1

Xenomelia: The Neurological Basis of a Foreign Limb Disorder

Khloe Frank


























2

Abstract
Xenomelia, also known as Body Integrity Identity Disorder (BIID) or
apotemnophilia, is a body image disorder characterized by the intense desire for the
amputation of a healthy and functional limb that feels extraneous and foreign to the
affected individual. The majority of xenomelia cases affect men in their left legs, and the
onset is usually early in childhood or adolescence. Though long regarded as a
psychological disorder, researchers have recently started to view xenomelia as
neurologically-based. People with xenomelia seem to have normal functionality of visual,
somatosensory, and pain afferents to the brain for their undesired limbs, indicating that
the disorder is likely caused by a dysfunction of higher-level integration of these inputs
into the brains representation of body image. Many researchers have begun examining
dysfunction of the right parietal lobe as a possible mechanism for xenomelia, as this area
is known to mediate other body image disorders. There is currently no effective treatment
for xenomelia.







3

Xenomelia (which translates from the Greek words as foreign limb) is a body
image disorder characterized by the intense desire for the amputation of a healthy and
functional limb that feels extraneous and foreign to the affected individual. The condition
goes by several other names as well, including apotemnophilia and Body Integrity
Identity Disorder (BIID). Though the disorder is very rare, a meta-analysis of several
interview and questionnaire studies surveying over 100 individuals has established some
basic trends in the manifestation of xenomelia (Aoyama et al, 2012). Xenomelia affects
the left legs of men more than the right side or arms, and the onset of the disorder is
usually early in childhood or adolescence.
Some affected individuals feel an erotic attraction to amputees and/or sometimes
pretend to be an amputee; however, because Xenomelia has not been officially declared
as a disorder in the Diagnostic and Statistical Manual or any other authoritative source for
classification, it is difficult to determine whether the elements of sexual attraction and
amputee simulation are symptoms of xenomelia or indicators of a similar but separate
body image or psychological disorder (Aoyama et al, 2012). Individuals who suffer from
xenomelia have been known to request surgical amputation of their undesired limbs, and
may even go to the extremes of performing an amputation on themselves or severely
damaging their limbs to necessitate an emergency amputation (Patrone, 2009 as cited by
Sedda, 2011; and McGeoch, 2011). Although some have questioned the ethics of
amputating a healthy and function limb, this seems to be the only treatment that relieves
the feeling of being over-complete, seeing as no drug treatment or psychotherapy has
yet been found to be effective (McGeoch et al, 2011; and Sedda, 2011).
4

For a long time, xenomelia was regarded as a psychological disorder possibly
motivated by factors such as a desire for attention, a sexual paraphilia, and/or an
encounter with an amputee early on in life (Brang et al, 2008). More recently, however,
researchers have begun looking at xenomelia as a disorder with a neurological basis.
Brang et al list three main reasons for this: the high incidence of left-side undesired limbs
suggests a neural rather than psychological origin, the ability of most xenomelia subjects
to consistently trace out the level at which they desire amputation, and a sense of having
the limb being not aversive rather than just not ideal (Brang et al, 2008). In addition, the
fact that subjects with xenomelia seem to have normal functionality of visual,
somatosensory, and pain afferents to the brain for their undesired limbs indicates that
xenomelia occurs not due to a dysfunction of those inputs, but rather a dysfunction of
their integration into the brains representation of body image (McGeoch et al, 2011).
Lesions of the right parietal lobe have been found to lead to various other body image
disorders, including left-sided neglect, anosognosia, misoplegia, and somatoparaphrenia,
among others (McGeoch et al, 2011). Therefore, many researchers have begun examining
dysfunction of the right parietal lobe as a possible mechanism for xenomelia.
Using magnetoencephalography (MEG) scans, McGeoch et al measured brain
activity in various regions of interest right and left of the superior parietal lobe (SPL),
inferior parietal lobe (IPL), S1, M1, insula, premotor cortex, and precuneus during
tactile stimulation of the left and right foot and thigh in four xenomelia subjects and four
control subjects. For the four xenomelia subjects, the foot stimulation was done below the
desired amputation line, and the thigh stimulation was done above it; the stimulations
5

