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(Curent Bilogy 24, 2681-2686, November 17, 2014 ©2014 Etsever Ltd Alright reserved pds dol org/t0.1016/ cub 2016.09.048 Report Neurological and Robot-Controlled Induction of an Apparition Olaf Blanke,"*" Polona Pozeg,”* Masayuki Hara,” Lukas Heydlrich,” Andrea Serino,’ Akio Yamamoto,” Toshiro Higuchi,” Roy Salomon,’ Margitta Seeck,? Theodor Landis,” Shahar Arzy,’ Bruno Herbelin, Hannes Bleuler,’ and Glullo Rognin!'“ "Genter for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne, Station 19, 1015 Lausanne, Switzerland 2Department of Neurology, University Hospital of Geneva, Rue ‘Michel-du-Crest 24, 1208 Geneva, Switzerland Laboratory of Cognitive Neuroscience, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Station 19, 1015 Lausanne, Switzerland ‘Laboratory of Robotic Systems, School of Engineering, Ecole Polytechnique Fédérale de Lausanne, Station 17, 1015 Lausanne, Switzerland "Advanced Mechatronic Laboratory, Department of Precision Enginoering, The University of Tokyo, 7-8-1 Hongo, Bunkyo-ku, 113-8656 Tokyo, Japan "Department of Neurology, Hadassah Hebrew University “Medical Center, P.O. Box 12000, 81120 Jerusalem, Israel ‘Summary Tales of ghosts, wraiths, and other apparitions have been reported in virtually all cultures. The strange sensation that somebody is nearby when no one is actually present and ceannot he seen (feeling of a presence, FoP) is a fascinating feat of the human mind, and this apparition is often covered inthe Iterature of divinity, occultism, and fiction. Although it Is described by neurological and psychiatric patients [1, 2] and healthy individuals in diferent situations [1, 3,4, itis not yet understood how the phenomenon is triggered by the brain. Here, we performed lesion analysis in neurological FoP p: tients, supported by an analysis of associated neurological deficlts. Our data show that the FoP is an illusory own-bedy perception with well-defined characteristics thats associated With sensorimotor loss and caused by lesions in three distinct brain regions: temporoparletal, Insular, and especially tron- toparietal cortex. Based on these data and recent experi- mental advances of multisensory own-body illusions [5-2] We designed a master-slave robotic system that generated specific sensorimotor conflicts and enabled us to induce the FoP and related illusory own-bodl perceptions experimentally in normal participants. These data show thatthe illusion of feeling another person nearby is caused by misperceiving the source and identity of sensorimotor (tactile, proprioce tive, and moter) signals of one's own body. Ourtindings reveal the neural mechanisms of the FoP, highlightthe subtle balance of brain mechanisms that generate the experience of “self” and “other,” and advance the understanding of the bra ‘mechanisms responsible for hallucinations in schizophrenia, Results and Discussion Descending with his brother from the summit of Nanga Parbat, fone of the ten highest mountains in the world, Reinhold oO Messner felt a third climber “descending with us, keeping regular distance, a litle to my right and a few steps away {rom me, just outside my field of vision” [10]. Messner “could not see the figure” but “was certain there was someone there, ‘Sensing "his presence” [1°]. This apparition, the sensation that ‘somebody is nearby when no one is actually present, is called the feeling of a presence (FoP) and has been described during periods of physical exhaustion [1, 3, 4, 11, 12} and has influ- fenced occult literature and fiction [13}. Although people do not see the “presence,” they may describe its spatial location land frequently turn around or offer food to the invisible pres- ‘ence [14, 15}. Although the FoP has been described in psychi atric [), 2, 15, 16] and neurological patients (2, 16], its neural ‘origin is unknown. A single case report showed that electrical stimulation in temporoparietal cortex induces the FoP, sug- ‘gesting that disturbed sensorimotor processing (tactile, pro- prioceptive, and motor cues) is important [17]. However, this has not been confirmed in ther patients, and the significance of these findings for the FoP in healthy subjects is unclear. Neurology and the FoP We performed lesion analysis