non nociceptive‐specific, multimodal neural processes, here we tested, for the first time, whether the observation of other's pain preferentially affects the brain responses elicited by nociceptive stimulation, or instead similarly modulates those elicited by stimuli belonging to a different sensory modality. Using 58‐channel electroencephalography (EEG), we recorded the cortical responses elicited by laser and auditory stimulation during the observation of videoclips showing either noxious or non‐noxious stimulation of a stranger's hand. We found that the observation of other's pain modulated the cortical activity consisting in an event‐related desynchronization in the β band (β ERD), and elicited by nociceptive laser stimuli, but not by auditory stimuli. Using three different source analysis approaches, we provide converging evidence that such modulation affected neural activity in the contralateral primary sensorimotor cortex. The magnitude of this modulation correlated well with a subjective measure of similarity between the model's hand and the onlooker's representation of the hand. Altogether, these findings demonstrate that the observation of other's pain modulates, in a somatosensory‐specific fashion, the cortical responses elicited by nociceptive stimuli in the sensorimotor cortex contralateral to the stimulated hand. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.     

Neural response to transcranial magnetic stimulation in adult hypothyroidism and effect of replacement treatment

PURPOSE: Despite clinical evidences that hypothyroidism is often associated with cognitive dysfunction, affective disorders and psychosis, the effects of thyroid hormone deficiency on the adult brain have been largely unexplored. We investigated the hypothesis that hypothyroidism might affect cortical excitability and modulates inhibitory and excitatory cortical circuits by using Transcranial Magnetic Stimulation. MATERIALS AND METHODS: Cortical excitability was probed in 10 patients with overt hypothyroidism and 10 age-matched healthy controls. We tested motor thresholds and corticospinal excitability, cortical silent period and peripheral silent period, short interval intracortical inhibition, intracortical facilitation. Patients were evaluated at the time of diagnosis, as well as after 3 and 6 months replacement therapy with l-thyroxin. RESULTS: At baseline, patients showed decreased cortical excitability, with increased resting and active motor threshold and decreased steepness of the motor evoked potential recruitment curves. These changes were paralleled by longer cortical silent period and decreased short interval intracortical inhibition. After 3 months replacement therapy, all the parameters but short interval intracortical inhibition were restored to normal values. Short interval intracortical inhibition returned to normal values only after 6 months of replacement therapy. CONCLUSIONS: Thyroid hormones are needed to modulate cortical excitability and cortical inhibitory circuits in adults.     

Familiarity modulates motor activation while other species' actions are observed: a magnetic stimulation study

Observing other people's actions facilitates the observer's motor system as compared with observing the same individuals at rest. This motor activation is thought to result from mirror‐like activity in fronto‐parietal areas, which enhances the excitability of the primary motor cortex via cortico‐cortical pathways. Although covert motor activation in response to observed actions has been widely investigated between conspecifics, how humans cope with other species' actions has received less attention. For example, it remains unclear whether the human motor system is activated by observing other species' actions, and whether prior familiarity with the non‐conspecific agent modulates this activation. Here, we combined single‐pulse transcranial magnetic stimulation and motor‐evoked potential recording to explore the impact of familiarity on motor activation during the observation of non‐conspecific actions. Videos displaying actions performed either by a conspecific (human) or by a non‐conspecific (dog) were shown to individuals who had prior familiarity or no familiarity at all with the non‐conspecific agent. We found that, whereas individuals with long‐lasting familiarity showed similar levels of motor activation for human and canine actions, individuals who had no familiarity showed higher motor activation for human than for canine actions. These findings suggest that the human motor system is flexible enough to resonate with other species, and that familiarity plays a key role in tuning this ability.     

Polarity and timing-dependent effects of transcranial direct current stimulation in explicit motor learning

Transcranial direct current stimulation (tDCS) is attracting increasing interest as a therapeutic tool for neurorehabilitation, particularly after stroke, because of its potential to modulate local excitability and therefore promote functional plasticity. Previous studies suggest that timing is important in determining the behavioural effects of brain stimulation. Regulatory metaplastic mechanisms exist to modulate the effects of a stimulation intervention in a manner dependent on prior cortical excitability, thereby preventing destabilization of existing cortical networks. The importance of such timing dependence has not yet been fully explored for tDCS. Here, we describe the results of a series of behavioural experiments in healthy controls to determine the importance of the relative timing of tDCS for motor performance. Application of tDCS during an explicit sequence-learning task led to modulation of behaviour in a polarity specific manner: relative to sham stimulation, anodal tDCS was associated with faster learning and cathodal tDCS with slower learning. Application of tDCS prior to performance of the sequence-learning task led to slower learning after both anodal and cathodal tDCS. By contrast, regardless of the polarity of stimulation, tDCS had no significant effect on performance of a simple reaction time task. These results are consistent with the idea that anodal tDCS interacts with subsequent motor learning in a metaplastic manner and suggest that anodal stimulation modulates cortical excitability in a manner similar to motor learning.     

