Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2016 Jul 1.
Published in final edited form as: Neurorehabil Neural Repair. 2014 Dec 11;29(6):548–556. doi: 10.1177/1545968314558603

Cortical excitability during passive action observation in hospitalized adults with subacute moderate to severe traumatic brain injury: A preliminary TMS study

Shirley FECTEAU A,B, Maya DICKLER A, Raul PELAYO C, Hatice KUMRU C, Monste BERNABEU C, Eloy OPISSO SALLERAS C, José Maria TORMOS C, Alvaro PASCUAL-LEONE B,C
PMCID: PMC4465410  NIHMSID: NIHMS636766  PMID: 25505219

Abstract

Studies indicate that motor functions in patients with traumatic brain injury (TBI) can be improved with action observation. It has been hypothesized that this clinical practice relies on modulation of motor cortical excitability elicited by passive action observation in patients with TBI, a phenomenon shown thus far only in normal controls. The purpose of this work was to test this hypothesis and characterize the modulation of motor cortex excitability during passive action observation in patients with subacute moderate to severe TBI. We measured motor evoked potentials induced by single pulse transcranial magnetic stimulation to the left primary motor cortex and recorded from the contralateral first dorsal interosseus while 20 participants observed videos of static and moving right index finger. Results were compared with those of 20 age and gender-matched healthy controls. As expected, greater excitability was elicited during moving than static stimuli in healthy subjects. However this was not observed in patients with TBI. Modulation of motor excitability during action observation is impaired in patients with TBI depending on motor dysfunction, lesion site and number of days post-injury. These preliminary results suggest a strategy to identify patients in whom action observation might be a valuable neuro-rehabilitative strategy.

Keywords: action observation, traumatic brain injury, primary motor cortex, transcranial magnetic stimulation

Introduction

Cortical excitability is increased when performing an action, but also by mere observation of a motor action.1,2,3,4,5 The activation of the internal representation of movement created by passive action observation may be beneficial for patients with brain damage and limited motor functions.6,7,8,9,10 Some studies have reported beneficial effects of action observation in patients with stroke, especially when used as an adjunct to physical therapy.11 For instance, Celnik and colleagues (2008) found enhanced motor memory formation when motor training was combined with action observation in eight patients with chronic stroke.12 Franceschini and colleagues (2010) reported improved upper limb function in twenty-eight chronic stroke patients who underwent a four-week treatment course of action observation combined with imitation of hand action with the affected limbs.13 These results support the use of action observation to augment physical therapy to improve motor functions in stroke. Similar arguments have been made regarding the clinical relevance of passive action observation in patients with spinal cord injury and traumatic brain injury (TBI). Action observation may promote re-learning of lost motor capacities by activating the action brain network. This implies that modulation of motor cortical outputs is possible during action observation in patients after TBI. Here, we tested this notion. However, we hypothesized, that patients with TBI affecting motor cortical connectivity, may show smaller modulation of motor excitability during action observation than healthy controls. If so, evaluation of modulation of motor cortical outputs might predict which patients with TBI may benefit from action observation and which would not or less so.

An important hypothesis is that modulation of motor responses during action observation reflects mirror-neuron mediated mechanisms of interpersonal motor resonance.14 The brain network of action observation has been extensively studied in healthy subjects, especially with single-pulse transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs) applied over the primary motor cortex (M1). For instance observation of a moving index finger modulates excitability of the corticospinal pathway, which induces MEPs that are greater than those elicited during observation of a static index finger. Moreover, this modulation of MEPs is congruent and muscle-specific. Observation of a moving index finger induces greater MEP size in the first dorsal interosseus (FDI) than from the abductor digiti minimi (ADM) or abductor pollicis brevis (APB).1,2

In this preliminary study, we assessed modulation of motor responses during action observation in patients with TBI and healthy controls. We applied single pulse TMS over the left M1 to assess motor excitability during presentation of static and moving right index finger videos and recorded TMS-induced MEPs from the right finger index (FDI) using electromyography (EMG). We further assessed four factors that may impact TMS-induced MEP size during action observation in TBI patients: motor capacities, presence or absence of a lesion in the frontal and parietal cortex, number of days since the injury and severity of the head injury (described below).

