YNIMG-10029; No.

of pages: 8; 4C: 3, 5
NeuroImage xxx (2013) xxx–xxx

Contents lists available at SciVerse ScienceDirect

NeuroImage
journal homepage: www.elsevier.com/locate/ynimg

1 2

Q1 3
4 5 6 7

Sook-Lei Liew a, b,⁎, 1, Tong Sheng a, c, Lisa Aziz-Zadeh a, b, c
a b c

a r t i c l e
8 9 10 11 13 12 14 15 16 17 18 19 20 21

i n f o

a b s t r a c t

41 40 42 43 44 45 46 47 48 49 50 51 52 53 54 55

E

C

T

Keywords: Action understanding Visual experience Body representation Shared circuits Action observation network Mirror neurons

E

D

P

Article history: Accepted 17 December 2012 Available online xxxx

Observing actions performed by others engages one's own sensorimotor regions, typically with greater activity for actions within one's own motor abilities or for which one has prior experience. However, it is unclear how experience modulates the neural response during the observation of impossible actions, beyond one's own abilities. Using fMRI, we scanned typically-developed participants as they observed actions performed by a novel biological effector (the residual limb of a woman born without arms) and a familiar biological effector (a hand). Participants initially demonstrated greater activity in the bilateral inferior and superior parietal cortices when observing actions made by the residual limb compared to the hand, with more empathic participants activating the right inferior parietal lobule, corresponding to the posterior component of the action observation network, more strongly. Activity in the parietal regions may indicate matching the kinematics of a novel effector to one's own existing sensorimotor system, a process that may be more active in more empathic individuals. Participants then received extended visual exposure to each effector, after which they showed little difference between activation in response to residual limb compared to hand actions, only in the right superior parietal lobule. This suggests that visual experience may attenuate the difference between how residual limb and hand actions are represented using one's own body representations, allowing us to flexibly map physically different others onto our own body representations. © 2012 Elsevier Inc. All rights reserved.

R O

Brain and Creativity Institute, University of Southern California, 3620A McClintock Avenue, Los Angeles, CA 90089-2921, United States Division of Occupational Science and Occupational Therapy, University of Southern California, 3620A McClintock Avenue, Los Angeles, CA 90089-2921, United States Neuroscience Graduate Program, University of Southern California, 3620A McClintock Avenue, Los Angeles, CA 90089-2921, United States

O

F

Experience with an amputee modulates one's own sensorimotor response during action observation

22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 39 38

When observing actions performed by another person, regions of one's own sensorimotor system become active, engaging specific cortical motor representations that correspond to the observed body parts (Buccino et al., 2001; Fadiga et al., 1995). This ‘motor resonance’ between observed actions and one's own motor representation occurs in a network of regions in the inferior frontal gyrus, ventral premotor cortex and inferior parietal lobule collectively referred to as the action observation network (AON; Caspers et al., 2010; Rizzolatti and Craighero, 2004). This network in humans may be related to mirror neurons, which were discovered in macaque monkeys as neurons that fired both when the monkey performed and observed actions (Gallese et al., 1996; Rizzolatti et al., 1996). Evidence suggests that our own motor experiences affect how we activate this network, with increased

R

Introduction

R

⁎ Corresponding author at: Brain and Creativity Institute, University of Southern California, 3620A McClintock Avenue, Los Angeles, CA 90089-2921, United States. Fax: + 1 213 821 3099. E-mail addresses: sliew@usc.edu, liews@mail.nih.gov (S.-L. Liew), tsheng@usc.edu (T. Sheng), lazizzad@usc.edu (L. Aziz-Zadeh). 1 Present address: Human Cortical Physiology and Stroke Neurorehabilitation Section, National Institute of Neurological Disorders and Stroke, NIH, 10 Center Drive, Bg 10 Rm 7D50, Bethesda, MD 20892. Fax: +1 301 402 7010. 1053-8119/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.neuroimage.2012.12.028

activity when observing individuals more similar to ourselves (Buccino et al., 2004; Molnar-Szakacs et al., 2007) or actions with which we are more familiar (Calvo-Merino et al., 2005; Cross et al., 2006). Thus, we may utilize our own motor representations to help understand other's actions (Keysers and Gazzola, 2007). How then do we understand actions made with a body that differs from our own? Recent studies demonstrate that we may also engage motor regions when observing actions beyond our own abilities (Aziz-Zadeh et al., 2011; Liew et al., 2011). However, these studies used actions or effectors that were visually familiar to the observer, and prior studies have shown that visual experience, even without motor practice, can still allow one to incorporate novel actions into one's own motor repertoire. For instance, individuals demonstrate increased sensorimotor activity when observing actions they have either performed or seen before (Cross et al., 2009). Even motor imagery training of phantom limbs in amputees led to changes in perceived ownership and kinematic qualities of the phantom limb, suggesting that even imagined training of a non-existent limb can affect sensorimotor representations for that limb (Moseley and Brugger, 2009). However, what remains to be explored is how we process actions made by individuals with novel body parts that we do not have and have not seen or imagined before, and the role of experience in modulating these responses. These questions hold important implications not only for the scientific community

56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78

Please cite this article as: Liew, S.-L., et al., Experience with an amputee modulates one's own sensorimotor response during action observation, NeuroImage (2013), http://dx.doi.org/10.1016/j.neuroimage.2012.12.028

