Forty-one healthy volunteers (32 female/9 male) aged between 18 and 30 years were included in the study (mean age = 21.5, SD = 2.0; range 18.0–28.3 years). Participants were recruited through advertisements at Leiden University and the Leiden University Research Participation system (SONA systems Ltd, Tallinn, Estonia). Inclusion criteria for participation were being aged between 18 and 30 years (to include a homogenous group considering that reaction times increase with age; Woods, Wyma, Yund, Herron, & Reed, 2015) and fluent in Dutch language. Exclusion criteria for participation were severe morbidity (e.g., multiple sclerosis, diabetes mellitus, heart or lung disease, rheumatoid arthritis, vasculitis), psychiatric disorders (e.g., depression), use of pacemaker, chronic itch or pain complaints, current use of medication, color blindness, and pregnancy. All participants were students or had just finished tertiary education. The protocol was approved by the local medical review ethics committee and all participants provided written informed consent.
A modified Stroop task, a dot-probe task, and a somatosensory attention task (SAT) for itch were used to measure attentional processing of itch. All tasks were presented using E-prime software (version 2.0, Psychology Software Tools Inc., Sharpsburg, PA, USA) using a Dell optiplex 3010 computer with Philips Brilliance 225 TFT screen (Resolution 1280 × 1024 at 60 Hz). Finger response buttons, attached to the table at a fixed position, were attached to a serial response box (Psychology Software Tools Inc. Sharpsburg, PA, USA).
Stroop task modified for itch
A previously developed modified version of the Stroop task was used to measure attentional processing of itch-related and other emotional words (van Beugen et al., 2016; Van Laarhoven et al., 2016). The task included eight words related to itch (itchy, mosquito bite, fleabite, nettle, head lice, itch, louse, scratching), eight neutral words (drinking mug, kettle, nutcracker, refrigerator, kitchen, tablecloth, light bulb, doorknob) as well as eight negative words, eight positive words, and eight words related to stigmatization (van Beugen et al., 2016). Only the itch and neutral category were relevant for the present research design and therefore reported here. The words related to itch had been validated, along with other word categories, in a pilot study by a group of 43 dermatology patients, healthy participants, and health professionals (see van Beugen et al., 2016). In this pilot study, the itch words were selected based on high applicability to itch and a slightly negative valence. The words in the other categories have also been used in our previous study (van Beugen et al., 2016) and were taken from the Dutch Emotional Word list (Arnold et al., 2011). All words were single words in Dutch and matched in length between categories. Each word category consisted of 40 words (8 words repeated 5 times) in different colors (i.e., white, green, blue, yellow, red) that had been randomized in advance (for each card the same order of colors); the background was black. The words of one category were displayed at once in random order (randomized by E-prime) on the computer screen (block-design). Participants were instructed to name aloud the print color of the words displayed, as quickly and accurately as possible. The card was displayed up until the participant finished naming aloud the colors of the displayed words and time was measured. No maximum time limit was determined in advance. However, participants’ performance was monitored by the test leader. The performance level of all participants was considered satisfactory.
Dot-probe task for itch
A dot-probe paradigm (e.g., Crombez et al., 2013) modified for itch was used to measure attention bias for itch-related pictures. For this task, ten itch pictures and ten neutral pictures were used. Itch pictures had been validated in the same pilot study as the itch words, with respect to the applicability on itch and a slightly negative valence (van Beugen et al., 2016). The neutral pictures were selected from the International Affective Picture System (IAPS) database, where they had been validated as neutral (numbers 7004, 7006, 7010, 7025, 7035, 7053, 7080, 7150, 7175, 7705) (Lang, Bradley, & Cuthbert, 2008) and matched as much as possible with the itch pictures with regard to complexity and color. Additionally, four pairs of neutral pictures (IAPS numbers 7000, 7002, 7009, 7090) were used for practicing purposes. For every trial, first a fixation cross was displayed for 500 ms in the middle of the computer screen. Thereafter, a pair of pictures (in randomized order) was displayed side by side on the screen for 500 ms, which display time has most commonly been used (Crombez et al., 2013; Schoth et al., 2012), followed by the presentation of a dot (probe), replacing one of the two pictures, for at maximum 2000 ms (i.e., response window). The width of all pictures was 11.5 cm on the screen, with most picture pairs presented in landscape format (height varying between 7.6 and 9.0 cm) and two pairs in portrait format (height 13.2 and 13.8 cm). The shape of both pictures within one pair always matched. The pictures were placed in the middle of the screen height and on 25 and 75% of the screen width leaving 6.8 cm between the two pictures. The size of the dot was 0.5 cm. Localization of the dots required attentional orienting. Participants were required to respond as quickly as possible to the location of the dot (left/right), by pressing (with the index finger) the corresponding response button. Upon responding, the dot disappeared. The interval in-between trials was 100 ms. Test trials consisted of sequentially displaying 40 pairs of an itch-related and a neutral picture. The target pictures as well as the probe were presented equally often at the left or right position of the screen and the dot probe was equally likely to replace either an itch picture or neutral picture. Replacement of the itch picture by the dot is referred to as “congruent trials”, whereas replacement of the neutral picture is referred to as “incongruent trials”.