Materials and methods

Participants

Right handed individuals with subacute TBI (20 adults, average age: 30.3 years old, range: 17–49 years) and healthy adults (20 adults, average age: 30.5 years old, range: 20–50 years), took part of the study. They were all recruited at the Institut Universitari de Neurorehabilitació Guttmann-UAB. Inclusion criteria for patients with TBI included having received a diagnosis of TBI based on clinical history and supported by neurological and neuroimaging findings. Exclusion criteria included pregnancy or medications that could modify seizure threshold.15 Individuals with TBI were all inpatients at the Institut Universitari de Neurorehabilitació Guttmann-UAB. They were tested within 147 days postinjury (average: 94.7 days, range: 46–147). Severity of the TBI was assessed at admission using the Galveston Orientation and Amnesia Test and the Glasgow coma scale (GCS). The TBI group was composed of moderate (N=6; GCS 9–12) or severe TBI (N=14; GCS ≤8). Average score of the motor subscale of the Functional Independence Measure (FIM)/Functional assessment measure (FAM) was 45 (range: 16–107). Thirteen patients displayed paresis (left hemiparesis: N=3; right hemiparesis: N=2; left tetraparesis: N=6; right tetraparesis: N=1; symmetric tetraparesis: N=1). Eleven patients had a history of substance use disorders and one had a history of depression prior to the TBI. Inclusion criteria for the healthy group included no history of any neurological or psychiatric disorders and eligible to undergo TMS following international guidelines.15 They were age-and gender-matched with the TBI group (Table 1). Participants or their legal guardian gave written informed consent prior to entering the study, which was approved by the local ethics committee.

Table 1.

Characteristics of the subjects; M: Male; F: Female.

Patients Age/Sex Lesion N days FIM/FAM motor subscale GSC Controls Age/Sex
P1 31/M F r/l 106 51 3 C1 31/M
P2 23/M F r, P r 101 16 11 C2 23/M
P3 27/M F r/l 58 61 9 C3 26/M
P4 25/M none 65 79 5 C4 25/M
P5 24/M F r, P r 114 22 6 C5 24/M
P6 30/M none 46 15 6 C6 30/M
P7 29/M F l, P l 66 24 5 C7 29/M
P8 28/M F r/l, P r 68 16 3 C8 28/M
P9 40/F none 60 x 7 C9 38/F
P10 33/M none 143 27 3 C10 34/M
P11 31/F F r/l, P r 67 20 9 C11 31/F
P12 25/M F l 109 22 4 C12 27/M
P13 43/M P r 140 x 12 C13 42/M
P14 38/M F r/l, P r/l 141 78 7 C14 36/M
P15 26/M F r/l, P l 132 x 5 C15 28/M
P16 17/M F l, P r/l 115 x 9 C16 20/M
P17 40/M F r, P r 82 42 4 C17 39/M
P18 49/M P r/l 87 88 3 C18 50/M
P19 28/M P l 147 107 9 C19 28/M
P20 18/M F l 46 50 8 C20 20/M
Open in a new tab

Experimental procedure

The experiment was performed in a quiet testing room at the research facilities of the Institut Universitari de Neurorehabilitació Guttmann-UAB. TMS-induced MEPs were recorded from the FDI and the ADM muscles while participants passively viewed movie-clips presented in a random order on a computer screen of movement of the right index toward a dot (movement condition) and still hand (static condition) (Figure 1). These stimuli were similar to those used in a previous study.16 Duration of each video was 8sec. For the movement condition, the index moved eight times at a pace of approximately 1Hz. The entire session was composed of 48 stimuli (24 for the movement condition; 24 for the static condition). A single suprathreshold pulse was delivered over the left M1 during each movie-clip presentation at 120% of resting motor threshold, which was measured in each subject following recommendations endorsed by the International Federation of Clinical Neurophysiology,17 with its standard definition of reaching a 50μV peak-to-peak amplitude FDI-MEP in at least 5 times out of 10 with the lowest stimulator intensity. Patients were wearing a swimming cap to mark the hot spot. Subjects were sitting at a distance of 1m from the computer screen. TMS was performed with a commercially available Magpro figure-of-eight coil and a Magpro X100 magnetic stimulator (Dantec-Medtronic, US). The average motor threshold stimulation intensity was 52±4% for the healthy group and 65± 4% for the TBI group. Relaxation of both muscles was documented by EMG recording for at least 20msec before each TMS pulse. MEPs were recorded using pairs of Ag/AgCl surface electrodes placed over both the FDI and ADM of the right hand in a belly-tendon montage with a circular ground electrode on the wrist. The EMG signal was recorded using a Medelec System (Oxford Instruments Medical Inc., UK).

Figure 1.

Figure 1

Open in a new tab

Study design. Participants were passively presented with movie-clips of a still hand (static condition) and a hand with the right index moving toward a dot (action condition) while receiving single pulse-TMS.

In order to further characterize the modulation of motor excitability in TBI patients, we tested whether the modulation of TMS-induced MEP size during action observation was related to any one of the following four patients’ characteristics:

Motor capacities

Most studies assessing motor excitability of action observation have been performed in healthy subjects and some reported that excitability of action observation can be differently modulated by motor expertise or experience.18,19 However, it is not known whether motor capacities per se have an impact on excitability during passive observation of action. We thus explored whether motor capacities have an impact on modulation of excitability during action observation, as indexed by the modulation of TMS-induced MEP size. We used the FIM+FAM motor subscale administered at admission as a measure of motor function with demonstrated good inter-rater reliability and validity.20,21,22 We choose this subscale, although it is not the most precise, because it was part of patients’ clinical assessment. As a preliminary study, we aimed here at using routine clinical assessments to explore whether some of them might be relevant for eliciting modulation of motor excitability during passive action observation. We predicted that weaker motor capacities would be associated with smaller modulation of MEP size compared to better motor capacities.