U

N C O

2

S.-L. Liew et al. / NeuroImage xxx (2013) xxx–xxx

79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139

R O

but also for our increasingly diverse society. In 2007, over 1.7 million individuals in the United States alone had limb differences such as amputations (Center, 2011), and many more have other uncommon physical differences. Such individuals cite perceived social stigma as a major barrier to participating in their communities, affecting their quality of life (Frank, 2000; Murray, 2009). Given that the average typically developed individual has limited exposure to individuals with physical differences, can experience change how we represent bodies unlike our own? To answer these questions, we used functional magnetic resonance imaging (fMRI) to scan participants who had no prior experience interacting with or observing with individuals with amputations (Novices) as they observed a woman with bilateral above-elbow arm amputations perform actions with her residual upper limb, which extend several inches past her shoulder, and a typically developed woman perform the same actions with her hand as a control. During the scanning session, individuals passively observed actions made by both effectors, then received extended visual exposure to each, and then were rescanned during action observation. We hypothesized that after visual exposure to the novel effector (e.g., residual limb), individuals would demonstrate activation in the same regions they engaged when observing a familiar effector (e.g., hand), resulting in no difference between residual limb and hand actions in the post-experience scan. Materials and methods Participants Nineteen healthy, typically-developed participants (9 females, 10 males; mean± SD= 24.8 ±4.8 years) who had minimal to no prior experience with individuals with amputations as assessed by a self-report questionnaire were recruited for this study. In specific, participants were asked to state how much contact they have had with individuals with amputations, if any, and to specify the amount (daily, weekly, monthly, yearly or less) and type of contact (friend, family member, acquaintance, or other). Individuals who had less than yearly contact with an acquaintance or stranger were included in the study. Due to technical difficulties, data from three novice participants was incomplete and excluded from the study, resulting in 16 novice participants total. Amount of experience for all participants was briefly quantified during the initial screening and further elaborated upon with an extensive behavioral questionnaire after the fMRI scanning procedure. Detailed questions were not asked prior to the fMRI experiment to avoid biasing participants to the goal of the study. All participants were right-handed, had normal or corrected-to-normal vision, and were safe for fMRI. Written informed consent was obtained from all participants before inclusion in the study. This study was approved by the University of Southern California Institutional Review Board and was performed in accordance with the 1964 Declaration of Helsinki.

Catch trials consisted of a red frame outlining an image of a hand, presented for 2 s, indicating that participants should press the button boxes they were given. Participants were informed that the buttonpress stimuli were to ensure they paid careful attention to the stimuli throughout each run. A fixation cross was presented during rest trials with a randomly varied duration between 2 and 8 s. Visual exposure runs To provide participants with increased visual exposure to both hand and residual limb actions, visual exposure stimuli consisted of 16-second blocks of short 4-second video clips of different actions of each effector, cropped to provide more of the body and context for each of the actions. Hand visual exposure observations included actions such as a hand and arm twisting off a bottle cap and threading a needle through a piece of fabric, while residual limb visual exposure actions included using the residual limb to push objects and using the residual limb plus mouth to manipulate a pencil. These videos were intended to provide subjects with visual experience of each effector in a more natural, realistic setting and to to provide the most context for the unique kinematics of each effector. Thus, actions during this run differed slightly between typically developed and congenital amputee actresses in order to highlight the kinematic range of each effector. fMRI data was collected during this run but excluded from the current analysis as it falls beyond the scope of the current investigation.

140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201

E

C

AON localizer run In order to identify neural regions that were active both during action observation and during action execution, participants performed one AON localizer run at the end of the scanning session. This entailed observing 3-second videos of hands picking up objects (e.g., keys, a mug), still images of a hand next to an object, rest trials with a fixation cross, and action execution trials. Action execution trials were cued by a red box flashing briefly for 500 ms before a static image of a hand was presented for the remaining 2500 ms. This cued participants to perform a basic hand action (see below) for the duration of the clip. Task design and procedure Participants were provided short training runs outside of the scanner, prior to the scanning session (for a complete schematic of the experimental paradigm, see Fig. S1). For action observation runs, participants were asked to watch the actions performed on the screen and pay attention to the movements and actions that they saw. They were further informed that at the end of each run, they might be asked “What was the last action you saw?” During the action observation training, they were shown 4 clips each of hand actions and residual limb actions to familiarize them with the format of stimulus presentation and the effectors they would be seeing in the scanner, and to train them to respond to the catch trials. An additional motive of these clips was to lessen any initial emotional or attentional effects the unfamiliar effector may evoke. Action observation runs consisted of 16 trials of each condition, plus a randomly varied rest period between 2 and 8 s. The trial order of the design was then optimized using a genetic algorithm (Wager and Nichols, 2003). The total run time was 5 min and 36 seconds (168 TRs), for each of 4 runs. For the analyses, the first two action observation runs (PRE) and the second two action observation runs (POST) were averaged for a total of 32 trials per condition in each analysis. After two action observation runs (PRE), there was a visual exposure run, during which participants observed longer video clips (16 s each) consisting of several actions, followed by longer rest trials with a fixation cross (12 s). Following this run, participants observed another two action observation runs (POST). For the AON localizer run, participants were asked to watch the actions performed on the screen and pay attention to the movements

Stimuli

Action observation runs Stimuli consisted of 2-second video clips of goal-oriented, goalmatched actions performed by an individual with physical differences using her upper residual limb and typically developed women using their hands (see Fig. 1 for the experimental scanning paradigm and action observation example run). Hand action observation (HAO) and residual limb action observation (RLAO) clips both contained the same set of actions (e.g., flip book page, squeeze binder clip, press down book crease, flick rubber ball), performed by the right hand or right residual limb respectively. These actions were chosen because they were goal-oriented and possible for both the actress with hands and the actress with residual limbs to perform using only one effector. Control stimuli consisted of still images of the hand (hand still; HS) or upper residual limb (residual limb still; RLS) and were also presented for 2 s.

