Increases of corticospinal excitability in self-related processing

Authors

  • Silvia Salerno,

    1. INSERM U1028, CNRS UMR5292, Lyon Neuroscience Research Centre, ImpAct Team, Lyon, France
    2. University Claude Bernard Lyon I, Lyon, France
    Search for more papers by this author
    • These authors contributed equally to the study.

  • Elisa Zamagni,

    1. INSERM U1028, CNRS UMR5292, Lyon Neuroscience Research Centre, ImpAct Team, Lyon, France
    2. University Claude Bernard Lyon I, Lyon, France
    3. Psychology Department, University of Bologna, Viale Berti Pichat, I-40127, Bologna, Italy
    Search for more papers by this author
    • These authors contributed equally to the study.

  • Christian Urquizar,

    1. INSERM U1028, CNRS UMR5292, Lyon Neuroscience Research Centre, ImpAct Team, Lyon, France
    2. University Claude Bernard Lyon I, Lyon, France
    Search for more papers by this author
  • Romeo Salemme,

    1. INSERM U1028, CNRS UMR5292, Lyon Neuroscience Research Centre, ImpAct Team, Lyon, France
    2. University Claude Bernard Lyon I, Lyon, France
    Search for more papers by this author
  • Alessandro Farnè,

    1. INSERM U1028, CNRS UMR5292, Lyon Neuroscience Research Centre, ImpAct Team, Lyon, France
    2. University Claude Bernard Lyon I, Lyon, France
    3. Hospices Civils de Lyon, Hôpital Neurologique, Mouvement et Handicap, Lyon, France
    Search for more papers by this author
    • These authors contributed equally to the study.

  • Francesca Frassinetti

    1. Psychology Department, University of Bologna, Viale Berti Pichat, I-40127, Bologna, Italy
    Search for more papers by this author
    • These authors contributed equally to the study.


Dr F. Frassinetti, as above.
E-mail:francesc.frassinetti@unibo.it

Abstract

Involvement of fronto-parietal structures within the right hemisphere in bodily self recognition has gained convergent support from behavioural, neuropsychological and neuroimaging studies. Increases in corticospinal excitability via transcranial magnetic stimulation (TMS) also testify to right hemisphere self-related processing. However, evidence for self-dependent modulations of motor excitability is limited to the processing of face-related information that, by definition, conveys someone’s identity. Here we tested the hypothesis that vision of one’s own hand, as compared with vision of somebody else’s hand, would also engage specific self-hand processing in the right hemisphere. Healthy participants were submitted to a classic TMS paradigm to assess changes in corticospinal excitability of the right (Experiment 1) and left (Experiment 2) motor cortex, while viewing pictures of a (contralateral) still hand, which could either be their own (Self) or not (Other). As a control for body selectivity, subjects were also presented with pictures of a hand-related, but non-corporeal object, i.e. a mobile phone, which could similarly be their own or not. Results showed a selective right hemisphere increase in corticospinal excitability with self-hand and self-phone stimuli with respect to Other stimuli. Such a Self vs. Other modulation of primary motor cortex appeared at 600 ms and was maintained at 900 ms, but was not present at earlier timings (100 and 300 ms) and was completely absent following stimulation of the left hemisphere. A similar pattern observed for self-hand and self-phone stimuli suggests that owned hands and objects may undergo similar self-processing, possibly via a different cortical network from that responsible for self-face processing.

Introduction

Several studies have identified brain areas for processing the body (fusiform body area) and body-parts (extrastriate body area) (Downing et al., 2001; Sugiura et al., 2006; Uddin et al., 2006; Devue et al., 2007; Urgesi et al., 2007) and specific networks for self and other body-parts processing (Keenan et al., 2000b, 2001; Sugiura et al., 2006; Frassinetti et al., 2008, 2009, 2010; Hodzic et al., 2009). Frassinetti et al. (2008, 2009) reported a behavioural facilitation (i.e. a self-advantage) when neurologically healthy subjects and left brain-damaged patients were presented with stimuli depicting their own compared with someone else’s body-parts (hand, foot). Instead, right brain-damaged patients did not show any self-advantage, pointing to a critical role for the right hemisphere in self-processing.

