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Sensory incongruence leading to hand disownership modulates somatosensory cortical processing Q2
Naofumi Otsuru a, Akira Hashizume b, Daichi Nakamura a, Yuuki Endo a, Koji Inui c, Ryusuke Kakigi c and Louis Yuge a,* a
Division of Bio-Environmental Adaptation Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan b Department of Neurosurgery, Hiroshima University, Hiroshima, Japan c Department of Integrative Physiology, National Institute for Physiological Sciences, Okazaki, Japan
article info
abstract
Article history:
The sense of body ownership is based on integration of multimodal sensory information,
Received 10 December 2013
including tactile sensation, proprioception, and vision. Distorted body ownership con-
Reviewed 21 February 2014
tributes to the development of chronic pain syndromes and possibly symptoms of psy-
Revised 24 March 2014
chiatric disease. However, the effects of disownership on cortical processing of
Accepted 12 May 2014
somatosensory information are unknown. In the present study, we created a “disowner-
Action editor Norihiro Sadato
ship” condition in healthy individuals by manipulating the visual information indicating
Published online xxx
the location of the subject's own left hand using a mirror box and examined the influence of this disownership on cortical responses to electrical stimulation of the left index finger
Keywords:
using magnetoencephalography (MEG). The event-related magnetic field in the right pri-
Magnetoencephalography
mary somatosensory cortex at approximately 50 msec (M50) after stimulus was enhanced
Somatosensory
under the disownership condition. The present results suggest that M50 reflects a cortical
Multimodal integration
incongruence detection mechanism involving integration of sensory inputs from visual
Sensory incongruence
and proprioceptive systems. This signal may be valuable for future studies of the mechanisms underlying sense of body ownership and the role that disrupted sense of ownership has in neurological disease. © 2014 Published by Elsevier Ltd.
1.
Introduction
The primary somatosensory cortex (S1) contains several continuous somatotopic representation of the contralateral body surface (Nakamura et al., 1998; Penfield & Boldrey, 1937).
However, because body posture is always changing, the brain must realign tactile coordinates to precisely detect the location of superficial stimuli in space. The coordinate system for this spatial perception is based on integration of multimodal information, including vision and proprioception in addition to tactile sensation. Moreover, this system is critical for body
* Corresponding author. Division of Bio-Environmental Adaptation Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan. E-mail address: [email protected] (L. Yuge). http://dx.doi.org/10.1016/j.cortex.2014.05.005 0010-9452/© 2014 Published by Elsevier Ltd.
Please cite this article in press as: Otsuru, N., et al., Sensory incongruence leading to hand disownership modulates somatosensory cortical processing, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.2014.05.005
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awareness or sense of body ownership (Serino & Haggard, 2010). To maintain this sense of body ownership, there must be congruence between these different sensory modalities. However, it has been reported that patients suffering from chronic pain syndromes such as complex regional pain syndrome (CRPS), fibromyalgia, and phantom limb pain have distorted body awareness (Flor, Nikolajsen, & Staehelin, 2006; McCabe et al., 2009; Moseley, 2005). Some chronic pain patients reported mismatches between felt and seen limbs, and others reported that they were not aware of their limb position (Lewis, Kersten, McCabe, McPherson, & Blake, 2007). Moreover, Bultitude and Rafal (2010) demonstrated that the disturbance of body awareness precedes the development of CRPS, suggesting that distorted body awareness may be a cause rather than a consequence of chronic pain. The rubber hand illusion (RHI) has been widely used to investigate the role of crossmodal interactions and sensory incongruence in body awareness (Botvinick & Cohen, 1998; Ehrsson, Holmes, & Passingham, 2005; Ehrsson, Spence, & Passingham, 2004). In the RHI, seeing a rubber hand being brushed in synchrony with the corresponding (real) hand at the same location leads to a shift in the sense of ownership towards the rubber hand, accompanied by a sense of disowership towards the real hand (Longo, Schu¨u¨r, Kammers, Tsakiris, & Haggard, 2008; Moseley et al., 2008). Recently, it was reported that the disownership induced by the RHI altered the acuity of tactile perception (Folegatti, de , 2009). However, the Vignemont, Pavani, Rossetti, & Farne influence of disownership on somatosensory cortical processing is yet to be elucidated. To investigate whether disownership modulates somatosensory cortical processing, we manipulated the visual feedback of hand position using a mirror box. By changing the location of the visual image of a subject's right hand, we created incongruence between the seen (image) and the felt (real) left hand, analogous to RHI. We used whole-head magnetoencephalography (MEG) to examine the cortical activity under different sensory incongruence conditions to clarify the influence of disownership on somatosensory cortical processing.
2.
Materials and methods
2.1.
Subjects
Nine healthy males (25.1 ± 3.8 years) participated in this study. None had a history of neurological disorder or took any medication before the experiment. All were right-handed as assessed by the Edinburgh Handedness Inventory (Oldfield, 1971). Written informed consent was obtained from each participant before the study, which was approved by the Ethics Committee at Hiroshima University.
2.2.
anode to the distal part. The duration of the stimulation was .5 msec and the stimulus intensity was adjusted to twice the sensory threshold. The inter-stimulus interval (ISI) was set at 1000 msec.
2.3.
Experimental conditions
The subjects, comfortably seated in a magnetically shielded room, inserted their hands into a mirror box with their right index finger extended, as shown in Fig. 1. A mirror image of the right hand was observed to the left, whereas the real left hand was hidden from view. Therefore, subjects saw the reversed image of the right hand instead of the actual left hand paired with the real right hand. The ring electrode was attached at the same position on each index finger. A small square attached to the far edge of the mirror served as a fixation point [Fig. 1(A)]. The electrical stimulus was always presented to the hidden left index finger positioned 1.5 cm left and 2.5 cm above from the fixation point. We measured brain activity under four conditions [Fig. 1(B)]. There were two positions of the right hand (symmetric or asymmetric relative to the left) and two mirror image conditions (Absent or Present). In the absent mirror image condition, the mirror was covered with a plastic plate to eliminate all visual information about the hand. These four conditions are as follows. The positions of the right hand was (1) symmetrical in the absent mirror image condition (no mirror image of the right hand, sym-abs), (2) symmetrical with left hand in the present mirror image condition (the mirror image of right hand was in the same virtual position as the masked left hand) (sym-pre), (3) asymmetrical in the absent mirror image condition (asymabs), or (4) asymmetrical in the present mirror image condition (the mirror image of the right hand was positioned 5 cm below the masked actual left hand) (asym-pre). In the asympre condition, there was incongruence between visual and proprioceptive information on left hand position. Before starting the measurements for each condition, the subjects were asked to report where they felt the stimulation. We confirmed that in the asym-pre condition, all subjects felt as if the mirror image of the right hand (virtual left hand) has been stimulated in response to stimulation of the masked (real) left hand. In other words, sense of ownership shifted toward the mirror image of the right hand, accompanied by a sense of disowership toward the real left hand. In the other conditions (sym-abs, sym-pre, and asym-abs), all subjects felt the stimulation on the real left hand. Subjects were instructed to gaze at the fixation point to control for effects of topedown spatial attention and gaze direction. In the experiment, cortical responses to the left index finger stimulation were recorded in separate sessions for each condition. In one session, 75 artifact-free epochs (consisting of a pre-stimulus baseline plus the response) were averaged, and two sessions were performed for each condition. Therefore, 150 responses were averaged for each condition. The order of the sessions was randomized among subjects.
