Perceptual simultaneity between nociceptive and visual stimuli depends on their spatial congruence.

To protect our body against physical threats, it is important to integrate the somatic and extra-somatic inputs generated by these stimuli. Temporal synchrony is an important parameter determining multisensory interaction, and the time taken by a given sensory input to reach the brain depends on the length and conduction velocity of the specific pathways through which it is transmitted. Nociceptive inputs are transmitted through very slow conducting unmyelinated C and thinly myelinated Aδ nociceptive fibers. It was previously shown that to perceive a visual stimulus and a thermo-nociceptive stimulus applied on the hand as coinciding in time, the nociceptive stimulus must precede the visual one by 76 ms for nociceptive inputs conveyed by Aδ fibers and 577 ms for inputs conveyed by C fibers. Since spatial proximity is also hypothesized to contribute to multisensory interaction, the present study investigated the effect of spatial congruence between visual and nociceptive stimuli. Participants judged the temporal order of visual and nociceptive stimuli, with the visual stimuli flashed either next to the stimulated hand or next to the opposite unstimulated hand, and with nociceptive stimuli evoking responses mediated by either Aδ or C fibers. The amount of time by which the nociceptive stimulus had to precede the visual stimulus for them to be perceived as appearing concomitantly was smaller when the visual stimulus occurred near the hand receiving the nociceptive stimulus as compared to when it occurred near the contralateral hand. This illustrates the challenge for the brain to process the synchrony between nociceptive and non-nociceptive stimuli to enable their efficient interaction to optimize defensive reaction against physical dangers.

No Evidence for an Effect of the Distance Between the Hands on Tactile Temporal Order Judgments.

Localizing somatosensory stimuli is an important process, as it allows us to spatially guide our actions toward the object entering in contact with the body. Accordingly, the positions of tactile inputs are coded according to both somatotopic and spatiotopic representations, the latter one considering the position of the stimulated limbs in external space. The spatiotopic representation has often been evidenced by means of temporal order judgment (TOJ) tasks. Participants' judgments about the order of appearance of two successive somatosensory stimuli are less accurate when the hands are crossed over the body midline than uncrossed but also when participants' hands are placed close together when compared with farther away. Moreover, these postural effects might depend on the vision of the stimulated limbs. The aim of this study was to test the influence of seeing the hands, on the modulation of tactile TOJ by the spatial distance between the stimulated limbs. The results showed no influence of the distance between the stimulated hands on TOJ performance and prevent us from concluding whether vision of the hands affects TOJ performance, or whether these variables interact. The reliability of such distance effect to investigate the spatial representations of tactile inputs is questioned.

Fast periodic visual stimulation to study tool-selective processing in the human brain.

Because tools are manipulated for the purpose of action, they are often considered to be a specific object category that associates perceptual and motor properties. Their neural processing has been studied extensively by comparing the cortical activity elicited by the separate presentation of tool and non-tool objects, assuming that observed differences are solely due to activity selective for processing tools. Here, using a fast periodic visual stimulation (FPVS) paradigm, we isolated EEG activity selectively related to the processing of tool objects embedded in a stream of non-tool objects. Participants saw a continuous sequence of tool and non-tool images at a 3.7 Hz presentation rate, arranged as a repeating pattern of four non-tool images followed by one tool image. We expected the stimulation to generate an EEG response at the frequency of image presentation (3.7 Hz) and its harmonics, reflecting activity common to the processing of tool and non-tool images. Most importantly, if tool and non-tool images evoked different neural responses, we expected this differential activity to generate an additional response at the frequency of tool images (3.7 Hz/5 = 0.74 Hz). To ensure that this response was not due to unaccounted for systematic differences in low-level visual features, we also tested a phase-scrambled version of the sequence. The periodic insertion of tool stimuli within a stream of non-tool stimuli elicited a significant EEG response at the tool-selective frequency and its harmonics. This response was reduced when the images were phase-scrambled. We conclude that FPVS is a promising technique to selectively measure tool-related activity.

Investigating the spatial characteristics of the crossmodal interaction between nociception and vision using gaze direction.

The present study investigated the influence of nociceptive stimuli on visual stimuli processing according to the relative spatial congruence between the two stimuli of different sensory modalities. Participants performed temporal order judgments on pairs of visual stimuli, one presented near the hand on which nociceptive stimuli were occasionally applied, the other one either to its left or to its right. The visual hemifield in which the stimulated hand and the near visual stimulus appeared was manipulated by changing gaze direction. The stimulated hemibody and the stimulated visual hemifield were therefore either congruent or incongruent, in terms of anatomical locations. Despite the changes in anatomical congruence, judgments were always biased in favor of the visual stimuli presented near the stimulated hand. This indicates that nociceptive-visual interaction may rely on a realignment of the respective initial anatomical representations of the somatic and retinotopic spaces toward an integrated, multimodal representation of external space.