Transcranial magnetic stimulation (TMS) has elucidated the role played by the right hemisphere in self-face processing. Keenan et al. (2001) have shown that observing self-faces morphed with faces of famous people is associated with a larger increase of motor cortex excitability in the right compared with the left hemisphere, even when self-faces are masked (Théoret et al., 2004). Moreover, Uddin et al. (2006) found that repetitive TMS over the right inferior parietal lobule selectively disrupted performance on a self–other face discrimination task. These studies converge in showing right hemispheric dominance in facial self-recognition processing.

Few studies have assessed whether viewing self body-parts (e.g. hand) engage self-processes similar to those observed for self-faces. Patuzzo et al. (2003) reported that while observing fingers extension-flexion increased the amplitude of motor-evoked potentials (MEPs, see Fadiga et al., 1995), and the observation of Self vs. Other movements did not produce any significant difference. However, they assessed corticospinal excitability of the left hemisphere. Funase et al. (2007) showed that observing directly and indirectly (via a mirror) self-hand movements induced an increase in MEP amplitude, but the visually presented hand always belonged to the experimental subject (Self). It thus remains unknown whether motor corticospinal excitability of the right hemisphere is solely affected by stimuli explicitly conveying the subject’s identity (i.e. the face) or reflects self-processing also for less explicitly self body-parts (e.g. the hand).

Here we tested the hypothesis that vision of one’s own hand, compared with somebody else’s hand, would engage self-processing. To this aim, healthy participants were submitted to a classic single-pulse TMS paradigm to assess changes in corticospinal excitability of their right (Experiment 1) and left (Experiment 2) motor cortex, while viewing pictures of a still hand that could either be their own (Self) or not (Other). As a control for the specificity of self-related processing for bodily representations, participants were also presented with pictures of their own or somebody else’s mobile phone, a common object that despite being strongly hand-related is not corporeal. As an index of corticospinal excitability, we recorded MEP amplitudes from an intrinsic muscle of the hand contralateral to the stimulated hemisphere. Larger MEPs following presentation of Self than Other hands in the right but not the left hemisphere would be taken as evidence of right hemispheric specialization for self body-parts processing.

Materials and methods

Experiment 1

Participants

Twelve right-handed healthy participants (eight female; age range 24–36 years, mean 29 years) with no history of previous neurological or psychiatric disease participated in the experiment after providing informed consent. They were naïve as to the purpose of the study, which was approved by the INSERM Ethics Board and run in accordance to the Declaration of Helsinki.

Stimuli and procedure

Stimuli were colour pictures of participants’ left hand (see Fig. 1) and mobile phone. Flash photographs were taken with a digital camera before the experimental session. Eleven subjects owned their mobile phone for more than 1 year, whereas one subject owned his mobile phone for 3 months. Pictures were taken in an indirectly illuminated environment while standing against a black uniform background. Images were equalized for visual properties such a brightness and contrast and digitally edited with Adobe Photoshop to reduce any visual dissimilarity, such as brightness and contrast.

Figure 1.

 Timeline of the experimental procedure.

In each trial, two stimuli from the same category (e.g. two hands or two mobile phones, 50% of trials for each category) were successively presented, and could either belong to the same person (‘same’ trials, 50%), or to different persons (‘different’ trials, 50%). In half of the trials the first stimulus in the pair represented the participant’s own hand or mobile phone (‘Self’ trials), whereas in the other half the first stimulus depicted hands or objects of another person (‘Other’ trials). Single TMS pulses were randomly delivered at 300, 600 or 900 ms after the onset of the first picture; an earlier interval of 100 ms was also tested in a subgroup of subjects.

The study was a 2 × 2 × 3 design with Stimuli (Hand, Mobile), Owner (Self, Other) and Interval (300, 600, 900 ms) as variables. The earlier interval (100 ms) was assessed separately (see below and Table 1). Each condition was repeated six times per block, for a total of 72 trials by block. Two blocks were presented in the same experimental session, for a total of 144 trials. The experimental conditions were fully randomized across trials. A short practice session of six trials was administered at the beginning of the session to familiarize participants with the task.

