Pain mechanisms in the transgender individual: a review.

Specific Aim: Provide an overview of the literature addressing major areas pertinent to pain in transgender persons and to identify areas of primary relevance for future research. Methods: A team of scholars that have previously published on different areas of related research met periodically though zoom conferencing between April 2021 and February 2023 to discuss relevant literature with the goal of providing an overview on the incidence, phenotype, and mechanisms of pain in transgender patients. Review sections were written after gathering information from systematic literature searches of published or publicly available electronic literature to be compiled for publication as part of a topical series on gender and pain in the Frontiers in Pain Research. Results: While transgender individuals represent a significant and increasingly visible component of the population, many researchers and clinicians are not well informed about the diversity in gender identity, physiology, hormonal status, and gender-affirming medical procedures utilized by transgender and other gender diverse patients. Transgender and cisgender people present with many of the same medical concerns, but research and treatment of these medical needs must reflect an appreciation of how differences in sex, gender, gender-affirming medical procedures, and minoritized status impact pain. Conclusions: While significant advances have occurred in our appreciation of pain, the review indicates the need to support more targeted research on treatment and prevention of pain in transgender individuals. This is particularly relevant both for gender-affirming medical interventions and related medical care. Of particular importance is the need for large long-term follow-up studies to ascertain best practices for such procedures. A multi-disciplinary approach with personalized interventions is of particular importance to move forward.

Aß-CT Affective Touch: Touch Pleasantness Ratings for Gentle Stroking and Deep Pressure Exhibit Dependence on A-Fibers.

Gentle stroking of the skin is a common social touch behavior with positive affective consequences. A preference for slow versus fast stroking of hairy skin has been closely linked to the firing of unmyelinated C-tactile (CT) somatosensory afferents. Because the firing of CT afferents strongly correlates with touch pleasantness, the CT pathway has been considered a social-affective sensory pathway. Recently, ablation of the spinothalamic pathway- thought to convey all C-fiber sensations- in patients with cancer pain impaired pain, temperature, and itch, but not ratings of pleasant touch. This suggested integration of afferent A and CT fiber input in the spinal cord, or mechanoreceptive A-fiber contributions to computations of touch pleasantness in the brain. However, contribution of mechanoreceptive A-fibers to touch pleasantness, in humans without pain, remains unknown. In the current, single-blinded study, we performed two types of peripheral nerve blocks in healthy adults to temporarily eliminate the contribution of A-fibers to touch perception. Our findings show that when mechanoreceptive A-fiber function is greatly diminished, the perceived intensity and pleasantness of both gentle stroking and deep pressure are nearly abolished. These findings demonstrate that explicit perception of the pleasantness of CT-targeted brushing and pressure both critically depend on afferent A-fibers.

Chronic pain patients low in social connectedness report higher pain and need deeper pressure for pain relief.

The experience of rejection and disconnection reliably amplifies pain. Yet, little is known about the impact of enduring feelings of closeness, or social connectedness, on experiences of chronic pain. The current secondary analysis tested the hypothesis that greater social connectedness would predict lower chronic pain ratings, mediated by lower depression and anxiety. In addition, based on the social-affective effects of deeper pressure, and our previous finding that deeper pressure from a weighted blanket reduced chronic pain ratings, we examined whether deeper pressure from a weighted blanket would induce greater pain relief in socially disconnected chronic pain patients. We assessed social connectedness, anxiety, and depression at baseline and pain levels before and after a remote, 7-day randomized-controlled trial of a heavy or light (control) weighted blanket in a predominately White (86%) and female (80%) sample of 95 chronic pain patients. Results revealed that lower social connectedness was associated with higher chronic pain ratings, which was mediated by anxiety, but not depression. Pressure level (light vs. deep) moderated associations between social connectedness and pain reductions, such that deeper pressure was necessary for pain relief in the most socially disconnected participants. Our findings suggest a close relationship between social connectedness and chronic pain through a mechanistic pathway of anxiety. Furthermore, our findings demonstrate that sensory-affective interventions such as a weighted blanket may be a beneficial tool for chronic pain sufferers who are prone to social disconnection, potentially by activating embodied representations of safety and social support. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Widespread Pressure Delivered by a Weighted Blanket Reduces Chronic Pain: A Randomized Controlled Trial.

