Attentional focus on subjective interoceptive experience in patients with fibromyalgia

Brain and Cognition 101 (2015) 35–43

Contents lists available at ScienceDirect

Brain and Cognition journal homepage: www.elsevier.com/locate/b&c

Attentional focus on subjective interoceptive experience in patients with fibromyalgia Céline Borg a,b,c,⇑, Fannie Carrier Emond c,d, David Colson a,c, Bernard Laurent a,e,f, George A. Michael c a

Neurology/Neuropsychology CMRR Unit, Hospital Nord, 42270 Saint Priest-en-Jarez, France Psychology Department, University of Lyon, 69002 Lyon, France c University Lyon 2, Laboratory EMC (EA 3082), 69676 Bron, France d Psychology Department, University of Montreal, Canada e Pain Center, Hospital Nord, 42270 Saint Priest-en-Jarez, France f Central Integration of Pain, Lyon Neuroscience Research Center, INSERM U1028 & University Jean Monnet, 42023 Saint-Etienne Cx 2, France b

a r t i c l e

i n f o

Article history: Received 27 April 2015 Revised 12 October 2015 Accepted 16 October 2015

Keywords: Interoception Spontaneous sensations Attention Pain Catastrophism Fibromyalgia

a b s t r a c t Objectives: The hypervigilance model of pain perception states that patients with fibromyalgia (FM) have an enhanced sensitivity to aversive and non-aversive stimuli. Few studies have focused on enhanced interoceptive sensitivity in FM. Therefore, the aim of the present study was to investigate spontaneous sensations (SPS) in FM. Design: SPS are those tingling, tickly and other kind of sensations usually perceived on the skin during periods of rest and without any external trigger. Therefore, we have investigated SPS by requiring participants to focus attention on each hand. Methods: Eighteen patients with a diagnosis of FM and 18 matched healthy participants had to direct their gaze toward the hand tested for a period of 10 s. Subsequently, they had to map and report the intensity, the number and the qualitative properties of sensations arising spontaneously. Finally, participants had to fill out questionnaires assessing cognitive and affective status that may influence the interoceptive sensations feedback. Results: Patients with FM perceived SPS as significantly more intense than controls did. Additionally, SPS were perceived by the FM group as occupying an overall larger area on the hand than those reported by controls. Importantly, entering scores of pain and catastrophism as covariates produced a relative effect on the feeling of SPS. Conclusions: The outcome of this study supports the generalized hypervigilance model, suggesting that patients with FM have a perceptual style of amplification of non-aversive interoceptive stimulation, modulated by pain and catastrophizing. This is discussed in relationship to interoceptive awareness. Ó 2015 Elsevier Inc. All rights reserved.

1. Introduction Pain, in its pathological chronic form, does not serve a protective or other biological function, and chronic pain syndromes seem to have an effect on attentional processes (Crombez, Van Damme, & Eccleston, 2005; Eccleston & Crombez, 1999), such as in fibromyalgia (FM). For instance, some researchers suggest that hypervigilance is a feature of FM. Hypervigilance is conceptualized here as an abnormal increase of attention to external stimuli to a large variety of painful (Gibson, Littlejohn, Gorman, Helme, & Granges, 1994; Glass et al., 2011; González et al., 2010; Granges ⇑ Corresponding author at: Neurology/Neuropsychology CMRR Unit, Hospital Nord, 42270 Saint-Priest-en-Jarez, France. E-mail address: [email protected] (C. Borg). http://dx.doi.org/10.1016/j.bandc.2015.10.002 0278-2626/Ó 2015 Elsevier Inc. All rights reserved.

& Littlejohn, 1993; Lautenbacher, Rollman, & McCain, 1994; Petzke, Clauw, Ambrose, Khine, & Gracely, 2003; Smith et al., 2008) and non-painful stimuli (Carrillo-de-la-Peña, Vallet, Pérez, & Gómez-Perretta, 2006; Dohrenbusch, Sodhi, Lamprecht, & Genth, 1997; Geisser et al., 2008; Hollins et al., 2009; McDermid, Rollman, & McCain, 1996; Smythe, 1986). Although such a phenomenon has been evidenced in previous studies, the underlying mechanism remains to be explained. FM is sometimes considered as an ‘‘amplification syndrome” (Barsky, Goodson, Lane, & Cleary, 1988). This phenomenon of amplification is characterized by three key elements: a hypervigilance toward bodily sensations, a tendency to focus on low and infrequent sensations, and a set of cognitive and emotional processes dramatizing and intensifying symptoms. According to the model of generalized hypervigilance (McDermid et al., 1996),

36

C. Borg et al. / Brain and Cognition 101 (2015) 35–43

patients with FM have an increased attention to external stimulation and a preoccupation with pain sensations. Hence, they have a tendency to systematically scan their body in anticipation of unpleasant sensations. This last characteristic has been exploited in the literature under the term ‘‘catastrophism” and strongly correlates with chronic pain syndromes (Campbell & Edwards, 2009). Catastrophism and pain are complementary models in order to understand the nature of mechanisms underlying the generalized hypervigilance of FM and are of particular interest for the study of interoception. The majority of the aforementioned studies were interested in the hypervigilance toward exteroceptive information but few studies, to our best knowledge, focused on both internal and nonpainful sensations in FM. From a homeostasis point of view, all relevant information concerning the state of the body is interoceptive (Craig, 2002, 2003) and this point of view opens a wider window on the conceptualization of ‘‘interoception”. When speaking ‘‘interoception”, we do not refer solely to visceral sensations, but to the perception of the physiological condition of the body, a process associated with the autonomic nervous system and with the generation of subjective feelings and states (Craig, 2009; Critchley, Wiens, Rotshein, Ohman, & Dolan, 2004; Herbert & Pollatos, 2012). Moreover, all of the aforementioned studies estimated that an attentional bias underlies the hypervigilance in FM. Interestingly, the Kinsbourne’s model (1998) proposes an attentional conceptualization of what we can call ‘‘body image”. According to this author, the evidence raised by research on asomatognosia intimates that the body image is an integrated construct that is distinct from somatosensory information. Awareness of parts of our body would arise only when our attention is focused on their representation. Additionally, studies showed that interoceptive attention/awareness (Cameron, 2001) is a body-related component of cognition that allows to detect afferent signals, alerting to the existence of internal imbalances such as injury to body. Emphasizing the role of top-down processes in the perception of the body, recent empirical and theoretical work in cognitive neuroscience are converging toward Bayesian approaches to embodiment (Barrett & Simmons, 2015; Seth, 2013). In such models, the brain constructs active inferences anticipating incoming sensory events in a probabilistic fashion to identify the cause of such inputs. The cortical activity generated by the prediction would be compared to the bottom-up signals produced by sensory events in a cortical structure, possibly the anterior insular cortex, in order to detect discrepancies. There have been various studies discussing the specific role of the insula in interoceptive attention (Craig, 2002; Critchley et al., 2004) and body ownership (Tsakiris, 2010; Tsakiris, Hesse, Boy, Haggard, & Fink, 2007). According to Melzack (1990), body awareness relies upon a large neural network where somatosensory cortex, posterior parietal lobe and insular cortex play crucial and different roles, as indicated by the effects of selective lesions in this network. Of particular relevance here, brain scans of patients with FM showed that their processing of nonpainful stimuli, such as sounds and touch, differed from that of normal controls (López-Solà et al., 2014). More precisely, in this study using functional magnetic resonance imaging, patients with FM processed visual, auditory, and tactile stimuli with reduced brain activity in primary sensory processing areas, combined with higher activity in sensory integration areas such as the insula, compared with normal controls. Not only can brain lesions induce profound changes in the way the body is perceived, but they also seem to affect how the body is represented. Growing evidence shows that the body image can be distorted in FM (Bojner, Kowalski, Theorell, & Anderberg, 2006; Lewis, Kersten, McCabe, McPherson, & Blake, 2007; Lotze & Moseley, 2007; Moseley, 2008). Unfortunately, data are incomplete and little is known about the relationship between distorted body

