Xenomelia: The Neurological Basis of a Foreign Limb Disorder
Khloe Frank
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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.
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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.
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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.