Stimulation 2.4.
The tactile stimulus used was a square-wave current pulse delivered to the left index finger through a ring electrode, with the cathode attached to the proximal part of the finger and the
MEG recording and analysis
The experiments were conducted in a magnetically shielded room. Somatosensory-evoked magnetic fields (SEFs) were
Please cite this article in press as: Otsuru, N., et al., Sensory incongruence leading to hand disownership modulates somatosensory cortical processing, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.2014.05.005
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3
Fig. 1 e Schematic illustration of the experimental paradigm used in this study. (A) Positions of left and right hand in symmetric and asymmetric conditions. (B) Experimental settings in each condition. Note that the position of the stimulated left hand and the fixation point were identical in all four conditions.
recorded with a helmet-shaped 306-channel MEG system (Vector-view, ELEKTA Neuromag, Helsinki, Finland) comprised of 102 identical triple-sensor elements. Each sensor element consisted of two orthogonal planar gradiometers and one magnetometer coupled to a multi-superconducting quantum interference device (SQUID), thus provided three independent measurements of the magnetic field. In this study, we analyzed MEG signals recorded from 204 planartype gradiometers. These planar gradiometers are powerful
enough to detect the largest signal just over local cerebral sources. The signals were recorded with a band-pass of .1e300 Hz and digitized at 1001 Hz. The epoch duration (recording period) for analysis was 500 msec, including a prestimulus baseline period of 100 msec. Trials with noise of >2700 fT/cm were rejected automatically from the averaging and 150 artifact-free trials were recorded in each condition. The MEG data were also filtered off-line with a band-pass filter of 1e100 Hz.
Please cite this article in press as: Otsuru, N., et al., Sensory incongruence leading to hand disownership modulates somatosensory cortical processing, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.2014.05.005
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We first calculated vector sums from the longitudinal and latitudinal derivatives of the MEG response recorded by the planar-type gradiometers at each of the 102 sensor locations. The data was obtained by squaring MEG signals for each of the two planer-type gradiometer at each sensor location, summing the squared signals, and then calculating the root of the sum as in previous studies (Kida et al., 2007; Raij, McEvoy, € kela € , & Hari, 1997) to look for the channel showing the Ma largest response. Next, we analyzed the areal mean signals (AMSs) from nine gradiometer pairs (one pair that showed the largest response and the surrounding eight in a 3 3 grid) computed by averaging these vector sums to measure amplitude in a region of interest (Fig. 2). This method of data
analysis replicated that of previous studies using the same € nen, & Salmelin, 2006; MEG system (Bonte, Parviainen, Hyto Nakata et al., 2008, 2009; Tarkiainen, Helenius, & Salmelin, 2003). To identify the cortical area activated in correspondence of M50 component, the inverse problem was solved using a timevarying equivalent current dipole (ECD) within a spherical conductor based on individual subject's magnetic resonance image (MRI) model. The MEG signals were evaluated at successive time points by a least-squares search using 14e20 sensors (7e10 x and y pairs of gradiometer) selected as described for measuring the M50 peak amplitude of AMS. These calculations yielded the three-dimensional (3D)
A
50 45 40 35 30 25 20 15 10 5
B
C
0 (fT/cm)
Fig. 2 e Magnetic fields evoked by electrical stimulation to the left index finger. (A) Waveforms recorded from 204 orthogonal planar-type gradiometers in the sym-pre condition in a representative subject. The red square represents the gradiometer pair that showed the largest response at approximately 50 msec after stimulus. Eight pairs surrounding the pair recording the largest response were used for calculating the areal mean signal (AMS). (B) Three-dimensional (3D) isocontour maps of magnetic fields at the peak of M50 in a representative subject. Areas surrounded with red and blue contour lines show the efflux and influx of magnetic fields, respectively. (C) Gradient map of the topography at the peak of M50. Please cite this article in press as: Otsuru, N., et al., Sensory incongruence leading to hand disownership modulates somatosensory cortical processing, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.2014.05.005
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location, orientation, and strength of the ECD. The goodnessof-fit value for a given ECD was calculated to indicate the percentage of field variance accounted for by the dipole, and model adequacy was assessed by examining the percent variance (Hari, Joutsiniemi, & Sarvas, 1988). Only ECDs explaining more than 85% of the field variance for selected periods of time were used for further analysis. Data acquisition and analysis were conducted as in a previous report € ma € la € inen, Hari, & Ilmoniemi, 1993). MRI scans were ob(Ha tained from all subjects with a 3.0-T Siemens Allegra scanner. T1-weighted coronal, axial, and sagittal image slices obtained every 1.5 mm were used for the 3D reconstruction of the brain surface. Before recording, a current was fed to four head position indicator (HPI) coils placed at known sites to obtain the exact location of the head with respect to the sensors. The resulting magnetic fields were then measured with the magnetometer to align the individual head coordinate system with the magnetometer coordinate system. The four HPI coils attached to the subject's head were measured with respect to three anatomical landmarks using a 3D digitizer to align MEG with MRI. The x-axis was fixed to the preauricular points, the positive direction being to the right. The positive y-axis passed through the nasion and the z-axis thus pointed upward. The statistical significance of the ECD location was assessed by a discriminant analysis using x, y, and z coordinates as variables. For the peak amplitude of the AMS and peak strength of ECD, a two-way analysis of variance (ANOVA) with repeated measures was performed with the mirror image condition (absent vs present) and position of the right hand (symmetric vs asymmetric relative to the true left hand) as factors. If the sphericity assumption was violated in Mauchly's sphericity test, the GreenhouseeGeisser correction coefficient epsilon was used to correct the degrees of freedom and the p values were recalculated. A post-hoc analysis was conducted using a paired t-test. In all statistical analyses, p < .05 was considered statistically significant. Data are expressed as the mean ± standard error (SE).