image, attention and pain. Studies additionally showed cortical reorganization in patients with chronic pain syndromes preventing them from perceiving their body as a whole (Lewis et al., 2007; Lotze & Moseley, 2007). The brain areas covered by this reorganization were the primary and secondary somatosensory cortices and the insula. Thus, as these cerebral areas are involved in the perception of the body (Berlucchi & Aglioti, 2010) and interoception (Craig, 2002), the reorganization of these neural circuits due to pain suggests that pain may have a strong influence on and distort the body image. Indeed, Lotze and Moseley (2007) reported a large number of studies showing a link between chronic pain syndromes and body image distortion. Interestingly, some studies showed that therapies for lowering pain allow patients to improve the perception of their body, suggesting that the representation of the body can be modulated by pain (Bojner et al., 2006) and attention (Kinsbourne, 1998). As aforementioned, body distortions and hypersensitivity to external non-painful, as well as painful, sensations were observed in FM. To the best of our knowledge, no study has specifically focused on non-painful interoceptive sensations in FM. However, it can be assumed that if the intensity of both exogenous nonpainful stimuli, aversive and non-aversive, and painful stimuli is exacerbated in FM, normal interoceptive sensations might be perceived as more intense as well (Rollman & Lautenbacher, 1993). Therefore, our main aim was to investigate the relationship in FM between pain and the ability to focus on and perceive internal sensations that contribute to the construction and the maintaining of the body image. One way to asses this ability is through spontaneous sensations (SPS) that may rise on the hands (Michael & Naveteur, 2011; Michael et al., 2012). SPS are common, nonpainful sensations that can be felt by anybody without any external stimulation. These normal and real phenomena feel like sensations triggered by external stimuli, such as tingling, itching and warming. Studies have shown that these sensations are felt all over the glabrous surface of the hand and follow a proximo-distal gradient, suggesting that they are probably the result of the spontaneous activity of cutaneous sensory receptors (Michael & Naveteur, 2011). They are linked to interoception (Michael, Naveteur, Dupuy, & Jacquot, 2015) and they may be involved in the construction and the maintaining of the body image in that they provide information about the spatial boundaries of the body (or at least the hands) and about the type of sensations that can be collected. Furthermore, both body image and SPS have a right hemispheric lateralization (Michael & Naveteur, 2011) are modulated by visual attention (Kinsbourne, 1998; Longo, Azano, & Haggard, 2010; Michael & Naveteur, 2011). Finally, specific primary somatosensory areas in conjunction with other left parietofrontal areas seem involved in the perception of SPS (Bauer, Barrios, & Diaz, 2014; Bauer, Díaz, Concha, & Barrios, 2014) and a recent study showed that individuals with good heartbeat perception experienced more numerous and more intense SPS (Michael et al., 2015). Furthermore, these authors suggested that heartbeat perception accuracy predicted the perceived intensity of SPS, their spatial extent, their variety, as well as confidence in their spatial characteristics. This overall set of data leads us to believe that the SPS perception task represents a valid standardized method to study endogenous sensations of interoceptive nature in FM. Even if direct evidence of the relationship between SPS and interoception remains at its seminal level (Michael et al., 2015), investigating the mechanisms underlying the hypervigilance observed in FM allows formulating interesting hypotheses. According to Gregory et al. (2003), hypervigilance contributes to the interoceptive consciousness. Since some models suggest that the generalized hypervigilance observed in FM may extend to internal, non-aversive sensations, we predicted that patients with FM would report SPS

C. Borg et al. / Brain and Cognition 101 (2015) 35–43

more frequently and would describe them as being more intense and extended on the hands and, probably, more diversified than in healthy controls. The emotional dimensions of pain, including the notion of catastrophism, are also important variables in any individual’s experience of pain, including FM patients (Gracely et al., 2004). Therefore, we not only postulated that a hypervigilance toward SPS would be observed in FM patients, but also that catastrophic beliefs would explain a portion of the difference in the perception of SPS between FM and normal controls. 2. Materials and methods 2.1. Participants This study was conducted according to the Helsinki Declaration and was approved by the Ethics Committee/Institutional Review Board of the CHU Saint-Etienne (n° IORG00077394). Participants were excluded if they reported no SPS on 50% or more of the trials. Three patients with FM and 3 controls were therefore excluded on the basis of this criterion. A total of 18 participants with a diagnosis of FM (all female; mean age: 50.4 ± 9.9; age range: 33–65) and 18 matched healthy female participants (mean age: 49.5 ± 7.8; age range: 32–59) were included. There was no difference in age between the two groups (t(34) = 0.3; p > 0.76). The mean body mass index was 26.4 ± 6.1 kg/m2 for FM and 24.9 ± 5.8 kg/m2 for the healthy controls (t(34) = 0.76; p > 0.45). The mean number of years of education was 11.3 ± 1.7 for FM and 13.6 ± 3.2 for controls (t(34) = 2.7; p < 0.012). According to the Edinburgh Handedness Inventory (Oldfield, 1971), 1 participant with FM was left-handed and 2 others were ambidextrous. Additionally, 1 healthy subject was left-handed. All participants gave their written informed consent for their participation prior to the test. 2.2. SPS protocol and procedure The experiment was run individually in a quiet room with an ambient temperature ranging from 20 to 23 °C. Upon entering the room, the participant was asked to take a seat behind a desk, to face the experimenter, to read and sign the consent form, and supply information about gender, age, number of years of education, height and weight. The experimenter then described what SPS are and provided a list of eleven types of sensations that might be felt (beat/pulse, itch, tickle, numbness, skin stretch, tingle, warming, cooling, muscular stiffness, flutter, and vibration). The list was constructed on the basis of the lists used in previous studies (Macefield, Gandevia, & Burke, 1990; Ochoa & Torebjörk, 1983) to study sensations evoked by microstimulation, and readapted in a recent study (Naveteur, Honoré, & Michael, 2005). Participants were then asked to remove any jewelry from their hands and wrists. For the sake of homogeneity of the glabrous surface of the skin, all participants were required to spend 15 s cleansing their hands with an antiseptic gel (AniosgelÒ 85 NPC, 3 ml per participant) in order to remove any external agents that might interfere with the task. A minimum latency of 15 s was respected between the cleansing operation and the start of the test (Naveteur et al., 2005). The experimenter then distributed to each participant one LyrecoÒ, untempered head HB pencil, a smooth 25  25 cm piece of white cotton tissue and a four-page handout, each page containing a standardized reduced picture of a hand (left or right) shown palm up (the distance between the tip of the middle finger and palm/wrist frontier was 11.2 cm), the list of the eleven types of SPS, and two visual analogue scales (i.e., two continuous horizontal lines without markers in each extreme end) for confidence ratings. The beginning of the test session was then announced. Participants were seated with their back supported on the back of a large chair.

37

The leg ipsilateral to the tested hand was laterally abducted by about 60° from the midline. Participants placed the white cotton tissue on their thigh and had their hand resting on it, with their arm as relaxed as possible. The hand was placed palm up so only a dorsal part of it, fingers excluded, was in contact with the thigh. The fingers were slightly spaced. Each hand was tested twice in a balanced order. The hand that was not tested was dangling along the side of the body. A ‘‘start” signal given verbally by the experimenter marked the beginning of each trial following which participants directed their gaze toward their tested hand for a period of 10 s. During that time, they had to focus on the whole hand and direct their attention toward any sensations that could occur in order to report them as precisely as possible afterwards. They were also told that it was possible that no sensations would occur. The experimenter announced the end of this time period with a ‘‘stop” signal. Participants were then immediately asked to take the report sheet and to indicate whether or not they had detected sensations in the tested hand. If they had, they were asked to (a) map the extent and topography of the sensations by shading-in the areas where sensations had occurred on the picture of the tested hand; (b) estimate the overall perceived intensity of the sensations on a 10-point scale (1 = just perceptible; 10 = very intense but not painful) (they were also told that if they were able to attribute a distinct intensity to each reported sensation, they were free to do so); (c) indicate on two 10 cm visual analogue scales how confident (not confident. . .very confident) they were that the location and extent of the sensations they reported matched the location and extent of the sensations they felt; and (d) identify the sensations using the list of descriptors, with the possibility of course of choosing more than one, or even adding descriptors that were not listed. The test lasted approximately 20 min. 2.3. Questionnaires Following the SPS protocol, each participant received a number of questionnaires meant to assess some important characteristics that may influence performance. The aim here was to uncover the way and degree at which these characteristics influence the perception of SPS. These questionnaires were grouped in three categories on the basis of the individual characteristics they targeted: general status, interoception and self-awareness, and pain perception. The general status category included questionnaires assessing cognitive status, state anxiety and depression. More precisely, cognitive status was assessed using the Montreal Cognitive Assessment (MOCA; Nasreddine et al., 2005), a one-page 30-point test assessing several cognitive domains. The State-Trait Anxiety Inventory (STAI; Spielberger, Gorsuch, Lushene, Vagg, & Jacobs, 1983) is self-completed inventory consisting of two sets of 20 items: one assessing trait anxiety and one assessing state anxiety. All items are rated on a 4-point scale (i.e., from ‘‘Almost Never” to ‘‘Almost Always”) for a total score varying from 20 to 80. For the present study, we used a validated French version of the state anxiety form (Bruchon-Schweitzer & Paulhan, 1993). Participants also completed a validated French translation of the Beck Depression Inventory (BDI; Beck, Ward, Mendelson, Mock, & Erbaugh, 1961; Collet & Cottraux, 1986) assessing the severity of depressive symptoms. The BDI is a 21-question multiple-choice self-report inventory, with each answer consisting of a scale value ranging from 0 to 3. Total scores vary between 0 and 63 and higher scores indicate more severe depressive symptoms. The interoception and self-awareness category comprised validated questionnaires that have been adapted for ad used with French population for the assessment heightened somatosensory perception and the tendency to experience somatic sensation as intense (The Somatosensory Amplification Scale, SSAS; Barsky et al., 1988; Naveteur, Antoine, & Charron, 2012), interoceptive