Pleasant sensation is an underexplored avenue for modulation of chronic pain. Deeper pressure is perceived as pleasant and calming, and can improve sleep. Although pressure can reduce acute pain, its effect on chronic pain is poorly characterized. The current remote, double-blind, randomized controlled trial tested the hypothesis that wearing a heavy weighted blanket - providing widespread pressure to the body - relative to a light weighted blanket would reduce ratings of chronic pain, mediated by improvements in anxiety and sleep. Ninety-four adults with chronic pain were randomized to wear a 15-lb. (heavy) or 5-lb. (light) weighted blanket during a brief trial and overnight for one week. Measures of anxiety and chronic pain were collected pre- and post-intervention, and ratings of pain intensity, anxiety, and sleep were collected daily. After controlling for expectations and trait anxiety, the heavy weighted blanket produced significantly greater reductions in broad perceptions of chronic pain than the light weighted blanket (Cohen's f = .19, CI [-1.97, -.91]). This effect was stronger in individuals with high trait anxiety (P = .02). However, weighted blankets did not alter pain intensity ratings. Pain reductions were not mediated by anxiety or sleep. Given that the heavy weighted blanket was associated with greater modulation of affective versus sensory aspects of chronic pain, we propose that the observed reductions are due to interoceptive and social/affective effects of deeper pressure. Overall, we demonstrate that widespread pressure from a weighted blanket can reduce the severity of chronic pain, offering an accessible, home-based tool for chronic pain. The study purpose, targeted condition, study design, and primary and secondary outcomes were pre-registered in ClinicalTrials.gov (NCT04447885: "Weighted Blankets and Chronic Pain"). PERSPECTIVE: This randomized-controlled trial showed that a 15-lb weighted blanket produced significantly greater reductions in broad perceptions of chronic pain relative to a 5-lb weighted blanket, particularly in highly anxious individuals. These findings are relevant to patients and providers seeking home-based, nondrug therapies for chronic pain relief.

Innocuous pressure sensation requires A-type afferents but not functional ΡΙΕΖΟ2 channels in humans.

The sensation of pressure allows us to feel sustained compression and body strain. While our understanding of cutaneous touch has grown significantly in recent years, how deep tissue sensations are detected remains less clear. Here, we use quantitative sensory evaluations of patients with rare sensory disorders, as well as nerve blocks in typical individuals, to probe the neural and genetic mechanisms for detecting non-painful pressure. We show that the ability to perceive innocuous pressures is lost when myelinated fiber function is experimentally blocked in healthy volunteers and that two patients lacking Aß fibers are strikingly unable to feel innocuous pressures at all. We find that seven individuals with inherited mutations in the mechanoreceptor PIEZO2 gene, who have major deficits in touch and proprioception, are nearly as good at sensing pressure as healthy control subjects. Together, these data support a role for Aß afferents in pressure sensation and suggest the existence of an unknown molecular pathway for its detection.

Pleasant Deep Pressure: Expanding the Social Touch Hypothesis.

Neuroscientific research on pleasant touch has focused on the C-tactile pathway for gentle stroking and has successfully explained how these sensory fibers transmit information about affective social touch to the brain and induce sensations of pleasantness. The C-tactile social/affective touch hypothesis even proposes that C-tactile fibers form a privileged pathway underlying social touch. However, deep pressure is a type of touch commonly considered pleasant and calming, occurring in hugs, cuddling, and massage. In this paper we introduce a paradigm for studying pleasant deep pressure and propose that it constitutes another important form of social touch. We describe development of the oscillating compression sleeve (OCS) as one approach to administering deep pressure and demonstrate that this touch is perceived as pleasant and calming. Further, we show that deep pressure can be imaged with functional magnetic resonance imaging (MRI) using the air-pressure-driven OCS and that deep pressure activates brain regions highly similar to those that respond to C-tactile stroking, as well as regions not activated by stroking. We propose that deep pressure constitutes another social touch pathway of evolutionary importance signaling the close proximity of conspecifics.

Is placebo analgesia for heat pain a sensory effect? An exploratory study on minimizing the influence of response bias.