Please cite this article as: Liew, S.-L., et al., Experience with an amputee modulates one's own sensorimotor response during action observation, NeuroImage (2013), http://dx.doi.org/10.1016/j.neuroimage.2012.12.028

U

N

C

O

R

R

T

E

D

P

O

F

S.-L. Liew et al. / NeuroImage xxx (2013) xxx–xxx

3

Fig. 1. Experimental scanning paradigm and example action observation run. A) The experimental scanning session included the acquisition of a T1-weighted anatomical image, followed by the pre-exposure action observation runs, the visual exposure run, then the post-exposure action observation runs (identical to pre-exposure action observation runs), and finally an action observation network localizer, during which participants both observed and executed right hand actions. Additional full experimental paradigm details can be found in Fig. S1. B) An example action observation run, which included observing hand actions, residual limb actions, hand still images, residual limb still images, and rests of random duration in an event-related design. Each run was presented twice in the pre-exposure session, and twice in the post-exposure session.

208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224

C

206 207

T

204 205

E

202 203

N C O

and actions that they saw. When they saw the red frame indicating an action execution trial, they were asked to move their right hand as though picking up a wine glass several times, for the duration of the clip (generally 2–3 times). They were further instructed to remain still for all other times. Once in the scanner, participants were monitored for extraneous movements via an MRI-safe mirror placed next to the scanner bed, which allowed for monitoring of hand movements from the control room. Non-task-related movements were monitored by an experimenter during the stimulus presentation, with no subject demonstrating non-task-related movement greater than 1% of trials. After the scanning session, participants completed a demographics questionnaire with in-depth questions about their prior experiences with individuals with physical differences and impressions of the observed videos. They also responded on a 10-point Likert scale to questions about their familiarity with both residual limb and hand actions, whether they felt watching the videos helped them to understand hand/residual limb actions better, and whether they felt watching the videos made them any more likely to interact with an individual with hands/residual limbs (1= very unfamiliar; unhelpful; unlikely to interact; 10= very familiar; helpful; likely to interact). Finally, participants also completed the Interpersonal Reactivity Index (IRI; (Davis, 1983)), a self-report behavioral measure of both cognitive and emotional empathy.

D

optimized event-related design, with 30 trials of each observation condition (AO, S) and 15 trials of action execution, as execution tends to produce a more robust signal, thus requiring less trials. This run lasted 492 s (246 TRs). A complete schematic of the experimental design can be found in Fig. S1. Image acquisition All images were acquired using a Siemens MAGNETOM Trio 3 T MRI scanner with standard head coil. A high resolution T1-weighted anatomical volume was acquired from each participant (176 slices, 256 × 256 × 208 matrix with a spatial resolution of 1 × 1 × 1 mm, TR = 1950 ms, TE= 2.26 ms, FOV= 256 mm; flip angle = 9°). Functional volumes were acquired while participants performed the action observation, visual exposure, and AON localizer runs. Thirty-seven axial slices of functional images covering the whole brain were acquired using a gradient-echo echo-planar pulse sequence (64 × 64× 37 matrix with a spatial resolution of 3.5 × 3.5× 3.5 mm, TR= 2000 ms, TE = 30 ms, FOV= 224 mm, flip angle = 90°). Functional volumes were acquired using Siemens' prospective acquisition correction (PACE) technique for motion correction in which head movements were calculated by comparing successively acquired volumes and were corrected online (Thesen et al., 2000). Data processing and analyses Functional data processing was carried out using FEAT (FMRI Expert Analysis Tool) Version 5.98, part of FSL (FMRIB's Software Library, www. fmrib.ox.ac.uk/fsl). The following pre-statistics processing were applied to individual subjects: motion correction using MCFLIRT (Jenkinson et al., 2002), slice-timing correction using Fourier-space time-series phase-shifting; non-brain removal using BET (Smith, 2002), spatial smoothing using a Gaussian kernel of FWHM 5 mm, grand-mean intensity normalisation of the entire 4D dataset by a single multiplicative factor, and highpass temporal filtering (Gaussian-weighted least-squares straight line fitting, with sigma= 65.0 s) (Jenkinson et al., 2002; Smith, 2002). For each subject, a time-series statistical analysis was

P

R O

O

F

237 238 239 240 241

242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257

225 226 227 228 229 230 231 232 233 234 235 236

Scanning procedure

U

R

R

E

258 259 260 261 262 263 264 265 266 267 268 269

The images were presented through a projector onto a rearprojection screen attached to the head coil and located above the subject's head. As described previously, participants' actions were monitored via an MRI-safe mirror placed adjacent to the scanner bed, allowing the experimenter to observe movements from the control room. The experiment utilized an event-related design in the Action Observation runs in which all conditions (HAO, RLAO, HS, RLS, rest) were evenly distributed across 4 runs, which lasted 336 s (168 TRs). The Visual Exposure run utilized a block design with 16-second blocks, counterbalanced across participants, with 12-second rests in between and lasted 464 seconds (232 TRs). The AON Localizer run utilized an

Please cite this article as: Liew, S.-L., et al., Experience with an amputee modulates one's own sensorimotor response during action observation, NeuroImage (2013), http://dx.doi.org/10.1016/j.neuroimage.2012.12.028