and analyzed the associated hallucinations and neurological symptoms in 12 FoP patients (able 1; Figure $1 available online). The presence was felt in all cases in clote proximity to and behind the patient's body (p< 0.01), The presence was lateralized (p < 0.01) in contrale- sional space (p < 0.01) and equally often in right or left hem: space (not significant, n.s.; Table 1). Sensorimotor deficits ( < 0.01) and the experience of ilusory movements of the presence during movements ofthe patient (n..) were frequent symptoms (Supplemental Experimental Procedures), For lesion analysis, we used a multimodal imaging approach, relying on combined functional and structural neuroimaging data to determine anatomical regions of maximal lesion over- lap [18-20]. This approach, which combined functional and structural lesion data, was necessary because many patients ‘sutfored from epilepsy, and in several patients, FoP was induced by electrical stimulation, and because the FoP is rare. Projecting all lesions onto the left hemisphere, lesion ‘overlap analysis highlighted three cortical regions: insular cor- tex, frontoparieta cortex, and the temporoparietal cortex (Fi3- ure’ TA). We next compared lesion extent within these three cortical regions between FoP patients and control patients matched for complex hallucinations, etiology, and sensori- motor deficits (Figure 1B; Supplemental Experimental Proce- dures): lesion extent did not differ between both groups in Brodmann area 22 (p = 0.18) and 48 (p = 0.68), whereas FoP. patients had significantly larger lesions in Brodmann area 7 (p= 0.01) These results show that although FoP is associated. with insular, temporoparietal, and frontoparietal lesions, only frontoparietal lesions (Brodmann area 7) were specifically associated with the FoP. Robotically Induced Bodily Iilusions In order to study the FoP in healthy subjects, we designed a master-slave robotic system [21] and investigated sonst motor signals and their role in inducing FoP experimentally by integrating our findings with principles from other body ils- sions [5] fnformed consent was obtained, and all the studies logy Vol 24 No 22 Table. Cnieal Daa for FoP Group Clnial Data Are Surmarized for Each FoP Patt Patent _DiagnosilEtelogy __Levion [esin Anafjals_NewologyiNewopsychology Semicleay FoP a peweeysteorcesls __Wortopartal coven) MRI gat disturoaneeila presence af person whe behing FoPb eplepy, satus post eiptoparetal cortex, MRI, EEG presence benind et shoulder {Eptiechemie stroke, fontoperatal cortex dete [thouete ike shadow of he nplesant most reqvonty ercevved while waleng Fore eplepsy ‘wontoparetal cortex (L) MRI, EEG, PET, right-sided weskness/ _presenew of "black person Ford eplpsy. sp resection insula. trontoparetl MRI. EEG, PET. right-sided numbness/_ presence of aman. bohnd‘o sreapilay angiomain cortex t) SPECT, cores! executive dete eight In pepersona space, Iseherie stoke paretallobe nse detetvarosoarest. Behind, tthe rint redupleaive paamnesia FOP! eplepsy, cerebral thalamocapeuar-caudate MRI,EEG ——efladed ayametateft pretence of “a perin’s back Netocytoss resin, ns (8 toatl negieet $hadow" to he left same poston {lose family member FoP 3 splay, ep Insuia cepsulclentcular — MRLLEEG —_rghtlded paresthesia and presence of four people in mosty Capeuolenteuir region hemipareaaegleclaprania, lel onal space, fail members FoPh eplepsy. Remiplegc insula paritooceptalMRILEEG right-sided paraesthesia presence ofa porso's “shadow rine cortex td weaknessaphesia™ —tohis ight behind Fort eplepsy mesial temporal lobe, MAL,PET, ___nermalipostctal aphasia sensation of somebody's presence, Sntecortempora lobe SPECT, i€£0 Behind othe lo ansety FoP] epilepsy. sp resection tomporopareta! MAL, EEG, PET, normavaphasa, anomis pretence of aml shadow, fal temper cortex) SPECT, cortea Beha othe right, same yep lesion stimtaton postion, eehoprana, Fork eplepsy Posterortemporaiiobe() MRl,corteal normaVaphesia pretence borin tothe ight, FOP eplepsy.ovacerebral_temporopareooccintal MRILEEG ight sided sensorimotor presence ofa person shadow Fematems cortex deteivaphasiaparaphasi, ‘ofa female person’, on her ght $ide (20-30 em), behind, while “tandng and walking, echopraxia Were conducted in conformity withthe Declaration of Helsink: Supplemental Experimental Procedures). We investigated whether the FoP is associated with illusory touch sensations (questionnaire) and mistocalization of the body (29, 22}; Sup- plemental Experimental Procedures) (Figure 2A; Figure $2 ‘Novie S1). While standing and blindfolded, participants moved their arms and thereby moved the master device (via their n- serted right index fingers) in front of them. These movements were sent to the slave robot, which applied tactile stimull in realtime to the participants’ backs (Figure 2A; Movie $2) [7 Participants moved the master robot for 3 min while they received tactile cues on thelr backs (by slave robot) and thelr right fingertips (by master robot; Movic $2). Stroking was applied sither synchronously or asynchronously (600 ms delay), with or without somatosensory force feedback at the hhand (2 x 2 factorial design) During synchronous, but not asynchronous, stimulation, participants (study 2; Supplemental Experimental Procedures) experienced the sensation of touching themselves (self- touch), despite extending thelr arms in front of their bodies (© <0.01; Figure 2B), Synchronous stimulation and stimulation with force feedback were further associated with a drift of the subject's body toward the front position, where they felt their hands (p < 0.05; Figure 20; Movie $2; Supplemental Exper'- ‘montal Procedures). Thus, sensorimotor signals trom tho fingertip (forward-extended arm) while a tactile cue is applied to the subject's back induce the illusory feeling of touching ‘one's own back with one’s own finger (selftouch) and bias ‘olfslocation toward the fingertip. These findings extend earior illusions due to sensory conflicts between two hands [5] or be- tween two hands and the nese [2] to an ilusion between hand and trunk (see also (8,7). Robotically Induced FoP More interesting effects were observed during stronger ‘sensorimotor conflicts; during asynchronous. stimulation, Participants showed a drift in selflocation in the opposite, backward direction (p < 0.01) and reported higher other touch than selfstouch. Moreover, during postcondition de- briefing, five subjects roported to have experienced a FoP. {Supplemental Experimental Procedures). In study 8 (Supple- mental Experimental Procedures), we investigated whether we could induce the FoP experimentally, predicting that Under asynchronous stimulation without somatosensory force feedback (fingertip), subjects would feel the presence ‘of a person that is touching them, associated with a back- ward drift in selfocation (toward the presence). Figure 3A ‘shows that participants experienced being in the presence ‘of another person in the asynchronous versus synchronous ‘stimulation condition (p < 0.01) and experienced being touched by that invisible presence behind them (p < 0.01). ‘Asynchronous stimulation induced a backward drift in sol location toward the position of the presence (p < 0.05; Fig- ure 3B; Movie $3} Et -an Apparition Figue 1. Lesion Analysis in Study 1 {A Lesion overlap analyse forthe FP group revealed hve regions where was maximal Theso regions wer a olows: temperopaetal cr tex tive patents; Brodmann area 2: Montreal Newologel Inet [MN X='50, y= 51, 222), tontopareal core (ive patent; Brodmann 32. = 54,262), and insula ve patents; Brodmann "The elo seals indeate he flowing bie represents tive patents, geen represents ou pallens, and red ep {G) Maximal lesion over forthe control group Te colar seal nae ates the folowing: green represents fur patients, yellow represents fve tients, and ved ropresents sk pabens. Five contol patents had & Hort lesion, and seven contol patients had alot esto: for analyse, alllesans To oxclude that the FoP was caused by explicit questioning correlated mechanisms, we designed a person numerosity task that tested implicitly the presence of another person close to the participant (etudy 4), While using the rabot in synchronous and asynchronous stimulation, participants estimated the number of people that they felt were close to them in the testing room (the following question was asked: “how many people do you fee! close to you?"). Data show that during the asynchronous. (FoP-inducing) condition, participants judged a significantly higher number of people as being close