833J Neurol Neurosurg Psychiatry July 2019 Vol 90 No 7
PostScript

Multisensory bionic limb to
achieve prosthesis embodiment
and reduce distorted phantom
limb perceptions
inTRoDuCTion
A major goal of neuroprosthetics is to
design artificial limbs that are expe-
rienced (‘embodied’) like real limbs.
However, despite important techno-
logical advances, this goal has not been
reached and prosthesis embodiment is
still very limited. Differently from our
physical body, current bionic limbs do
not provide the continuous multisensory
feedback required for a limb to be expe-
rienced as one’s own. Here, we present
a novel neuroprosthetic approach that
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834 J Neurol Neurosurg Psychiatry July 2019 Vol 90 No 7
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combines peripheral neurotactile stim-
ulation—inducing tactile sensation
on the missing limb—and immersive
digital technology—providing visual
illumination of the prosthetic hand. We
tested whether coherent multisensory
visuo-tactile neural stimulation (VTNS)1
induced higher prosthesis embodiment
and reduced the distorted perception of
the phantom limb (telescoping, ie, the
phantom limb is perceived as shorter
than the intact limb).
MeThoDS
Patient 1 and patient 2 are transradial
left forearm chronic amputees, who
suffered upper limb telescoping. Patients
were implanted with transverse intrafas-
cicular multichannel electrodes (TIMEs),
which induced the sensation of a vibra-
tion in a circumscribed skin region of
the finger 2 via medial nerve stimula-
tion in patient 1 (online supplementary
figure 1A) and in a skin region of finger
5 via ulnar nerve stimulation in patient
2 (online supplementary figure 1B and
material 1). Neurotactile stimulation2
was coupled with automatised visual illu-
mination of a skin region on the patient’s
prosthetic hand that corresponded to the
somatotopic location of touch sensa-
tions experienced on the phantom hand
(VTNS; online supplementary video 1,
online supplementary figure 1, online
supplementary material 1). VTNS was
administered in two conditions, either
with synchronous visual and neurotac-
tile stimulation or in a control condition
of asynchronous stimulation (1.5–2.5s
delay).
Prosthesis embodiment was measured
via a questionnaire, whereas changes in
phantom limb perception were tested via
a body landmark task where patients indi-
cated the perceived position of different
parts of the phantom limb by moving
a ruler in absence of visual stimulation
(figure 1B). The experimental proce-
dures were approved by the competent
ethical committee.
ReSulTS
Prosthesis embodiment. In both patients,
embodiment ratings based on question-
naires revealed significantly higher scores
during synchronous than asynchronous
VTNS stimulation (ps<0.001; Fisher test;
control items for suggestibility were not
modulated: ps>0.073; figure 1A).
Reduction of abnormal phantom limb
perception: telescoping. During the
embodiment-inducing condition, VTNS
improved telescoping (online supplemen-
tary video 1). Both patients perceived the
phantom finger of the stimulated limb in a
more distal position as compared with asyn-
chronous stimulation (t=2.13, p<0.01,
patient 1; t=3.6, p<0.001, patient 2;
figure 1C), while there was no change
in the perceived elbow position (control)
between conditions (p=0.76, patient 1;
p=0.099, patient 2). Thus, synchronous
VTNS increased the perceived length of
the phantom hand. Importantly, this effect
persisted 10min after VTNS had ended
(t=1.95, p=0.026, one-tailed, patient
1; t=1.94, p=0.029, one-tailed, patient
2; figure 1D). See online supplementary
material 1 for extended results.
DiSCuSSion
By combining immersive digital tech-
nology, neuroprosthetics and paradigms
from cognitive neuroscience, in two
amputees, we administered direct tactile
stimulation to the phantom limb via an
intraneural implant into the residual
limb nerves. Such stimulation, combined
with personalised and coherent visual
stimulation using immersive digital tech-
nology, VTNS, induced embodiment for
the prosthetic hand, and importantly,
reduced telescoping of the phantom limb
thus improving abnormal phantom limb
perceptions.
Our approach presents several advan-
tages with respect to earlier therapeutic
approaches aimed at inducing owner-
ship in amputees,3–5 as those require the
external application of tactile cues on skin
regions of the residual limb, which had
to be applied manually3 or via a robotic5
device as well as the concurrent appli-
cation of a physical visual stimuli on the
prosthetic device.3–5 This way, such proce-
dures are difficult to apply during contin-
uous prosthetic use in daily-life activities,
thus limiting the intensity and duration
of the induced prosthesis embodiment
and thereby reducing their clinical rele-
vance. Moreover, these previous studies
did not test whether embodiment affected
phantom limb sensations, that are critical
for prosthesis acceptance.6 Our VTNS
stimulation procedure shows that multi-
sensory stimulation necessary to induce
prosthesis embodiment does not need to
be linked to realistic4 5 or functionally
relevant interactions4 as long as VTNS
respects the fundamental constraints
of embodiment and multisensory inte-
gration (eg, synchronous multisensory
stimulation).1
Abnormal phantom limb perceptions.