4

S.-L. Liew et al. / NeuroImage xxx (2013) xxx–xxx

270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330

R

carried out using FILM GLM with local autocorrelation correction (Woolrich et al., 2001). Z (Gaussianised T/F) statistic images were then thresholded at p= 0.001 (uncorrected), and registered to a high resolution standard space image (2 × 2 ×2 mm3 Montreal Neurological Institute (MNI) space) using FLIRT (FSL's Linear Image Registration Tool) (Jenkinson and Smith, 2001; Jenkinson et al., 2002). A second-level analysis to average across the two runs in PRE and POST conditions respectively was carried out using a fixed effects model, by forcing the random effects variance to zero in FLAME (FMRIB's Local Analysis of Mixed Effects) (Beckmann et al., 2003; Woolrich, 2008; Woolrich et al., 2004). Group-level analyses were then completed using FLAME stage 1, which employed a mixed effects model that includes both fixed effects and random effects from cross session/subject variance (Beckmann et al., 2003; Woolrich, 2008; Woolrich et al., 2004). Z (Gaussianised T/F) statistic images at this level were thresholded using clusters determined by Z> 2.3 and a (corrected) cluster significance threshold of P = 0.05 (Worsley, 2001). To test for an interaction between observing Residual Limb versus Hand actions, between PRE versus POST conditions, lower-level feat directories for each subject were entered into a 2 × 2 repeated measures ANOVA, with factors of Effector (Residual Limb, Hand) and Experience (Pre, Post). Region of interest analyses were also performed for a priori regions in the AON (bilateral IFG/PMv and IPL). These regions were defined by the overlap between action observation and action execution during the AON localizer run. As this overlap included many regions outside of the canonical AON, including large occipital and temporal lobe clusters, we further constrained the functional overlap data with anatomical definitions of the AON based on the probabilistic Harvard–Oxford atlas, using the bilateral IFG/PMv and IPL. The resulting AON ROIs are displayed in Fig. S2. IFG and ventral premotor regions were combined into one region of interest as prior metaanalyses of the AON suggest that both comprise the frontal component of the AON (Van Overwalle and Baetens, 2009). Percent signal change (%SC) for the observation of each effector (HAO/RLAO) compared to the control still image (HS/RLS) was then extracted using Featquery in FSL and contrasted in paired t-tests. Finally, correlation analyses between the %SC values from the ROI analyses and scores on the Interpersonal Reactivity Index empathy questionnaire and the demographics questionnaire were run in SPSS (Release Version 18.0, © SPSS, Inc., 2009, Chicago, IL, www.spss.com).

(MT/V5 into V1). In the direct contrast between Residual Limb and Hand Action Observation (RLAO >HAO), there was activity in the bilateral IPL including the supramarginal gyrus, postcentral gyrus, and extending into the superior parietal lobules and the posterior middle temporal gyrus (MT/V5; see Fig. 2). Hand versus Residual Limb Action Observation (HAO > RLAO) generated activity in the bilateral occipital poles (BA 17/18) only (see Fig. 2). Action observation POST-visual exposure After the Visual Exposure run, participants viewing Residual Limb Action Observation versus Residual Limb Still images (RLAO >RLS) activated the bilateral inferior and superior parietal lobules and bilateral occipital cortices from MT/V5 extending into V1, similar to the pre-visual exposure runs. Hand Action Observation versus Hand Still images (HAO>HS) resulted in a similar pattern of activity with clusters of activity in bilateral superior parietal regions, left inferior parietal lobule, right posterior superior temporal sulcus into the inferior parietal lobule, and strong bilateral occipital activation (MT/V5 into V1). Residual Limb versus Hand Action Observation (RLAO > HAO) in the POST run demonstrated activity in the right superior parietal lobule and bilateral posterior middle temporal gyri (MT/V5; see Fig. 2). In contrast, Hand versus Residual Limb Action Observation (HAO > RLAO) again generated activity in the bilateral occipital poles (BA 17/18) only (see Fig. 2).

331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390

C

E

fMRI results

Action observation PRE-visual exposure During the PRE-visual exposure action observation runs, Residual Limb Action Observation versus Residual Limb Still images (RLAO >RLS) activated the right dorsal and ventral premotor cortices, the bilateral inferior and superior parietal lobules, and the bilateral lateral occipital cortices from the posterior middle temporal gyrus (MT/V5) into the medial lingual gyri (BA 17/18; see SI Tables 1–3 for all coordinates of significant clusters of activation). Hand Action Observation versus Hand Still images (HAO > HS) generated a similar pattern of activity in bilateral inferior and superior parietal lobules and the bilateral occipital cortices

Please cite this article as: Liew, S.-L., et al., Experience with an amputee modulates one's own sensorimotor response during action observation, NeuroImage (2013), http://dx.doi.org/10.1016/j.neuroimage.2012.12.028

U

Participants rated being significantly more likely to interact with an individual with an upper residual limb after watching the videos of residual limbs and hands, as compared to likeliness to interact with an individual with typically developed hands (RL: 5.69 ± 2.52, H: 4.43 ± 2.61, t = -2.21, p = .043). In addition, the videos helped participants to understand residual limb actions significantly more than they helped participants to understand hand actions (RL: 8.13 ± 1.93, H: 5.188 ± 2.95, t = -5.74, p b .00005).

C

O

Behavioral results

R

Results

N

T

ANOVA results The 2 × 2 repeated measures ANOVA with factors of Effector (Residual Limb, Hand) and Experience (Pre, Post) demonstrated a significant simple effect, with Pre > Post RLAO activating the right inferior parietal lobule, with none of the other conditions (Pre > Post HAO, Post > Pre RLAO, Post > PRE HAO) demonstrating significant effects. There was also a main effect of RLAO, also in the right inferior parietal lobule, overlapping with the simple effect (see Fig. S3, Table S3 for activation patterns and coordinates). There was no significant interaction effect between effector and experience. Correlations Percent signal change in AON regions of interest positively correlated with several scores on the Interpersonal Reactivity Index empathy subscales. Participants in the PRE condition demonstrated a significant positive correlation between activity in the R IPL during RLAO > RLS with both the empathic concern (IRI EC; r = .66, p = .006; see Fig. 3) and the perspective taking (IRI PT) subscales (r= .54, p = .03). This also occurred at the R IPL for the contrast RLAO>HAO with empathic concern (IRI EC; r = .51, p = .04). There were no significant correlations for novices in the POST condition with empathy. Discussion The current study examined how we process actions made by bodies different from our own and how this pattern of activation changes with experience. Novice participants, who had little to no prior experience with amputees, observed an individual with residual limbs and an individual with hands perform actions, before and after visual exposure during an fMRI session. The results show that novices initially engage their own sensorimotor regions, particularly in the right inferior parietal lobule, more when observing individuals with different bodies, despite the fact that the observed effector has not been seen before and lacks corresponding motor representations in the observer's body. In addition, more empathic novices demonstrated an increased sensorimotor response when observing residual limbs than less empathic individuals. Visual experience introduced during the experiment led to an attenuation of the difference in neural signal when viewing residual limb actions after experience as compared to hands. This evidence suggests that moderate amounts of visual experience can reduce differences between how body parts one does and does not have are