to them (mean = 2.0) as compared to the synchronous condl= tion (mean = 1.6; p < 0.01; Figure 30), ‘Our neurological data reveal thatthe FoP is caused by focal brain lesions and that the FoP is most often experienced uni- laterally, within peripersonal space behind the body, and as- sociated with illusory own-body perceptions. FoP patients also show frequent somatosensory-motor deficits that we contralateral tothe lesion on the same side as the presence, ‘Compatible withthe variability in lesion location across earlier clinical studies, we found that lesions associated with the FoP were focal but were linked to temporoparietal,frontoparietal, and insular cortex (of elther hemisphere). Previous work showed that brain interference or lesions in FoP patients wore in temporopariotal cortex [17] and frontoparietal cortex [2]. The present data also highight that the FoP follows insular lesions and indicated lesion location with greater precision than previous work. Additional analysis in control patients (matched for complex hallucinations, etiology, and sensor'- ‘motor deficits) revealed that from the three lesion overlap zones, only the frontoparital site was specifically associated With the FoP, highlighting the importance of the latter region in the FoP. Interestingly, temporoparietal cortex [20], insula [24], and frontoparietal cortex [5, 25] have been associated with bodily sell-consciousness and are areas that integrate ‘sensorimotor or multisensory bodily signals, as shown in hu- rman [25] and nonhuman primates [27, 28], compatible with the sensorimotor deficits we observed. The present findings highlight that the FoP is characterized by its own distinct phe- nomenology (compared to out-of-body experiences [OBES], heautoscopy, and autoscopic hallucinations) and interference with frontoparietal cortex, All latter conditions have been linked to a single and hemisphere-specific lesion site ['8, 20] and to disorders of multisensory integration that do not involve the sensorimotor system. OBEs are attributed to visuoso- matosonsory-vestibular disintegration (20, 28], heautoscopy is attrbuted to visuosomatosensary-interoceptve disintegra- tion, and autoscopic hallucinations are attributed to visuoso- matosensory disintegration (18, 0]. Instead, the present FoP data give most importance to abnormal integration of sen- ‘sorimotor signals caused by frontoparietal lesions of either hemisphere. We note that these lesion overlap data have to be regarded with caution, as we included different types of brain lesions and included functional intracranial electroon= ‘cephalogram [EEG], cortical stimulation, and PET) and struc- tural (MRI) lesion data. Moreover, our lesion overlap analysis also associated temporoparietal cortex and the insula with the FoP, but this was not corroborated by comparison with ccontrol patients. More work is needed to understand how these three regions differ in their involvement in the FoP. The robotic data corroborate and apply our neurological findings to healthy subjects and show that sensorimotor con- flicts using well-controlled bodily stimulations are sulficient to induce the FoP (albeit more weakly than in neurological pa- tients). Based on clinical data and previous body ilusion work [5, 7,23], our robotic data show that the FoP can be induced. when exposed to conflicting sensorimotor signals that are ‘spatially and temporally incompatible with physical slt-touch. ining sensorimotor signals from forward-extended arms without force feedback atthe fingertips (motor-proprioceptive ‘cues), with delayed tactile feedback at the subjects’ backs, ‘was sufficient to induce the FoP. Under such stimulation, sub~ jects reported being in the presence of another person behind them and being touched by that invisible presence. This was associated with a backward drift in selt-location toward the Presence and with elevated person numerosity judgments, ‘corroborating our experiential findings behaviorally. The robot- ically induced FoP thus mimics the FoP in clinical populations. ‘and healthy subjects and is associated with abnormal per- ception of one's own body. These are major quantitative achievements because previous reports consisted of post hoc anecdotal accounts occurring far away from the