Table 1.   Experimental conditions and number of trials for each condition as a function of TMS timings
 100 ms* (n)300 ms† (n)600 ms† (n)900 ms† (n)
  1. Each experimental session consisted of two fully intermingled blocks.

  2. *Additional TMS timing tested in experiment 3.

  3. †TMS timings tested in experiment 1 and 2.

Self hand12121212
Other hand12121212
Self mobile12121212
Other mobile12121212
Total48484848

The temporal structure of a representative trial is illustrated in Fig. 1. Each trial started with a central fixation cross displayed in the centre of the screen (1500 ms duration), followed by the sequential presentation of two images. The trial was timed-out by the participant’s response (up to 10 s). Participants sat in front of the screen, at a distance of about 50 cm. Stimulus presentation and randomization were controlled using Presentation® software (Neurobehavioral Systems Inc, Albany, CA) running on a personal computer. Inter-trial timing was determined manually by the experimenter. To maintain the subject’s attention across the study, participants were instructed to decide whether the two stimuli in the pair were physically the ‘Same’ or ‘Different’, regardless of the self/other identity, by pressing two response buttons with the index finger of the left hand (Keenan et al., 2000a).

Transcranial magnetic stimulation

Electromyographic (EMG) recordings were made from the first dorsal interosseous (FDI) muscle of the left hand using a single differential surface EMG electrode, placed over the muscle belly. The ground electrode was placed over the left elbow. The EMG signal was amplified 1000 times with a BagnoliTM System, band-filtered (25–250 Hz) with a sampling rate of 2 kHz and digitized using a BioPac MP100 system (http://www.biopac.com) and stored for off-line analysis. A MagStim Rapid2 stimulator (The Magstim Company, Carmarthenshire, Wales, UK) was used with a standard figure-of-eight, 70-mm-diameter TMS coil. First, the individual optimal scalp position over the hand motor area of each subject was found by determining the scalp positioning at which the lower stimulation evoked the largest MEP. The intensity of single-pulse TMS was then adjusted to evoke MEPs with a mean peak-to-peak amplitude of ∼0.5 mV in a series of ten consecutive pulses in the relaxed left FDI (baseline). To stimulate primary motor cortex, the coil was always placed tangentially to the scalp at a 45° angle to the midline to induce a posterior–anterior current flow across the central sulcus. Throughout the experimental session, the TMS coil was held in place by a mechanical arm fixed on an adjustable tripod, and one experimenter stood directly behind the subject and continuously monitored the coil position, correcting the position of the subjects’ head in case of involuntary small head displacements. Based on results from a pilot study, magnetic pulses were randomly delivered at 300, 600 or 900 ms after the onset of the first picture in the pair and were triggered by the program used for stimuli presentation. The precise timing of stimulus onset and TMS triggering pulse were checked by means of an oscilloscope. Two baselines (ten pulses each) were acquired for each experimental block. The mean MEP amplitude of the baselines (i.e. before and after presentation of blocks) did not differ and were thus averaged to normalize MEP amplitude. Two baselines (ten pulses each) were acquired, one before and one after, for each experimental block. The mean of the baselines was calculated and used to normalize MEP amplitude. For each trial, MEP amplitude was expressed as a percentage of the mean peak-to-peak amplitude of the averaged baseline.

Experiment 2

Compared with Experiment 1, Experiment 2 reproduced a perfectly specular combination of stimulated hemisphere and recording/responding hand.

Participants

Twelve right-handed healthy participants (eight female; age range 19–39 years, mean 28 years), selected according to the same criteria as for Experiment 1, participated in the experiment after providing informed consent. Eight were naïve as to the purpose of the study and four participated also in the first experiment, which was approved by the INSERM Ethics Board and run in accordance with the Declaration of Helsinki.

Stimuli and procedure

The same stimuli and procedure as in Experiment 1 were used, except that stimuli were pictures of the participants’ right hand. Also, subjects answered the same/different task with their right hand.

Transcranial magnetic stimulation

The same TMS protocol was applied, except for the stimulated hemisphere. In this experiment we stimulated the left hemisphere, recording from the right FDI muscle.