E

D

P

R O

O

F

S.-L. Liew et al. / NeuroImage xxx (2013) xxx–xxx

5

Fig. 3. Correlation between percent signal change in right inferior parietal lobule during residual limb observation and empathic concern scores. Percent signal change in the R IPL when novices observed Residual Limb Action Observation> Residual Limb Still (RLAO > RLS) in the PRE condition correlated with Empathic Concern scores on the Interpersonal Reactivity Index (r= .66, p = .006). Correlations also occurred between the R IPL and the Perspective Taking subscale the IRI, and the R IPL and Empathic Concern during RLAO >HAO.

Please cite this article as: Liew, S.-L., et al., Experience with an amputee modulates one's own sensorimotor response during action observation, NeuroImage (2013), http://dx.doi.org/10.1016/j.neuroimage.2012.12.028

U

N C O

R

R

E

C

Fig. 2. fMRI results when participants observe residual limb and hand actions for the first time (PRE) and after visual exposure (POST). TOP — PRE. ORANGE: Residual Limb > Hand activated sensorimotor regions, including the bilateral inferior and superior parietal lobules, and occipital regions. BLUE: Hand > Residual Limb generated significant activation in the bilateral occipital poles. BOTTOM — POST. ORANGE: Residual Limb > Hand activated the right superior parietal lobule and occipital regions, including MT/V5. BLUE: Hand > Residual Limb generated significant activation in the bilateral occipital poles. All results thresholded at Z > 2.3, p b 0.05 (cluster corrected for multiple comparisons).

T

E

D

P

R O

O

F

6

S.-L. Liew et al. / NeuroImage xxx (2013) xxx–xxx

391 392 393

represented. Taken together, these results demonstrate the flexible engagement of one's own sensorimotor regions in representing novel and experienced actions during observation.

394 395 396 397 398 399 400 401 402 403 404 405 406 407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432 433 434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453

Increased sensorimotor activity for the novel effector Observing the novel effector activated one's own sensorimotor regions more than observing the familiar effector. This challenges the traditional notion that we activate our own sensorimotor regions more for actions within our motor repertoire, as found in expert ballet dancers watching ballet compared to capoeria or individuals watching dance moves they had rehearsed versus not rehearsed (Calvo-Merino et al., 2005; Cross et al., 2006, 2009). These studies concluded that action observation engages one's existing motor repertoire to understand others' actions, with more activation when observing actions for which one has a more detailed motor representation. However, here we find the opposite, with more activation when observing actions for which one has less of a motor representation. This occurs despite the fact that the novel actions are not only beyond one's current motor abilities, but also beyond one's future capabilities, as they are performed by a body part that one does not possess. Increased activation occurred in both the right inferior and superior parietal lobules when Novices observed the novel versus familiar effector, with the right inferior parietal lobule appearing robustly. Together, these regions are associated with a multitude of tasks, including directing attention, spatial integration of visuomotor information, and encoding the kinematics and orientation of movements within body space (Colby and Goldberg, 1999; Oztop et al., 2006; Rizzolatti et al., 1997). We propose that novice individuals engage their own sensorimotor regions in an attempt to match the unfamiliar kinematics of the observed, novel actions to a corresponding body part in their own motor schema as one way of better understanding it. Importantly, while the observed actions and effector were novel, the goal of the actions were familiar (e.g., flipping a book page), and thus participants may have a motor schema for how they themselves might perform the action. They may thus use their existing knowledge of motor kinematics, based on their own bodily experiences, to map the affordances of the residual limb onto their own bodies. In doing so, they may dissect the kinematics of each part of the effector onto the closest match in their own body, matching the novel limb either to the part they themselves would use to achieve the goal of the action or matching it to the closest kinematically-similar effector — in this case, matching the residual limb to one's own lower or upper arm (Arbib et al., 2009; Bonaiuto and Arbib, 2010). However, stronger evidence to dissociate how exactly the novel limb is being mapped onto one's own body would necessitate finer mapping of the sensorimotor system in each observer, using a localizer to identify representations for various points along the limb, which may be a promising area of future inquiry. Prior research suggests that this kinematic match does not need to be perfect, however. Motor training of incongruent motor performance and action observation (e.g., observing finger flexion while performing finger extension; Catmur et al., 2007), observation of biomechanically impossible actions (Romani et al., 2005), and even observation of actions performed by a tool versus by a hand (Van Elk et al., 2011), can all still result in greater motor excitability for the paired or observed effector, regardless of whether it is possible or impossible, a biological effector or a tool. These studies suggest that sensorimotor activation is not effector-specific and that activation of one's own motor representations can be elicited by the observation of body movements or tools that are beyond our own motor repertoire. Similar to these prior studies, our results suggest that activation of the AON may occur during goal-directed movements in which the goal of the action is familiar to the observer, such as squeezing a binder clip or turning a book page, even if the effector is not.