Frontal and parietal lobe status

Studies in healthy subjects have repeatedly reported the involvement of the frontal and parietal cortex in action observation, although there is no clear consensus in regards to the hemispheric contribution and no studies establishing a causal role of these brain regions in modulation of motor excitability. Some studies have found bilateral activations during action observation,2,23,24 while others argue for a left dominance.25,26 We thus explored the impact of the status of the patients’ left and right frontal and parietal cortices on the modulation of motor excitability during action observation. Information was based on the medical records from patients’ brain CT or MRI scans. We postulated that patients with lesions in these regions would display weaker modulation of MEP size than patients with no lesion in these regions.

Number of days post injury

Previous work has indicated that brain network reorganization is especially important during the subacute phase after the injury.27 We thus tested whether the number of days between patients’ injury and participation in this study had an impact on the findings. We assumed that lesser number of days would be associated with weaker modulation of MEP size.

Severity of the head injury

Severity of the head injury may impact cortical excitability at rest as measured by TMS.28 We thus investigated whether severity of the head injury had an impact on the modulation of motor excitability during action observation. Severity of the TBI was indexed using the Glasgow Coma Scale (GCS), one of the most common methods used to characterize severity of head injuries.29 We proposed that more severe head injury would be associated with weaker modulation of motor excitability.

Data analysis

Peak-to-peak amplitude of the MEPs was measured using Matlab software (The MathWorks, US). For each participant MEPs were averaged per stimulus condition (static, movement). First, we performed paired t-test to compare TMS-induced MEP amplitude during action and static stimuli for each groups. Then, given the expectation that MEP size and its modulation would show substantial inter-variability in the TBI group according to above patients’ characteristics, we calculated for each patient a percent change in MEP amplitude between the moving and static finger conditions, as described previously.16,30 In order to test whether motor capacities, number of days since the injury and severity of the head injury influenced TMS-induced amplitude of action observation, we performed Pearson correlations for each of these factors. Finally, in order to test whether the presence or absence of a lesion in the frontal and parietal cortex had an impact on the TMS-induced amplitude of action observation, we performed an ANOVA. Statistical analyses were performed using SPSS software (version 22.0, SPSS Inc, Chicago, Illinois). Results with a p-value ≤0.05 were considered significant.

Results

None of the participants experienced or reported significant adverse effects during or after TMS even when explicitly asked.

TMS-induced MEP during action observation

We first analyzed FDI-MEPs when healthy subjects passively observed videos of static and moving index to confirm that stimuli elicit differential neurophysiologic responses. There was an effect of stimulus conditions (static, action; paired t-test; t=−;5.62; p=.0001; Figure 2). There was no significant difference between static and movement conditions for the ADM-MEPs (paired t-test; t=−;1.87; p=.078).

Figure 2.

Figure 2

Open in a new tab

FDI-MEP size of the static and action condition healthy subjects. Error bars indicate SEM.

We then investigated FDI-MEPs in participants with TBI and found no significant difference between stimulus conditions (static, action; paired t-test; t=−;1.57; p=.132; Figure 3). Furthermore, there was no significant difference between stimulus conditions for the ADM-MEPs (paired t-test; t=1.79; p=.089).

Figure 3.

Figure 3

Open in a new tab

A) FDI-MEP size of the static and action condition patients with TBI. Error bars indicate SEM. B) FDI-MEP size of action observation in patients with TBI according to their motor capacities. Of note, FIM/FAM data were missing in 4 subjects.

TMS-induced MEP in the TBI group according to motor capacities

We examined whether motor capacities had an effect on the modulation of motor excitability during action observation. There was a correlation between FIM+FAM scores of the motor subscale and FDI-MEP size (percent of change from moving to static stimuli; Pearson correlation; r=.536; 1-tailed value: p=.016; Figure 4). There was no significant correlation between motor capacities and ADM-MEP size (Pearson correlation: r=−;0.394; 1-tailed value: p=.066).

Figure 4.

Figure 4

Open in a new tab

FDI-MEP size of action observation in patients with TBI according to the frontal lobe status. Error bars indicate SEM.

TMS-induced MEP in the TBI group according to the frontal cortex status

We investigated whether the frontal cortex status had an impact on the modulation of FDI-MEP size. Twelve patients had a lesion in the frontal cortex and eight patients had no lesion in the frontal cortex. We found a difference between groups based on their frontal cortex status (absence, presence of a lesion; ANOVA; F1,19=5.66; p=.029; Figure 5). These two groups did not differ in modulation of ADM-MEP size (ANOVA; F1,19=.38; p=.546).