Does Body Perception Shape Visuospatial Perception?

How we perceive our body is shaped by sensory experiences with our surrounding environment, as witnessed by poor performance in tasks during which participants judge with their hands crossed the temporal order between two somatosensory stimuli, one applied on each hand. This suggests that somatosensory stimuli are not only processed according to a somatotopic representation but also a spatiotopic representation of the body. We investigated whether the perception of stimuli occurring in external space, such as visual stimuli, can also be influenced by the body posture and somatosensory stimuli. Participants performed temporal order judgements on pairs of visual stimuli, one in each side of space, with their hands uncrossed or crossed. In Experiment 1, participants' hands were placed either near or far from the visual stimuli. In Experiment 2, the visual stimuli were preceded, either by 60 ms or 360 ms, by tactile stimuli applied on the hands placed near the visual stimuli. Manipulating the time interval was intended to activate either a somatotopic or a spatiotopic representation of somatic inputs. We did not obtain any evidence for an influence of body posture on visual temporal order judgment, suggesting that body perception is less relevant for processing extrabody stimuli than the reverse.

Overlap of movement planning and movement execution reduces reaction time.

Motor planning is the process of preparing the appropriate motor commands in order to achieve a goal. This process has largely been thought to occur before movement onset and traditionally has been associated with reaction time. However, in a virtual line bisection task we observed an overlap between movement planning and execution. In this task performed with a robotic manipulandum, we observed that participants (n = 30) made straight movements when the line was in front of them (near target) but often made curved movements when the same target was moved sideways (far target, which had the same orientation) in such a way that they crossed the line perpendicular to its orientation. Unexpectedly, movements to the far targets had shorter reaction times than movements to the near targets (mean difference: 32 ms, SE: 5 ms, max: 104 ms). In addition, the curvature of the movement modulated reaction time. A larger increase in movement curvature from the near to the far target was associated with a larger reduction in reaction time. These highly curved movements started with a transport phase during which accuracy demands were not taken into account. We conclude that an accuracy demand imposes a reaction time penalty if processed before movement onset. This penalty is reduced if the start of the movement consists of a transport phase and if the movement plan can be refined with respect to accuracy demands later in the movement, hence demonstrating an overlap between movement planning and execution. NEW & NOTEWORTHY: In the planning of a movement, the brain has the opportunity to delay the incorporation of accuracy requirements of the motor plan in order to reduce the reaction time by up to 100 ms (average: 32 ms). Such shortening of reaction time is observed here when the first phase of the movement consists of a transport phase. This forces us to reconsider the hypothesis that motor plans are fully defined before movement onset.

Orienting attention in visual space by nociceptive stimuli: investigation with a temporal order judgment task based on the adaptive PSI method.

Despite their high relevance for defending the integrity of the body, crossmodal links between nociception, the neural system specifically coding potentially painful information, and vision are still poorly studied, especially the effects of nociception on visual perception. This study investigated if, and in which time window, a nociceptive stimulus can attract attention to its location on the body, independently of voluntary control, to facilitate the processing of visual stimuli occurring in the same side of space as the limb on which the visual stimulus was applied. In a temporal order judgment task based on an adaptive procedure, participants judged which of two visual stimuli, one presented next to either hand in either side of space, had been perceived first. Each pair of visual stimuli was preceded (by 200, 400, or 600 ms) by a nociceptive stimulus applied either unilaterally on one single hand, or bilaterally, on both hands simultaneously. Results show that, as compared to the bilateral condition, participants' judgments were biased to the advantage of the visual stimuli that occurred in the same side of space as the hand on which a unilateral, nociceptive stimulus was applied. This effect was present in a time window ranging from 200 to 600 ms, but importantly, biases increased with decreasing time interval. These results suggest that nociceptive stimuli can affect the perceptual processing of spatially congruent visual inputs.

Using temporal order judgments to investigate attention bias toward pain and threat-related information. Methodological and theoretical issues.

Recently, Vanden Bulcke, Crombez, Durnez, and Van Damme (2015) investigated whether the attentional prioritization of a specific location due to the anticipation of pain is modality specific or multisensory. They used a temporal order judgment task in which participants judged the order of either two tactile or two visual stimuli, one presented on each hand. Additionally, participants either expected the occurrence of a painful stimulus on one hand or the absence of any pain. Results showed that participants' judgments were biased to the advantage of the stimuli, tactile or visual, presented at the location where pain was expected. The authors concluded that the anticipation of pain leads to a multisensory prioritization of information presented at the threatened spatial location. Here, we would like to question their conclusion in terms of a genuine attentional modulation of multisensory nature, based on methodological and theoretical grounds.