Expanding on this literature, it appears that the AON not only is more active when observing novel versus familiar effectors, but it is also more active when observing a novel effector during the performance of a familiar goal-directed action. This finding is in complement to recent work, which shows that observing novel compared to familiar gestures also increases activation in one's own parietal regions (Liew et al., 2011). In this case, the goal of the action – the end hand-state creating the gesture – is unfamiliar, but the effector (e.g., hand) is familiar. Another study demonstrated increased activation of both premotor and parietal regions when observing robot-like compared to humanlike movements (Cross et al., 2011), where both goal of the action (a robotic pose versus a human pose) and the kinematics of the effector are novel. Finally, an additional study found activity in premotor, parietal, and dorsolateral prefrontal regions when observing novel versus familiar guitar patterns, which the authors suggested reflects an increased effort towards observational learning (Vogt et al., 2007). We propose that similar processes are occurring here, with participants mapping the observed novel actions or observed novel effectors, onto their own sensorimotor representations, possibly though through covert imitation, to better learn and understand the kinematics and affordances of the novel limb. In support of this, the behavioral results demonstrate that novices report understanding the residual limb better after observing the video stimuli—a finding that warrants more rigorous exploration in future studies. Overall, this data suggests that one's own sensorimotor regions are flexibly engaged to support action understanding of many different types of actions and effectors, both within one's realm of expertise and beyond what one has ever seen before.

454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473 474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515

Increased right parietal activity correlates with empathy in novices

U

N

C

O

R

R

E

C

Please cite this article as: Liew, S.-L., et al., Experience with an amputee modulates one's own sensorimotor response during action observation, NeuroImage (2013), http://dx.doi.org/10.1016/j.neuroimage.2012.12.028

T

E

If understanding another's actions relies in part on our ability to engage our own corresponding sensorimotor regions, then individuals who are more empathic may also engage their own body representations more when observing others. This has been demonstrated in a number of studies, with greater sensorimotor activity correlating with higher scores on trait empathy, such as perspective taking (Aziz-Zadeh et al., 2010; Gazzola et al., 2006; Kaplan and Iacoboni, 2006). These studies suggest that more empathic individuals engage their own motor regions more than less empathic individuals when perceiving others' actions. Similarly, here we find that participants who score higher on either cognitive or affective measures of empathy demonstrate more right inferior parietal activation when observing residual limb actions. This correlation is especially notable when novices initially view the novel effector, and is no longer significant once the effector becomes more familiar. This suggests that our ability to map the actions of unfamiliar, dissimilar others onto our own sensorimotor representations may support our capacity to understand and empathize with individuals who are different from ourselves. Put another way, the more empathic an individual is, the more he or she may attempt to represent very different bodies onto their own, as though literally “putting oneself in another's shoes.” Visual experience represents novel effectors similar to familiar ones After visual exposure to the novel limb, the contrast between observing residual limb actions compared to hand actions only yielded activity in the right superior parietal and occipitotemporal regions, with none of the robust AON regions active as found in the PRE condition. This suggests that after sufficient experience with an observed effector, one may effectively map the kinematics of a novel effector onto one's own existing system. Subsequent observation of the effector thus no longer requires extensive parietal activation to generate a kinetic representation of it, and can thus be represented onto similar regions as more familiar effectors — in this case, such as hand. The right superior parietal activation seen in the POST condition may be indicative of participants updating their internal model of the

D

P

R O

O

F

S.-L. Liew et al. / NeuroImage xxx (2013) xxx–xxx

7

516 517 518 519 520 521 522 523 524 525 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 545 546 547 548 549 550 551 552 553 554 555 556 557 558 559 560 561 562 563 564 565 566 567 568 569 570 571 572 573 574 575

Future directions References Experience may modulate the sensorimotor response by driving attention to both the more novel effector and the more ‘expert’ actions, and then to both effectors equally after novelty wears off, either through visual or real-life experience. Studies directly examining the effects of attention on motor resonance during action observation suggest that selective attention increases motor resonance (Bach et al., 2007; Chong et al., 2009). Here we propose that the observed effects are the result of a complex interplay between 1) attention and 2) one's existing motor abilities based on prior experiences. It is likely that these two factors modulate sensorimotor activity together, and this proposed interplay between experience and attention may also explain the apparent contradiction between these findings and prior research. In particular, sensorimotor activity may increase for expert or practiced actions partially because individuals tend to pay more attention to actions within their own interests. Conversely, at other times, we may pay more attention to things that are novel or different to us — such as a new body part, robotic movements, or uncommon hand gestures (Cross et al., 2011; Liew et al., 2011). Future research may explore the intricate interplay between our prior experiences and our current attentional focus in driving the sensorimotor response during when observing others’ actions. Conclusion

O

F

different effector, fine-tuning their model with specific kinematic parameters observed in the second session (Iacoboni and Zaidel, 2004; Wolpert et al., 1998). In addition, the different effector may also evoke more visual activation, particular in regions of the lateral occipital cortex associated with biological movement. In the observed study, there was no interaction between effector and experience, suggesting that the reduction in signal when observing the residual limb actions after experience may also occur when observing hand actions, although to a lesser degree. Altogether, this suggests that the visual experience introduced in the experiment allows the viewer to develop similar neural patterns for novel, different bodies as for familiar, similar ones. Experience with an observed effector and observed actions may thus modulate how much we use our own sensorimotor representations to map the kinematics of other's actions.

the Dana and David Dornsife Neuroimaging Center; and the Brain and 576 Creativity Institute. 577 Acknowledgments We thank Dr. Michael Arbib, Dr. Jonas Kaplan, Dr. Florence Clark, Dr. Ann Neville-Jan, and Mona Sobhani for insightful discussions and Mustafa Seckin, Alicia Johnson, and Ahra Roh for their assistance with conducting this study. Appendix A. Supplementary data