Our results reveal another important
clinical benefit: the reduction of tele-
scoping. VTNS was able to reshape subjec-
tive sensations of upper limb dimensions,
as to make it being perceived as more
similar to the actual size of the missing
limb and the prosthesis. Interestingly,
previous research on phantom sensations
in a large sample of amputee patients
found that prosthesis embodiment sensa-
tions are more frequent in patients with
an extended phantom as compared with
patients with a telescoped phantom.6
Two theories have tried to account for
cortical reorganisation and phantom sensa-
tions following amputation.7 8 On the one
hand, the maladaptive plasticity theory
posits that abnormal phantom sensations
and phantom pain arise from maladaptive
cortical reorganisation, triggered by loss
of sensory input,7 thus associating greater
pain with increased local cortical reorgan-
isation. Recent data, on the other hand,
suggest that cortical changes following
limb amputation may also be due to a
combination of loss/altered sensory inputs
from the periphery and phantom pain
experience, resulting in a maintained brain
structural and functional representation
of the missing limb in the sensorimotor
cortices, but disturbed long-range connec-
tivity.8 Our multisensory neuroprosthetic
approach might act on either mechanism
for the phantom limb syndrome and might
be used to reduce telescoping, or in future
studies to alleviate phantom pain, if such
effects were to be found. Indeed, VTNS
provides multisensory coherent bodily
stimulation which may target central body
representations, but also aims at restoring
peripheral inputs from the residual nerves,
in turn affecting long-range connectivity.
At the moment, it is not possible to deter-
mine which mechanism is at the basis of
the present effect.
Limitations of our study include the
small number of participants tested, and
the use of only one measure of embod-
iment (questionnaire). Future studies
investigating prosthesis embodiment in
amputees with peripheral neural implants
should examine several aspects of embod-
iment in greater detail. Other limita-
tions are the fact that the experimenters
conducting the tests were not blinded to
the experimental conditions and that the
investigations were only carried out over
a limited amount of time (ie, for several
hours over different days).
Taken together, our results open up
new opportunities to enhance prosthetic
acceptance and advance the engineering
of personalised artificial limbs that, by
providing continuous multisensory feed-
back, might feel like real limbs.
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Figure 1 (A) Prosthesis embodiment. Average ratings of embodiment (Q1–3) and suggestibility items (Q4–5) are shown for all experimental conditions
are shown for both patient 1 and patient 2 (see online supplementary material 1). Embodiment was highest when VTNs was administered synchronously
with illumination of the prosthetic hand (as compared with the asynchronous condition). The synchronous stimulation was characterised by a delay smaller
than 10ms between the neurally induced tactile sensation and the visual illumination, whereas in the asynchronous condition the temporal mismatch (1.5–
2.5s) between the neural stimulation and the visual illumination was randomly selected on each trial. In patient 1, suggestibility items were always rated 0
(shown as coloured lines). (B) reduction of abnormal phantom limb perceptions (telescoping). To measure the perceived length of the phantom limb, both
patients were asked to operate a movable cursor inside a ruler with their right hand. The difference between the perceived position of this phantom finger
and elbow was used to estimate the perceived length (in cm) of the phantom limb (average scores are reported). (C) During synchronous VTNs (blue) both
perceived the tip of their phantom finger in a more distal position (vs asynchronous condition; p<0.01; red), compatible with an increase in the perceived
length of their phantom limb (B; online supplementary video 2). (D) This condition-specific change in telescoping persisted, in both patients, 10min after
VTNs had ended. Error bars show sE of the mean. *P<0.05; **P<0.01. VTNs, visuo-tactile neural stimulation.