Figure 5.

Figure 5

Open in a new tab

FDI-MEP size of action observation in patients with TBI according to the number of days postinjury.

We then explored whether a lesion in the left frontal cortex played a role in motor excitability elicited during action observation. Ten patients presented a lesion in the left frontal cortex and ten had no lesion in the left frontal cortex. There was an effect of left frontal cortex status (absence, presence of a lesion; ANOVA; F1,19=4.46; p=.049). Patients did not differ in modulation of ADM-MEP size (absence, presence of a lesion in the left frontal cortex; ANOVA; F1,19=.49; p=.827).

We also tested whether a lesion in the right frontal cortex played a role in motor excitability of action observation. Nine patients had lesion in the right frontal cortex and eleven had no lesion in the right frontal cortex. There was no difference between these two groups on the FDI-MEP size (ANOVA; F1,19=1.08; p=.313), nor on the ADM-MEP size (F1,19=.99; p=.333).

TMS-induced MEP in the TBI group according to the parietal cortex status

We examined whether the parietal cortex status had an impact on neurophysiologic responses of action observation. Twelve patients displayed a lesion in the parietal cortex and eight patients had no lesion in the parietal cortex. There was no difference between these two groups on FDI-MEP size (ANOVA; F1,19=.02; p=.902), nor on ADM-MEP size (ANOVA; F1,19=1.67; p=.212).

TMS-induced MEP in the TBI group according to the number of days postinjury

We investigated whether the number of days between the injury and the experiment had an effect on the modulation of neurophysiologic responses elicited by action observation. There was a correlation between the number of days and modulation of FDI-MEPs (Pearson correlation; r=.397; 1-tailed value: p=.042). There was no significant correlation between the number of days and ADM-MEPs (Pearson correlation: r=−;0.082; 1-tailed value: p=.366).

TMS-induced MEP in the TBI group according to severity of the head injury

Finally, we examined whether severity of the head injury had an effect on the modulation of motor excitability during action observation. There was no significant correlation between GCS scores and modulation of FDI-MEPs (Pearson correlation; r=−;.011; 1-tailed value: p=.481) and between the GCS scores and ADM-MEPs (Pearson correlation: r=−;0.139; 1-tailed value: p=.279).

Discussion

The goal of this preliminary study was to investigate the modulation of neurophysiologic responses from M1 elicited during passive observation of static and moving index finger in subacute patients with moderate to severe TBI. Observation of static and moving finger index elicited differential responses in healthy controls: Confirming prior findings, FDI-MEPs were greater during observation of action than static index finger. This is in line with an extensive literature reporting that action observation enhances motor excitability in healthy subjects.31,32 This was however not the case in patients with TBI: FDI-MEP was not significantly different between observation of action and static finger index. We further investigated motor excitability responses of action observation in patients with TBI according to factors that, based on the literature, could impact these responses: motor capacities, lesion in the frontal and parietal cortex, the number of days post injury and severity of the head injury.

Effects of motor capacities on TMS-induced MEP during action observation in TBI

There was a positive correlation between motor capacities, as measured by the FIM+FAM motor scores, and modulation of FDI-MEP size during action observation. This reveals that better motor function is associated with greater modulation of motor excitability when passively observing movements. None of the patients who failed to show the expected modulation of FDI-MEP size during observation of index finger movements were able to execute themselves the isolated ab-adduction movement of the index finger. It thus appears that being able to execute a movement might be essential to preserve the resonance of the motor system to an observed action. In future work, it would be interesting to measure in a longitudinal design brain activations of action observation in patients who improve their motor capacities with time or therapy. Furthermore, a more specific motor functioning scale to the hands, such as such as the Wolf Motor Function test, should be included in future work. The FIM+FAM motor subscale may not be the optimal scale as it reflects upper and lower extremities as well as head and fails to provide a more fine-grained evaluation of specific motor deficits or limitation. It is however a clinically validated and broadly used measure of overall motor discapacity. As mentioned earlier, we decided to use this subscale because it was part of the routine clinical assessment.

Effects of frontal cortex status on TMS-induced MEP during action observation in TBI

Motor excitability of action observation was different between TBI patients with no lesion in the frontal cortex and those with lesions in the frontal cortex. This is in line with the literature on activations in the frontal cortex associated with action observation in healthy subjects.33 For instance, Caspers and colleagues (2010) performed a meta-analysis on brain activations associated with action observation as assessed by fMRI and PET. They found that observation of right hand actions elicited activations in both inferior frontal gyri (pars opercularis), among other regions such as the dorsal premotor cortex and the inferior and superior parietal lobule.23 Our results extend such findings and provide causal information on the role of the frontal role in modulation of motor cortical excitability during action observation. Of note, motor resonance likely requires perceptual awareness, which involves the frontal cortex.34 For instance, Pobric and Hamilton (2006) found that TMS of the pars opercularis impaired perceptual judgments about other people’s actions.35 Also, Chong and colleagues (2008) found that attention can suppress activity in the left inferior frontal gyrus during passive action observation.36 Therefore, it is possible that perceptual awareness was impaired in TBI patients with lesion in the frontal cortex, which could in turn interfere with motor resonance.