We explored the ongoing question of whether placebo analgesia alters afferent nociceptive processing in a novel paradigm designed to minimize the role of response bias in placebo measurement. First, healthy adult participants received a standard heat placebo induction and conditioning procedure using a topical "analgesic" cream applied to one arm. During a subsequent placebo testing procedure, participants rated stimuli on the placebo-treated arm and untreated arm, using a task that minimized subjects' ability to guess the expected response, thus reducing experimenter demand. Retrospectively participants reported moderate analgesia effectiveness (mean=5.3/10), but for individual temperature ratings, only 2 subjects exhibited a perceptual placebo response >5 points. Next, these subjects completed a novel, exploratory task designed to measure changes in inter-arm in discriminative accuracy that would be expected from changes in afferent nociception. Both placebo responders (but no non-responders) showed reduced discriminative ability when the hotter stimulus occurred on the placebo arm, an effect consistent with alterations in nociceptive afferent flow and unlikely to be caused by response bias.

Guided Imagery Improves Mood, Fatigue, and Quality of Life in Individuals With Multiple Sclerosis: An Exploratory Efficacy Trial of Healing Light Guided Imagery.

Multiple sclerosis is a disabling and progressive neurological disease that has significant negative effects on health-related quality of life. This exploratory efficacy study examined the effects of Healing Light Guided Imagery (HLGI), a novel variant of guided imagery, compared with a wait-list control in patients with relapsing-remitting multiple sclerosis. Changes in the Beck Depression Inventory, Fatigue Severity Scale, and Multiple Sclerosis Quality of Life instrument (physical and mental components) were compared between groups. Patients who completed HLGI (N = 9) showed significant reductions in depressed mood ( P < .05) and fatigue ( P < .01) and showed significant gains in physical ( P = .01) and mental ( P < .01) quality of life compared with journaling (N = 8). Our results suggest that HLGI can improve self-reported physical and mental well-being in patients with relapsing-remitting multiple sclerosis. Further research is needed to study the effectiveness of this therapy, as well as its mind-body mechanisms of action.

Inhibitory rTMS of secondary somatosensory cortex reduces intensity but not pleasantness of gentle touch.

Research suggests that the discriminative and affective aspects of touch are processed differently in the brain. Primary somatosensory cortex is strongly implicated in touch discrimination, whereas insular and prefronal regions have been associated with pleasantness aspects of touch. However, the role of secondary somatosensory cortex (S2) is less clear. In the current study we used inhibitory repetitive transcranial magnetic stimulation (rTMS) to temporarily deactivate S2 and probe its role in touch perception. Nineteen healthy adults received two sessions of 1-Hz rTMS on separate days, one targeting right S2 and the other targeting the vertex (control). Before and after rTMS, subjects rated the intensity and pleasantness of slow and fast gentle brushing of the hand and performed a 2-point tactile discrimination task, followed by fMRI during additional brushing. rTMS to S2 (but not vertex) decreased intensity ratings of fast brushing, without altering touch pleasantness or spatial discrimination. MRI showed a reduced response to brushing in S2 (but not in S1 or insula) after S2 rTMS. Together, our results show that reducing touch-evoked activity in S2 decreases perceived touch intensity, suggesting a causal role of S2 in touch intensity perception.

Altered White Matter and Sensory Response to Bodily Sensation in Female-to-Male Transgender Individuals.

While most people take identification with their body for granted, conditions such as phantom limb pain, alien hand syndrome, and xenomelia suggest that the feeling of bodily congruence is constructed and susceptible to alteration. Individuals with xenomelia typically experience one of their limbs as over-present and aversive, leading to a desire to amputate the limb. Similarly, many transgender individuals describe their untreated sexed body parts as incongruent and aversive, and many experience phantom body parts of the sex they identify with (Ramachandran, 2008). This experience may relate to differences in brain representation of the sexed body part, as suggested in xenomelia (McGeoch et al., 2011). We utilized magnetoencephalography imaging to record brain activity during somatosensory stimulation of the breast-a body part that feels incongruent to most presurgical female-to-male (FtM)-identified transgender individuals-and the hand, a body part that feels congruent. We measured the sensory evoked response in right hemisphere somatosensory and body-related brain areas and found significantly reduced activation in the supramarginal gyrus and secondary somatosensory cortex, but increased activation at the temporal pole for chest sensation in the FtM group (N = 8) relative to non-transgender females (N = 8). In addition, we found increased white matter coherence in the supramarginal gyrus and temporal pole and decreased white matter diffusivity in the anterior insula and temporal pole in the FtM group. These findings suggest that dysphoria related to gender-incongruent body parts in FtM individuals may be tied to differences in neural representation of the body and altered white matter connectivity.