Giulio Rognini,1,2,3 Francesco Maria Petrini,1,4
Stanisa Raspopovic,5 Giacomo Valle,1,4,6
Giuseppe Granata,7 ivo Strauss,1,4,6
Marco Solcà,1,2 Javier Bello-Ruiz,1,2
Bruno herbelin,1,2 Robin Mange,1,2
edoardo D'anna,1,4 Riccardo Di iorio,7
Giovanni Di Pino,8,9 David andreu,10
David Guiraud,10 Thomas Stieglitz,11
Paolo Maria Rossini,7,12 andrea Serino,1,2
Silvestro Micera,1,4,6 olaf Blanke1,2,13
1Center for Neuroprosthetics, Ecole Polytechnique
Fédérale de Lausanne, Lausanne, switzerland
2Laboratory of Cognitive Neuroscience, Brain Mind
Institute, Ecole Polytechnique Fédérale de Lausanne,
Lausanne, switzerland
3Laboratory of robotic systems, school of Engineering,
Ecole Polytechnique Fédérale de Lausanne, Laboratory
of robotic systems, switzerland
4Translational Neural Engineering Laboratory, Institute
of Bioengineering, school of Engineering, Ecole
Polytechnique Fédérale de Lausanne, Lausanne,
switzerland
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5ETH Zürich, Department of Health sciences and
Technology, Institute for robotics and Intelligent
systems, TAN E 2, Zürich, switzerland
6The Biorobotics Institute, scuola superiore sant’Anna,
Pisa, Italy
7Area of Neurosciences, Policlinic A Gemelli foundation,
Catholic University of the sacred Heart, rome, Italy
8Neurophysiology and Neuroengineering of Human-
Technology Interaction, Campus Bio-Medico University,
rome, Italy
9Institute of Neurology, Campus Bio-Medico University,
rome, Italy
10NrIA Camin Team, University of Montpellier – LIrMM
860 rue saint Priest, Montpellier, France
11Laboratory for Biomedical Microtechnology,
Department of Microsystems Engineering–IMTEK,
University of Freiburg, Freiburg, Germany
12IrCCs san raffaele Pisana, rome, Italy
13Department of Neurology, University Hospital of
Geneva, Geneva, switzerland
Correspondence to Professor silvestro Micera,
Center for Neuroprosthetics, Ecole Polytechnique
Fédérale de Lausanne, Lausanne CH-1015, switzerland;
silvestro. micera@ epfl. ch
acknowledgements The Authors are deeply grateful
to the two patients who freely donated weeks of their
life for the advancement of knowledge and for a better
future of People with hand amputation. The Authors
are also grateful to Professor Fernandez for the surgical
implantation of the TIMEs.
Contributors Gr designed the study, performed
the experiments, analysed the data and wrote the
paper. FMP and sr developed the software for the
neural stimulation, contributed to the design of the
study, performed the experiments and wrote the
paper (Gr, FMP and sr equally contributed to the
work). GG, rDI, Is, GV and ED collaborated during the
development of the neural stimulation software and
during the experiment. Ms designed, performed and
analysed the telescoping experiment. rM developed the
augmented reality software and integrated it with the
neural stimulation device. JB-r and BH integrated the
augmented reality software with the neural stimulation
device, contributed to the design of the experiments
and performed part of the experiments. GDP selected
the patients and collaborated during the experiments.
Ts developed the TIME electrodes. DA and DG
developed the device for the neural stimulation. PMr
selected the patients and supervised the experiments.
As designed the study, performed the experiments,
analysed the data and wrote the paper. sM and OB
designed the study, supervised the experiments and
wrote the paper (As, sM and OB equally contributed
to the work). All the authors read and approved the
manuscript.
Funding This work was partly supported by the EU
Grant CP-FP-INFsO 224012 TIME project (Transverse
Intrafascicular Multichannel Electrode system), by the
EU Grant FET 611687 NEBIAs Project (NEurocontrolled
BIdirectional Artificial upper limb and hand prosthesis),
by the EU Grant Health 602547 EPIONE project
(Natural sensory feedback for phantom limb pain
modulation and therapy), by the EU Grant ErC-sTG
678908 rEsHAPE project, by the project NEMEsIs
(Neurocontrolled mechatronic hand prosthesis) funded
by the Italian Ministry of Health, by the Bertarelli
Foundation, by the Wyss Center for Bio and Neuro-
engineering and by the swiss National Competence
Center in research (NCCr) in robotics.
Competing interests sM, sr, FMP hold shares
of sensars Neuroprosthetics, a company working
to commercialise novel solutions for transradial
amputees.
Patient consent Not required.
ethics approval The experimental procedures were
approved by both the Institutional Ethics Committees
of Policlinic A Gemelli at Catholic University and the
IrCCs s raffaele Pisana (rome). Informed consent was
obtained from both patients.
Provenance and peer review Not commissioned;
externally peer reviewed.
© Author(s) (or their employer(s)) 2019. No commercial
re-use. see rights and permissions. Published by BMJ.
► Additional material is published online only. To
view please visit the journal online (http:// dx. doi. org/
10. 1136jnnp- 2018- 318570).
Gr, FMP and sr contributed equally.
As, sM and OB contributed equally.
To cite rognini G, Petrini FM, raspopovic s, et al. J
Neurol Neurosurg Psychiatry 2019;90:833–836.
received 5 April 2018
revised 28 June 2018
Accepted 25 July 2018
Published Online First 12 August 2018
J Neurol Neurosurg Psychiatry 2019;90:833–836.
doi:10.1136/jnnp-2018-318570
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