Somatosensory attention task
The somatosensory attention task (SAT) was used to measure attentional processing of somatosensory itch stimuli (see Fig. 1 for a schematic representation of the setup). This task was based on the cross-modal attention task for pain-related attention developed by Van Damme et al. (2007). However, tonic itch stimuli were used in the SAT as the on- and offset of the itch sensation after phasic stimuli cannot be reliably predicted, as itch is often delayed. More importantly, tonic itch stimuli better represent clinical itch. A black curved screen of ca. 50 cm height was placed in front of the participant. There were three LED lights in the screen at circa 10 cm height. The middle, green LED was the fixation light, while two red LEDs, attached approximately 25° to the left and right from the middle LED, functioned as target lights. Right below the left and right LED, there was a platform on which a left and right response button, respectively, was attached.
Itch was induced by electrical stimulation, delivered by a constant current stimulator (Isolated Bipolar Constant Current Stimulator DS5, Digitimer, United Kingdom) (see also Bartels et al., 2014). According to a standardized protocol, which was previously developed with the aim of inducing substantial levels of pure itch in a large proportion of people (e.g., Bartels et al., 2014; Van Laarhoven et al., 2016), electrodes were attached to the inner side of the wrist through two surface electrodes (a disk electrode of ø 1 cm and a reference electrode of ø 2 cm, VCM Medical, Leusden, the Netherlands). Electrodes were attached unilaterally (randomized based on hand dominancy) to minimize crossover effects between itch blocks and control blocks, as itch takes considerable time to disappear after stimulus termination (e.g., Papoiu, Tey, Coghill, Wang, & Yosipovitch, 2011). According to our standard protocol (Bartels et al., 2014; Van Laarhoven et al., 2016), the itch stimuli were delivered at 50 Hz frequency, 0.1 ms pulse duration, 0.05 mA/s ramping, and at a maximum current intensity of 5.00 mA. Practice trials for familiarization with the electrocutaneous stimuli consisted of two measurements from 0.01 mA up to the intensity at which the participants indicated the moment that they experienced a sensation for the first time and the first moment they felt some itch. The intensity of the itch stimuli for the SAT was individually tailored on the basis of two measurements of the itch threshold “the first moment you feel the urge to scratch”, previously shown to induce itch levels of ≥2 on a scale from 0 (no itch) to 10 (worst itch ever experienced) in over 90% of participants (Bartels et al., 2014). To ascertain that the participants felt itch during the attention task, the average current intensity of the itch thresholds was the start intensity of the 35-s itch stimuli used before (i.e., baseline stimuli) and during the SAT. Given the continuously ramping of 0.05 mA/s, the end current intensity was the start intensity plus 1.75 mA. In the case the electrical current would exceed 5.00 mA, the stimulation started at 3.25 mA and ended at 5.00 mA. In this study, the mean start intensity was 2.11 mA (SD = 0.83). The level of experienced itch during the SAT was scored on a numerical rating scale (NRS) ranging from 0 (no itch) to 10 (worst itch ever experienced).
The SAT consisted of eight blocks of 35 s each, of which four blocks had itch stimuli (itch blocks) and four blocks were without itch stimuli (control blocks). Within each 35-s block, there were ten trials in which first the fixation light (green LED light) was turned on for 1000 ms, extinguished, and then either the left or right target (red LED light) was turned on for 200 ms. The response window for pressing a button was 1500 ms (based on Van Damme et al., 2007). Over all blocks, half of the visual targets were presented at the body side where the electrodes were attached (“congruent trials”) and half of the visual targets were presented at the opposite side (“incongruent trials”). Within a single block, the ten targets were given in random order (congruent or incongruent), either in 5/5, 4/6 or 6/4 ratio to maximally avoid the predictability of the target location. Also, the time interval after a target before the onset of the next fixation light was random and varied between 1000 and 2500 ms. E-prime randomized the order of the eight blocks per participant without restrictions (resulting in 3 participants having all itch blocks at the end and 3 participants having all itch blocks in the beginning). Participants were not aware of the number or distribution of itch and control blocks. The standard interval between blocks was 1 min, which was extended by 1 min up to a maximum of 5 min interval in the case the NRS itch exceeded 1.0 [mean interval duration = 1.4 (SD = 0.92) and 1.1 (SD = 0.40) min, during itch and control blocks, respectively].