Encoding of Touch Intensity But Not Pleasantness in Human Primary Somatosensory Cortex.

UNLABELLED: Growing interest in affective touch has delineated a neural network that bypasses primary somatosensory cortex (S1). Several recent studies, however, have cast doubt on the segregation of touch discrimination and affect, suggesting that S1 also encodes affective qualities. We used functional magnetic resonance imaging (fMRI) and repetitive transcranial magnetic stimulation (rTMS) to examine the role of S1 in processing touch intensity and pleasantness. Twenty-six healthy human adults rated brushing on the hand during fMRI. Intensity ratings significantly predicted activation in S1, whereas pleasantness ratings predicted activation only in the anterior cingulate cortex. Nineteen subjects also received inhibitory rTMS over right hemisphere S1 and the vertex (control). After S1 rTMS, but not after vertex rTMS, sensory discrimination was reduced and subjects with reduced sensory discrimination rated touch as more intense. In contrast, rTMS did not alter ratings of touch pleasantness. Our findings support divergent neural processing of touch intensity and pleasantness, with affective touch encoded outside of S1. SIGNIFICANCE STATEMENT: Growing interest in affective touch has identified a neural network that bypasses primary somatosensory cortex (S1). Several recent studies, however, cast doubt on the separation of touch discrimination and affect. We used functional magnetic resonance imaging and repetitive transcranial magnetic stimulation to demonstrate the representation of touch discrimination and intensity in S1, but the representation of pleasantness in the anterior cingulate cortex, not S1. Our findings support divergent neural processing of touch intensity and pleasantness, with affective touch encoded outside of S1. Our study contributes to growing delineation of the affective touch system, a crucial step in understanding its dysregulation in numerous clinical conditions such as autism, eating disorders, depression, and chronic pain.

Touch Perception Altered by Chronic Pain and by Opioid Blockade.

Touch plays a significant role in human social behavior and social communication, and its rewarding nature has been suggested to involve opioids. Opioid blockade in monkeys leads to increased solicitation and receipt of grooming, suggesting heightened enjoyment of touch. We sought to study the role of endogenous opioids in perception of affective touch in healthy adults and in patients with fibromyalgia, a chronic pain condition shown to involve reduced opioid receptor availability. The pleasantness of touch has been linked to the activation of C-tactile fibers, which respond maximally to slow gentle touch and correlate with ratings of pleasantness. We administered naloxone to patients and healthy controls to directly observe the consequences of µ-opioid blockade on the perceived pleasantness and intensity of touch. We found that at baseline chronic pain patients showed a blunted distinction between slow and fast brushing for both intensity and pleasantness, suggesting reduced C-tactile touch processing. In addition, we found a differential effect of opioid blockade on touch perception in healthy subjects and pain patients. In healthy individuals, opioid blockade showed a trend toward increased ratings of touch pleasantness, while in chronic pain patients it significantly decreased ratings of touch intensity. Further, in healthy individuals, naloxone-induced increase in touch pleasantness was associated with naloxone-induced decreased preference for slow touch, suggesting a possible effect of opioid levels on processing of C-tactile fiber input. These findings suggest a role for endogenous opioids in touch processing, and provide further evidence for altered opioid functioning in chronic pain patients.

Common coding and dynamic interactions between observed, imagined, and experienced motor and somatosensory activity.

Motor imagery and perception - considered generally as forms of motor simulation - share overlapping neural representations with motor production. While much research has focused on the extent of this "common coding," less attention has been paid to how these overlapping representations interact. How do imagined, observed, or produced actions influence one another, and how do we maintain control over our perception and behavior? In the first part of this review we describe interactions between motor production and motor simulation, and explore apparent regulatory mechanisms that balance these processes. Next, we consider the somatosensory system. Numerous studies now support a "sensory mirror system" comprised of neural representations activated by either afferent sensation or vicarious sensation. In the second part of this review we summarize evidence for shared representations of sensation and sensory simulation (including imagery and observed sensation), and suggest that similar interactions and regulation of simulation occur in the somatosensory domain as in the motor domain. We suggest that both motor and somatosensory simulations are flexibly regulated to support simulations congruent with our sensorimotor experience and goals and suppress or separate the influence of those that are not. These regulatory mechanisms are frequently revealed by cases of brain injury but can also be employed to facilitate sensorimotor rehabilitation.