38

C. Borg et al. / Brain and Cognition 101 (2015) 35–43

body awareness and attention to the body (The Multidimensional Assessment of Interoceptive Awareness, MAIA; Mehling et al., 2012), and public and private self-awareness (Self-Consciousness Scale, SCS; Fenigstein, Scheier, & Buss, 1975; Rimé & Le Bon, 1984). More precisely, somatosensory amplification refers to the tendency to experience somatic sensations as intense, noxious and disturbing (Barsky et al., 1988). The SSAS is a 10-item selfreport questionnaire which requires the respondents to rate, on an ordinal scale of 1–5, the degree to which each statement is characteristic of them in general. A higher total score indicates greater symptom amplification. The MAIA questionnaire measures interoceptive awareness. It consists of 32 items comprising eight scales ranging from 3 to 7 items each. On one of the scales, respondents have to score their propensity to become aware of their body sensations, such as heartbeat and breath, on a scale value of 0–5. The other seven dimensions include regulatory aspects of body awareness, that is, how the body and its felt sensations are internally ‘used’ by the subject (to regulate attention or distress, or to gain insight about emotions); reactive aspects, that is, how people respond to body sensations (e.g., with worry or distraction); the awareness of the connection between body sensations and emotional states, and the extent to which the body is experienced as a comforting place, as safe and trustworthy. Finally, the SelfConsciousness scale was designed to assess both private and public self-consciousness. It is a 23 items self-report questionnaire using 5-point ratings (0 = extremely uncharacteristic to 4 = extremely characteristic) divided in three sub-scales: private selfconsciousness, public self-consciousness and social anxiety. The last category comprised questionnaires that targeted pain perception, sensory and affective aspects of pain (Questionnaire Douleur Saint-Antoine, QDSA; Bourreau, Luu, Doubrere, & Gay, 1984), catastrophizing and negative response to anticipated or actual pain (The Pain Catastrophizing Scale, PCS; Sullivan, Bishop, & Pivik, 1995), and body satisfaction and global self-perception (Questionnaire de Satisfaction Corporelle et de Perception Globale de Soi, QSCPGS; Evers & Verbanck, 2010), which is also linked to catastrophism. The QDSA is a French adaptation of the McGill Pain Questionnaire (Melzack, 1975) that allows an assessment of both quantitative and qualitative aspects of pain, with a focus the sensory and affective components. In this questionnaire, words that can be used to qualify pain (e.g. stabbing, throbbing, stinging) are grouped into 4 classes and 20 subclasses, with words of each subclass arranged in an order of increasing severity. Only for the words that correspond to their subjective experience of pain, patients have to evaluate the degree to which each word adequately qualifies their present pain. A French version of the Pain Catastrophizing Scale (PCS; French et al., 2005; Sullivan et al., 1995) was used in this study. The PCS is a 13 items self-report questionnaire divided in three subgroups: rumination, exaggeration and vulnerability. Participants had to assess their personal experience with a fivepoint scoring from 0 to 4. Final scores vary from 0 to 52. Finally, the body satisfaction and global self-perception questionnaire (QSCPGS) allows the estimation of ‘‘body satisfaction and globalperception”. It includes 10 items (i.e. you consider your body as) and 10 items (i.e. generally you feel like) assessed on a scale from 5 to 5 points.

3. Results 3.1. Questionnaires The results to the psychometric instruments are presented in Table 1. As compared to the controls, patients with FM presented with a reduced cognitive performance (MOCA; FM = 27.61 (±2.78); Controls = 25.38 (±2.91); t(34) = 2.22; P < 0.02), and

Table 1 Comparison of the mean scores, observed in overall cognitive assessment and the different questionnaires administered, between control participants and patients with fibromyalgia, and respective T Student values and P-values. Standard deviations are presented in parentheses. Significant differences at least at P < 0.05 are noted by an asterisk.

MOCA State Anxiety Beck Depression QDSA SSAS SCS PCS QSCPGS MAIA

Controls

FM

T student

P-value

25.38 (2.91) 40.27 (11.71) 2.94 (4.49) 22.88 (21.99) 22.55 (6.91) 47.72 (10.57) 11.33 (9.99) 36.66 (31.02) 87.33 (28.21)

27.61 (2.78) 48.33 (5.61) 12.94 (7.52) 109.05 (32.55) 31.33 (8.28) 51,72 (11.91) 31.61 (12.1) 14.27 (27.39) 91 (29.11)

2.22 2.62 4.84 9.34 3.32 1.06 5.48 5.22 0.34

0.02⁄ 0.01⁄ <0.0001⁄ <0.0001⁄ 0.02⁄ 0.27 <0.0001⁄ <0.0001⁄ 0.7

reported more anxious (STAI; FM = 48.33 (±5.61); Controls = 40.27 (±11.71); t(34) = 2.62; P < 0.01) and depressive (BDI; FM = 12.94 (±7.52); Controls = 2.94 (±4.49); t(34) = 4.84; P < 0.0001) symptoms, higher catastrophism scores (PCS; FM = 31.61 (±12.1); Controls = 11.33 (±9.99); t(34) = 5.48; P < 0.0001), as experiencing more pain (QDSA; FM = 109.05 (±32.55); Controls = 22.88 (±21.99); t(34) = 9.34; P < 0.0001), heightened bodily sensations (SSAS; FM = 31.33 (±8.28); Controls = 22.55 (±6.91); t(34) = 3.32; P < 0.02), and less satisfaction as regards their body (QSCPGS; FM = 14.27 (±27.39); Controls = 36.66 (±31.02); t(34) = 5.22; p < 0.0001). No differences were found between patients with FM and controls in self-consciousness (SCS; FM = 51.72 (±11.91); Controls = 47.72 (±10.57); t(34) = 1.06; P < 0.27), nor in interoceptive awareness (MAIA; FM = 91 (±29.11); Controls = 87.33 (±28.21); t(34) = 0.34; p < 0.7). 3.2. SPS 3.2.1. Topography This analysis was carried out in order to detect significant differences in the spatial distribution of SPS between patients with FM and controls. Shaded areas on each printed hand were projected onto a 140  140 grid with 1 mm2 resolution and then converted into binary codes (0 = not shaded cell; 1 = shaded cell). The result, for each hand of each participant, was an individual map of spatially distributed binary codes representing the shaded areas. Four frequency maps (two per hand) were obtained by superimposing the individual binary maps, with the value in each cell representing the percentage of participants having shaded it in (flanker hands in Fig. 1). The comparison between the left and the right hand was not of interest here because not all participants were right-handed. Topographical statistics were compiled by means of cell-by-cell comparisons between control participants and patients with FM. The exact test for binary independent measures was used (Barnard, 1945) to produce significance maps (the central hand in Fig. 1) depicting the cells where reliable differences were found between groups. The alpha level was set to 0.05 bicaudal. The significance maps resulting from the abovementioned comparisons were subsequently subjected to binary conversion (0 = nonsignificant; 1 = significant) and a spatial scan procedure for binary data (Kulldorff, 1997) was subsequently used. This consists in a circular window that scans the maps, detects and localizes significant clusters. On the basis of previous simulations (Oldfield, 1971), the maximal radius was set at 6 cells (representing a maximal scanned surface of 113 cells). Only significant clusters at P < 0.001 level bicaudal are presented here. All spatial analyses were carried out using home-made software. As may be seen from the flanker hands and the central significance map (Fig. 1), patients with FM reported more sensations than controls