Experiment 3

To investigate if any effect attributable to right-hemisphere self-processing would be present at earlier timings than those used in Experiment 1, as previously shown for the face (Théoret et al., 2004), we additionally investigated six subjects (five female; age range 26–39 years, mean 31 years), who had already taken part to Experiment 1 and were available to participate in this experiment. Stimuli and procedure were identical to those used in Experiment 1, as were the TMS procedures and protocol, with the exception that only one time interval of stimulation at 100 ms was used.

Results

Experiment 1

Participants were highly accurate in performing the behavioural task (mean of the accuracy for Hand = 98% and Mobile = 98%). An anova was conducted on the mean MEP percentage with Stimuli (Hand vs. Mobile), Owner (Self vs. Other) and Interval (300, 600, 900 ms) as within-participant variables. Fisher’s least significance difference post-hoc tests were applied. No main effect of Stimuli, Owner or Interval was found. Only the interaction Owner × Interval was significant (F2,22 = 5.06, P < 0.02): As illustrated in Fig. 2A, MEPs were larger when stimuli depicted ‘self’ as compared with ‘other’ images when TMS was delivered at 600 ms (< 0.04) and at 900 ms (< 0.04), but not at 300 ms (n.s.).

Figure 2.

 Experiment 1: mean MEP amplitude (SEM) calculated for Self and Other conditions following stimulation of the right hemisphere with respect to the baseline (grey dotted horizontal line at 100%), as a function of each timing for hand and mobile collapsed (A), and for hand and mobile separated (B). Asterisks indicate significant differences between conditions (< 0.05).

The three-way interaction including Stimuli (Hand, Mobile) was far from significant (= 0.54). As shown in Fig. 2B, MEP amplitude was seemingly modulated across TMS timings, irrespective of the nature of the observed object. To investigate the effect found at 600 and 900 ms, paired t-tests (one-tailed) were additionally conducted: a Self vs. Other difference was significant at 600 ms for Mobile (< 0.003) and marginally significant for the Hand (= 0.089) at 900 ms, confirming the joint contribution of Stimuli, as implied by the non-significant three-way interaction.

Experiment 2

Participants were very accurate in performing the behavioural task (mean of the accuracy for Hand = 94% and Mobile = 98%). As in Experiment 1, an anova was conducted on the mean MEP percentage with Stimuli (Hand vs. Mobile), Owner (Self vs. Other) and Interval (300, 600, 900 ms) as within-participant variables. No main effect or interaction was significant, the three-way interaction being far from significance (= 0.63; Fig. 3). Interestingly, the interaction Owner × Interval significant for the right hemisphere stimulation results was far from significant after stimulation of left motor cortex (F2,22 = 0.823, P = 0.452).

Figure 3.

 Experiment 2: mean MEP amplitude (SEM) calculated for Self and Other conditions following stimulation of the left hemisphere with respect to the baseline (grey dotted horizontal line at 100%), as a function of each timing for hand and mobile collapsed (A), and for hand and mobile separated (B).

Experiment 3

Participants were also very accurate at a behavioral level (mean of the accuracy for Hand = 97% and Mobile = 99%). An anova was conducted on the mean MEP percentage with Stimuli (Hand vs. Mobile) and Owner (Self vs. Other) as within-participant variables. No main effect or interaction was significant. For completeness, the results of the two-way interaction, which was far from significant (= 0.72), are illustrated in Fig. 4.

Figure 4.

 Experiment 3: mean MEP amplitude (SEM) following stimulation of the right hemisphere for the 100-ms TMS stimulation delay, as a function of stimuli condition for right hemisphere stimulation. Conventions as in Figs 2 and 3.