were done at homologous sites on the control subjects legs. The researchers found that
the foot/thigh ratio of brain activation (i.e. the ratio of the amount of brain activation in
response to foot stimulation to the amount of brain activation in response to thigh
stimulation) was significantly lower in the right SPL when stimulating the limbs desired
to be amputated compared with the unaffected limbs and the limbs of control subjects
(McGeoch et al, 2011). They did not find a significant difference in activity patterns
between these groups for any of the other 13 brain regions of interest. This observed
phenomenon of reduced right SPL activity in response to tactile stimulation of the portion
of a limb perceived as foreign indicates that right SPL dysfunction and hypo-activation
is likely involved in the failure of this limb to be properly incorporated into a xenomelia
subjects body image representation.
As mentioned above, dysfunction of the posterior part of right parietal lobe, which
includes the SPL and IPL, is linked with many other body image disorders (McGeoch et
al, 2011). The SPL receives afferent inputs from the dorsal visual stream, S1, S2, the
premotor cortex, and M1, and therefore seems a likely candidate for the localization of
body image representation (Hyvarinen, 1982 and Felleman et al, 1991 as cited by
McGeoch et al, 2011). A structural magnetic resonance imaging (MRI) study of 13
xenomelia subjects and 13 matched controls has shown that xenomelia subjects have less
cortical thickness in the right SPL and less cortical surface area on the right side for the
S1, S2, IPL, and the anterior insular cortex regions of interest (Hilti et al, 2013). These
underlying structural abnormalities may be responsible for the atypical right parietal lobe
processing that is associated with xenomelia.
6

In a 2008 study of two xenomelia subjects, Brang et al measured the skin
conductance response (SCR) to pinprick stimulations and found that there was
significantly more SCR in the limbs desired to be amputated compared with the
unaffected limbs and the limbs of control subjects (Brang et al, 2008). Because skin
conductance is an indicator of sympathetic nervous system responsiveness, the
researchers concluded that the dysfunctional body image representation in the brains of
xenomelia subjects may lead to atypical sympathetic responsiveness. They hypothesize
that a unified representation of body image is localized in the right superior parietal
lobule, which receives afferents from various sensory areas and the right insula. They
conclude that an incoherent body image representation in xenomelia subjects causes the
abnormal outputs from the insula, resulting in atypical sympathetic responsiveness. Other
researchers interpreting the results of this study have speculated that the increased
sympathetic response in undesired limbs may be caused by hyperattention directed
towards that part as the brain senses that body image integration is abnormal (Aoyama et
al, 2012).
In their analysis, Brang et al especially emphasized the point that in xenomelia
subjects, somatosensory afferents to S1 are normal, but those from S1/S2 to right superior
parietal lobule may be dysfunctional. The right superior parietal lobule projects to limbic
structures, including the insula, which may allow for the manifestation of these
dysfunctional connections as a perceived feeling of lack of limb ownership in xenomelia
subjects and the accompanying desire for amputation. In other words, the incongruity
between xenomelia subjects seeing and feeling sensory inputs from a limb on their actual
7

body while simultaneously perceiving that that limb disconnected from their internal
body image representation and autonomic functions may lead to the foreign limb
perception.
A functional magnetic resonance imaging (fMRI) study of five xenomelia
subjects and ten control subjects by Van Dijk et al helped further delineate the differences
in frontoparietal processing that may be responsible for xenomelia. The researchers found
that tactile stimulation of the left and right lower leg (i.e. both the accepted leg and the
leg desired to be amputated) resulted in greater frontoparietal network activity in
xenomelia subjects compared with controls. As mentioned above, this may be due to
hyperattention toward the undesired limb. In addition, in xenomelia subjects, tactile
stimulation of the limb portion desired to be amputated resulted in reduced ventral and
dorsal premotor (PMv and PMd) activity compared to the amount of activity measured in
response to tactile stimulation of the accepted limb. Performance of motor activity
(flexing and pointing the toes of the left and right feet), showed no significant differences
in activity for any of the brain regions of interest when comparing xenomelia and control
subjects or when comparing the accepted versus undesired limbs of the xenomelia
subjects. These results suggest that abnormalities in premotor cortex processing may be
responsible for the occurrence of xenomelia, even though motor activity is normal. Thus,
the researchers conclude that xenomelia may be caused by the altered integration of
somatosensory and proprioceptive information (Van Dijk et al, 2013).
1n 2012, Aoyama et al showed that five subjects with xenomelia had abnormal
spatial-temporal integration of their undesired limbs compared to their accepted limbs.
8