research laboratory and because the FoP has never before been induced experimentally [1, 3, 4, 11,12) ‘A prominent model for motor control and bodlly experience posits that efferent copy signals from the sensorimotor system ‘reused to make predictions about the sensory consequences ‘of movement and that such integration is fundamental for normal bodily experionce [8,31]. Predicted sensory conse- ‘quences based on motar commands are compared with the reafferent sensory inputs during motor execution. A match be- tween the predicted sensory information and the actual sen- ‘sory information is considered to be self-generated, whereas differences between predicted sensory consequences and the reafferent signals are indicative of the influence of an ‘extemal object or another agent. Our master-slave robot ‘generated a spatiotemporal mismatch between our partici ants’ arm movements (motor-proprioceptive signals) and their sensory consequence (tactile feedback on their back), which was delayed and spatially incompatible with respect to the arm-related signals. This spatiotemporal confict was resolved by our participants generating the illusory experience logy Vol 24 No 22 robot oe = 1 Sore u a i i stn tn c ! Sire ro 5 Figue 2. Master Siive Robotic Sytem and Tactile Ful-Body Main in study 2 WA senematic view of the master haptic interface Phantom Orn SensableTechnologs) andthe slave rbot are shown fe lowe Iss lure s2 Supplemental Expurmea Provedte) Peston of he ve robet ls controled by the master robe, resulting In ttl eamespondence Be tween the movements fhe two devices trate delay <1 ms The pare ipantmoved the master robots ih ine the robot, which actuated the movements of thes touches to the parieipants back In oder to test the impacto eboleally contalled sensorimotor cenfiets to induce enanges In bos seco couaness, we tested the following four experimental conatons: (2 % 2 factorial design) 1) synchronous wih fore feedback, (2) asynchronous with fore feedback, (9) syncionous wth no free feedback and tesy ‘hronous with no force feedback During the asynchronous conten, the ‘movements pertonned atthe master device were deaye by 00 me before boing transite to the slave device (ator delay: syneonous of a8 ‘hronews- A “Wirtual ack” n ont of arte pants was erated oder fo have a mechanea! stop (occuring synchronous} of asynetvonoush) 1 the touch tha he pareipant ceived onthe Back factor free leedback force or notre) that the felt touch was not caused by themselves but by another person behind them who was touching their backs. ‘This was revealed by subjective evidence, that is, a decrease in the reported feeling of touching one's own body, an in- crease in the feeling of being touched by somebody else, and an increase in feeling the presence of another person un- der asynchronous stimulation. Such reductions in self-touch land agency for one's actions have been reported before (vi ‘sua-motor, audio-motor, and somatosensory-motor conflicts [31-2"), Ourdata are the frst to induce such changes in asso- Ciation withthe apparition or presence of another agent. Based fon the present findings, earlier data using trunk stimulation [50], and theoretical considerations [35], we argue that the ‘sensorimotor arm-trunk conflict in association with strong ‘spatial incompatibility of sef-touch induced the FoP. In addition to explaining a fascinating phenomenon with a fich cultural history, the present data are also of relevance tor the understanding of schizophrenic symptoms. Abnormal integration of sensorimotor signals and their cortical repre- sentations has been described in schizophrenic patients [35] and has been associated with positive hallucinatory and. ‘delusional symptoms [37, 38]- According to this view, positive ‘schizophrenic symptoms, such as alien voices and delusions ‘of control, are caused by central deficits in integrating pre- dicted sensory consequences of own movements and the respective reatferent signals. As a consequence, schizo- phrenic patients under certain conditions may not perceive selfegenerated sounds and movements as such but may misperceive them as being generated by external agents (as in the experiance of alien voices or control of own movernonts. by others), and this is corraborated by behavioral and