Prevalence of Phantom Phenomena in Congenital and Early-Life Amputees.

Phantom limb pain (PLP) is a common consequence of the amputation of a limb. Persons with congenital limb absence (congenital amputees) or an acquired limb amputation at an early age seem to rarely experience PLP. However, the number of available studies and their sample sizes are low. In the present cross-sectional study, we assessed the presence of several phantom phenomena in a sample of 99 adult unilateral congenital amputees (con) of whom 34 had a limb correction later in life (limbc) and 153 adult participants with a unilateral amputation before the age of 6 years (subgroups: amputation between birth and 2 years (0-2y; n = 48), 3-4 years (3-4y; n = 46), and 5 to 6 years (5-6y; n = 59)). We found a higher prevalence and intensity of PLP in the 5-6y group compared to the other groups. Residual limb pain (RLP) intensity was higher in the 3 to 4 y and 5 to 6 y groups compared to the con group. Non-painful phantom limb sensation (PLS) intensity and telescoping intensity were higher in the 5 to 6 y group compared to the con and 0 to 2 y groups. Our results indicate that PLP prevalence as well as intensity is low when the limb loss happened before the age of 5 years. PERSPECTIVE: The prevalence of phantom limb pain, residual limb pain, and non-painful phantom limb sensation in congenital amputees and participants with an amputation early in life is low. This might be due to the missing or reduced nociceptive input from the residual limb to the brain and higher development-associated adaptability of the somatosensory system.

Illusory tactile movement crosses arms and legs and is coded in external space.

Humans often misjudge where on the body a touch occurred. Theoretical accounts have ascribed such misperceptions to local interactions in peripheral and primary somatosensory neurons, positing that spatial-perceptual mechanisms adhere to limb boundaries and skin layout. Yet, perception often reflects integration of sensory signals with prior experience. On their trajectories, objects often touch multiple limbs; therefore, body-environment interactions should manifest in perceptual mechanisms that reflect external space. Here, we demonstrate that humans perceived the cutaneous rabbit illusion - the percept of multiple identical stimuli as hopping across the skin - along the Euclidian trajectory between stimuli on two body parts and regularly mislocalized stimuli from one limb to the other. A Bayesian model based on Euclidian, as opposed to anatomical, distance faithfully reproduced key aspects of participants' localization behavior. Our results suggest that prior experience of touch in space critically shapes tactile spatial perception and illusions beyond anatomical organization.

Phantom limb pain after unilateral arm amputation is associated with decreased heat pain thresholds in the face.

BACKGROUND: The mechanisms underlying chronic phantom limb pain (PLP) are complex and insufficiently understood. Altered sensory thresholds are often associated with chronic pain but quantitative sensory testing (QST) in PLP has so far been inconclusive due to large methodological variation between studies and small sample sizes. METHODS: In this study, we applied QST in 37 unilateral upper-limb amputees (23 with and 14 without PLP) and 19 healthy controls. We assessed heat pain (HPT), pressure pain, warmth detection and two-point discrimination thresholds at the residual limb, a homologous point and the thenar of the intact limb as well as both corners of the mouth. RESULTS: We did not find significant differences in any of the thresholds between the groups. However, PLP intensity was negatively associated with HPT at all measured body sites except for the residual limb, indicating lower pain thresholds with higher PLP levels. Correlations between HPT and PLP were strongest in the contralateral face (r = -0.65, p < 0.001). Facial HPT were specifically associated with PLP, independent of residual limb pain (RLP) and various other covariates. HPT at the residual limb, however, were significantly associated with RLP, but not with PLP. CONCLUSION: We conclude that the association between PLP and, especially facial, HPT could be related to central mechanisms. SIGNIFICANCE: Phantom limb pain (PLP) is still poorly understood. We show that PLP intensity is associated with lower heat pain thresholds, especially in the face. This finding could be related to central nervous changes in PLP.

The Prevalence and Characteristics of Phantom Limb Pain and Non-Painful Phantom Phenomena in a Nationwide Survey of 3,374 Unilateral Limb Amputees.