Participants completed a battery of validated self-report questionnaires. All were administered using the online system Qualtrics (Provo, Utah, USA).
The presence of physical symptoms during the past 2 weeks was assessed by the two visual analog scales (VAS) ranging from 0 (no itch/pain) to 10 (worst itch/pain experienced) for itch and pain from the Impact of Chronic Skin Disease on Daily Life (ISDL) health status inventory (Evers et al., 2008).
Psychological distress was measured via the Hospital Anxiety and Depression Scale (HADS) (Zigmond and Snaith 1983). The Cronbach alpha was 0.63 for the subscale depression and 0.71 for the subscale anxiety.
Neuroticism was measured with the Eysenck Personality Questionnaire revised short scale (EPQ-RSS) (Sanderman et al., 1995), from which the total score of the neuroticism subscale (Cronbach alpha 0.78) was calculated.
Attentional focus on bodily sensations was measured using the Body Vigilance Scale (BVS) (Schmidt, Lerew, & Trakowski, 1997), the Body Sensations Questionnaire (BSQ)-frequency version (De Ruiter, Garssen, Rijken, & Kraaimaat, 1989; Arrindell, 1993) similarly to our previous study (Van Laarhoven et al., 2010). Additionally, due to the lack of questionnaires focusing on itch-related attention, we adjusted the Pain Vigilance and Awareness Questionnaire (Roelofs, Peters, McCracken, & Vlaeyen, 2003) for use in itch by substituting the word “pain” by “physical sensations” for all concerned items (PVAQ-A). The Cronbach alpha of the BVS and BSQ in the present study was 0.59 and 0.81, respectively. For the PVAQ-A, adjusted to physical sensations, Cronbach alpha was 0.87.
Catastrophizing about physical sensations was measured using the Pain Catastrophizing Scale (Sullivan, Bishop, & Pivik, 1995), adjusted for physical sensations by substituting the word “pain” for “physical sensations” for all concerned items. The Cronbach alpha for the adjusted pain catastrophizing scale (PCS-A) in the present study was 0.77.
Potential participants were informed about the study by written information and asked to fill in online screening questionnaires (demographics, presence of physical symptoms, EPQ-RSS, and HADS). In the case of uncertainties about eligibility based on the screening questionnaires, inclusion and exclusion criteria were additionally checked by a telephone call. Eligible participants made an appointment for participation. Participants were instructed not to take medication 12 h prior to testing and refrain from intake of alcohol and drugs 24 h before attending the experiment. Upon arrival at the test facility, participants were informed about the procedure and they were told that they were free to terminate the experiment at any time. Then all participants signed the informed consent. Participants rated their current levels of itch and pain on an NRS ranging from 0 (no itch/pain) to 10 (worst itch/pain ever experienced) and filled out the remaining questionnaires assessing individual characteristics related to attentional processing of physical sensations (PCS-A, BVS, BSQ, PVAQ-A).
To prepare for the electrical stimuli during the SAT (see also Attention tasks—Somatosensory attention task), participants held their wrist to be stimulated (randomized either dominant or non-dominant) for 3 min in a warm water bath of ca. 32 °C (Bartels et al., 2014). After attaching the electrodes to the wrist, the participants were familiarized with the practice measurements. Subsequently, the itch threshold was determined twice. Then, the baseline itch stimulus was applied for 35 s, after which the SAT began. Participants’ wrists rested on the platform of the SAT with the index fingers of both hands positioned on the left and right response button, respectively. Participants were instructed to respond as quickly as possible to the location of a lightened target LED, by pressing the button congruently to the side of the target. Before each block, participants were informed whether they would receive an itch stimulus (i.e., in an itch block) or not (i.e., in a control block). At the start of each block, the experimenter counted down from 3 to 0, to indicate the start of a block. Directly following each block, participants were asked to report the levels of itch experienced during the block on an NRS ranging from 0 (no itch) to 10 (worst itch ever experienced). After each block, there was a 1-min interval, after which the NRS was asked again. Based on this score, the interval was either extended or not and the next block began. After eight blocks of the SAT, the electrodes were removed. The modified Stroop task and the dot-probe task for itch followed, of which the order was randomized across participants. For the modified Stroop task, participants were instructed to name aloud the print color of the words displayed, as quickly and accurately as possible. The experimenter, blinded to the word category that was displayed, remained in the room and pressed a button after the participant finished naming the colors of all words of one card (to standardize the measurement of finishing a card; Van Beugen et al., 2016), which was recorded by E-prime, and registered the number of mistakes per card (Van Laarhoven et al., 2016). For the dot-probe task, the participants were first instructed how to perform the task in four practice trials with a pair of neutral pictures on the screen after which a dot appeared to which participants responded. When the task was clear to the participant, he/she was left alone in the laboratory to conduct the 40 trials with pairs of itch-related and neutral pictures. After performing all tasks, participants were asked about their expectations and experience of the tests, were given a short debriefing, and received a monetary reimbursement.