neuro- imaging investigations (87, 39, 4]. The present data not only ‘account for a loss of agency in such patients but also show that a conflict between proprioceptive-motor signals. and tactile feedback at a physically impossible postion induced the feeling of being in the presence of an alien agent and being touched by that invisible person. Furthering the mechanistic insight into the functional brain processes generating halluci= nations and delusions, we show that simple sensorimotor Conflicts induced, in healthy subjects, an experience that ‘shares crucial aspects with postive, frst-rank symptoms in ‘schizophrenia, including the apparition of the alien agent (40, 41) The FoP has fascinated mankind from time immemorial ‘across all cultures, impacting the literature of divinity, oc- ‘cuttism, and fiction, The phenomenon continues to fascinate humans today, as testified by several recent case collections. 4] and documentaries [13]. Collectively, the present neuroi- maging and robotics data provide a solid scientific explanation {By Ratings fr unary touch and conivel quevlons we shown Note that chronous cortion {p< 0.01 and also significantly lager than ratings of ‘he conte tems (p< 0.0) {G) Paricpante showed s cit in selttocation toward the vitusl back Reward the fingertip that was larger during the synchronous than synchro nous conditions (p < 001) and was larger in the conltion with versus ‘thou somatosensory force feedoacx tothe patipants ngerp fp < 0.05) owe $2} SettHgeaton wes quantified ving the mental ball owing {ak during wich paripants were sbkea ta eximate fy pressing bl ton) he time that ball they were eldingintheirhands wou take 0 reach ‘he wall they wer to thvow i {Supolemer'al Experimental Procedures) ‘The conan neh fe subjects spontaneously noted aFoPlsineated 28 -an Apparition Ae, * a aie: Solftouch Touched by FoP ‘other ‘Questionnaire item Control B & ge “L Aayne 0 °|| 0 t00 c : = Ht Aye Average rating (0-4) ° ‘Numerosity judgment Figure 3, Roboticaly Induced FoP in Staies 3 and 4 (Ay Fo questions, touched-by-oter questions, ilusory slitoueh ques tions, and conve questions are show As predite, during asynchronous ‘Stimula'on participants experenced another person standing beh her (PoP; p <0), touching them Rovehed by ether p< 0.01) As say 2, Synchronous simulation induced disor eeltouch (p< 0.) {BIA siaritennt ference n selection was found between te synchro nous faackward erection, associated with FP} and synchronous condition In study 3p < 0.065; Vovlo So (G) Number of people (0-4) thet patipans judge as being closet them {he folowing qvetton wes eked: "how many people do you fel closet you?" person romeroaty ta) dng synchronous and asynchronous ‘Sensormetor stimulation. As preditea parcpants reported asigntearty higher numberof people during the Fo? condton (asynchronous than the synchronous condition (p< 0"). Hote that during the experiment, nobody tras ever clo to the paripart. ror bar show the SEM. for the FoP and link a phenomenon that appears strange and complex at first sight to basic mechanisms of sensorimotor signal integration in a cortical network centering in frontopar- etal cortex and to a prominent account of positive symptoms In schizophrenia. Apart from explaining a fascinating phenom= tenon and its potential clinical impact, the present data reveal the fine balance between the distributed cortical brain mecha- isms in humans that generate the experience of “self” and other,” which, if distorted, give rise to the FoP. ‘Supplemental Information Judes Supplemental Ex utes, two Ngues, oe table, and tree movies and ean {ele onne tip! edoorg0-1010,eub 201408088 ‘Acknowledgments ‘This work was supported by the Natlonal Center of Competence In Researeh - Synapay (The Syraplic Gases of Mental Diseases) and bythe ‘pan Society forth Promotion of Sclnce, and twas fnanced by the ‘Sse National Seieneo Foundation (#81 AU#0, 2575), th Roger de Spee Received: August 2, 2014 Revined: September 15, 2014 ‘Accepted: Sopteribo 16,2014 1. Citehiy, M1955. The idea of a presence. Acta Psychiat. Neural ‘Sean, 2, 155-168, 2. Brgger B Regard M. an Lands, T (1886), Unilateral fl “pres- ances": the nouropsychary of one's invisible doppelganger. 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