The experience of phantom limb pain (PLP) is a common consequence of limb amputation, resulting in severe impairments of the affected person. Previous studies have shown that several factors such as age at or site of amputation are associated with the emergence and maintenance of PLP. In this cross-sectional study we assessed the presence of several phantom phenomena including PLP and other amputation-related information in a sample of 3,374 unilateral upper and lower limb amputees. Clinical and demographic variables (age at amputation, level of amputation) explained 10.6% of the variance in PLP and perceptual variables (intensity of phantom limb sensation [PLS], referred sensations, intensity of telescoping, residual limb pain [RLP] intensity) explained 16.9% of the variance. These variables were specific for PLP and not for RLP. These results suggest that distinct variables are associated with PLP (age at amputation, level of amputation, PLS intensity, referred sensations, intensity of telescoping, RLP intensity) and RLP (PLP intensity) and point at partly different mechanisms for the emergence and maintenance of PLP and RLP. PERSPECTIVE: Clinical/demographic variables as well as perceptual variables are 2 major components related to PLP and explain ∼11% and ∼17% of the variance. These results could potentially help clinicians to understand which factors may contribute to chronic phantom limb pain.

Relationship of prosthesis ownership and phantom limb pain: results of a survey in 2383 limb amputees.

ABSTRACT: Phantom limb pain (PLP) accounts for a significant reduction in quality of life and is difficult to treat. Prosthesis use has been shown to negatively covary with PLP. Recent research on body perception in amputees suggest that prosthesis ownership, defined as the extent to which a prosthesis is experienced as being part of the body rather than an artificial device foreign to the body, might interact with PLP. We used survey data from 2383 unilateral prosthesis-using upper-limb or lower-limb amputees and performed regression analyses to determine the relationship between prosthesis ownership and PLP. To test for specificity, we examined the role of prosthesis ownership also for residual limb pain (RLP) and nonpainful phantom limb sensations (npPLS). Prosthesis ownership was reduced in older participants and higher in lower-limb compared to upper-limb amputees. A longer residual limb and more frequent prosthesis use as well as a longer time since amputation also yielded higher values. Prostheses based on natural principles were associated with higher prosthesis ownership. Phantom limb pain and RLP were lower with higher prosthesis ownership, and RLP but not PLP was lower when prosthesis use was frequent. There were no significant associations for npPLS. The regression results differ in some aspects from those revealed by univariate analyses, emphasizing the importance of multivariate statistical approaches. Our findings provide insights into the interplay of body- and pain-related sensations after amputation, and could help to develop new treatment approaches for both PLP and RLP.

Assessment of cortical reorganization and preserved function in phantom limb pain: a methodological perspective.

Phantom limb pain (PLP) has been associated with reorganization in primary somatosensory cortex (S1) and preserved S1 function. Here we examined if methodological differences in the assessment of cortical representations might explain these findings. We used functional magnetic resonance imaging during a virtual reality movement task, analogous to the classical mirror box task, in twenty amputees with and without PLP and twenty matched healthy controls. We assessed the relationship between task-related activation maxima and PLP intensity in S1 and motor cortex (M1) in individually-defined or group-conjoint regions of interest (ROI) (overlap of task-related activation between the groups). We also measured cortical distances between both locations and correlated them with PLP intensity. Amputees compared to controls showed significantly increased activation in M1, S1 and S1M1 unrelated to PLP. Neural activity in M1 was positively related to PLP intensity in amputees with PLP when a group-conjoint ROI was chosen. The location of activation maxima differed between groups in S1 and M1. Cortical distance measures were unrelated to PLP. These findings suggest that sensory and motor maps differentially relate to PLP and that methodological differences might explain discrepant findings in the literature.

Brain-behaviour correlates of habitual motivation in chronic back pain.

Chronic pain may sap the motivation for positive events and stimuli. This may lead to a negative behavioural cycle reducing the establishment of appetitive habitual engagement. One potential mechanism for this might be biased learning. In our experiment, chronic back pain patients and healthy controls completed an appetitive Pavlovian-instrumental transfer procedure. We examined participants` behaviour and brain activity and reported pain, depression and anxiety. Patients showed reduced habitual behaviour and increased responses in the hippocampus than controls. This behavioural bias was related to motivational value and reflected in the updating of brain activity in prefrontal-striatal-limbic circuits. Moreover, this was influenced by pain symptom duration, depression and anxiety (explained variance: up to 50.7%). Together, findings identify brain-behaviour pathways for maladaptive habitual learning and motivation in chronic back pain, which helps explaining why chronic pain can be resistant to change, and where clinical characteristics are significant modulators.

Online sensory feedback during active search improves tactile localization.