C. Borg et al. / Brain and Cognition 101 (2015) 35–43

39

Fig. 1. Topographical analyses of the frequency of sensations. The hand is shown palm up. The colored scale of the reduced-size flanker hands represents the percentage of participants having reporting sensations. Note that the scales are not the same because of differences in the overall number of sensations reported by each group. The central hand is an exact probability map based on the difference between controls and patients with fibromyalgia. Only clusters significant at P < 0.001 are presented. Reddish cells denote the supremacy of the controls whilst bluish cells denote the supremacy of FM. Color shades n the probability map represent different probabilities associated to each cell. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

on almost all the glabrous surface of the hand, except for the areas where tactile sensitivity is the most prominent, i.e., the fingertips.

3.2.2. Other parameters All other recorded parameters were rank-transformed and submitted to three successive analyses of covariance (ANCOVAs) with the group (FM vs. controls) as the unique between-participants factor. In all analyses age and body mass index were used as covariates since a previous study showed that these factors may influence the perception of SPS (Michael & Naveteur, 2011), and a third covariate, the number of years of education, was also included because the two groups differed significantly on this variable. In the first analysis, these covariates were entered alone. In the second analysis, we added the scores of the questionnaires of the second category as covariates in order to uncover the effects of interoception and self-awareness. Finally, in the third analysis, we added the scores of the third category to the standard covariates in order to uncover the effects of pain and catastrophism. Changes in the proportion of variance (R2) explained in each step by the sole differences between FM and control participants are presented in Table 2. Intensity of sensations: In the first analysis, the main effect of group was significant (F(1, 31) = 14.7; P < 0.003, R2 = 0.32) insofar as sensations were perceived as more intense by the FM group (3.3 ± 1.9 points) than controls (1.5 ± 1.2 points). Entering scores of interoception and self-consciousness as covariates produced little change in this pattern (F(1, 28) = 11.4; P < 0.0006, R2 = 0.29), whilst entering scores of pain and catastrophism as covariates

erased the difference between the two groups (F(1, 29) = 0.17; P > 0.68, R2 = 0.01). Number of disjoined sensitive areas: The main effect of group was not found to be significant (F(1, 31) = 2.01; P > 0.16, R2 = 0.06) since the FM group reported as many areas (8.5 ± 8.0) as controls did (6.0 ± 5.5). Entering scores of interoception and selfconsciousness as covariates produced little change (F(1, 28) = 1.5; P > 0.23, R2 = 0.05), as it was the case when entering scores of pain and catastrophism as covariates (F(1, 29) = 0.1; P > 0.75, R2 = 0.004). Total surface of sensations: The overall surface of reported sensations was divided by the total surface of the protocol hand and multiplied by 100 in order to obtain a percentage of surface of the hand occupied by SPS. The main effect of group was significant (F(1, 31) = 17.4; P < 0.0002, R2 = 0.36) insofar as sensations were perceived by the FM group as occupying an overall larger area of the hand (29.1 ± 29.0%) than by controls (4.5 ± 4.3%). Entering scores of interoception and self-consciousness as covariates produced little changes in this pattern (F(1, 28) = 9.5; P < 0.005, R2 = 0.25), while entering scores of pain and catastrophism as covariates erased the difference between the two groups (F(1, 29) = 1.21; P > 0.28, R2 = 0.04). Size of sensations: The mean size of sensations, expressed in %, was obtained by dividing the total surface by the number of disjoined sensitive areas. The main effect of group was significant (F(1, 31) = 17.7; P < 0.0001, R2 = 0.36) since sensations reported by the FM group were occupying larger areas (18.4 ± 23.4%) than those reported by the controls (2.9 ± 3.9%). Entering scores of interoception and self-consciousness as covariates produced little

40

C. Borg et al. / Brain and Cognition 101 (2015) 35–43

Table 2 Proportions of explained variance (R2 values) for each one of the 7 dependent variables collected in the present study after controlling for demographic factors (ANCOVA 1), demographic factors and questionnaire measures of interoception and self-awareness (ANCOVA 2), and demographic factors, questionnaire measures of interoception and selfmeasures, and questionnaire measures of pain perception, sensory and affective aspects of pain (ANCOVA 3). Changes in R2 at steps 2 and 3 are presented in parentheses.

ANCOVA 1 ANCOVA 2 ANCOVA 3

Intensity

Number of areas

% Surface

Size

Variety

Confidence in location

Confidence in extent

0.32 0.29 (0.03) 0.01 (0.32)

0.06 0.05 (0.01) 0.004 (0.06)

0.36 0.25 (0.11) 0.04 (0.32)

0.36 0.26 (0.11) 0.11 (0.25)

0.24 0.20 (0.04) 0.0001 (0.24)

0.11 0.08 (0.03) 0.003 (0.11)

0.13 0.08 (0.06) 0.003 (0.13)

changes (F(1, 28) = 9.6; P < 0.005, R2 = 0.26), whilst entering scores of pain and catastrophism as covariates greatly reduced, but not totally erased, the difference between the two groups (F(1, 29) = 3.7; P > 0.06, R2 = 0.11). Variety of sensations: The number of different sensations reported by each participant differed between the two groups (F(1, 31) = 9.7; P < 0.004, R2 = 0.24). Patients with FM reported a larger variety of sensations (mean number: 5.4 ± 2.9) than controls (mean number: 3.1 ± 1.5). Entering scores of interoception and self-consciousness as covariates produced little changes (F(1, 28) = 6.9; P < 0.02, R2 = 0.20), while entering scores of pain and catastrophism as covariates eliminated the difference between the two groups (F(1, 29) = 0.1; P > 0.95, R2 = 0.0001). Confidence ratings: Confidence in the location of SPS did not differ between the two groups (FM = 5.6 ± 2.1; Controls = 4.3 ± 1.7; F(1, 30) = 3.7; P > 0.06, R2 = 0.11). Entering scores of interoception and self-consciousness as covariates produced little change (F(1, 27) = 2.3; P > 0.14, R2 = 0.08), as was the case when entering scores of pain and catastrophism as covariates (F(1, 29) = 0.1; P > 0.78, R2 = 0.003). Confidence in the extent of SPS differed between the two groups (FM = 5.3 ± 1.9; Controls = 4.1 ± 1.8; F(1, 31) = 4.6; P < 0.04, R2 = 0.13). Entering scores of interoception and self-consciousness as covariates erased this difference (F(1, 27) = 2.3; P > 0.14, R2 = 0.08), as was the case when entering scores of pain and catastrophism as covariates (F(1, 29) = 0.1; P > 0.78, R2 = 0.003). Types of sensations: The types of the reported sensations were analyzed with chi-square tests. All eleven proposed sensations were reported at least once, and two more sensations were spontaneously added by participants: pins-and-needles and electric flux. These sensations were not reported equally frequently (v2(12) = 190.1; P < 0.00001). When the frequency of each sensation was compared between the two groups, significant differences were found for sensations of itch (FM = 0.6%; Controls = 6.3%; v2(1) = 4.6; P < 0.033), cooling (FM = 7.1%; Controls = 21.3%; v2(1) = 7.1; P < 0.008), flutter (FM = 7.7%; Controls = 1.3%; v2(1) = 4.6; P < 0.031), and pins-and-needles (FM = 3.8%; Controls = 0.0%; v2(1) = 3.9; P < 0.05). The results of this analysis are presented in Table 3. Table 3 Comparison of the percentage of sensations between control participants and patients with fibromyalgia, and respective v2 values and P-values. Significant differences at least at P < 0.05 are noted by an asterisk.