This was determined by administering a pair of tactile stimuli to each subjects undesired
leg one below the line of desired amputation (distal) and the other above it
(proximal) applied either in synchrony or with differential timing onsets of 15, 30,
60, 120, or 240 milliseconds. For the accepted leg, the tactile stimuli were administered
to homologous locations and with the same set of various time courses. With each
stimulation, the subjects pressed buttons to indicate either which part of the limb (distal
foot or proximal thigh) they perceived to have been stimulated first, or whether they
perceived the stimuli as being simultaneous.
The researchers found that for the accepted leg, subjects were significantly more
likely to perceive the stimuli as simultaneous when the distal foot stimulation had been
applied first by several milliseconds. For the undesired legs, however, subjects were
significantly more likely to perceive the stimuli as simultaneous when the proximal
thigh stimulation had been applied first by several milliseconds. Aoyama et al
rationalized that the results observed for the accepted limbs follow the logic that the time
course for neural transmission from the proximal thigh to the brain is shorter than that
of the distal foot, and therefore the brain perceives synchrony when the distal foot is
stimulated several milliseconds prior to the proximal thigh. The observation that the
undesired limbs deviate from this spatial-temporal pattern (in fact, showing the opposite
pattern) could explain why these limbs are not coherently integrated into the body image
representation in the brains of xenomelia subjects and thus are considered foreign.
A study in 2014 by Bekrater-Bodmann et al used fMRI analysis of 25 normal
subjects during administration of the virtual hand illusion (VHI) in order to study the
9

importance of synchrony and timing of visual and tactile stimuli for perceived illusory
ownership of a limb. In the VHI, subjects observe a virtual representation of a left hand
touched by a rod while their real left hand is hidden from view and stimulated with a
mechanical tactor. In previous studies, these simultaneous visual and tactile stimuli
have resulted in illusory ownership of the artificial hand and bilateral activity in the
ventral premotor cortex (PMv) (Ehrsson et al, 2004 as cited by Bekrater-Bodmann et al,
2014). Bekrater-Bodmann et al investigated this phenomenon further by testing five
conditions per subject: 1) simultaneous visual stimulation (of the virtual hand) and tactile
stimulation (of the real, hidden hand), 2) visual stimulation 300ms prior to tactile
stimulation (+300), 3) visual stimulation 600ms prior to tactile stimulation (+600), 4)
tactile stimulation 300ms prior to visual stimulation (-300), and 5) tactile stimulation
600ms prior to visual stimulation (-600). After executing each condition, they
translated the subjects self-reported experiences into VHI vividness scores in order to
quantify the intensity of the VHI phenomenon.
The results showed no significant difference in VHI vividness scores, whole brain
activity, or brain activity in any given region of interest when comparing the
simultaneous visual and tactile stimulation to the +300 or -300 conditions. For the
+600 and -600 conditions, however, the researchers did observe a significant
decrease in VHI vividness scores, as well as significant decreases in brain activity in the
right PMv region compared to simultaneous visual-tactile and -300 or +300
conditions (Bekrater-Bodmann et al, 2014). These results indicate that the order of visual
and tactile stimulation is negligible in determining intensity of the illusory limb
10

ownership experience (i.e. VHI), but the temporal synchrony of these stimuli does affect
VHI intensity, likely mediated by activity in the right PMv. Although the mechanisms for
representing and perceiving an illusory sense of limb ownership may differ from those
for representing and perceiving actual limbs, this study is relevant to the phenomenon of
xenomelia because it shows further evidence that the right PMv plays a role in the
representation of body image and perceived limb ownership. It also provides further
evidence that temporal synchrony between various stimuli may be necessary for coherent
integration of a physical limb into the body image representation in the brain, and that
abnormalities in this synchrony may be responsible for the occurrence of xenomelia.
The results of the aforementioned studies may be informative for developing
future treatments for xenomelia so that people with the disorder have alternatives to
amputation. For example, based on their results, Van Dijk et al suggest that manipulating
premotor activity using endogenous neurofeedback (fMRI or electroencephalography) or
exogenous neurostimulation (transcranial magnetic stimulation or direction current
stimulation) may be effective (Van Dijk et al, 2013). V.S. Ramachandran and Paul
McGeoch suggest that vestibular caloric stimulation may be an effective treatment option
to help realign the physical reality of a patients body with their body image
representation (Ramachandran and McGeoch, 2007). McGeoch et al suggest that
adrenoceptor antagonists may be an effective treatment by decreasing the hyper-
responsive sympathetic activity of undesired limbs (McGeoch et al, 2011). Other
manipulations addressing the asynchrony between the various inputs (visual,
11