Natural motor behavior is usually refined by ongoing sensory input in closed feedback loops. Research has suggested that humans make systematic errors when localizing touch on the skin, and that perceptual body representations underlying these behaviors are distorted. However, experimental procedures usually prevent participants from touching the target limb, interrupting the natural action-perception loop. It is currently unknown how such experimental strategies affect localization and systematic perceptual distortions. Here, participants received a brief touch on their left forearm and, with closed eyes, searched for the target location by moving the right index finger across the left arm. Tactile search significantly reduced the localization error present at touchdown of the searching finger on the target arm. Localization improvement was largely absent when a barrier above the target arm prevented online tactile feedback of the target region. Vision of the arms while reaching to, and searching on, the skin, greatly reduced the localization error at touchdown, but tactile search further improved localization slightly. Thus, both tactile and visual feedback help matching the positions of reaching and target limbs during localization. Yet, even if small, the unique improvement through tactile information confirms the importance of target-related, closed-loop tactile feedback for tactile localization. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Volumetric brain correlates of approach-avoidance behavior and their relation to chronic back pain.

Avoiding any harm, such as painful experiences, is an important ability for our physical and mental health. This avoidance behavior might be overactive under chronic pain, and the cortical and subcortical brain volumetry, which also often changes in chronic pain states, might be a significant correlate of this behavior. In the present study, we thus investigated the association between volumetric brain differences using 3 T structural magnetic resonance imaging and pain- versus pleasure-related approach-avoidance behavior using an Approach Avoidance Task in the laboratory in chronic back pain (N = 42; mean age: 51.34 years; 23 female) and healthy individuals (N = 43; mean age: 45.21 years; 15 female). We found significant differences in hippocampal, amygdala and accumbens volumes in patients compared to controls. The patients` hippocampal volume was significantly positively related to pain avoidance, the amygdala volume to positive approach, and the accumbens volume negatively to a bias to pain avoidance over positive approach. These associations were significantly moderated by pain symptom duration. Cortical structure may thus contribute to an overacting pain avoidance system in chronic back pain, and could, together with a reduction in approaching positive stimuli, be related to maladaptive choice and decision-making processes in chronic pain.

What does "moderate pain" mean? Subgroups holding different conceptions of rating scales evaluate experimental pain differently.

BACKGROUND: Pain ratings are almost ubiquitous in pain assessment, but their variability is high. Low correlations of continuous/numerical rating scales with categorical scales suggest that individuals associate different sensations with the same number on a scale, jeopardizing the interpretation of statistical results. We analysed individual conceptions of rating scales and whether these conceptions can be utilized in the analysis of ratings of experimental stimuli in pain-free healthy individuals and people with reoccurring/persistent pain. METHODS: Using a free positioning task, healthy participants (N = 57) and people with reoccurring/persistent pain (N = 57) ad libitum positioned pain descriptors on lines representing intensity and un-/pleasantness scales. Furthermore, participants rated experimental thermal stimuli on visual analogue scales with the same end anchors. A latent class regression approach was used to detect subgroups with different response patterns in the free positioning task, indicating different conceptions of pain labels, and tested whether these subgroups differed in their ratings of experimental stimuli. RESULTS: Subgroups representing different conceptions of pain labels could be described for the intensity and the un-/pleasantness scale with in part opposing response patterns in the free positioning task. Response patterns did not differ between people with and without pain, but in people with pain subgroups showed differential ratings of high intensity experimental stimuli. CONCLUSIONS: Individuals' conceptions of pain labels differ. These conceptions can be quantified and utilized to improve the analysis of ratings of experimental stimuli. Identifying subgroups with different conceptions of pain descriptions could be used to improve predictions of responses to pain in clinical contexts. SIGNIFICANCE: The present results provide a novel approach to incorporate individual conceptualizations of pain descriptors, which can induce large distortions in the analysis of pain ratings, in pain assessment. The approach can be used to achieve better pain estimates, representing individual conceptions of pain and achieving a better comparability between individuals but also between pain-free persons and patients with chronic pain. Particularly, in clinical settings this could improve quantification of perceived pain and the patient-clinician communication.

Synchronous Stimulation With Light and Heat Induces Body Ownership and Reduces Pain Perception.

In this study, we investigated whether illusionary body ownership over artificial hands and non-corporeal objects modulates pain perception. Previous research has yielded to mixed results, but has separated painful stimulation used to test pain perception from the stimulation that was used to induce the illusion. Here, we used a variant of the rubber hand illusion (RHI) paradigm and induced the illusion directly via a combination of visual and painful stimuli. We presented heat pain stimuli at the real hand and visual stimuli beneath a rubber hand (part1), or a glass ball (part2). Illusion ratings were higher and pain ratings were lower in the synchronous compared to the asynchronous condition in both parts of the experiment. This study demonstrated the successful induction of a body illusion using a new visual-thermal method with painful stimuli. We showed that the RHI and interestingly also the glass ball has an analgesic effect on the perception of the heat pain stimuli. Our data suggests that induced ownership over artificial limbs but also over non-corporeal objects can reduce the perceived pain perception. This might be mediated via a partial referral of the perceived location of pain or respectively a distribution of pain over 2 locations. PERSPECTIVE: This article presents a new visual-thermal method with painful stimuli for the induction of the Rubber Hand Illusion. An illusionary body ownership over artificial hands and non-corporeal has an analgesic effects on the perception of pain. Similar approaches might be useful to alleviate chronic pain, but needs further testing.