Functional connectivity between cortical hand motor and language areas during recovery from aphasia

Previous data indicate that in healthy subjects, there is a connectivity between cortical areas for hand movement and language on the left hemisphere. This link is possibly mediated by the so-called mirror neuron system. The present study investigated the functional relationship between linguistic and hand movement processing in patients who were recovering from post-stroke aphasia. The excitability of the right- and left-hand motor cortex during language production in patients who were recovering from post-stroke aphasia and age-matched controls was investigated. As control, phonation was investigated. Hand motor cortex excitability was assessed with Motor Evoked Potentials which were elicited by Transcranial Magnetic Stimulation (TMS). In patients, reading aloud enhanced the excitability of the right hemispheric hand motor cortex, whereas phonation had no effect on hand motor cortex excitability. In the control group, an increased excitability of the left hemispheric hand motor system was found during reading aloud in accordance with previous data. The present data suggest a functional connectivity between regions mediating hand movements and reading. This may indicate that the right hemisphere participates in language processing as far as involved in single word reading in patients recovering from aphasia. The coactivation between cerebral representations of hand movements and language may be used therapeutically for aphasia rehabilitation.     

Mirror neuron activation as a function of explicit learning: changes in mu‐event‐related power after learning novel responses to ideomotor compatible,partially compatible,and non‐compatible stimuli

Questions regarding the malleability of the mirror neuron system (MNS) continue to be debated. MNS activation has been reported when people observe another person performing biological goal‐directed behaviors, such as grasping a cup. These findings support the importance of mapping goal‐directed biological behavior onto one's motor repertoire as a means of understanding the actions of others. Still, other evidence supports the Associative Sequence Learning (ASL) model which predicts that the MNS responds to a variety of stimuli after sensorimotor learning, not simply biological behavior. MNS activity develops as a consequence of developing stimulus‐response associations between a stimulus and its motor outcome. Findings from the ideomotor literature indicate that stimuli that are more ideomotor compatible with a response are accompanied by an increase in response activation compared to less compatible stimuli; however, non‐compatible stimuli robustly activate a constituent response after sensorimotor learning. Here, we measured changes in the mu‐rhythm, an EEG marker thought to index MNS activity, predicting that stimuli that differ along dimensions of ideomotor compatibility should show changes in mirror neuron activation as participants learn the respective stimulus‐response associations. We observed robust mu‐suppression for ideomotor‐compatible hand actions and partially compatible dot animations prior to learning; however, compatible stimuli showed greater mu‐suppression than partially or non‐compatible stimuli after explicit learning. Additionally, non‐compatible abstract stimuli exceeded baseline only after participants explicitly learned the motor responses associated with the stimuli. We conclude that the empirical differences between the biological and ASL accounts of the MNS can be explained by Ideomotor Theory.     

Transcranial magnetic stimulation studies in complex regional pain syndrome type I: A review

The sensory and motor cortical representation corresponding to the affected limb is altered in patients with complex regional pain syndrome (CRPS). Transcranial magnetic stimulation (TMS) represents a useful non‐invasive approach for studying cortical physiology. If delivered repetitively, TMS can also modulate cortical excitability and induce long‐lasting neuroplastic changes. In this review, we performed a systematic search of all studies using TMS to explore cortical excitability/plasticity and repetitive TMS (rTMS) for the treatment of CRPS. Literature searches were conducted using PubMed and EMBASE. We identified 8 articles matching the inclusion criteria. One hundred fourteen patients (76 females and 38 males) were included in these studies. Most of them have applied TMS in order to physiologically characterize CRPS type I. Changes in motor cortex excitability and brain mapping have been reported in CRPS‐I patients. Sensory and motor hyperexcitability are in the most studies bilateral and likely involve corresponding regions within the central nervous system rather than the entire hemisphere. Conversely, sensorimotor integration and plasticity were found to be normal in CRPS‐I. TMS examinations also revealed that the nature of motor dysfunction in CRPS‐I patients differs from that observed in patients with functional movement disorders, limb immobilization, or idiopathic dystonia. TMS studies may thus lead to the implementation of correct rehabilitation strategies in CRPS‐I patients. Two studies have begun to therapeutically use rTMS. This non‐invasive brain stimulation technique could have therapeutic utility in CRPS, but further well‐designed studies are needed to corroborate initial findings.     