Beat/pulse Itch Tickle Numbness Skin stretch Tingle Warming Cooling Musc stiffness Flutter Vibration Pins & needles Electric flux

Controls

FM

v2

P-value

15 6.3 2.5 10 3.8 21.3 11.3 21.3 5 1.3 2.5 0 0

9.6 0.6 2.6 10.9 1.3 28.8 15.4 7.1 9 7.7 2.6 3.8 0.6

1.2 4.6 0.0 0.0 1.2 1.2 0.6 7.1 1.1 4.6 0.0 3.8 0.6

0.278 0.033⁄ 0.977 0.844 0.271 0.283 0.423 0.008⁄ 0.288 0.031⁄ 0.977 0.050⁄ 0.423

4. Discussion The aim of the present study was to investigate the generalized hypervigilance hypothesis of FM by assessing non-aversive perceptions like those arising spontaneously on the hands (i.e., SPS). On the basis of the existent literature, we hypothesized that patients with FM would report SPS more frequently and would describe them as being more intense, more extended, and more diversified than healthy controls. Furthermore, we hypothesized that catastrophism would modulate the differences between FM and controls since it was shown that catastrophic beliefs can play a role in the perception of internal sensations (Yoris et al., 2015). Consistent with our predictions, our results showed an amplification of SPS in FM in comparison with the control group. Since focusing attention increases the perception of SPS (Michael & Naveteur, 2011; Michael et al., 2012; Naveteur, Dupuy, Gabrieli, & Michael, in press), this finding is particularly relevant for discussing the generalized hypervigilance hypothesis in FM (Glass et al., 2011; González et al., 2010; McDermid et al., 1996). Firstly, SPS were perceived by the FM group as occupying an overall larger area of the hand and as being more intense than the control group. Although the number of SPS and of disjoined sensitive areas reported by patients with FM was similar to the one reported by the control group, our results suggest an amplification in the perception of non-painful internal sensations. In FM, it is therefore possible that pain but also other somatic sensations induce a hypervigilance. The interoceptive experience is not only based on sensory/discriminative processing but also on emotional/attentional components (Craig, 2003; Aldrich, Eccleston, & Crombez, 2000; Eccleston & Crombez, 1999; Peyron, Laurent, & Garcia-Larrea, 2000; Peyron et al., 1999; Vlaeyen & Linton, 2000). Therefore, many different factors, related to either the direct experience of chronic pain and pain apprehension, or distortions in the representation of the body, may contribute to explain the differences observed between the SPS reported by both groups. Bayesian approach to embodiment (Seth, 2013) could also be an interesting framework to study SPS, since our results both support and challenge this probabilistic model. Indeed, a task requiring individuals to focus their attention on the spontaneous sensations that might arise on their hands could trigger automatic predictions about the sensations that can be felt. If that were the case, these predictions would be congruent with the individuals’ past sensory experiences of their hands, such as a proximo-distal gradient, and be shaped by their general level of interoceptive awareness and past experience of chronic pain. In this study, pain and catastrophism entered as covariates explained from 6% to 32% of the difference between patients with FM and healthy controls in the perception of SPS. These results are in agreement with the prediction that catastrophizing has an impact on pain perception by modifying the attentional and anticipatory mechanisms and by increasing the emotional response to pain (Gracely et al., 2004). In the present experiment, we aimed at investigating whether a singular pain experience, such as FM, can change the perception of interoceptive sensations. Our results show that catastrophizing and pain are clearly related to an increase in the perception of SPS. Furthermore, the FM group used

C. Borg et al. / Brain and Cognition 101 (2015) 35–43

a larger variety of the eleven descriptors that were proposed to label the SPS, and also spontaneously added the pins-and-needles sensations. Interestingly, one of the key factors of FM seems to be a dysfunction in the system that prevents non-painful stimuli from becoming painful (Julien, Goffaux, Arsenault, & Marchand, 2005; Staud, Robinson, Vierck, & Price, 2003). Although pins-andneedles sensations can be felt as non-painful, they seem to be at the threshold of pain. Generally, somatic signals appear non aversive or irrelevant in a particular context and are filtered out from our awareness (Broadbent & Petrie, 2007). It therefore seems possible that in fibromyalgia, the perception of interoceptive information is so amplified, partly by a catastrophic attitude, that it may become painful. These results are consistent with the Barsky and Klerman’s hypothesis (1983) that people who report pain in the absence of an identifiable organic etiology attend to and amplify normal bodily sensations (Ahles, Cassens, & Stalling, 1987). According to the fear-avoidance model of chronic musculoskeletal pain (Vlaeyen & Linton, 2000), when pain is interpreted as threatening, as it is the case in catastrophism, fear related to pain as well as hypervigilance toward painful sensations increases, which in turn amplifies the experienced pain. Then, beliefs about pain as being unbearable and uncontrollable emerge with a feeling of helplessness and a dramatization that further aggravates the person’s fearful attitude toward pain (Schutze, Rees, Preece, & Schutze, 2010). It is know that catastrophism influences the perception of pain (Edwards, Bingham, Bathon, & Haythornthwaite, 2006), but our results support the hypothesis that it also has an impact on the general perception of normal internal sensations. Therefore, therapeutic techniques that aim to help chronic pain patients learn to reduce their hypervigilant attitude toward bodily sensations could be particularly useful. In that regard, studies have shown that listening to music reduces both acute and chronic pain (Guétin et al., 2012; Korhan et al., 2013; Roy, Lebuis, Hugueville, Peretz, & Rainville, 2012). Recently, Garza-Villarreal et al. (2014) showed that music reduces pain and increases functional mobility in FM. In light of the existent literature, the authors discussed how music could be an effective trigger for mechanisms that are known to alleviate pain such as distraction, relaxation, pleasantness and pleasure, as well as memory evoked emotions (e.g., Mitchell & MacDonald, 2006; Salimpoor, Benovoy, Larcher, Dagher, & Zatorre, 2011; Tracey et al., 2002; Villemure & Bushnell, 2009). In the same vein, mindful meditation has been shown to significantly reduce pain through a number of brain mechanisms such as afferent processing in the primary somatosensory cortex, known to be involved in the evaluation of pain (Zeidan, Grant, Brown, McHaffie, & Coghill, 2013). López-Solà et al. (2014) suggested that sensory treatments such as whole-body vibration or even Tai Chi, which has shown some effectiveness in patients with FM, may help patients adjust the way they process sensations and perhaps alleviate pain. Mindful meditation, listening to music and other techniques represent a way to elicit positive emotions and distract patients from their pain, thus creating an alternative to catastrophic thoughts and expectations. Although these techniques seem to have the potential to indirectly change the perception of interoceptive sensations or pain (Garland et al., 2012; Schutze et al., 2010), a recent metaanalysis emphasized the need for more empirical evidence to support mindfulness-based stress reduction as an effective treatment for FM (Lauche, Cramer, Dobos, Langhorst, & Schmidt, 2013). The cognitive modulation of pain, and in general, the cognitive modulation of interoceptive perception, can be influenced by a number of factors including attention, beliefs, conditioning, expectations, mood, and the regulation of the emotional response to sensory events. Recognizing the connection between pain and hypersensitivity may help clinicians who might otherwise dismiss symptoms of pain in FM.