We examined a potential difference between patients with lesions in the left or right frontal cortex. There was a weaker modulation of action observation in patients with lesions in the left, but not the right, frontal cortex. This finding supports the notion of a lateralization of fontal lobe role in motor resonance. However, MEPs were only recorded from the right hand, elicited by TMS delivered over the left hemisphere, and visual stimuli represented the right hand. The finding that left frontal lesions were associated with impaired MEP modulation may thus also be due to this unilateral testing procedure. Future work should also include MEP recording from the left hand with TMS delivered over the right hemisphere while presenting left hand stimuli.

Effects of parietal cortex status on TMS-induced MEP during action observation in TBI

Status of the parietal cortex had no significant impact on modulation of cortical excitability by action observation: Patients with a lesion in the parietal cortex displayed similar modulation than patients with no lesion in the parietal cortex. Some studies have reported activation in the inferior parietal areas during action observation23,37 and some data indicate that the parietal cortex is associated with observation of goal-oriented movement more than observation of intransitive movement. For instance, Lorey and colleagues (2013) tested presentation of different conditions of action observation using fMRI. They found that the posterior parietal cortex was activated during observation for squeezing movement and observation of aiming movement, but not during observation of extension-flexion movement.38 Similarly, Suchan and colleagues (2007) found that action observation with the instruction to subsequently imitate the viewed movement, as compared to judge the velocity of the movement, activated the left parietal cortex as measured by PET.39 It is therefore possible that the lack of difference between our patients with lesion and no lesion in the parietal cortex might reflect that our stimuli did not sufficiently imply a goal (Figure 1). It is also possible, as mentioned above, that due to neural reorganization following a TBI the role of the normal parietal cortex in motor resonance might have been altered in our patients.

Effects of number of days post injury and severity of the head injury on TMS-induced MEP during action observation in TBI

Modulation of motor cortical excitability during action observation was correlated with the number of days postinjury. Greater modulation was observed with greater number of days. This supports the notion that modulation of motor excitability changes with time, indicating a natural improvement of the modulation of cortical excitability. Severity of the head injury (moderate, severe) as indexed by the GCS scores did not impact motor excitability of action observation. It is possible that severity of the head injury does not impact differently motor excitability of action observation. It is also possible that, in the subacute phase, both moderate and severe TBI are associated to weaker modulation of motor excitability, but with time they would show different neurophysiologic responses. Also, it is possible that the GCS scores are not sensitive enough for this given experiment focusing on moderate and severe TBI. Future longitudinal work with greater sample size including patients with mild, moderate and severe TBI is required to further understand whether change in the modulation of motor excitability during action observation may occur over time.

Study limitations and perspectives

This study has important limitations to be considered. First, the sample size was modest (six patients with moderate and 14 patients with severe TBI) in their subacute phase, tested between 46 to 147 days post-injury). Thus the lack of significance in some analyses, such as severity of the head injury, might be attributed to underpowered analyses. Studies with larger sample size are needed to conduct multiple regression analyses to shed light on how patients’ characteristics interact and to evaluate the unique contribution of each one of these factors. Second, we did not directly analyze the CT and MRI scans (e.g., lesion size; inter-rater reliability tests) because we only had access to the medical records. Also, future work should explore whether the types of lesions (e.g., diffuse axonal injury, hemorrhage, contusions) and total lesion volume play a role on motor excitability. Longitudinal studies with greater sample size and repeated assessments of motor functions are warranted to explore potential clinical value of action observation in TBI patients. Such design would identify whether some patients show spontaneous remission and those who do not. In addition, studies including multiple methods of neuroimaging, especially functional connectivity MRI and diffusion tensor imaging, are warranted because MEPs are likely to reflect intact and damage connections between various brain regions, whether a given region is intact or not according to an anatomical MRI or CT brain scan as used here. Another limitation is the lack of an eye tracking system to ensure that patients were observing the stimuli. Further, the cognitive status and cooperation of the patients during testing is a possible confounding factor in the results, as it may affect processing of the visual stimuli.

Despite these caveats, findings from this preliminary work support the notion that motor excitability of action observation is impaired in moderate and severe TBI in the subacute phase, especially in patients with limited motor capacities and/or lesion to the left frontal cortex. Passive action observation is believed to contribute to action understanding40 and motor learning,41 which appear to be impaired in TBI.42,43 From a practical perspective, assessment of the integrity of motor excitability of action observation may hold clinical value and ultimately guide rehabilitation strategies.