The rubber hand universe: On the impact of methodological differences in the rubber hand illusion.

The rubber hand illusion (RHI) is a widely applied paradigm to investigate changes in body representations. Extensive scientific interest has produced a great variability in the observed results and many contradictory findings have been reported. Taking into account the numerous variations in the experimental implementation of the RHI, many of these contradictive findings can be reconciled, but to date a thorough analysis of the methodological differences between RHI studies is lacking. Here we summarize and analyse methodological differences between RHI studies. In distinction from other reviews focusing on the integration of findings from various studies, the present paper is devoted to the differences in (i) the experimental setup, (ii) the method used to induce the RHI, (iii) the quantification of its effects, and (iv) aspects of the experimental design and data analysis. This approach will provide a reference frame for the interpretation of previous studies as well as for the design of future studies.

The rubber hand illusion induced by visual-thermal stimulation.

In the rubber hand illusion (RHI), synchronous touch of a real hand and an artificial hand leads to the feeling of the artificial hand belonging to one's own body. This study examined whether the RHI can be induced using visual-thermal instead of visual-tactile stimulus patterns and to which extent the congruency between temperature and colour of the visual stimulus influences the RHI. In a within-subject design, we presented cold vs. warm thermal stimuli to the participants' hidden hand combined with red vs. blue visual stimuli presented synchronously vs. asynchronously at a fake hand. The RHI could be induced using visual-thermal stimuli, yielding RHI vividness ratings comparable to the visual-tactile variant. Congruent (warm-red, cold-blue) synchronous stimulus patterns led to higher RHI vividness than incongruent (warm-blue, cold-red) synchronous combinations; in the asynchronous conditions, an inverse effect was present. Temperature ratings mainly depended on the actual stimulus temperature and were higher with synchronous vs. asynchronous patterns; they were also slightly higher with red vs. blue light, but there were no interactions with temperature or synchrony. In conclusion, we demonstrated that the RHI can be induced via visual-thermal stimuli, opening new perspectives in research on multi-sensory integration and body representations.

Psychological Factors Associated with Phantom Limb Pain: A Review of Recent Findings.

Phantom limb pain (PLP) is a common phenomenon occurring after the amputation of a limb and can be accompanied by serious suffering. Psychological factors have been shown to play an important role in other types of chronic pain, where they are pivotal in the acquisition and maintenance of pain symptoms. For PLP, however, the interaction between pain and psychological variables is less well documented. In this review, we summarize research on the role of emotional, motivational, cognitive, and perceptual factors in PLP. The reported findings indicate that emotional factors modulate PLP but might be less important compared to other types of chronic pain. Additional factors such as the amount of disability and adjustment to the amputation appear to also play a role. Bidirectional relationships between stress and PLP have been shown quite consistently, and the potential of stress and tension reduction in PLP treatment could be further exploited. Little is known about the role of cognitive variables such as attention or expectation. Catastrophizing seems to aggravate PLP and could be targeted in treatment. Body perception is altered in PLP and poses a potential target for novel mechanistic treatments. More research on psychological factors and their interactions in PLP is needed.

Perceptual drifts of real and artificial limbs in the rubber hand illusion.

In the rubber hand illusion (RHI), transient embodiment of an artificial hand is induced. An often-used indicator for this effect is the "proprioceptive drift", a localization bias of the real hand towards the artificial hand. This measure suggests that the real hand is attracted by the artificial hand. Principles of multisensory integration, however, rather suggest that conflicting sensory information is combined in a "compromise" fashion and that hands should rather be attracted towards each other. Here, we used a new variant of the RHI paradigm in which participants pointed at the artificial hand. Our results indicate that the perceived positions of the real and artificial hand converge towards each other: in addition to the well-known drift of the real hand towards the artificial hand, we also found an opposite drift of the artificial hand towards the real hand. Our results contradict the notion of perceptual substitution of the real hand by the artificial hand. Rather, they are in line with the view that vision and proprioception are fused into an intermediate percept. This is further evidence that the perception of our body is a flexible multisensory construction that is based on integration principles.