First, data of the dot-probe task, modified Stroop task, and SAT were extracted from E-prime. For the dot-probe task, RT was excluded when <150 or >1500 ms (0.2% of the RT) and when responses were incorrect (3.7% of the RT) (based on Van Damme et al., 2007). Also for the SAT, trials with RT < 150 ms (0.2% of the RT) and RT for incorrect responses (0.04% of the RT) were excluded. As the response window for the SAT was already 1500 ms, there was no additional cutoff for maximum RT. The SAT data of 34 participants were used since SAT data turned out to be unavailable or insufficient (i.e., ≤70% of adequate SAT data) for 7 participants as a result of technical problems, e.g., a broken electrode (n = 1), malfunctioning electrical stimulator and therefore lack of time (n = 2), malfunctioning response button (n = 1), cables of SAT response buttons inadequately attached to the serial response box (n = 2), or network error (n = 1). The SAT data were preprocessed using Matlab and Statistics Toolbox Release 2012b (The MathWorks, Inc., Natick, MA, USA) by calculating the mean RT per trial type (congruent and incongruent trials during both itch and control blocks) for each participant as well as the mean RT when blocks were split into two segments of 17.5 s. For each trial type within both segments, the Cronbach’s alpha was calculated.
Statistical analyses were conducted using SPSS 23.0 software (IBM SPSS Statistics for Windows, Armonk, NY, USA). Accuracy (i.e., number of mistakes made) was checked for each task, enabling removing participants making an excessive number of mistakes (i.e., >30%). No subjects had to be removed based on this criterion. Variables were checked for normal distribution and log-transformed whenever needed. Transformation was successful for the majority of the variables except for the RT of the Stroop card for itch, due to an outlier (>3 SD from the mean) and the attentional bias indices for the dot-probe task and the modified Stroop task.
For the dot-probe task, a 2 × 2 repeated measures analysis of variance (RM-ANOVA) was carried out with the presentation side of the dot (left/right) and the position of the itch picture (left/right) as within-subject variables (log-transformed), thereby taking into account potential associative mapping of emotional valence in physical space (Casasanto, 2009). For the modified Stroop task, RT values for the itch and neutral word category (within-subjects factor) were compared in an RM-ANOVA. These analyses were also performed without any outlier. For the SAT, as manipulation check an RM-ANOVA was applied comparing the NRS itch scores in the itch blocks with the control blocks. To test whether RT for congruent and incongruent trials during the itch and control blocks significantly differed, a 2 × 2 RM-ANOVA was carried out with congruency (congruent/incongruent; as opposed to the side of the attached electrodes) and block type (itch/control blocks) as within-subject factors. The main effects of congruency and block type were calculated, as well as the congruency × block type interaction. In addition, to explore the course of attention over time, a 2 × 2 × 2 RM-ANOVA was then conducted, with log-transformed variables, using three factors, i.e., congruency (congruent/incongruent), block type (itch/control blocks) and time (first half/second half of the blocks). The main effects of time and the congruency × block type × time interaction were calculated.
For all the RM-ANOVAs conducted (within-subjects design), a generalized eta squared was calculated (Lakens, 2013). Post hoc analyses were carried out by performing the main analyses for the three behavioral attention tasks while including participant’s sex (centered) as covariate. In additional post hoc analyses, the side of itch stimulation during the SAT (centered) was included as covariate in the main analyses for the SAT and the dot-probe task (performed after the SAT). The split-half reliability of the dot-probe task and SAT was investigated by calculating the Spearman–Brown coefficient, for each trial type separately.
Finally, attentional bias (AB) indices were calculated for the three tasks. For the modified Stroop task, the RT for the neutral words was subtracted from the mean RT for the itch words. For the dot-probe task, the mean RT of the congruent trials was subtracted from the mean RT of the incongruent trials while taking into account the display side of the itch picture (((RTIncongruentleft − RTcongruentleft) + (RTIncongruentright − RTcongruentright))/2) (Schoth et al., 2012). For the SAT, the mean RT of the incongruent trials was subtracted from the mean RT of the congruent trials during the itch blocks (RTincongruentitchblock − RTcongruentitchblock). A positive AB index for all these tasks indicated that attention was biased toward itch. Subsequently, correlation coefficients were calculated between total scores of the self-report questionnaires measuring neuroticism (EPQ-RSS), self-reported attention (BVS, BSQ-f, PVAQ-A), and catastrophizing (PCS-A) and the AB indices of the SAT (Pearson correlation coefficients) and the dot-probe task and modified Stroop task (Spearman correlation coefficients).