External self-representations improve self-awareness in a child with autism.

We have previously suggested that the social symptoms of autism spectrum disorder (ASD) could be caused in part by a dysfunctional mirror neuron system (MNS). Since the recursive activity of a functioning MNS might enable the brain to integrate visual and motor sensations into a coherent body schema, the deficits in self-awareness often seen in ASD might be caused by the same mirror neuron dysfunction. CL is an autistic adolescent who is profoundly fascinated with his reflection, looking in mirrors at every opportunity. We demonstrate that CL's abnormal gait improves significantly when using a mirror for visual feedback. We also show that both the fascination and the happiness that CL derives from looking at a computer-generated reflection diminish when a delay is introduced between the camera input and screen output. We believe that immediate, real-time visual feedback allows CL to integrate motor sensations with external visual ones into a coherent body schema that he cannot internally generate, perhaps due to a dysfunctional MNS.

Aberrant neural mediation of verbal fluency in autism spectrum disorders.

OBJECTIVE: Contrasts of verbal fluency and automatic speech provide an opportunity to evaluate the neural underpinnings of generativity and flexibility in autism spectrum disorders (ASD). METHOD: We used functional magnetic resonance imaging (fMRI) to contrast brain activity in high functioning ASD (n=17, mean verbal IQ=117) and neurotypical (NT; n=20, mean verbal IQ=112) adolescent and young adult males (12-23years). Participants responded to three word generation conditions: automatic speech (reciting months), category fluency, and letter fluency. RESULTS: Our paradigm closely mirrored behavioral fluency tasks by requiring overt, free recall word generation while controlling for differences in verbal output between the groups and systematically increasing the task demand. The ASD group showed reduced neural response compared to the NT participants during fluency tasks in multiple regions of left anterior and posterior cortices, and sub-cortical structures. Six of these regions fell in cortico-striatal circuits previously linked to repetitive behaviors (Langen, Durston, Kas, van Engeland, & Staal, 2011), and activity in two of them (putamen and thalamus) was negatively correlated with autism repetitive behavior symptoms in the ASD group. In addition, response in left inferior frontal gyrus was differentially modulated in the ASD, relative to the NT, group as a function of task demand. CONCLUSIONS: These data indicate a specific, atypical brain response in ASD to demanding generativity tasks that may have relevance to repetitive behavior symptoms in ASD as well as to difficulties generating original verbal responses.

Heightened motor and sensory (mirror-touch) referral induced by nerve block or topical anesthetic.

Mirror neurons allow us to covertly simulate the sensation and movement of others. If mirror neurons are sensory and motor neurons, why do we not actually feel this simulation- like "mirror-touch synesthetes"? Might afferent sensation normally inhibit mirror representations from reaching consciousness? We and others have reported heightened sensory referral to phantom limbs and temporarily anesthetized arms. These patients, however, had experienced illness or injury of the deafferented limb. In the current study we observe heightened sensory and motor referral to the face after unilateral nerve block for routine dental procedures. We also obtain double-blind, quantitative evidence of heightened sensory referral in healthy participants completing a mirror-touch confusion task after topical anesthetic cream is applied. We suggest that sensory and motor feedback exist in dynamic equilibrium with mirror representations; as feedback is reduced, the brain draws more upon visual information to determine- perhaps in a Bayesian manner- what to feel.

Alternating gender incongruity: a new neuropsychiatric syndrome providing insight into the dynamic plasticity of brain-sex.