3.
Results
3.1.
Evoked magnetic fields
33.7 ± 4.8 fT/cm in the sym-abs, 29.8 ± 2.9 fT/cm in the sympre, 29.7 ± 4.0 fT/cm in the asym-abs, and 33 ± 4.0 fT/cm in the asym-pre condition. Fig. 3 shows grand-averaged waveforms of AMS across nine subjects. ANOVA revealed a significant interaction of the mirror image condition (absent vs present) and position of the right hand relative to the left (symmetric vs asymmetric) on the peak AMS amplitude of M50 (p ¼ .01), but no simple main effect of the mirror image condition or position. Post-hoc paired t-test showed the amplitude of M50 was significantly larger in asym-pre than asym-abs (p ¼ .02). These results imply that mean M50 amplitude was significantly increased when there was a mismatch between felt and observed left hand positions.
3.3.
ECD analysis
To examine whether incongruence between felt and observed hand position affects M50 at the cortical level, the peak strengths of the ECDs were compared among conditions. Fig. 4 shows the location of the ECDs superimposed on MR images for a representative subject. The ECD of M50 was located around the posterior bank of the central sulcus, corresponding to area 3b of the primary somatosensory cortex (S1). The mean location and peak strength of the M50 source is shown in Table 1. Discriminant analyses indicated that the ECD location M50
Symmetric position
200 (ms)
0
10 fT/cm M50
Electrical stimulation to the left index finger (mean, 2.7 ± .7 mA) elicited clear magnetic responses in the right parietal area (Fig. 2) in all subjects tested. This parietal signal peaked at approximately 50 msec (M50). An earlier component generated in the contralateral primary somatosensory cortex at approximately 20 msec after stimulus and a later component generated in the contralateral secondary somatosensory cortex at 100 msec after stimulus were found only in some subjects. Therefore, we used the M50 components for the subsequent analysis.
3.2.
AMS analysis
Asymmetric position
0
200 (ms) Absent
To examine whether incongruence between felt and observed hand position changes M50 at the sensor level, the peak AMS amplitudes obtained under the four experimental conditions were compared. The mean peak amplitude was
Present
Fig. 3 e The grand-averaged AMS of all nine subjects in each condition. Arrow head indicates the peak of M50.
Please cite this article in press as: Otsuru, N., et al., Sensory incongruence leading to hand disownership modulates somatosensory cortical processing, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.2014.05.005
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vs asymmetric) (p ¼ .04), but no simple main effect of condition or position. Post-hoc paired t-test showed the strength of ECD was significantly larger in asym-pre than asym-abs (p ¼ .01).Therefore, in accord with sensor level analysis, we also confirmed the activity at cortical level was significantly increased when there was a mismatch between felt and observed left hand position (Fig. 4).
Symmetric position M50
0
4. Absent Present
5 nAm 50 ms
Asymmetric position M50
0
Absent Present
Fig. 4 e Results of the ECD analysis. Left: location of ECDs superimposed on MR images of a representative subject. Right: time course of the strength of the activity in the primary somatosensory cortex (grand-averaged waveforms across subject). Filled circles and squares in MR images indicate the location of the ECD. Bars indicate the direction of the upward deflection in the waveform.
for M50 in S1 did not differ significantly between conditions (p ¼ .64.98). Similar to the AMS waveforms (Fig. 3), results of ANOVA for the ECD from S1 showed a significant interaction between the mirror image condition (absent vs present) and position of the right hand relative to the left (symmetric
Table 1 e Location and peak strength of the dipole in correspondence to M50 response component. Condition
Location x (mm)
Sym-abs Sym-pre Asym-abs Asym-pre
44.6 45.6 47.6 45.8
± 2.4 ± 1.8 ± 1.8 ± 1.8
y (mm) 23.3 23.4 20.6 22.5
± 3.5 ± 3.5 ± 3.3 ± 3.9
Peak strength z (mm) 90.9 ± 89.4 ± 91.0 ± 89.9 ±
2.7 2.2 3.1 2.7
(nAm) 16.1 ± 15.2 ± 13.8 ± 15.7 ±
2.7 2.0 2.3 2.4
Data are expressed as the mean ± SE. The x-axis was fixed with the preauricular points, the positive direction being to right. The positive y-axis passed through the nasion and z-axis thus pointed upward. Location was consistent with the response generated within the primary somatosensory cortex (S1).
Discussion
The present study investigated whether body part disownership caused by incongruence between felt and observed hand position modulates cortical activation, in this specific case right S1 activation in response to electrical stimulation to the left index finger. In the asym-pre condition, all the subjects felt as if the mirror image of the right hand (virtual left hand) has been stimulated in response to stimulation of the masked (real) left hand. That is, the asym-pre condition successfully produced disownership towards the real left hand as shown in previous RHI studies (Longo et al., 2008; Moseley et al., 2008). Moreover, we observed significant enhancement of the M50 component in the contralateral (right) S1 in the asym-pre condition. These results suggest that S1 activity at approximately 50 msec after stimulation reflects changes in body awareness (dependent on integration of visual and proprioceptive information) and that this signal is enhanced when there is distortion of body awareness induced by a visualeproprioceptive mismatch. While it is known that spatial attention and gaze direction also modulate sensory processing in S1 (Forster & Eimer, 2005; Gillmeister, Sambo, & Forster, 2010; Mima, Nagamine, Nakamura, & Shibasaki, 1998), the position of the stimulated left finger was fixed, and subjects were instructed to gaze at a fixation point throughout the experiment. Therefore, it is unlikely that topedown spatial attention and gaze direction influenced these results.