In healthy subjects, emotionally-loaded stimuli elicited greater TMS-induced motor excitability than neutral stimuli.44 Here patients displayed weak motor excitability when passively viewing simple finger movement. It would be interesting in future work to present larger set of stimuli, including movements that are individually impaired and intact in TBI patients in order to explore whether more meaningful stimuli would elicit greater modulation of excitability. Moreover, we previously showed that behavioral experience, such as visual priming, can refine these neurophysiologic responses.30 This might also be relevant in neurorehabilitation in TBI, such as priming the brain network in order to elicit greater modulation of motor excitability. Finally, future protocols should also include additional conditions, for instance observation with the intent to imitate the observed movement such as Ertelt and colleagues (2007), who found improved motor functions in stroke patients who were asked to observe movements and execute them.8

Acknowledgments

We thank all participants and their families for participating to this research project. This work was supported by grants from the Canada Research Chair in Cognitive Neuroplasticity to SF, from the National Center for Research Resources: Harvard-Thorndike General Clinical Research Center at Beth Israel Deaconess Medical Center (NCRR MO1 RR01032) and Harvard Clinical and Translational Science Center (UL1 RR025758 TO APL), and by the Foundation La Marató TV3 (071931) and grant PI082004 from the Instituto de Salud Carlos III to JMT.

Contributor Information

Shirley FECTEAU, Email: shirley.fecteau@fmed.ulaval.ca.

Maya DICKLER, Email: maya.dickler.1@ulaval.ca.

Raul PELAYO, Email: rpelayo@guttmann.com.

Hatice KUMRU, Email: hkumru@guttmann.com.

Monste BERNABEU, Email: mbernabeu@guttmann.com.

Eloy OPISSO SALLERAS, Email: eopisso@guttmann.com.

José Maria TORMOS, Email: jmtormos@guttmann.com.

Alvaro PASCUAL-LEONE, Email: apleone@bidmc.harvard.edu.