Between the two extreme ends of human sexuality - male and female - lie a poorly understood and poorly studied spectrum of ambiguously defined sexual identities that are very much a part of the human condition but defy rigid classification. "Bigender" is a recently formed sub-category of transgenderism, describing individuals who experience a blending or alternation of gender states. While recognized nominally by the APA, no scientific work to our knowledge has addressed this fascinating condition, or proposed any physiological basis for it. In addition, the alternation aspect has not been proposed as a nosological entity distinct from blending. We present descriptive data suggesting that many bigender individuals experience an involuntary switching of gender states without any amnesia for either state. In addition, similar to transsexual individuals, the majority of bigender individuals experience phantom breasts or genitalia corresponding to the non-biologic gender when they are in a trans-gender state. Finally, our survey found decreased lateralization of handedness in the bigender community. These observations suggest a biologic basis of bigenderism and lead us to propose a novel gender condition, "alternating gender incongruity" (AGI). We hypothesize that AGI may be related to an unusual degree or depth of hemispheric switching and corresponding callosal suppression of sex appropriate body maps in parietal cortex- possibly the superior parietal lobule- and its reciprocal connections with the insula and hypothalamus. This is based on two lines of reasoning. First, bigender individuals in our survey sample reported an elevated rate of bipolar disorder, which has been linked to slowed hemispheric switching. We hypothesize that tracking the nasal cycle, rate of binocular rivalry, and other markers of hemispheric switching will reveal a physiological basis for AGI individuals' subjective reports of gender switches. Switching may also trigger hormonal cascades, which we are currently exploring. Second, we base our hypotheses on ancient and modern associations between the left and right hemispheres and the male and female genders. By providing a case of sharp brain-sex shifts within individuals, we believe that the study of AGI could prove illuminating to scientific understanding of gender, body representation, and the nature of self.

Diminished size-weight illusion in anorexia nervosa: evidence for visuo-proprioceptive integration deficit.

Individuals with anorexia nervosa (AN) experience pronounced body image distortion in combination with a pernicious desire to maintain a dangerously low body weight. Relatively little is known, however, about the mechanism underlying body image distortion in AN. Despite having normal visual perception, individuals with AN both feel and see themselves as large-bodied and show deficits in interoception and haptic perception, suggesting a potential deficit in visual and tactile integration. The size-weight illusion (SWI) arises when two objects of equal weight but different sizes are held. Typical individuals experience a strong and robust illusion that the smaller object feels much heavier than the larger object because of an implicit assumption that weight scales with size. The current study compared the strength of the SWI in individuals with AN to healthy control participants. Individuals with AN exhibited a markedly reduced SWI relative to controls, even though their ability to discriminate weight was unaffected. Because the SWI is strongly modulated by visual appearance, we believe our finding reflects decreased integration of visual and proprioceptive information in anorexia. This finding may explain the puzzling observation that visual perception of the body in a mirror does not correct an AN patient's distorted body image. We speculate that methods to correct visuo-proprioceptive integration in constructing body image may help rehabilitate patients' judgments of size and weight regarding their own bodies. We also suggest that a dysfunction in interactions between inferior parietal lobule (concerned with body image), insula, and hypothalamus may underlie AN.

Impaired visual scanning and memory for faces in high-functioning autism spectrum disorders: it's not just the eyes.

Prior studies suggest that autism spectrum disorders (ASD) are associated with a domain-specific memory impairment for faces. The underlying cause of this problem and its relation to impaired visual scanning of faces--particularly of the eyes--remains to be determined. We recorded eye movements while 22 high-functioning ASD and 21 typically developing (TD) adolescents encoded and later recognized faces and objects from a single, nonsocial object category (electric fans). Relative to TD subjects, ASD individuals had poorer memory for faces, but not fans. Correlational analyses showed significant relationships between recognition memory and fixations. Eye tracking during encoding revealed that TD subjects made more fixations to faces than fans, whereas ASD individuals did not differ in number of fixations made to each stimulus type. Moreover, although both the TD and ASD groups showed a strong preference for fixating the eyes more than the mouth, the ASD subjects were less likely than TD subjects to scan regions of the face outside of the primary facial features (i.e., eyes, nose, and mouth). We concluded that ASD individuals have a domain-specific memory impairment for faces relative to mechanical objects and that this impairment may be related to abnormal scanning during encoding.

The phantom head.

A student volunteer was asked to stand just behind a mannequin so that the student was looking at the back of the mannequin's plastic head. The experimenter stood off to one side and used her two hands to stroke and tap the back of the student's head in perfect synchrony with the back of the mannequin's head. After 1-2 min the majority of naive subjects tested began experiencing the sensations as emerging from the mannequin's head rather than from their own, demonstrating a novel 'phantom-head' illusion. The fact that sensory referral here occurs to a part of the body that is not normally visually accessible challenges the leading Hebbian explanation of the well-studied rubber-hand illusion.