4.1. Multisensory modulation in the primary somatosensory cortex The M50 component following finger stimulation has been described in previous papers as originating mainly from 3b area of S1 (Braun et al., 2001; Elbert, Pantev, Wienbruch, Rockstroh, & Taub, 1995; Schaefer, Flor, Heinze, & Rotte, 2006), consistent with the present results. We observed that the activity in S1 following electrical stimulation was modulated by the conflict between felt (proprioceptive) and seen (visual) information about the left hand, suggesting that the S1 activity is involved in multisensory integration. Previous studies demonstrated that viewing one's own hand during digit stimulation modulates S1 activity and improves tactile acuity (Cardini, Longo, & Haggard, 2011). Moreover, this improved acuity was abolished by disruptive transcranial magnetic stimulation (TMS) of S1 (Fiorio & Haggard, 2005), supporting the notions that S1 is involved in the integration system using visual and somatosensory information. The posterior parietal cortex (PPC), an area that receives convergent inputs from both the visual and somatosensory systems ve, Olivier, Pouget, & Duhamel, 2005; Graziano, (Avillac, Dene 2000), is widely regarded as a critical center of multimodal
Please cite this article in press as: Otsuru, N., et al., Sensory incongruence leading to hand disownership modulates somatosensory cortical processing, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.2014.05.005
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sensory integration. A previous TMS study in humans demonstrated a direct role of PPC in the integration of multi, & Pienkos, sensory inputs (Ro, Wallace, Hagedorn, Farne 2004). Therefore, the enhanced S1 response by incongruence between the felt and seen left hand may arise from the feedback from PPC. A previous MEG study investigating serial processing of tactile stimulation confirmed that tactile information reaches PPC at approximately 22 msec after hand stimulation (Inui, Wang, Tamura, Kaneoke, & Kakigi, 2004), allowing sufficient time for feedback from PPC to influence the M50 signal in S1.
4.2.
Features of M50 and relevance to body awareness
The M20 component is the earliest waveform detected in S1 following median nerve stimulation (Allison et al., 1989; Wood, Cohen, Cuffin, Yarita, & Allison, 1985) that has a clear somatotopic representation and faithfully reflects the in€ ki & Forss, 1998). On tensity of peripheral stimulation (Jousma the other hand, previous studies reported that M50 appeared to be influenced by visual information of own body. Cardini et al. (2011) showed that vision of the hand modulates the suppression of P50, the EEG counterpart of M50. Furthermore, Schaefer et al. (2006) showed that manipulating visual information about the hand alters the source of the M50 component in S1 following digit stimulation. Specifically, cortical representation of the stimulated digit was modulated according to whether a touch observed on video was perceived as own. However, in the present study, we found no significant difference in S1 dipole location among conditions, probably because participants did not have to attend to left hand location and fixated their gaze on a point between felt and observed hand in the asym-pre condition. These studies strongly supported the inference that information about own body location affects M50 activity in S1.
4.3. Possible roles of M50 in the arousal system and relevance to chronic pain In the present study, we found significant enhancement of M50 when there was incongruence between felt and observed hand position. Incongruence caused by a conflict between visual input and proprioceptive feedback has been implicated in the pathophysiology of chronic pain (Harris, 1999). For example, McCabe, Haigh, Halligan, and Blake (2005) showed that incongruence can induce sensory disturbance, including pain, even in healthy subjects and concluded that this abnormal sensory state triggers a warning mechanism and alters the processing of nociceptive inputs. Akatsuka et al. (2007) found a mismatch-like S1 response peaking at 30e70 msec using an oddball stimulus paradigm. This mismatch cortical response is elicited by infrequent stimuli within a train of frequent (predictable) stimuli and is considered to reflect pre-attentive activity of a change-detection system related to arousal or warning. These findings support the ideas that the observed enhancement of M50 represents activation of a cortical arousal system due to the abnormal incongruence state, and that the prolonged influence of this incongruence on S1 activation and processing may cause chronic pain. Consistent with these proposals, Bultitude and
7
Rafal (2010) reported that disturbed body awareness preceded the development of CRPS, indicating that pain is a consequence of distorted body awareness. Furthermore, in patients with fibromyalgia and CRPS, abnormal inhibition and enhancement of P50 has been observed (Juottonen et al., 2002; Montoya et al., 2005, 2006), which support our ideas.
5.
Conclusions
We provide compelling evidence that disownership caused by incongruence between felt and observed hand position modulates the M50 activity in S1. We suggest that activity in S1 reflects not just somatosensory inputs but the integrated activity of multiple sensory modalities, including visual and proprioceptive inputs, to form a sense of body awareness. Incongruence between these inputs appears to trigger a cortical arousal system that may alter sensory processing. Previous results suggest that one consequence of this arousal is enhanced pain perception. Further study is required to identify the neurological processes underlying M50 in the arousal system and the possible contribution of this arousal system to chronic pain. In any case, M50 may be a useful biomarker for future studies on sense of body ownership.
Acknowledgments This study was supported by a Grant-in-aid for Young Scientists (B) (24700578) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. Q1
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Please cite this article in press as: Otsuru, N., et al., Sensory incongruence leading to hand disownership modulates somatosensory cortical processing, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.2014.05.005
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Ehrsson, H. H., Holmes, N. P., & Passingham, R. E. (2005). Touching a rubber hand: feeling of body ownership is associated with activity in multisensory brain areas. The Journal of Neuroscience, 25, 10564e10573. Ehrsson, H. H., Spence, C., & Passingham, R. E. (2004). That's my hand! Activity in premotor cortex reflects feeling of ownership of a limb. Science, 305, 875e877. Elbert, T., Pantev, C., Wienbruch, C., Rockstroh, B., & Taub, E. (1995). Increased cortical representation of the fingers of the left hand in string players. Science, 270, 305e307. Fiorio, M., & Haggard, P. (2005). Viewing the body prepares the brain for touch: effects of TMS over somatosensory cortex. European Journal of Neuroscience, 22, 773e777. Flor, H., Nikolajsen, L., & Staehelin, J. T. (2006). Phantom limb pain: a case of maladaptive CNS plasticity? Nature Reviews. Neuroscience, 7, 873e881. , A. Folegatti, A., de Vignemont, F., Pavani, F., Rossetti, Y., & Farne (2009). Losing one's hand: visual-proprioceptive conflict affects touch perception. PloS One, 4, e6920. Forster, B., & Eimer, M. (2005). Vision and gaze direction modulate tactile processing in somatosensory cortex: evidence from event-related brain potentials. Experimental Brain Research, 165, 8e18. Gillmeister, H., Sambo, C. F., & Forster, B. (2010). Which finger? Early effects of attentional selection within the hand are absent when the hand is viewed. European Journal of Neuroscience, 31, 1874e1881. Graziano, M. S. (2000). Coding the location of the arm by sight. Science, 290, 1782e1786. € ma € la € inen, M., Hari, R., & Ilmoniemi, R. (1993). Ha Magnetoencephalographydtheory, instrumentation, and applications to noninvasive studies of the working human brain. Reviews of Modern Physics, 65, 413e497. Hari, R., Joutsiniemi, S. L., & Sarvas, J. (1988). Spatial resolution of neuromagnetic records: theoretical calculations in a spherical model. Electroencephalography and Clinical Neurophysiology, 71, 64e72. Harris, A. J. (1999). Cortical origin of pathological pain. Lancet, 354, 1464e1466. Inui, K., Wang, X., Tamura, Y., Kaneoke, Y., & Kakigi, R. (2004). Serial processing in the human somatosensory system. Cerebral Cortex, 14, 851e857. € ki, V., & Forss, N. (1998). Effects of stimulus intensity on Jousma signals from human somatosensory cortices. NeuroReport, 9, 3427e3431. n, T., Hurri, H., Hari, R., & Forss, N. Juottonen, K., Gockel, M., Sile (2002). Altered central sensorimotor processing in patients with complex regional pain syndrome. Pain, 98, 315e323. Kida, T., Inui, K., Wasaka, T., Akatsuka, K., Tanaka, E., & Kakigi, R. (2007). Time-varying cortical activations related to visualetactile cross-modal links in spatial selective attention. Journal of Neurophysiology, 97, 3585e3596. Lewis, J. S., Kersten, P., McCabe, C. S., McPherson, K. M., & Blake, D. R. (2007). Body perception disturbance: a contribution to pain in complex regional pain syndrome (CRPS). Pain, 133, 111e119. Longo, M. R., Schu¨u¨r, F., Kammers, M. P. M., Tsakiris, M., & Haggard, P. (2008). What is embodiment? A psychometric approach. Cognition, 107, 978e998. McCabe, C. S., Cohen, H., Hall, J., Lewis, J., Rodham, K., & Harris, N. (2009). Somatosensory conflicts in complex regional
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Research report
Sensory incongruence leading to hand disownership modulates somatosensory cortical processing Q2
Naofumi Otsuru a, Akira Hashizume b, Daichi Nakamura a, Yuuki Endo a, Koji Inui c, Ryusuke Kakigi c and Louis Yuge a,* a
Division of Bio-Environmental Adaptation Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan b Department of Neurosurgery, Hiroshima University, Hiroshima, Japan c Department of Integrative Physiology, National Institute for Physiological Sciences, Okazaki, Japan
article info
abstract
Article history:
The sense of body ownership is based on integration of multimodal sensory information,
Received 10 December 2013
including tactile sensation, proprioception, and vision. Distorted body ownership con-
Reviewed 21 February 2014
tributes to the development of chronic pain syndromes and possibly symptoms of psy-
Revised 24 March 2014
chiatric disease. However, the effects of disownership on cortical processing of
Accepted 12 May 2014
somatosensory information are unknown. In the present study, we created a “disowner-
Action editor Norihiro Sadato
ship” condition in healthy individuals by manipulating the visual information indicating
Published online xxx
the location of the subject's own left hand using a mirror box and examined the influence of this disownership on cortical responses to electrical stimulation of the left index finger
Keywords:
using magnetoencephalography (MEG). The event-related magnetic field in the right pri-
Magnetoencephalography
mary somatosensory cortex at approximately 50 msec (M50) after stimulus was enhanced
Somatosensory
under the disownership condition. The present results suggest that M50 reflects a cortical
Multimodal integration
incongruence detection mechanism involving integration of sensory inputs from visual
Sensory incongruence
and proprioceptive systems. This signal may be valuable for future studies of the mechanisms underlying sense of body ownership and the role that disrupted sense of ownership has in neurological disease. © 2014 Published by Elsevier Ltd.
1.
Introduction
The primary somatosensory cortex (S1) contains several continuous somatotopic representation of the contralateral body surface (Nakamura et al., 1998; Penfield & Boldrey, 1937).
However, because body posture is always changing, the brain must realign tactile coordinates to precisely detect the location of superficial stimuli in space. The coordinate system for this spatial perception is based on integration of multimodal information, including vision and proprioception in addition to tactile sensation. Moreover, this system is critical for body
* Corresponding author. Division of Bio-Environmental Adaptation Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan. E-mail address: [email protected] (L. Yuge). http://dx.doi.org/10.1016/j.cortex.2014.05.005 0010-9452/© 2014 Published by Elsevier Ltd.
Please cite this article in press as: Otsuru, N., et al., Sensory incongruence leading to hand disownership modulates somatosensory cortical processing, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.2014.05.005
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awareness or sense of body ownership (Serino & Haggard, 2010). To maintain this sense of body ownership, there must be congruence between these different sensory modalities. However, it has been reported that patients suffering from chronic pain syndromes such as complex regional pain syndrome (CRPS), fibromyalgia, and phantom limb pain have distorted body awareness (Flor, Nikolajsen, & Staehelin, 2006; McCabe et al., 2009; Moseley, 2005). Some chronic pain patients reported mismatches between felt and seen limbs, and others reported that they were not aware of their limb position (Lewis, Kersten, McCabe, McPherson, & Blake, 2007). Moreover, Bultitude and Rafal (2010) demonstrated that the disturbance of body awareness precedes the development of CRPS, suggesting that distorted body awareness may be a cause rather than a consequence of chronic pain. The rubber hand illusion (RHI) has been widely used to investigate the role of crossmodal interactions and sensory incongruence in body awareness (Botvinick & Cohen, 1998; Ehrsson, Holmes, & Passingham, 2005; Ehrsson, Spence, & Passingham, 2004). In the RHI, seeing a rubber hand being brushed in synchrony with the corresponding (real) hand at the same location leads to a shift in the sense of ownership towards the rubber hand, accompanied by a sense of disowership towards the real hand (Longo, Schu¨u¨r, Kammers, Tsakiris, & Haggard, 2008; Moseley et al., 2008). Recently, it was reported that the disownership induced by the RHI altered the acuity of tactile perception (Folegatti, de , 2009). However, the Vignemont, Pavani, Rossetti, & Farne influence of disownership on somatosensory cortical processing is yet to be elucidated. To investigate whether disownership modulates somatosensory cortical processing, we manipulated the visual feedback of hand position using a mirror box. By changing the location of the visual image of a subject's right hand, we created incongruence between the seen (image) and the felt (real) left hand, analogous to RHI. We used whole-head magnetoencephalography (MEG) to examine the cortical activity under different sensory incongruence conditions to clarify the influence of disownership on somatosensory cortical processing.
2.
Materials and methods
2.1.