Do mirror glasses have the same effect on brain activity as a mirror box? Evidence from a functional magnetic resonance imaging study with healthy subjects.

Since its original proposal, mirror therapy has been established as a successful neurorehabilitative intervention in several neurological disorders to recover motor function or to relieve pain. Mirror therapy seems to operate by reactivating the contralesional representation of the non-mirrored limb in primary motor- and somatosensory cortex. However, mirror boxes have some limitations which prompted the use of additional mirror visual feedback devices. The present study evaluated the utility of mirror glasses compared to a mirror box. We also tested the hypothesis that increased interhemispheric communication between the motor hand areas is the mechanism by which mirror visual feedback recruits the representation of the non-mirrored limb. Therefore, mirror illusion capacity and brain activations were measured in a within-subject design during both mirror visual feedback conditions in counterbalanced order with 20 healthy subjects inside a magnetic resonance imaging scanner. Furthermore, we analyzed task-dependent functional connectivity between motor hand representations using psychophysiological interaction analysis during both mirror tasks. Neither the subjective quality of mirror illusions nor the patterns of functional brain activation differed between the mirror tasks. The sensorimotor representation of the non-mirrored hand was recruited in both mirror tasks. However, a significant increase in interhemispheric connectivity between the hand areas was only observed in the mirror glasses condition, suggesting different mechanisms for the recruitment of the representation of the non-mirrored hand in the two mirror tasks. We conclude that the mirror glasses might be a promising alternative to the mirror box, as they induce similar patterns of brain activation. Moreover, the mirror glasses can be easy applied in therapy and research. We want to emphasize that the neuronal mechanisms for the recruitment of the affected limb representation might differ depending on conceptual differences between MVF devices. However, our findings need to be validated within specific patient groups.

Post-amputation pain is associated with the recall of an impaired body representation in dreams-results from a nation-wide survey on limb amputees.

The experience of post-amputation pain such as phantom limb pain (PLP) and residual limb pain (RLP), is a common consequence of limb amputation, and its presence has negative effects on a person's well-being. The continuity hypothesis of dreams suggests that the presence of such aversive experiences in the waking state should be reflected in dream content, with the recalled body representation reflecting a cognitive proxy of negative impact. In the present study, we epidemiologically assessed the presence of post-amputation pain and other amputation-related information as well as recalled body representation in dreams in a sample of 3,234 unilateral limb amputees. Data on the site and time of amputation, residual limb length, prosthesis use, lifetime prevalence of mental disorders, presence of post-amputation pain, and presence of non-painful phantom phenomena were included in logistic regression analyses using recalled body representation in dreams (impaired, intact, no memory) as dependent variable. The effects of age, sex, and frequency of dream recall were controlled for. About 22% of the subjects indicated that they were not able to remember their body representation in dreams, another 24% of the amputees recalled themselves as always intact, and only a minority of less than 3% recalled themselves as always impaired. Almost 35% of the amputees dreamed of themselves in a mixed fashion. We found that lower-limb amputation as well as the presence of PLP and RLP was positively associated with the recall of an impaired body representation in dreams. The presence of non-painful phantom phenomena, however, had no influence. These results complement previous findings and indicate complex interactions of physical body appearance and mental body representation, probably modulated by distress in the waking state. The findings are discussed against the background of alterations in cognitive processes after amputation and hypotheses suggesting an innate body model.

Illusion-related brain activations: a new virtual reality mirror box system for use during functional magnetic resonance imaging.

Extended viewing of movements of one's intact limb in a mirror as well as motor imagery have been shown to decrease pain in persons with phantom limb pain or complex regional pain syndrome and to increase the movement ability in hemiparesis following stroke. In addition, mirrored movements differentially activate sensorimotor cortex in amputees with and without phantom limb pain. However, using a so-called mirror box has technical limitations, some of which can be overcome by virtual reality applications. We developed a virtual reality mirror box application and evaluated its comparability to a classical mirror box setup. We applied both paradigms to 20 healthy controls and analyzed vividness and authenticity of the illusion as well as brain activation patterns. In both conditions, subjects reported similar intensities for the sensation that movements of the virtual left hand felt as if they were executed by their own left hand. We found activation in the primary sensorimotor cortex contralateral to the actual movement, with stronger activation for the virtual reality 'mirror box' compared to the classical mirror box condition, as well as activation in the primary sensorimotor cortex contralateral to the mirrored/virtual movement. We conclude that a virtual reality application of the mirror box is viable and that it might be useful for future research.