References

  • 1.Fadiga L, Craighero L, Olivier E. Human motor cortex excitability during the perception of others’ action. Curr Opin Neurobiol. 2005;15:213–218. doi: 10.1016/j.conb.2005.03.013. [DOI] [PubMed] [Google Scholar]
  • 2.Fadiga L, Fogassi L, Pavesi G, Rizzolatti G. Motor facilitation during action observation: a magnetic stimulation study. J Neurophysiol. 1995;73:2608–2611. doi: 10.1152/jn.1995.73.6.2608. [DOI] [PubMed] [Google Scholar]
  • 3.Jeannerod M. Neural simulation of action: a unifying mechanism for motor cognition. Neuroimage. 2001;14:S103–109. doi: 10.1006/nimg.2001.0832. [DOI] [PubMed] [Google Scholar]
  • 4.Urgesi C, Candidi M, Fabbro F, Romani M, Aglioti SM. Motor facilitation during action observation: topographic mapping of the target muscle and influence of the onlooker’s posture. Eur J Neurosci. 2006;23:2522–2530. doi: 10.1111/j.1460-9568.2006.04772.x. [DOI] [PubMed] [Google Scholar]
  • 5.Cross ES, Kraemer DJ, Hamilton AF, Kelley WM, Grafton ST. Sensitivity of the action observation network to physical and observational learning. Cereb Cortex. 2009;19:315–326. doi: 10.1093/cercor/bhn083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Fregni F, Pascual-Leone A. Hand motor recovery after stroke: tuning the orchestra to improve hand motor function. Cogn Behav Neurol. 2006;19:21–33. doi: 10.1097/00146965-200603000-00003. [DOI] [PubMed] [Google Scholar]
  • 7.Nudo RJ. Mechanisms for recovery of motor function following cortical damage. Curr Opin Neurobiol. 2006;16:638–644. doi: 10.1016/j.conb.2006.10.004. [DOI] [PubMed] [Google Scholar]
  • 8.Ertelt D, Small S, Solodkin A, Dettmers C, McNamara A, Binkofski F, Buccino G. Action observation has a positive impact on rehabilitation of motor deficits after stroke. Neuroimage. 2007;36:T164–173. doi: 10.1016/j.neuroimage.2007.03.043. [DOI] [PubMed] [Google Scholar]
  • 9.Garrison KA, Winstein CJ, Aziz-Zadeh L. The mirror neuron system: a neural substrate for methods in stroke rehabilitation. Neurorehabil Neural Repair. 2010;24:404–412. doi: 10.1177/1545968309354536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Franceschini M, Agosti M, Cantagallo A, Sale P, Mancuso M, Buccino G. Mirror neurons: action observation treatment as a tool in stroke rehabilitation. Eur J Phys Rehabil Med. 2012;46:517–523. [PubMed] [Google Scholar]
  • 11.Ewan LM, Kinmond K, Holmes PS. An observation-based intervention for stroke rehabilitation: experiences of eight individuals affected by stroke. Disabil Rehabil. 2010;32:2097–2106. doi: 10.3109/09638288.2010.481345. [DOI] [PubMed] [Google Scholar]
  • 12.Celnik P, Webster B, Glasser DM, Cohen LG. Effects of action observation on physical training after stroke. Stroke. 2008;39:1814–1820. doi: 10.1161/STROKEAHA.107.508184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Franceschini M, Ceravolo MG, Agosti M, Cavallini P, Bonassi S, Dall’Armi V, Sale P. Clinical relevance of action observation in upper-limb stroke rehabilitation: a possible role in recovery of functional dexterity. A randomized clinical trial. Neurorehabil Neural Repair. 2012;26:456–462. doi: 10.1177/1545968311427406. [DOI] [PubMed] [Google Scholar]
  • 14.Uithol S, van Rooij I, Bekkering H, Haselager P. Understanding motor resonance. Soc Neurosci. 2011;6:388–397. doi: 10.1080/17470919.2011.559129. [DOI] [PubMed] [Google Scholar]
  • 15.Rossi S, Hallett M, Rossini PM, Pascual-Leone A, Safety of TMS Consensus Group Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009;120:2008–2039. doi: 10.1016/j.clinph.2009.08.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Fecteau S, Lassonde M, Theoret H. Modulation of motor cortex excitability during action observation in disconnected hemispheres. Neuroreport. 2005;16:1591–1594. doi: 10.1097/01.wnr.0000179079.54906.1b. [DOI] [PubMed] [Google Scholar]
  • 17.Rossini PM, Barker AT, Berardelli A, Caramia MD, Caruso G, Cracco RQ, et al. 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. Electroencephalogr Clin Neurophysiol. 1994;91:79–92. doi: 10.1016/0013-4694(94)90029-9. [DOI] [PubMed] [Google Scholar]
  • 18.Vogt S, Buccino G, Wohlschlager AM, Canessa N, Shah NJ, Zilles K, Fink GR. Prefrontal involvement in imitation learning of hand actions: effects of practice and expertise. Neuroimage. 2007;37:1371–1383. doi: 10.1016/j.neuroimage.2007.07.005. [DOI] [PubMed] [Google Scholar]
  • 19.Candidi M, Maria Sacheli L, Mega I, Aglioti SM. Somatotopic mapping of piano fingering errors in sensorimotor experts: TMS studies in pianists and visually trained musically naives. Cereb Cortex. 2014;24:435–443. doi: 10.1093/cercor/bhs325. [DOI] [PubMed] [Google Scholar]
  • 20.Wilson FC, Wheatley-Smith L, Downes C. Analysis of intensive outpatient neuro rehabilitation outcomes using FIM+FAM(UK) NeuroRehabilitation. 2009;24:377–382. doi: 10.3233/NRE-2009-0492. [DOI] [PubMed] [Google Scholar]
  • 21.Nichol AD, Higgins AM, Gabbe BJ, Murray LJ, Cooper DJ, Cameron PA. Measuring functional and quality of life outcomes following major head injury: common scales and checklists. Injury. 2011;42:281–287. doi: 10.1016/j.injury.2010.11.047. [DOI] [PubMed] [Google Scholar]
  • 22.Grauwmeijer E, Heijenbrok-Kal MH, Haitsma IK, Ribbers GM. A prospective study on employment outcome 3 years after moderate to severe traumatic brain injury. Arch Phys Med Rehabil. 2012;93:993–999. doi: 10.1016/j.apmr.2012.01.018. [DOI] [PubMed] [Google Scholar]