Subjects
Nine healthy males (25.1 ± 3.8 years) participated in this study. None had a history of neurological disorder or took any medication before the experiment. All were right-handed as assessed by the Edinburgh Handedness Inventory (Oldfield, 1971). Written informed consent was obtained from each participant before the study, which was approved by the Ethics Committee at Hiroshima University.
2.2.
anode to the distal part. The duration of the stimulation was .5 msec and the stimulus intensity was adjusted to twice the sensory threshold. The inter-stimulus interval (ISI) was set at 1000 msec.
2.3.
Experimental conditions
The subjects, comfortably seated in a magnetically shielded room, inserted their hands into a mirror box with their right index finger extended, as shown in Fig. 1. A mirror image of the right hand was observed to the left, whereas the real left hand was hidden from view. Therefore, subjects saw the reversed image of the right hand instead of the actual left hand paired with the real right hand. The ring electrode was attached at the same position on each index finger. A small square attached to the far edge of the mirror served as a fixation point [Fig. 1(A)]. The electrical stimulus was always presented to the hidden left index finger positioned 1.5 cm left and 2.5 cm above from the fixation point. We measured brain activity under four conditions [Fig. 1(B)]. There were two positions of the right hand (symmetric or asymmetric relative to the left) and two mirror image conditions (Absent or Present). In the absent mirror image condition, the mirror was covered with a plastic plate to eliminate all visual information about the hand. These four conditions are as follows. The positions of the right hand was (1) symmetrical in the absent mirror image condition (no mirror image of the right hand, sym-abs), (2) symmetrical with left hand in the present mirror image condition (the mirror image of right hand was in the same virtual position as the masked left hand) (sym-pre), (3) asymmetrical in the absent mirror image condition (asymabs), or (4) asymmetrical in the present mirror image condition (the mirror image of the right hand was positioned 5 cm below the masked actual left hand) (asym-pre). In the asympre condition, there was incongruence between visual and proprioceptive information on left hand position. Before starting the measurements for each condition, the subjects were asked to report where they felt the stimulation. We confirmed that in the asym-pre condition, all subjects felt as if the mirror image of the right hand (virtual left hand) has been stimulated in response to stimulation of the masked (real) left hand. In other words, sense of ownership shifted toward the mirror image of the right hand, accompanied by a sense of disowership toward the real left hand. In the other conditions (sym-abs, sym-pre, and asym-abs), all subjects felt the stimulation on the real left hand. Subjects were instructed to gaze at the fixation point to control for effects of topedown spatial attention and gaze direction. In the experiment, cortical responses to the left index finger stimulation were recorded in separate sessions for each condition. In one session, 75 artifact-free epochs (consisting of a pre-stimulus baseline plus the response) were averaged, and two sessions were performed for each condition. Therefore, 150 responses were averaged for each condition. The order of the sessions was randomized among subjects.
Stimulation 2.4.
The tactile stimulus used was a square-wave current pulse delivered to the left index finger through a ring electrode, with the cathode attached to the proximal part of the finger and the
MEG recording and analysis
The experiments were conducted in a magnetically shielded room. Somatosensory-evoked magnetic fields (SEFs) were
Please cite this article in press as: Otsuru, N., et al., Sensory incongruence leading to hand disownership modulates somatosensory cortical processing, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.2014.05.005
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3
Fig. 1 e Schematic illustration of the experimental paradigm used in this study. (A) Positions of left and right hand in symmetric and asymmetric conditions. (B) Experimental settings in each condition. Note that the position of the stimulated left hand and the fixation point were identical in all four conditions.
recorded with a helmet-shaped 306-channel MEG system (Vector-view, ELEKTA Neuromag, Helsinki, Finland) comprised of 102 identical triple-sensor elements. Each sensor element consisted of two orthogonal planar gradiometers and one magnetometer coupled to a multi-superconducting quantum interference device (SQUID), thus provided three independent measurements of the magnetic field. In this study, we analyzed MEG signals recorded from 204 planartype gradiometers. These planar gradiometers are powerful
enough to detect the largest signal just over local cerebral sources. The signals were recorded with a band-pass of .1e300 Hz and digitized at 1001 Hz. The epoch duration (recording period) for analysis was 500 msec, including a prestimulus baseline period of 100 msec. Trials with noise of >2700 fT/cm were rejected automatically from the averaging and 150 artifact-free trials were recorded in each condition. The MEG data were also filtered off-line with a band-pass filter of 1e100 Hz.
Please cite this article in press as: Otsuru, N., et al., Sensory incongruence leading to hand disownership modulates somatosensory cortical processing, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.2014.05.005
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We first calculated vector sums from the longitudinal and latitudinal derivatives of the MEG response recorded by the planar-type gradiometers at each of the 102 sensor locations. The data was obtained by squaring MEG signals for each of the two planer-type gradiometer at each sensor location, summing the squared signals, and then calculating the root of the sum as in previous studies (Kida et al., 2007; Raij, McEvoy, € kela € , & Hari, 1997) to look for the channel showing the Ma largest response. Next, we analyzed the areal mean signals (AMSs) from nine gradiometer pairs (one pair that showed the largest response and the surrounding eight in a 3 3 grid) computed by averaging these vector sums to measure amplitude in a region of interest (Fig. 2). This method of data
analysis replicated that of previous studies using the same € nen, & Salmelin, 2006; MEG system (Bonte, Parviainen, Hyto Nakata et al., 2008, 2009; Tarkiainen, Helenius, & Salmelin, 2003). To identify the cortical area activated in correspondence of M50 component, the inverse problem was solved using a timevarying equivalent current dipole (ECD) within a spherical conductor based on individual subject's magnetic resonance image (MRI) model. The MEG signals were evaluated at successive time points by a least-squares search using 14e20 sensors (7e10 x and y pairs of gradiometer) selected as described for measuring the M50 peak amplitude of AMS. These calculations yielded the three-dimensional (3D)
A
50 45 40 35 30 25 20 15 10 5
B
C
0 (fT/cm)