578 579 580 581 582

583

Supplementary data to this article can be found online at http:// 584 dx.doi.org/10.1016/j.neuroimage.2012.12.028. 585

586 587 588 589 590 591 592 593 594 595 596 597 598 599 600 601 602 603 604 605 606 607 608 609 610 611 612 613 614 615 616 617 618 619 620 621 622 623 624 625 626 627 628 629 630 631 632 633 634 635 636 637 638 639 640 641 642 643 644 645 646 647 648

The current work suggests that we understand other people's actions by engaging our own motor regions in order to gain a simulated form of motor experience, simply through observation. Here we examine how experience modulates activity in neural regions associated with action perception. While prior research suggested that we activate our own sensorimotor regions more for actions we have practiced or experienced ourselves, the work presented here provides evidence that we may also activate certain components of our own sensorimotor regions, particularly in the right parietal lobule and AON, when observing goal-directed movements that we have not seen before and cannot perform ourselves. Visual experience may support a similar response to both possible actions and impossible actions as they become more familiar. Altogether, these findings demonstrate the flexibility of the human action observation network in representing actions beyond our own abilities and suggest a further role of these regions in acquiring and generating internal motor patterns for new, even impossible, actions through observation alone. Funding This work was supported by the National Science Foundation Graduate Research Fellowship (grant number 2009072048 to S.-L.L.); the University of Southern California Provost's PhD Fellowship (to S.-L.L.); the Division of Occupational Science and Occupational Therapy;

Arbib, M.A., Bonaiuto, J.B., Jacobs, S., Frey, S.H., 2009. Tool use and the distalization of the end-effector. Psychol. Res. 73, 441–462. Aziz-Zadeh, L., Sheng, T., Gheytanchi, A., 2010. Common premotor regions for the perception and production of prosody and correlations with empathy and prosodic ability. PLoS One 5, e8759. Aziz-Zadeh, L., Sheng, T., Liew, S.L., Damasio, H., 2011. Understanding otherness: the neural bases of action comprehension and pain empathy in a congenital amputee. Cereb. Cortex http://dx.doi.org/10.1093/cercor/bhr139. Bach, P., Peatfield, N.A., Tipper, S.P., 2007. Focusing on body sites: the role of spatial attention in action perception. Exp. Brain Res. 178, 509–517. Beckmann, C.F., Jenkinson, M., Smith, S.M., 2003. General multilevel linear modeling for group analysis in FMRI. Neuroimage 20, 1052–1063. Bonaiuto, J., Arbib, M.A., 2010. Extending the mirror neuron system model, II: What did I just do? A new role for mirror neurons. Biol. Cybern. 102, 341–359. Buccino, G., Binkofski, F., Fink, G.R., Fadiga, L., Fogassi, L., Gallese, V., Seitz, R.J., Zilles, K., Rizzolatti, G., Freund, H.J., 2001. Action observation activates premotor and parietal areas in a somatotopic manner: an fMRI study. Eur. J. Neurosci. 13, 400–404. Buccino, G., Lui, F., Canessa, N., Patteri, I., Lagravinese, G., Benuzzi, F., Porro, C.A., Rizzolatti, G., 2004. Neural circuits involved in the recognition of actions performed by nonconspecifics: An FMRI study. J. Cogn. Neurosci. 16, 114–126. Calvo-Merino, B., Glaser, D.E., Grezes, J., Passingham, R.E., Haggard, P., 2005. Action observation and acquired motor skills: an FMRI study with expert dancers. Cereb. Cortex 15, 1243–1249. Caspers, S., Zilles, K., Laird, A.R., Eickhoff, S.B., 2010. ALE meta-analysis of action observation and imitation in the human brain. Neuroimage 50, 1148–1167. Catmur, C., Walsh, V., Heyes, C., 2007. Sensorimotor learning configures the human mirror system. Curr. Biol. 17, 1527–1531. Center, N.L.L.I., 2011. Limb Loss FAQ's. Chong, T.T., Cunnington, R., Williams, M.A., Mattingley, J.B., 2009. The role of selective attention in matching observed and executed actions. Neuropsychologia 47, 786–795. Colby, C.L., Goldberg, M.E., 1999. Space and attention in parietal cortex. Annu. Rev. Neurosci. 22, 319–349. Cross, E.S., Hamilton, A.F., Grafton, S.T., 2006. Building a motor simulation de novo: observation of dance by dancers. Neuroimage 31, 1257–1267. Cross, E.S., Kraemer, D.J.M., Hamilton, A.F.C., Kelley, W.M., Grafton, S.T., 2009. Sensitivity of the action observation network to physical and observational learning. Cereb. Cortex 19, 315. Cross, E.S., Liepelt, R., de, C.H.A.F., Parkinson, J., Ramsey, R., Stadler, W., Prinz, W., 2011. Robotic movement preferentially engages the action observation network. Hum. Brain Mapp. http://dx.doi.org/10.1002/hbm.21361. Davis, M.H., 1983. Measuring individual differences in empathy: evidence for a multidimensional approach. J. Pers. Soc. Psychol. 44, 113–126. Fadiga, L., Fogassi, L., Pavesi, G., Rizzolatti, G., 1995. Motor facilitation during action observation: a magnetic stimulation study. J. Neurophysiol. 73, 2608–2611. Frank, G., 2000. Venus on wheels: Two decades of dialogue on disability, biography, and being female in America. University of California Press, Los Angeles, CA, p. 284. Gallese, V., Fadiga, L., Fogassi, L., Rizzolatti, G., 1996. Action recognition in the premotor cortex. Brain 119, 593–609. Gazzola, V., Aziz-Zadeh, L., Keysers, C., 2006. Empathy and the somatotopic auditory mirror system in humans. Curr. Biol. 16, 1824–1829. Iacoboni, M., Zaidel, E., 2004. Interhemispheric visuo-motor integration in humans: the role of the superior parietal cortex. Neuropsychologia 42, 419–425. Jenkinson, M., Smith, S., 2001. A global optimisation method for robust affine registration of brain images. Med. Image Anal. 5, 143–156. Jenkinson, M., Bannister, P., Brady, M., Smith, S., 2002. Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage 17, 825–841. Kaplan, J.T., Iacoboni, M., 2006. Getting a grip on other minds: mirror neurons, intention understanding, and cognitive empathy. Soc. Neurosci. 1, 175–183. Keysers, C., Gazzola, V., 2007. Integrating simulation and theory of mind: From self to social cognition. Trends Cogn. Sci. 11, 194–196.