  • 23.Caspers S, Zilles K, Laird AR, Eickhoff SB. ALE meta-analysis of action observation and imitation in the human brain. Neuroimage. 2010;50:1148–1167. doi: 10.1016/j.neuroimage.2009.12.112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Lui F, Buccino G, Duzzi D, Benuzzi F, Crisi G, Baraldi P, Rizzolatti G. Neural substrates for observing and imagining non-object-directed actions. Soc Neurosci. 2008;3:261–275. doi: 10.1080/17470910701458551. [DOI] [PubMed] [Google Scholar]
  • 25.Rizzolatti G, Arbib MA. Language within our grasp. Trends Neurosci. 1998;21:188–194. doi: 10.1016/s0166-2236(98)01260-0. [DOI] [PubMed] [Google Scholar]
  • 26.Iacoboni M, Molnar-Szakacs I, Gallese V, Buccino G, Mazziotta JC, Rizzolatti G. Grasping the intentions of others with one’s own mirror neuron system. PLoS Biol. 2005;3:e79. doi: 10.1371/journal.pbio.0030079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Cecatto RB, Chadi G. The importance of neuronal stimulation in central nervous system plasticity and neurorehabilitation strategies. Funct Neurol. 2007;22:137–143. [PubMed] [Google Scholar]
  • 28.Chistyakov AV, Soustiel JF, Hafner H, Trubnik M, Levy G, Feinsod M. Excitatory and inhibitory corticospinal responses to transcranial magnetic stimulation in patients with minor to moderate head injury. J Neurol Neurosurg Psychiatry. 2001;70:580–587. doi: 10.1136/jnnp.70.5.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974;2:81–84. doi: 10.1016/s0140-6736(74)91639-0. [DOI] [PubMed] [Google Scholar]
  • 30.Fecteau S, Tormos JM, Gangitano M, Theoret H, Pascual-Leone A. Modulation of cortical motor outputs by the symbolic meaning of visual stimuli. Eur J Neurosci. 2010;32:172–177. doi: 10.1111/j.1460-9568.2010.07285.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Cochin S, Barthelemy C, Roux S, Martineau J. Observation and execution of movement: similarities demonstrated by quantified electroencephalography. Eur J Neurosci. 1999;11:1839–1842. doi: 10.1046/j.1460-9568.1999.00598.x. [DOI] [PubMed] [Google Scholar]
  • 32.Hari R, Forss N, Avikainen S, Kirveskari E, Salenius S, Rizzolatti G. Activation of human primary motor cortex during action observation: a neuromagnetic study. Proc Natl Acad Sci U S A. 1998;95:15061–15065. doi: 10.1073/pnas.95.25.15061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Iacoboni M, Woods RP, Brass M, Bekkering H, Mazziotta JC, Rizzolatti G. Cortical mechanisms of human imitation. Science. 1999;286:2526–2528. doi: 10.1126/science.286.5449.2526. [DOI] [PubMed] [Google Scholar]
  • 34.Mattiassi AD, Mele S, Ticini LF, Urgesi C. Conscious and Unconscious Representations of Observed Actions in the Human Motor System. J Cogn Neurosci. 2014 doi: 10.1162/jocn_a_00619. [DOI] [PubMed] [Google Scholar]
  • 35.Pobric G, Hamilton AF. Action understanding requires the left inferior frontal cortex. Curr Biol. 2006;16:524–529. doi: 10.1016/j.cub.2006.01.033. [DOI] [PubMed] [Google Scholar]
  • 36.Chong TT, Williams MA, Cunnington R, Mattingley JB. Selective attention modulates inferior frontal gyrus activity during action observation. Neuroimage. 2008;40:298–307. doi: 10.1016/j.neuroimage.2007.11.030. [DOI] [PubMed] [Google Scholar]
  • 37.Molenberghs P, Hayward L, Mattingley JB, Cunnington R. Activation patterns during action observation are modulated by context in mirror system areas. Neuroimage. 2012;59:608–615. doi: 10.1016/j.neuroimage.2011.07.080. [DOI] [PubMed] [Google Scholar]
  • 38.Lorey B, Naumann T, Pilgramm S, Petermann C, Bischoff M, Zentgraf K, Munzert J. How equivalent are the action execution, imagery, and observation of intransitive movements? Revisiting the concept of somatotopy during action simulation. Brain Cogn. 2003;81:139–150. doi: 10.1016/j.bandc.2012.09.011. [DOI] [PubMed] [Google Scholar]
  • 39.Suchan B, Melde C, Herzog H, Homberg V, Seitz RJ. Activation differences in observation of hand movements for imitation or velocity judgement. Behav Brain Res. 2008;188:78–83. doi: 10.1016/j.bbr.2007.10.021. [DOI] [PubMed] [Google Scholar]
  • 40.Rizzolatti G, Sinigaglia C. The functional role of the parieto-frontal mirror circuit: interpretations and misinterpretations. Nat Rev Neurosci. 2010;11:264–274. doi: 10.1038/nrn2805. [DOI] [PubMed] [Google Scholar]
  • 41.Stefan K, Classen J, Celnik P, Cohen LG. Concurrent action observation modulates practice-induced motor memory formation. Eur J Neurosci. 2008;27:730–738. doi: 10.1111/j.1460-9568.2008.06035.x. [DOI] [PubMed] [Google Scholar]
  • 42.Incoccia C, Formisano R, Muscato P, Reali G, Zoccolotti P. Reaction and movement times in individuals with chronic traumatic brain injury with good motor recovery. Cortex. 2004;40:111–115. doi: 10.1016/s0010-9452(08)70924-9. [DOI] [PubMed] [Google Scholar]
  • 43.Kliegel M, Eschen A, Thone-Otto AI. Planning and realization of complex intentions in traumatic brain injury and normal aging. Brain Cogn. 2004;56:43–54. doi: 10.1016/j.bandc.2004.05.005. [DOI] [PubMed] [Google Scholar]
  • 44.Hill AT, Fitzgibbon BM, Arnold SL, Rinehart NJ, Fitzgerald PB, Enticott PG. Modulation of putative mirror neuron activity by both positively and negatively valenced affective stimuli: a TMS study. Behav Brain Res. 2013;249:116–123. doi: 10.1016/j.bbr.2013.04.027. [DOI] [PubMed] [Google Scholar]

RESOURCES