Fig. 2 e Magnetic fields evoked by electrical stimulation to the left index finger. (A) Waveforms recorded from 204 orthogonal planar-type gradiometers in the sym-pre condition in a representative subject. The red square represents the gradiometer pair that showed the largest response at approximately 50 msec after stimulus. Eight pairs surrounding the pair recording the largest response were used for calculating the areal mean signal (AMS). (B) Three-dimensional (3D) isocontour maps of magnetic fields at the peak of M50 in a representative subject. Areas surrounded with red and blue contour lines show the efflux and influx of magnetic fields, respectively. (C) Gradient map of the topography at the peak of M50. Please cite this article in press as: Otsuru, N., et al., Sensory incongruence leading to hand disownership modulates somatosensory cortical processing, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.2014.05.005
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location, orientation, and strength of the ECD. The goodnessof-fit value for a given ECD was calculated to indicate the percentage of field variance accounted for by the dipole, and model adequacy was assessed by examining the percent variance (Hari, Joutsiniemi, & Sarvas, 1988). Only ECDs explaining more than 85% of the field variance for selected periods of time were used for further analysis. Data acquisition and analysis were conducted as in a previous report € ma € la € inen, Hari, & Ilmoniemi, 1993). MRI scans were ob(Ha tained from all subjects with a 3.0-T Siemens Allegra scanner. T1-weighted coronal, axial, and sagittal image slices obtained every 1.5 mm were used for the 3D reconstruction of the brain surface. Before recording, a current was fed to four head position indicator (HPI) coils placed at known sites to obtain the exact location of the head with respect to the sensors. The resulting magnetic fields were then measured with the magnetometer to align the individual head coordinate system with the magnetometer coordinate system. The four HPI coils attached to the subject's head were measured with respect to three anatomical landmarks using a 3D digitizer to align MEG with MRI. The x-axis was fixed to the preauricular points, the positive direction being to the right. The positive y-axis passed through the nasion and the z-axis thus pointed upward. The statistical significance of the ECD location was assessed by a discriminant analysis using x, y, and z coordinates as variables. For the peak amplitude of the AMS and peak strength of ECD, a two-way analysis of variance (ANOVA) with repeated measures was performed with the mirror image condition (absent vs present) and position of the right hand (symmetric vs asymmetric relative to the true left hand) as factors. If the sphericity assumption was violated in Mauchly's sphericity test, the GreenhouseeGeisser correction coefficient epsilon was used to correct the degrees of freedom and the p values were recalculated. A post-hoc analysis was conducted using a paired t-test. In all statistical analyses, p < .05 was considered statistically significant. Data are expressed as the mean ± standard error (SE).
3.
Results
3.1.
Evoked magnetic fields
33.7 ± 4.8 fT/cm in the sym-abs, 29.8 ± 2.9 fT/cm in the sympre, 29.7 ± 4.0 fT/cm in the asym-abs, and 33 ± 4.0 fT/cm in the asym-pre condition. Fig. 3 shows grand-averaged waveforms of AMS across nine subjects. ANOVA revealed a significant interaction of the mirror image condition (absent vs present) and position of the right hand relative to the left (symmetric vs asymmetric) on the peak AMS amplitude of M50 (p ¼ .01), but no simple main effect of the mirror image condition or position. Post-hoc paired t-test showed the amplitude of M50 was significantly larger in asym-pre than asym-abs (p ¼ .02). These results imply that mean M50 amplitude was significantly increased when there was a mismatch between felt and observed left hand positions.
3.3.
ECD analysis
To examine whether incongruence between felt and observed hand position affects M50 at the cortical level, the peak strengths of the ECDs were compared among conditions. Fig. 4 shows the location of the ECDs superimposed on MR images for a representative subject. The ECD of M50 was located around the posterior bank of the central sulcus, corresponding to area 3b of the primary somatosensory cortex (S1). The mean location and peak strength of the M50 source is shown in Table 1. Discriminant analyses indicated that the ECD location M50
Symmetric position
200 (ms)
0
10 fT/cm M50
Electrical stimulation to the left index finger (mean, 2.7 ± .7 mA) elicited clear magnetic responses in the right parietal area (Fig. 2) in all subjects tested. This parietal signal peaked at approximately 50 msec (M50). An earlier component generated in the contralateral primary somatosensory cortex at approximately 20 msec after stimulus and a later component generated in the contralateral secondary somatosensory cortex at 100 msec after stimulus were found only in some subjects. Therefore, we used the M50 components for the subsequent analysis.
3.2.
AMS analysis
Asymmetric position
0
200 (ms) Absent
To examine whether incongruence between felt and observed hand position changes M50 at the sensor level, the peak AMS amplitudes obtained under the four experimental conditions were compared. The mean peak amplitude was
Present
Fig. 3 e The grand-averaged AMS of all nine subjects in each condition. Arrow head indicates the peak of M50.
Please cite this article in press as: Otsuru, N., et al., Sensory incongruence leading to hand disownership modulates somatosensory cortical processing, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.2014.05.005
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vs asymmetric) (p ¼ .04), but no simple main effect of condition or position. Post-hoc paired t-test showed the strength of ECD was significantly larger in asym-pre than asym-abs (p ¼ .01).Therefore, in accord with sensor level analysis, we also confirmed the activity at cortical level was significantly increased when there was a mismatch between felt and observed left hand position (Fig. 4).
Symmetric position M50
0
4. Absent Present
5 nAm 50 ms
Asymmetric position M50
0
Absent Present
Fig. 4 e Results of the ECD analysis. Left: location of ECDs superimposed on MR images of a representative subject. Right: time course of the strength of the activity in the primary somatosensory cortex (grand-averaged waveforms across subject). Filled circles and squares in MR images indicate the location of the ECD. Bars indicate the direction of the upward deflection in the waveform.
for M50 in S1 did not differ significantly between conditions (p ¼ .64.98). Similar to the AMS waveforms (Fig. 3), results of ANOVA for the ECD from S1 showed a significant interaction between the mirror image condition (absent vs present) and position of the right hand relative to the left (symmetric
Table 1 e Location and peak strength of the dipole in correspondence to M50 response component. Condition
Location x (mm)
Sym-abs Sym-pre Asym-abs Asym-pre
44.6 45.6 47.6 45.8
± 2.4 ± 1.8 ± 1.8 ± 1.8
y (mm) 23.3 23.4 20.6 22.5
± 3.5 ± 3.5 ± 3.3 ± 3.9
Peak strength z (mm) 90.9 ± 89.4 ± 91.0 ± 89.9 ±
2.7 2.2 3.1 2.7
(nAm) 16.1 ± 15.2 ± 13.8 ± 15.7 ±
2.7 2.0 2.3 2.4
Data are expressed as the mean ± SE. The x-axis was fixed with the preauricular points, the positive direction being to right. The positive y-axis passed through the nasion and z-axis thus pointed upward. Location was consistent with the response generated within the primary somatosensory cortex (S1).