41

Not only do pain and catastrophism seem to play in the amplification of SPS in FM patients, but the replication in the present study of the proximo-distal gradient observed in previous SPS studies (e.g., Michael & Naveteur, 2011) also suggests that those amplified SPS might contribute to amplified body awareness. Indeed, as can be seen in Fig. 1 (flanker hands), the two groups reported more numerous SPS over the distal phalanges, and the number diminished sharply over the intermediate phalanges and then more gently over the proximal phalanges and palm. This spatial distribution, a proximo-distal gradient, is characteristic of the organization in the density of cutaneous receptors, especially mechanoreceptors (Michael & Naveteur, 2011). This specific topography supports the hypothesis of the involvement of the representation of the body located in the somatosensory cortex in the experience of SPS (Bauer, Díaz, et al., 2014; Beaudoin & Michael, 2014) even the perception of these sensations can be modulated by attention and visual input (Michael & Naveteur, 2011; Michael et al., 2012). Our study shows that the sensory representation of the hand is preserved in FM since a similar gradient appears in both groups, despite the overall amplification observed in FM. Interestingly, in the present study, scores of interoception and self-consciousness explained from 1% to 11% of the difference in the perception of SPS between patients with FM and controls also supports a link between SPS and body awareness. Direct evidence in the literature between SPS and the brain areas mediating interoception is lacking, nevertheless, one compelling cue is the activation of the insula, a structure strongly involved in interoception (Craig, 2002; Critchley et al., 2004; Montgomery & Jones, 1984) during sustained attention paid to SPS (Bauer, Barrios, et al., 2014; Bauer, Díaz, et al., 2014). Recently, López-Solà et al. (2014) found that FM patients showed strong attenuation of brain responses to nonpainful events in early sensory cortices, accompanied by an amplified response at later stages of sensory integration in the insula. Importantly, López-Solà et al. (2014) showed that all measures of sensory hypersensitivity observed in FM were significantly correlated with spontaneous pain, suggesting that subjective pain may arise from augmented processing of nociceptive sensory information. Consistent with the idea that bodily sensations arising from within the body contribute to how the self is perceived (Kinsbourne, 1998), it was proposed that SPS play a role to access the representation of the body and to maintain it active in consciousness (Michael et al., 2012, 2015). It has been shown that the retrieval and processing of somatosensory experiences can be modulated by top-down attentional processes during a subjective experience (Iguchi, Hoshi, Tanosaki, & Hashimoto, 2002; Michael & Naveteur, 2011; Michael et al., 2012). Furthermore, neuroimaging studies showed that specific somatosensory areas as well as other parieto-frontal areas became active while participants had to sustain their attention on the SPS arising from the thumb (Bauer, Barrios, et al., 2014; Bauer, Díaz, et al., 2014). It has been shown that the parietal cortex mediates selective attention to external stimuli and is involved in actively orienting attention to interoceptive stimuli (Hämäläinen, Hiltyunen, & Titievskaja, 2002; Mima, Nagamine, Nakamura, & Shibasaki, 1998; Tracy et al., 2007), which is thought to allow the construction as well as the maintenance of the consciousness of one’s own body (Kinsbourne, 1998; Wolpert, Goodbody, & Husain, 1998). Given that the parietal cortex, which was found to be implicated in the perception of SPS, receives direct projections from the insula, which is known to be involved in interoceptive attention (Craig, 2002; Critchley et al., 2004) and body ownership (Tsakiris, 2010; Tsakiris et al., 2007), it is plausible that hypervigilance toward bodily sensations in FM arises through these connections. Future research assessing both attentional demands and sensations may help to explore the functional connectivity between the parieto-frontal junction and the insula, in order to

42

C. Borg et al. / Brain and Cognition 101 (2015) 35–43

better understand how the perception of interoceptive sensations is modulated by attention. 5. Conclusions In conclusion, our pattern of results shows that patients with FM felt their body (or at least their hands) differently from controls. This heightened interoceptive awareness reflects what might be expected on the basis of the generalized hypervigilance hypothesis. Available experimental data give further support to the possibility of a dual functional alteration in FM in response to nonpainful sensory stimulation. For instance, neuroimaging studies showed reduced activation in primary/secondary visual and auditory areas, and augmented responses in the insula and anterior lingual gyrus (López-Solà et al., 2014). This pattern of results suggests that beyond the pain, patients with FM show hypersensitivity to information coming from any sensorial modality (Geisser et al., 2008). Many researchers are trying to understand whether a cognitive dysfunction, such as abnormal pain perception or even abnormal perception of sensations in general, is a primary symptom or is the direct consequence of pain itself. It seems that the cognitive dysfunction (i.e., an attentional bias toward non aversive stimulation) that is observed in the FM group in the present study is closely related to pain which is modulated by a catastrophizing style. Thus, it appears essential to investigate further how chronic pain mobilizes attentional resources, perhaps leading to an abnormal cognitive style. Acknowledgments This study benefited from funding support from the LABEX CORTEX (ANR-11-LABX-0042) of the University of Lyon, under the ‘‘Investissements d’Avenir” program (ANR-11-IDEX-0007) run by the French National Research Agency (ANR). Additionally, we thank the team of the Pain Centre at the CHU Saint-Etienne for their precious help with the recruitment of the clinical sample. Finally, we thank Christelle Creac’h who provided insight and expertise on fibromyalgia, which greatly assisted the research. References Ahles, T. A., Cassens, H. L., & Stalling, R. G. (1987). Private body consciousness, anxiety and the perception of pain. Journal of Behavioral Therapy and Experimental Psychiatry, 18, 215–222. Aldrich, S., Eccleston, C., & Crombez, G. (2000). Worrying about chronic pain: Vigilance to threat and misdirected problem solving. Behaviour Research and Therapy, 38(5), 457–470. Barnard, G. A. (1945). A new test for 2  2 tables. Nature, 156, 177. Barrett, L. F., & Simmons, W. K. (2015). Interoceptive predictions in the brain. Nature Reviews Neuroscience, 16(7), 419–429. Barsky, A. J., Goodson, J. D., Lane, R. S., & Cleary, P. D. (1988). The amplification of somatic symptoms. Psychosomatic Medicine, 50, 510–519. Barsky, A. J., & Klerman, G. L. (1983). Overview: Hypochondriasis, bodily complaints, and somatic styles. American Journal of Psychiatry, 140, 273–283. Bauer, C. C., Barrios, F. A., & Diaz, J. L. (2014). Subjective somatosensory experiences disclosed by focused attention: Cortical–hippocampal–insular and amygdala contributions. PLoS One, 9(8), e104721. http://dx.doi.org/10.1371/journal. pone.0104721. Bauer, C. C., Díaz, J. L., Concha, L., & Barrios, F. A. (2014). Sustained attention to spontaneous thumb sensations activates brain somatosensory and other proprioceptive areas. Brain and Cognition, 87, 86–96. Beaudoin, R., & Michael, G. A. (2014). Gating of spontaneous somatic sensations by movement. Somatosensory Research, 31, 111–121. Beck, A. T., Ward, C. H., Mendelson, M., Mock, J., & Erbaugh, J. (1961). An inventory for measuring depression. Archives of General Psychiatry, 4, 561–571. Berlucchi, G., & Aglioti, S. M. (2010). The body in the brain revisited. Experimental Brain Research, 200, 25–35. Bojner, H. E., Kowalski, J., Theorell, T., & Anderberg, U. M. (2006). Dance/movement therapy in fibromyalgia patients: Changes in self-figure drawings and their relation to verbal self-rating scales. The Arts in Psychotherapy, 33, 11–25. Bourreau, F., Luu, M., Doubrere, J., & Gay, C. (1984). Elaboration d’un questionnaire d’auto-évaluation de la douleur par liste de qualificatifs: Comparaison avec le Mac Gill pain questionnaire de Melzack. Thérapie, 39, 119–129.