Effects of deep brain stimulation on the primary motor cortex: Insights from transcranial magnetic stimulation studies

Deep brain stimulation (DBS) implanted in different basal ganglia nuclei regulates the dysfunctional neuronal circuits and improves symptoms in movement disorders. However, the understanding of the neurophysiological mechanism of DBS is at an early stage. Transcranial magnetic stimulation (TMS) can be used safely in movement disorder patients with DBS, and can shed light on how DBS works. DBS at a therapeutic setting normalizes the abnormal motor cortical excitability measured with motor evoked potentials (MEP) produced by primary motor cortical TMS. Abnormal intracortical circuits in the motor cortex tested with paired-pulse TMS paradigm also show normalization with DBS. These changes are accompanied with improvements in symptoms after chronic DBS. Single-pulse DBS produces cortical evoked potentials recorded by electroencephalography at specific latencies and modulates motor cortical excitability at certain time intervals measured with MEP. Combination of basal ganglia DBS with motor cortical TMS at stimulus intervals consistent with the latency of cortical evoked potentials delivered in a repetitive mode produces plastic changes in the primary motor cortex. TMS can be used to examine the effects of open and closed loop DBS. Patterned DBS and TMS delivered in a repetitive mode may be developed as a new therapeutic method for movement disorder patients.     

Transcranial magnetic stimulation reveals modulation of corticospinal excitability when observing actions with the intention to imitate

Studies using transcranial magnetic stimulation have demonstrated that action observation can modulate the activity of the corticospinal system. This has been attributed to the activity of an 'action observation network', whereby premotor cortex activity influences corticospinal excitability. Neuroimaging studies have demonstrated that the context in which participants observe actions (i.e. whether they simply attend to an action, or observe it with the intention to imitate) modulates action observation network activity. The study presented here examined whether the context in which actions were observed revealed similar modulatory effects on corticospinal excitability. Eight human participants observed a baseline stimulus (a fixation cross), observed actions in order to attend to them, or observed the same actions with the intention to imitate them. Whereas motor evoked potentials elicited from the first dorsal interosseus muscle of the hand were facilitated by attending to actions, observing the same actions in an imitative capacity led to no facilitation effect. Furthermore, no motor facilitation effects occurred in a control muscle. Electromyographic data collected when participants physically imitated the observed actions revealed that the activity of the first dorsal interosseus muscle increased significantly during action execution compared with rest. These data suggest that an inhibitory mechanism acts on the corticospinal system to prevent the immediate overt imitation of observed actions. These data provide novel insight into the properties of the human action observation network, demonstrating for the first time that observing actions with the intention to imitate them can modulate the effects of action observation on corticospinal excitability.     

Early semantic and phonological effects on temporal- and muscle-specific motor resonance

Previous studies using functional magnetic resonance imaging and transcranial magnetic stimulation (TMS) explored the relationships between linguistic processing and motor resonance, i.e. the activation of the motor system while perceiving others performing an action. These studies have mainly investigated a specific linguistic domain, i.e. semantics, whereas phonology has been largely neglected. Here we used single‐pulse TMS to compare the effects of semantic and phonological processing with motor resonance effects. We applied TMS to the primary motor hand area while subjects observed object‐oriented actions and performed semantic and phonological tasks related to the observed action. Motor evoked potentials were recorded in two hand muscles, one of them more involved in the execution of the observed actions than the other one, at three different timepoints (0, 200 and 400 ms after stimulus onset). The results demonstrated increased corticospinal excitability that was muscle‐specific (i.e. restricted to the hand muscle involved in the observed action), hemisphere‐specific (left), and time‐specific (400 ms after stimulus onset). The results suggest an additive effect of independent semantic and phonological processing on motor resonance. The novel phonological effect reported here expands the links between language and the motor system and is consistent with a theory of shared control for hand and mouth. Furthermore, the timing of the semantic effect suggests that motor activation during semantic processing is not an ‘epiphenomenon’ but rather is essential to the construction of meaning.     