Discussion
The present study investigated whether body part disownership caused by incongruence between felt and observed hand position modulates cortical activation, in this specific case right S1 activation in response to electrical stimulation to the left index finger. In the asym-pre condition, all the subjects felt as if the mirror image of the right hand (virtual left hand) has been stimulated in response to stimulation of the masked (real) left hand. That is, the asym-pre condition successfully produced disownership towards the real left hand as shown in previous RHI studies (Longo et al., 2008; Moseley et al., 2008). Moreover, we observed significant enhancement of the M50 component in the contralateral (right) S1 in the asym-pre condition. These results suggest that S1 activity at approximately 50 msec after stimulation reflects changes in body awareness (dependent on integration of visual and proprioceptive information) and that this signal is enhanced when there is distortion of body awareness induced by a visualeproprioceptive mismatch. While it is known that spatial attention and gaze direction also modulate sensory processing in S1 (Forster & Eimer, 2005; Gillmeister, Sambo, & Forster, 2010; Mima, Nagamine, Nakamura, & Shibasaki, 1998), the position of the stimulated left finger was fixed, and subjects were instructed to gaze at a fixation point throughout the experiment. Therefore, it is unlikely that topedown spatial attention and gaze direction influenced these results.
4.1. Multisensory modulation in the primary somatosensory cortex The M50 component following finger stimulation has been described in previous papers as originating mainly from 3b area of S1 (Braun et al., 2001; Elbert, Pantev, Wienbruch, Rockstroh, & Taub, 1995; Schaefer, Flor, Heinze, & Rotte, 2006), consistent with the present results. We observed that the activity in S1 following electrical stimulation was modulated by the conflict between felt (proprioceptive) and seen (visual) information about the left hand, suggesting that the S1 activity is involved in multisensory integration. Previous studies demonstrated that viewing one's own hand during digit stimulation modulates S1 activity and improves tactile acuity (Cardini, Longo, & Haggard, 2011). Moreover, this improved acuity was abolished by disruptive transcranial magnetic stimulation (TMS) of S1 (Fiorio & Haggard, 2005), supporting the notions that S1 is involved in the integration system using visual and somatosensory information. The posterior parietal cortex (PPC), an area that receives convergent inputs from both the visual and somatosensory systems ve, Olivier, Pouget, & Duhamel, 2005; Graziano, (Avillac, Dene 2000), is widely regarded as a critical center of multimodal
Please cite this article in press as: Otsuru, N., et al., Sensory incongruence leading to hand disownership modulates somatosensory cortical processing, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.2014.05.005
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sensory integration. A previous TMS study in humans demonstrated a direct role of PPC in the integration of multi, & Pienkos, sensory inputs (Ro, Wallace, Hagedorn, Farne 2004). Therefore, the enhanced S1 response by incongruence between the felt and seen left hand may arise from the feedback from PPC. A previous MEG study investigating serial processing of tactile stimulation confirmed that tactile information reaches PPC at approximately 22 msec after hand stimulation (Inui, Wang, Tamura, Kaneoke, & Kakigi, 2004), allowing sufficient time for feedback from PPC to influence the M50 signal in S1.
4.2.
Features of M50 and relevance to body awareness
The M20 component is the earliest waveform detected in S1 following median nerve stimulation (Allison et al., 1989; Wood, Cohen, Cuffin, Yarita, & Allison, 1985) that has a clear somatotopic representation and faithfully reflects the in€ ki & Forss, 1998). On tensity of peripheral stimulation (Jousma the other hand, previous studies reported that M50 appeared to be influenced by visual information of own body. Cardini et al. (2011) showed that vision of the hand modulates the suppression of P50, the EEG counterpart of M50. Furthermore, Schaefer et al. (2006) showed that manipulating visual information about the hand alters the source of the M50 component in S1 following digit stimulation. Specifically, cortical representation of the stimulated digit was modulated according to whether a touch observed on video was perceived as own. However, in the present study, we found no significant difference in S1 dipole location among conditions, probably because participants did not have to attend to left hand location and fixated their gaze on a point between felt and observed hand in the asym-pre condition. These studies strongly supported the inference that information about own body location affects M50 activity in S1.
4.3. Possible roles of M50 in the arousal system and relevance to chronic pain In the present study, we found significant enhancement of M50 when there was incongruence between felt and observed hand position. Incongruence caused by a conflict between visual input and proprioceptive feedback has been implicated in the pathophysiology of chronic pain (Harris, 1999). For example, McCabe, Haigh, Halligan, and Blake (2005) showed that incongruence can induce sensory disturbance, including pain, even in healthy subjects and concluded that this abnormal sensory state triggers a warning mechanism and alters the processing of nociceptive inputs. Akatsuka et al. (2007) found a mismatch-like S1 response peaking at 30e70 msec using an oddball stimulus paradigm. This mismatch cortical response is elicited by infrequent stimuli within a train of frequent (predictable) stimuli and is considered to reflect pre-attentive activity of a change-detection system related to arousal or warning. These findings support the ideas that the observed enhancement of M50 represents activation of a cortical arousal system due to the abnormal incongruence state, and that the prolonged influence of this incongruence on S1 activation and processing may cause chronic pain. Consistent with these proposals, Bultitude and
7
Rafal (2010) reported that disturbed body awareness preceded the development of CRPS, indicating that pain is a consequence of distorted body awareness. Furthermore, in patients with fibromyalgia and CRPS, abnormal inhibition and enhancement of P50 has been observed (Juottonen et al., 2002; Montoya et al., 2005, 2006), which support our ideas.
5.
Conclusions
We provide compelling evidence that disownership caused by incongruence between felt and observed hand position modulates the M50 activity in S1. We suggest that activity in S1 reflects not just somatosensory inputs but the integrated activity of multiple sensory modalities, including visual and proprioceptive inputs, to form a sense of body awareness. Incongruence between these inputs appears to trigger a cortical arousal system that may alter sensory processing. Previous results suggest that one consequence of this arousal is enhanced pain perception. Further study is required to identify the neurological processes underlying M50 in the arousal system and the possible contribution of this arousal system to chronic pain. In any case, M50 may be a useful biomarker for future studies on sense of body ownership.
Acknowledgments This study was supported by a Grant-in-aid for Young Scientists (B) (24700578) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. Q1
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Please cite this article in press as: Otsuru, N., et al., Sensory incongruence leading to hand disownership modulates somatosensory cortical processing, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.2014.05.005
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