somatosensory, proprioceptive, etc.) being integrated into the body image representation
may also be helpful, for example using the mirror box paradigm (Sedda, 2011).
There were some general limitations that pertained to most of the studies
reviewed here. Firstly, because xenomelia has a very low prevalence in the population, all
of the studies that used xenomelia subjects had small sample sizes five subjects or
fewer (except for the interview and questionnaire surveys). Also, xenomelia subjects
included some with the left lower leg and others with the right lower leg desired to be
amputated. The restriction of visual and audio information during several of the studies
does not closely mimic the natural, unrestricted environment in which xenomelia
manifests, so it may not be a highly valid model.
Nevertheless, I believe that the results of the studies reviewed above are cohesive
with each other and with the hypothesis that xenomelia arises when the integration of
various sensory signals from the undesired limb is abnormal, resulting in a dysfunctional
representation of this limb as part of the perceived body image. I think it makes sense that
this dysfunctional representation would cause a person to feel dis-ownership of their
limb and thus desire for it to be amputated. Although several of the studies differed in
which specific brain regions had results showing significant data for increased or
decreased activation with the stimulation of undesired limbs (e.g. reduced PMv and PMd
activity for the undesired limb in the Van Dijk et al study versus reduced SPL activity for
the undesired limb in the McGeoch et al study), these differences may have resulted from
differences in imaging techniques, region of interest partitioning software, stimulation
techniques, statistical analyses, etc. Furthermore, all of the specific brain regions
12

implicated in the studies were part of the frontoparietal network, which is known to
mediate body image representation.
Understanding xenomelia will allow us to better treat those people who are
affected by the disorder, and it will also improve our understanding of how body image
representation is encoded in the brain. In addition, understanding this phenomenon will
elucidate the neurological basis of body-image-related mental disorders that drive
abnormal human behaviors. Therefore, future research in this field will be beneficial to
individuals who suffer from xenomelia and to society as a whole.














13

References
Aoyama, Atsushi, et al. Impaired Spatial-Temporal Integration of Touch in Xenomelia
(Body Integrity Identity Disorder). Spatial Cognition & Computation 12 (2012):
96-110.
Bekrater-Bodmann, Robin et al. The Importance of Synchrony and Temporal Order of
Visual and Tactile Input for Illusory Limb Ownership Experiences An fMRI
Study Applying Virtual Reality. PLoS ONE 9:1 (2014): 1-9.
Brang, David, et al. Apotemnophilia: A Neurological Disorder. Cognitive
Neuroscience and Neuropsychology 19:13 (2008): 1305-1306.
Hilti, Leonie Maria, et al. The Desire for Healthy Limb Amputation: Structural Brain
Correlates and Clinical Features of Xenomelia. Brain: A Journal of Neurology
136 (2013): 318-329.
McGeoch, Paul D., et al. Xenomelia: A New Right Parietal Lobe Syndrome. Journal of
Neurology, Neurosurgery, & Psychiatry 82 (2011): 1314-1319.
Ramachandran, V.S. and Paul McGeoch. Can Vestibular Caloric Stimulation Be Used to
Treat Apotenmnphilia? Medical Hypotheses 62:2 (2007): 250-252.
Sedda, Anna. Body Integrity Identity Disorder: From A Psychological to a Neurological
Syndrome. Neuropsychology Review 21 (2011): 334-336.
Van Dijk, Milenna T., et al. Neural Basis of Limb Ownership in Individuals with Body
Integrity Identity Disorder. PLoS ONE 8:8 (2013): 1-6.