Broadbent, E., & Petrie, K. J. (2007). Symptom perception. In S. Ayers, A. Baum, C. McManus, S. Newman, K. Wallston, J. Weinmman, & R. West (Eds.), Cambridge handbook of psychology, health & medicine (pp. 219–222). Cambridge: Cambridge University Press. Bruchon-Schweitzer, M., & Paulhan, I. (1993). Adaptation française de l’Inventaire d’Anxiété Trait-Etat. Forme Y (STAI Y). Paris: Les Éditions du Centre de Psychologie Appliquée. Cameron, O. G. (2001). Interoception: The inside story – A model for psychosomatic processes. Psychosomatic Medicine, 63, 697–710. Campbell, C. M., & Edwards, R. R. (2009). Mind–body interactions in pain: The neurophysiology of anxious and catastrophic pain-related thoughts. Translation Research, 153, 97–101. Carrillo-de-la-Peña, M. T., Vallet, M., Pérez, M. I., & Gómez-Perretta, C. (2006). Intensity dependence of auditory-evoked cortical potentials in fibromyalgia patients: A test of the generalized hypervigilance hypothesis. The Journal of Pain: Official Journal of the American Pain Society, 7(7), 480–487. Collet, L., & Cottraux, J. (1986). Inventaire abrégé de la dépression de Beck (13 items). Étude de la validité concurrente avec les échelles de Hamilton et de ralentissement de Wildlöcher. Encéphale, 12, 77–79. Craig, A. D. (2002). How do you feel? Interoception: The sense of the physiological condition of the body. Nature Reviews Neuroscience, 3, 655–666. Craig, A. D. (2003). Interoception: The sense of the physiological condition of the body. Current Opinion in Neurobiology, 13, 500–505. Craig, A. D. (2009). How do you feel – Now? The anterior insula and human awareness. Nature Reviews Neuroscience, 10, 59–70. Critchley, H. D., Wiens, P., Rotshein, A., Ohman, A., & Dolan, R. J. (2004). Neural systems supporting interoceptive awareness. Nature Neuroscience, 7, 189–195. Crombez, G., Van Damme, S., & Eccleston, G. (2005). Hypervigilance to pain: An experimental and clinical analysis. Pain, 116, 4–7. Dohrenbusch, R., Sodhi, H., Lamprecht, J., & Genth, E. (1997). Fibromyalgia as a disorder of perceptual organization? An analysis of acoustic stimulus processing in patients with widespread pain. Zeitschrift für Rheumatologie, 56, 334–341. Eccleston, C., & Crombez, G. (1999). Pain demands attention: A cognitive–affective model of the interruptive function of pain. Psychological Bulletin, 125, 356–366. Edwards, R. R., Bingham, C. O., 3rd, Bathon, J., & Haythornthwaite, J. A. (2006). Catastrophizing and pain in arthritis, fibromyalgia, and other rheumatic diseases. Arthritis & Rheumatology, 55(2), 325–332. Evers, L., & Verbanck, P. (2010). Creation of a body satisfaction and global selfperception questionnaire: The QSCPGS. Norms and first validation. L’Encéphale, 36, 21–27. Fenigstein, A., Scheier, M. F., & Buss, A. H. (1975). Public and private selfconsciousness: Assessment and theory. Journal of Consulting and Clinical Psychology, 43, 522–527. French, D. J., Noël, M., Vigneau, F., French, J. A., Cyr, C. P., & Thomas, R. (2005). L’Échelle de dramatisation face à la douleur PCS-CF: Adaptation canadienne en langue française de l’échelle Pain Catastrophizing Scale. [PCS-CF: A Frenchlanguage, French-Canadian adaptation of the Pain Catastrophizing Scale]. Canadian Journal of Behavioural Science, 37(3), 181–192. Garland, E. L., Gaylord, S. A., Palsson, O., Faurot, K., Douglas Mann, J., & Whitehead, W. E. (2012). Therapeutic mechanisms of a mindfulness-based treatment for IBS: Effects on visceral sensitivity, catastrophizing, and affective processing of pain sensations. Journal of Behavioral Medicine, 35(6), 591–602. Garza-Villarreal, E. A., Wilson, A., Vase, L., Brattico, E., Barrios, F. A., Jensen, T. S., ... Vuust, P. (2014). Music reduces pain and increases functional mobility in fibromyalgia. Frontiers in Psychology. http://dx.doi.org/10.3389/ fpsyg.2014.00090. Geisser, M. E., Glass, J. M., Rajcevska, L. D., Clauw, D. J., Williams, D. A., Kileny, P. R., & Gracely, R. H. (2008). A psychophysical study of auditory and pressure sensitivity in patients with fibromyalgia and healthy controls. Journal of Pain, 9, 417–422. Gibson, S. J., Littlejohn, G. O., Gorman, M. M., Helme, R. D., & Granges, G. (1994). Altered heat pain thresholds and cerebral event-related potentials following painful CO2 laser stimulation in subjects with fibromyalgia syndrome. Pain, 58, 185–193. Glass, J. M., Williams, D. A., Fernandez-Sanchez, M. L., Kairys, A., Barjola, P., Heitzeg, M. M., ... Schmidt-Wilcke, T. (2011). Executive function in chronic pain patients and healthy controls: Different cortical activation during response inhibition in fibromyalgia. Journal of Pain, 12, 1219–1229. González, J. L., Mercado, F., Barjola, P., Carretero, I., López- López, A., Bullones, M. A., ... Alonso, M. (2010). Generalized hypervigilance in fibromyalgia patients: An experimental analysis with the emotional Stroop paradigm. Journal of Psychosomatic Research, 69, 279–287. Gracely, R. H., Geisser, M. E., Giesecke, T., Grant, M. A., Petzke, F., Williams, D. A., & Clauw, D. J. (2004). Pain catastrophizing and neural response to main among persons with fibromyalgia. Brain, 127, 835–843. Granges, G., & Littlejohn, G. O. (1993). Pressure pain threshold in pain-free subjects, in patients with chronic regional pain syndromes, and in patients with fibromyalgia syndrome. Arthritis & Rheumatology, 36, 642–646. Gregory, J., Yaguez, L., Williams, S. C., Altmann, C., Coen, S. J., Ng, V., ... Aziz, Q. (2003). Cognitive modulation of the cerebral processing of human oesophageal sensation using functional magnetic resonance imaging. Gut, 52, 1671–1677. Guétin, S., Giniès, P., Siou, D. K., Picot, M. C., Pommié, C., Guldner, E., ... Touchon, J. (2012). The effects of music intervention in the management of chronic pain: A single-blind, randomized, controlled trial. Clinical Journal of Pain, 28, 329–337.

C. Borg et al. / Brain and Cognition 101 (2015) 35–43 Hämäläinen, H., Hiltyunen, J., & Titievskaja, I. (2002). Activation of somatosensory cortical areas varies with attentional state: An fRMI study. Behavioural Brain Research, 135, 159–165. Herbert, B. M., & Pollatos, O. (2012). The body in the mind: On the relationship between interoception and embodiment. Topics in Cognitive Science, 4(4), 692–704. http://dx.doi.org/10.1111/j.1756-8765.2012.01189.x. Hollins, M., Harper, D., Gallagher, S., Owings, E. W., Lim, P. F., Miller, V., ... Maixner, W. (2009). Perceived intensity and unpleasantness of cutaneous and auditory stimuli: An evaluation of the generalized hypervigilance hypothesis. Pain, 141, 215–221. Iguchi, Y., Hoshi, Y., Tanosaki, M., & Hashimoto, I. (2002). Selective attention regulates spatial and intensity information processing in the human primary somatosensory cortex. NeuroReport, 13, 2335–2339. Julien, N., Goffaux, P., Arsenault, P., & Marchand, S. (2005). Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition. Pain, 114, 295–302. Kinsbourne, M. (1998). Awareness of one’s own body: An attentional theory of its nature, development, and brain basis. In N. Elian (Ed.), The body and the self (pp. 205–223). Cambridge, MA: MIT Press. Korhan, E. A., Uyar, M., Eyigör, C., Yönt, G. H., Çelik, S., & Khorshıd, L. (2013). The effects of music therapy on pain in patients with neuropathic pain. Pain Management Nursing. 10.1016/j.pmn.2012.10.006. Kulldorff, M. (1997). A spatial scan statistic. Communication in Statistics, 26, 1481–1496. Lauche, R., Cramer, H., Dobos, G., Langhorst, J., & Schmidt, S. (2013). A systematic review and meta-analysis of mindfulness-based stress reduction for the fibromyalgia syndrome. Journal of Psychomatic Research, 75(6), 500–510. Lautenbacher, S., Rollman, G. B., & McCain, G. A. (1994). Multi-method assessment of experimental and clinical pain in patients with fibromyalgia. Pain, 59, 45–53. Lewis, J. S., Kersten, P., McCabe, C. S., McPherson, K. M., & Blake, D. R. (2007). Body perception disturbance: A contribution to pain in complex regional pain syndrome (CRPS). Pain, 133, 111–119. Longo, M. R., Azano, E., & Haggard, P. (2010). More than skin deep: Body representation beyond primary somatosensory cortex. Neurospychologia, 48, 655–668. López-Solà, M., Pujol, J., Garcia-Fontanals, A., Blanco-Hinojo, L., Garcia-Blanco, S., Poca-Dias, V., ... Deus, J. (2014). Altered functional magnetic resonance imaging responses to nonpainful sensory stimulation in fibromyalgia patients. Arthritis & Rheumatology, 66(11), 3200–3209. Lotze, M., & Moseley, G. L. (2007). Role of distorted body image in pain. Current Rheumatology Reports, 9, 488–496. Macefield, G., Gandevia, S., & Burke, D. (1990). Perceptual responses to microstimulation of single afferents innervating joints, muscles and skin of the human hand. Journal of Physiology, 429, 113–129. McDermid, A. J., Rollman, G. B., & McCain, G. A. (1996). Generalized hypervigilance in fibromyalgia: Evidence of perceptual amplification. Pain, 66, 133–144. Mehling, W., Price, C., Daubenmier, J., Acree, M., Bartmess, E., & Stewart, A. (2012). The multidimensional assessment of interoceptive awareness (MAIA). BMC Complementary and Alternative Medicine, 12(Suppl. 1), P421. Melzack, R. (1975). The McGill Pain Questionnaire: Major properties and scoring methods. Pain, 1, 275–299. Melzack, R. (1990). Phantom limbs and the concept of a neuromatrix. Trends in Neurosciences, 13, 88–92. Michael, G. A., Dupuy, M. A., Deleuze, A., Humblot, M., Simon, B., & Naveteur, J. (2012). Interacting effects of vision and attention in perceiving spontaneous sensations arising on the hands. Experimental Brain, 236, 21–34. Michael, G. A., & Naveteur, J. (2011). The tickly homunculus and the origins of spontaneous sensations arising on the hands. Consciousness and Cognition, 20, 603–617. Michael, G. A., Naveteur, J., Dupuy, M. A., & Jacquot, L. (2015). My heart is in my hands: The interoceptive nature of the spontaneous sensations felt on the hands. Physiology & Behavior, 143, 113–120. Mima, T., Nagamine, T., Nakamura, K., & Shibasaki, H. (1998). Attention modulates both primary and second somatosensory cortical activities in humans: A magnetoencephalographic study. Journal of Neurophysiology, 80, 2215–2221. Mitchell, L. A., & MacDonald, R. A. R. (2006). An experimental investigation of the effects of preferred and relaxing music listening on pain perception. Journal of Music Therapy, 43, 295–316. Montgomery, W. A., & Jones, G. E. (1984). Laterality, emotionality, and heartbeat perception. Psychophysiology, 21, 459–465. Moseley, G. L. (2008). I can’t find it! Distorted body image and tactile dysfunction in patients with chronic back pain. Pain, 140, 239–243. Nasreddine, Z., Phillips, N. A., Bédirian, V., Charbonneau, S., Whitehead, V., Collin, I., ... Chertkow, H. (2005). The Montreal Cognitive Assessment (MoCA): A brief screening tool for mild cognitive impairment. Journal of American Geriatrics Society, 53, 695–699.