Please cite this article as: Liew, S.-L., et al., Experience with an amputee modulates one's own sensorimotor response during action observation, NeuroImage (2013), http://dx.doi.org/10.1016/j.neuroimage.2012.12.028

U

N C O

R

R

E

C

T

E

D

P

R O

8

S.-L. Liew et al. / NeuroImage xxx (2013) xxx–xxx Thesen, S., Heid, O., Mueller, E., Schad, L.R., 2000. Prospective acquisition correction for head motion with image-based tracking for real-time fMRI. Magn. Reson. Med. 44, 457–465. Van Elk, M., Van Schie, H.T., Bekkering, H., 2011. Imitation of hand and tool actions is effector-independent. Exp. Brain Res. 214, 539–547. Van Overwalle, F., Baetens, K., 2009. Understanding others' actions and goals by mirror and mentalizing systems: a meta-analysis. Neuroimage 48, 564–584. Vogt, S., Buccino, G., Wohlschläger, A.M., Canessa, N., Shah, N.J., Zilles, K., Eickhoff, S.B., Freund, H.J., Rizzolatti, G., Fink, G.R., 2007. Prefrontal involvement in imitation learning of hand actions: effects of practice and expertise. Neuroimage 37, 1371–1383. Wager, T.D., Nichols, T.E., 2003. Optimization of experimental design in fMRI: a general framework using a genetic algorithm. Neuroimage 18, 293–309. Wolpert, D.M., Goodbody, S.J., Husain, M., 1998. Maintaining internal representations: the role of the human superior parietal lobe. Nat. Neurosci. 1, 529–533. Woolrich, M., 2008. Robust group analysis using outlier inference. Neuroimage 41, 286–301. Woolrich, M.W., Ripley, B.D., Brady, M., Smith, S.M., 2001. Temporal autocorrelation in univariate linear modeling of FMRI data. Neuroimage 14, 1370–1386. Woolrich, M.W., Behrens, T.E., Beckmann, C.F., Jenkinson, M., Smith, S.M., 2004. Multilevel linear modelling for FMRI group analysis using Bayesian inference. Neuroimage 21, 1732–1747. Worsley, K.J., 2001. Statistical analysis of activation images. Functional MRI: an introduction to methods.

R O

O

649 650 651 652 653 654 655 656 657 658 659 660 661 662 663 664 665 666 667 668 669 670 671 672 698

Liew, S.L., Han, S., Aziz-Zadeh, L., 2011. Familiarity modulates mirror neuron and mentalizing regions during intention understanding. Hum. Brain Mapp. 32, 1986–1997. Molnar-Szakacs, I., Wu, A.D., Robles, F.J., Iacoboni, M., 2007. Do you see what I mean? Corticospinal excitability during observation of culture-specific gestures. PLoS One 2, e626. Moseley, G.L., Brugger, P., 2009. Interdependence of movement and anatomy persists when amputees learn a physiologically impossible movement of their phantom arm. Proc. Natl. Acad. Sci. U. S. A. 106, 18798–18802. Murray, C.D., 2009. Being like everybody else: the personal meanings of being a prosthesis user. Disabil. Rehabil. 31, 573–581. Oztop, E., Imamizu, H., Cheng, G., Kawato, M., 2006. A computational model of anterior intraparietal (AIP) neurons. Neurocomputing 69, 1354–1361. Rizzolatti, G., Craighero, L., 2004. The mirror-neuron system. Annu. Rev. Neurosci. 27, 169–192. Rizzolatti, G., Fadiga, L., Gallese, V., Fogassi, L., 1996. Premotor cortex and the recognition of motor actions. Cogn. Brain Res. 3, 131–141. Rizzolatti, G., Fogassi, L., Gallese, V., 1997. Parietal cortex: from sight to action. Curr. Opin. Neurobiol. 7, 562–567. Romani, M., Cesari, P., Urgesi, C., Facchini, S., Aglioti, S.M., 2005. Motor facilitation of the human cortico-spinal system during observation of bio-mechanically impossible movements. Neuroimage 26, 755–763. Smith, S.M., 2002. Fast robust automated brain extraction. Hum. Brain Mapp. 17, 143–155.

673 674 675 676 677 678 679 680 681 682 683 684 685 686 687 688 689 690 691 692 693 694 695 696 697

Please cite this article as: Liew, S.-L., et al., Experience with an amputee modulates one's own sensorimotor response during action observation, NeuroImage (2013), http://dx.doi.org/10.1016/j.neuroimage.2012.12.028

U

N

C

O

R

R

E

C

T

E

D

P

F

Master your semester with Scribd & The New York Times

Special offer for students: Only $4.99/month.

Master your semester with Scribd & The New York Times

Cancel anytime.