Discussion

Our own hand is a peculiar effector with at least partially separate representation in extrastriate body area (EBA) (Bracci et al., 2010). Indeed, the hand is the part of our body that mainly contributes to interacting with objects in the external environment. The present study tackled the question of whether vision of one’s own hand, compared with somebody else’s hand, engages self-processes, which are known to modulate corticospinal excitability (Keenan et al., 2001). To this aim, we derived TMS-induced MEPs as a measure of the right hemisphere corticospinal excitability while subjects were presented with pictures of a hand (their own or not), as well as a mobile phone (their own or not). To control for right hemispheric specialization for self-processes, we additionally measured corticospinal excitability of the left hemisphere. Our findings showed a right hemisphere-dependent increase in corticospinal excitability with Self stimuli that appeared at 600 ms and was maintained at 900 ms, being absent at earlier timings (100 and 300 ms).

The modulation observed when stimuli depicted one’s own hand is in agreement with similar effects found by other authors using face stimuli (Keenan et al., 2001; Théoret et al., 2004). These previous studies have shown that when presented with their own face, subjects’ corticospinal excitability measured from the right hemisphere is clearly increased (Keenan et al., 2001; Théoret et al., 2004). In the present study, the modulation observed with self-stimuli indicated three important points. First, the modulatory effects induced by self-processes on corticospinal excitability are not limited to vision of one’s own face, but are extended also to vision of one’s own hand. Second, we concur in showing that the right hemisphere, but not the left, is specialized in self-processing and extend this notion to hands and own objects (Fig. 5) (Keenan et al., 2001; Théoret et al., 2004; Frassinetti et al., 2008). Third, motor areas of the right hemisphere become sensitive to self-hand and self-mobile stimuli at relatively late time intervals (600 and 900 ms), but not at earlier intervals (100 and 300 ms).

Figure 5.

 Self-Other MEP ratios calculated on raw data for left (A) and right hemisphere (B). Light grey columns represent Hand stimuli while dark grey columns represent Mobile stimuli at the three intervals. Vertical lines denote SEM.

When considering the first point, very few studies have used hand stimuli to investigate self-processing modulation of corticospinal excitability. In one of these studies (Funase et al., 2007), self and other hand processing was not directly compared. More specifically, Funase et al. (2007) examined if direct (without a mirror) and indirect (with a mirror) observation of self movement in healthy subjects induced changes in MEP by TMS. They found that observation of self movement with and without a mirror increased MEP amplitude. This work, however, leaves any difference potentially due to specific self-hand processing unaddressed. When the effects produced by self vs. other’s hand observation were directly compared (Patuzzo et al., 2003), no significant differences were found in modulation of motor cortex excitability. In the latter study (Patuzzo et al., 2003), however, TMS pulses were delivered to the left hemisphere. Moreover, in both previous reports the modulation of corticospinal excitability was strictly related to the observation of moving hands. In contrast, the present study was designed to explicitly test for self-processing sensu stricto, by applying TMS to both the left and the right hemisphere, according to the critical role of the latter in bodily self-processing (Devue et al., 2007; Frassinetti et al., 2008; Hodzic et al., 2009) and without any confound possibly due to either overt or implicit (Urgesi et al., 2010) movement in hand stimuli. Therefore, the increase in corticospinal excitability of the right hemisphere, observed here following presentation of self-hands as compared with other people’s hands, is more directly attributable to self-recognition processes, possibly emerging from activation of the parieto-frontal network of the right hemisphere that has been assigned by functional magnetic resonance imaging, TMS and neuropsychological findings, with the role of coding for self-related information (Sugiura et al., 2006; Prabhu et al., 2007; Frassinetti et al., 2008).