43

Naveteur, J., Antoine, P., & Charron, C. (2012). Santé et vieillissement: Effet de l’âge et des douleurs sur l’amplification somatosensorielle. Paper presented at the 7th congress of the Association Francophone de Psychologue de la Santé, Lille, France. Naveteur, J., Dupuy, M. A., Gabrieli, F., Michael, & G. A. (in press). Aging and how we perceive our own hands: The effect of attention and gender. Somatosensory & Motor Research. doi http://dx.doi.org/10.3109/08990220.2015.1086326. Naveteur, J., Honoré, J., & Michael, G. A. (2005). How to detect an electrocutaneous shock that is not delivered? Overt spatial attention influences decision. Behavioural Brain Research, 165, 254–261. Ochoa, J., & Torebjörk, R. (1983). Sensations evoked by intraneural microstimulation of a single mechanoreceptor units innervating the human hand. Journal of Physiology, 342, 633–654. Oldfield, R. C. (1971). The assessment and analysis of handedness: The Edinburgh inventory. Neuropsychologia, 9, 97–113. Petzke, F., Clauw, D. J., Ambrose, K., Khine, A., & Gracely, R. H. (2003). Increased pain sensitivity in fibromyalgia: Effects of stimulus type and mode of presentation. Pain, 105, 403–413. Peyron, R., Garcia-Larrea, L., Grégoire, M. C., Costes, N., Convers, P., & Lavenne, F. (1999). Haemodynamic brain responses to acute pain in human: Sensory and attentional networks. Brain, 122, 1765–1780. Peyron, R., Laurent, B., & Garcia-Larrea, L. (2000). Functional imaging of brain response to pain. A review and meta-analysis. Clinical Neurophysiology, 30(5), 263–288. Rimé, B., & Le Bon, C. (1984). Le concept de conscience de soi et ses opérationnalisations. L’année Psychologique, 84, 535–553. Rollman, G. B., & Lautenbacher, S. (1993). Hypervigilance effects in fibromyalgia: Pain experience and pain perception. In H. Væroy & H. Merskey (Eds.), Progress in fibromyalgia and myofascial pain (pp. 149–159). Amsterdam: Elsevier. Roy, M., Lebuis, A., Hugueville, L., Peretz, I., & Rainville, P. (2012). Spinal modulation of nociception by music. European Journal of Pain, 16, 870–877. Salimpoor, V. N., Benovoy, M., Larcher, K., Dagher, A., & Zatorre, R. J. (2011). Anatomically distinct dopamine release during anticipation and experience of peak emotion to music. Nature Neuroscience, 14, 257–262. Schutze, R., Rees, C., Preece, M., & Schutze, M. (2010). Low mindfulness predicts pain catastrophizing in a fear-avoidance model of chronic pain. Pain, 148(1), 120–127. Seth, A. K. (2013). Interoceptive inference, emotion, and the embodied self. Trends in Cognitive Sciences, 17(11), 565–573. Smith, B. W., Tooley, E. M., Montague, E. Q., Robinson, A. E., Cosper, C. J., & Mullins, P. G. (2008). Habituation and sensitization to heat and cold pain in women with fibromyalgia and healthy controls. Pain, 140, 420–428. Smythe, H. (1986). Referred pain and tender points. American Journal of Medicine, 81, 90–92. Spielberger, C., Gorsuch, R., Lushene, R., Vagg, P., & Jacobs, G. (1983). Manual for the state-trait anxiety inventory. Consulting Psychologists Press Inc. Staud, R., Robinson, M. E., Vierck, C. J., & Price, D. D. (2003). Diffuse noxious inhibitory controls (DNIC) attenuate temporal summation of second pain in normal males but not in normal females of fibromyalgia patients. Pain, 101, 167–174. Sullivan, M. J. L., Bishop, S. R., & Pivik, J. (1995). The pain catastrophizing scale: Development and validation. Psychological Assessment, 7, 524–532. Tracey, I., Ploghaus, A., Gati, J. S., Clare, S., Smith, S., Menon, R. S., & Matthews, P. M. (2002). Imaging attentional modulation of pain in the periaqueductal gray in humans. The Journal of Neuroscience, 22, 2748–2752. Tracy, J., Goyal, N., Flanders, A., Weening, R., Laskas, J., Natale, P., & Waldron, B. (2007). Functional magnetic resonance imaging analysis of attention to one’s heartbeat. Psychosomatic Medicine, 69, 952–960. Tsakiris, M. (2010). My body in the brain: A neurocognitive model of bodyownership. Neuropsychologia, 48(3), 703–712. Tsakiris, M., Hesse, M. D., Boy, C., Haggard, P., & Fink, G. R. (2007). Neural signatures of body ownership: A sensory network for bodily self-consciousness. Cerebral Cortex, 17(10), 2235–2244. Villemure, C., & Bushnell, M. C. (2009). Mood influences supraspinal pain processing separately from attention. The Journal of Neuroscience, 29, 705–715. Vlaeyen, J. W., & Linton, S. J. (2000). Fear-avoidance and its consequences in chronic musculoskeletal pain: A state of the art. Pain, 85(3), 317–332. Wolpert, D. M., Goodbody, S. J., & Husain, M. (1998). Maintaining internal representations: The role of the human superior parietal lobe. Nature Neuroscience, 1(6), 529–533. Yoris, A., Esteves, S., Couto, B., Melloni, M., Kichic, R., Cetkovich, M., ... Sedeño, L. (2015). The roles of interoceptive sensitivity and metacognitive interoception in panic. Behavioral and Brain Functions, 8, 11–14. Zeidan, F., Grant, J. A., Brown, C. A., McHaffie, J. G., & Coghill, R. C. (2013). Mindfulness meditation-related pain relief: Evidence for unique brain mechanisms in the regulation of pain. Neuroscience Letters, 520, 165–173.