Interaction of sound and sight during action perception: Evidence for shared modality-dependent action representations

Seeing or hearing manual actions activates the mirror neuron system, i.e., specialized neurons within motor areas which fire not only when an action is performed but also when it is passively perceived. Although it has been shown that mirror neurons respond to either action-specific vision or sound, it remains a topic of debate whether and how vision and sound interact during action perception.Here we used transcranial magnetic stimulation to explore multimodal interactions in the human motor system, namely at the level of the primary motor cortex (M1). Corticomotor excitability in M1 was measured while subjects perceived unimodal visual (V), unimodal auditory (A), or multimodal (V + A) stimuli of a simple hand action. In addition, incongruent multimodal stimuli were included, in which incongruent vision or sound was presented simultaneously with the auditory or visual action stimulus. A selective response increase was observed to the congruent multimodal stimulus as compared to the unimodal and incongruent multimodal stimuli.These findings speak in favour of ‘shared’ action representations in the human motor system that are evoked in a ‘modality-dependent’ way, i.e., they are elicited most robustly by the simultaneous presentation of congruent auditory and visual stimuli. Multimodality in the perception of hand movements bears functional similarities to speech perception, suggesting that multimodal convergence is a generic feature of the mirror system which applies to action perception in general.     

Transcranial direct current stimulation for the treatment of focal hand dystonia

The treatment of writer's cramp, a task‐specific focal hand dystonia, needs new approaches. A deficiency of inhibition in the motor cortex might cause writer's cramp. Transcranial direct current stimulation modulates cortical excitability and may provide a therapeutic alternative. In this randomized, double‐blind, sham‐controlled study, we investigated the efficacy of cathodal stimulation of the contralateral motor cortex in 3 sessions in 1 week. Assessment over a 2‐week period included clinical scales, subjective ratings, kinematic handwriting analysis, and neurophysiological evaluation. Twelve patients with unilateral dystonic writer's cramp were investigated; 6 received transcranial direct current and 6 sham stimulation. Cathodal transcranial direct current stimulation had no favorable effects on clinical scales and failed to restore normal handwriting kinematics and cortical inhibition. Subjective worsening remained unexplained, leading to premature study termination. Repeated sessions of cathodal transcranial direct current stimulation of the motor cortex yielded no favorable results supporting a therapeutic potential in writer's cramp. © 2011 Movement Disorder Society     

Motor ‘surround inhibition’ is not correlated with activity in surround muscles

Surround inhibition (SI) is a neural process that has been extensively investigated in the sensory system and has been recently probed in the motor system. Muscle‐specific modulation of corticospinal excitability at the onset of an isolated finger movement has been assumed to reflect the presence of SI in the motor system. This study attempted to characterise this phenomenon in a large cohort of normal volunteers and investigate its relationship with muscle activity in the hand. Corticospinal excitability of the pathways projecting to three hand muscles [first dorsal interosseus (FDI), abductor pollicis brevis (APB) and abductor digiti minimi (ADM)] and electromyographic (EMG) activity of the same muscles were assessed in 31 healthy volunteers during an isolated index finger movement. In the agonist FDI muscle both corticospinal excitability and EMG activity were found to be increased at the onset of the movement (P < 0.001 and P < 0.001, respectively). On the contrary, in the surround ADM, there was dissociation between the corticospinal excitability (decreased: P < 0.001) and EMG activity (increased: P < 0.001). Cross‐correlation analysis of the EMG activity showed that neuronal signals driving the agonist and surround muscles are not synchronised when SI is present. The results suggest a distinctive origin of the neuronal signals driving the agonist and surround muscles. In addition, they indicate that cortical output might be simultaneously modulated by voluntary and non‐voluntary activity, generated in cortical and subcortical structures, respectively.     

Modulation of premotor mirror neuron activity during observation of unpredictable grasping movements

Using transcranial magnetic stimulation, we explored the properties of premotor mirror neurons during the passive observation of a reaching-grasping movement in human subjects. Two different experiments were run using video-clips as visual stimuli. Video-clips showed a normally performed (control stimulus) or an anomalous reaching-grasping movement executed by delaying the time of the appearance of the maximal finger aperture (experiment 1), or substituting it with an unpredictable closure (experiment 2). Motor evoked potentials were recorded at different time-points during the observation of the video-clips. Profiles of cortical excitability were drawn and compared with the kinematic profiles of the corresponding movement. Passive observation of the natural movement evoked a profile of cortical excitability that is in concordance with the timing of the kinematic profile of the shown finger movements. Observation of the uncommon movements did not exert any modulation (experiment 1) or evoked an activity that matched, at the beginning, the modulation obtained with observation of the natural movement (experiment 2). Results show that the resonant motor plan is loaded as whole at the beginning of observation and once started tends to proceed to its completion regardless of changes to the visual cues. The results exclude the possibility of a temporal fragmentation of the resonant plan, because activation of different populations of mirror neurons for each phase of the ongoing action. They further support the notion of the role of the mirror system as neural substrate for the observing-execution matching system and extend the current knowledge regarding mechanisms that trigger the internal representation of an action.