It is worth noting that the increase in MEP amplitude for self-hands was not specific for corporeal objects, as it was similarly observed when participants were shown their own mobile phone, as compared with somebody else’s phone. Previous studies, examining the neural responses associated with viewing objects (Chao & Martin, 2000; Buccino et al., 2009), showed that viewing pictures of objects associated with a specific hand movement (e.g. a hammer) may activate the ventral premotor cortex (Chao & Martin, 2000). The same activation was not found for stimuli depicting non-graspable objects (e.g. houses), animals and faces. In a similar vein, behavioural and neurophysiological studies have demonstrated that mere observation of an object involves accessing motor programmes for interaction with the object, even in the absence of explicit intentions to act. For example, it has been shown that pragmatic features of an object automatically trigger components of specific actions, such as reaching or grasping (Tucker & Ellis, 1998, 2001, 2004; Craighero et al., 1999; Ellis & Tucker, 2000; Philipps & Ward, 2002). In light of these findings, one could argue that the observation of an object we are used to manipulating modulates the corticospinal excitability of parts of the primary motor cortex that control muscles implicated in this action. Here we recorded EMG activity from the FDI muscle, which is at least partially involved in grasping objects of the size and shape of a mobile phone. The interesting finding we observed in this respect is that corticospinal excitability was modulated by the ownership of the seen object, in that it was larger following the presentation of an owned, as compared with a non-owned mobile phone. While this result may suggest a specific functional organization of the motor cortex for our objects, this conclusion is partially at odd with studies that analysed the difference of motor excitability during the observation of graspable vs. non-graspable objects (e.g. Buccino et al., 2005), or the time course of changes in motor excitability before the execution of grasping movements, as compared with the mere observation of an object (Prabhu et al., 2007). Overall, activation due to graspability processes emerges within a short time-window after the presentation of a graspable object. Buccino et al. (2005), for example, found a difference between graspable and non-graspable objects 200 ms after object presentation. Prabhu et al. (2007) reported that corticospinal excitability was augmented only when it was measured about 100 ms before the actual grasping execution, whereas no changes were manifest during passive observation of a graspable object (i.e. outside the mental set of performing an action). In light of these reports, and the absence of any change in corticospinal excitability observed here when stimulating the left hemisphere, we can dismiss the hypothesis that the increase in excitability of the right hemisphere observed when subjects were displayed either Self or Other mobile phones could be ascribed to general effects of graspability. Finally, it appeared that corporeal (hand) and non-corporeal stimuli (phone) contributed to the increase in corticospinal excitability observed at later time intervals (600 and 900 ms), provided that they belonged to the observer (Self condition).

Besides extending our knowledge of self-processes to hand and hand-associated objects, the present findings also provide insight about the time course of these processes, by showing that consistent MEP increase can be observed at relatively late timings. Previous studies focusing on hand stimuli did not explore the time course of self-hand processing (Patuzzo et al., 2003; Funase et al., 2007). In contrast, the temporal profile of self-related processing has been investigated in studies using face stimuli. Théoret et al. (2004) analysed three distinct intervals (100, 200, 400 ms), but did not find significant differences among these timings, which all displayed an increase in corticospinal excitability following observation of self-face stimuli. Thus, at odds with the results reported here, the face seems to undergo fast self-recognition processes that, in turn, might be able to affect corticospinal excitability at very early stages. The consistent MEP increase observed at long time intervals (600 and 900 ms) after the presentation of Self hands (or mobile phones) could thus indicate that the motor cortex is informed at later stages about the self-status of visual stimuli. This additional new finding may indicate that right-hemisphere-dependent self-body and self-object processing is relatively slow compared with self-face processing (Théoret et al., 2004) and suggests the existence of two different networks subserving self-body parts vs. self-face processing. Such a possibility is supported by a previous neuropsychological study demonstrating that some patients with right-brain damage may have no self-advantage for self-body part processing, but preserved self-face processing (Frassinetti et al., 2010).

In conclusion, the results from this study suggest that a common stage for self-processing of hand and hand-associated objects may exist, which similarly affects corticospinal excitability. Future studies will, we hope, distinguish whether such processing emerges as the result of a functional reorganization of the motor cortex, possibly due to motor learning processes (Classen et al., 1998; Muellbacher et al., 2001; Alaerts et al., 2010), or as the consequence of an ‘extended’ representation of the body (Aglioti et al., 1996; Cardinali et al., 2009a,b; Carlson et al., 2010).

Acknowledgements

This work was supported by the DISCOS Marie Curie RTN project to S.S., a Lyon I – Bologna University mobility fellowship and a Vinci fellowship to E.Z., ANR and James S. McDonnell Foundation grants to A.F. and RFO Bologna University grant to F.F.

Abbreviations:
EMG

electromyographic

FDI

first dorsal interosseous

MEP

motor-evoked potential

TMS

transcranial magnetic stimulation

Ancillary