EEG frequency tagging to dissociate the cortical responses to nociceptive and nonnociceptive stimuli.

Whether the cortical processing of nociceptive input relies on the activity of nociceptive-specific neurons or whether it relies on the activity of neurons also involved in processing nonnociceptive sensory input remains a matter of debate. Here, we combined EEG "frequency tagging" of steady-state evoked potentials (SS-EPs) with an intermodal selective attention paradigm to test whether the cortical processing of nociceptive input relies on nociceptive-specific neuronal populations that can be selectively modulated by top-down attention. Trains of nociceptive and vibrotactile stimuli (Experiment 1) and trains of nociceptive and visual stimuli (Experiment 2) were applied concomitantly to the same hand, thus eliciting nociceptive, vibrotactile, and visual SS-EPs. In each experiment, a target detection task was used to focus attention toward one of the two concurrent streams of sensory input. We found that selectively attending to nociceptive or vibrotactile somatosensory input indistinctly enhances the magnitude of nociceptive and vibrotactile SS-EPs, whereas selectively attending to nociceptive or visual input independently enhances the magnitude of the SS-EP elicited by the attended sensory input. This differential effect indicates that the processing of nociceptive input involves neuronal populations also involved in the processing of touch, but distinct from the neuronal populations involved in vision.

Top-down attention does not modulate mechanical hypersensitivity consecutive to central sensitization: insights from an experimental analysis.

ABSTRACT: According to the neurocognitive model of attention to pain, when the attentional resources invested in a task unrelated to pain are high, limited cognitive resources can be directed toward the pain. This is supported by experimental studies showing that diverting people's attention away from acute pain leads to experiencing less pain. Theoretical work has suggested that this phenomenon may present a top-down modulatory mechanism for persistent pain as well. However, conclusive empirical evidence is lacking. To fill this gap, we used a preregistered, double-blind, between-subject study design to investigate whether performing a tailored, demanding, and engaging working memory task unrelated to pain (difficult) vs a task that requires less mental effort to be performed (easy), could lead to lower development of secondary hypersensitivity-a hallmark of central sensitization. Eighty-five healthy volunteers, randomly assigned to one of the 2 conditions, performed a visual task with a different cognitive load (difficult vs easy), while secondary hypersensitivity was induced on their nondominant forearm using high-frequency stimulation. To assess the development of secondary hypersensitivity, sensitivity to mechanical stimuli was measured 3 times: T0, for baseline and 20 (T1) and 40 (T2) minutes after the procedure. We did not observe any significant difference in the development of secondary hypersensitivity between the 2 groups, neither in terms of the intensity of mechanical sensitivity nor its spatial extent. Our results suggest that a top-down modulation through attention might not be sufficient to affect pain sensitization and the development of secondary hypersensitivity.

Biological and psychological early prognostic factors in complex regional pain syndrome: A systematic review.

BACKGROUND AND OBJECTIVE: Several risk factors for the onset of CRPS have been found, but evidence for prognostic factors associated with the progression of this condition remains sparse. However, the detection and management of these factors are necessary to design secondary prevention strategies. The objective of this systematic review was to identify prognostic factors in adult individuals with early CRPS. DATABASE AND DATA TREATMENT: PubMed, Embase, PsycINFO, Cochrane Library and Scopus, were published between January 1990 and November 2021. Two independent investigators selected cross-sectional and longitudinal studies looking at early (<12 weeks from onset) prognostic factors for pain, CRPS severity score, disability, return to work, or quality of life. The quality in prognostic studies (QUIPS) tool was used to assess the risk of bias. A qualitative meta-synthesis was performed. RESULTS: Out of 4652 different articles, six studies met the inclusion criteria. We identified 21 early factors associated with a poorer prognosis in type I CRPS. We found moderate evidence to support six of them: higher pain intensity, self-rated disability, anxiety, pain-related fear, being a female and high-energy triggering event. Only two studies had an overall low risk of bias. CONCLUSIONS: This study showed an important lack of information on early prognostic factors in CRPS. Only one article investigated the link with psychological characteristics. There is a crucial need for larger studies, with a well-defined population using validated measures. SIGNIFICANCE: This systematic review highlights the lack of knowledge about early prognostic factors in CRPS. A few putative prognostic factors were identified. Most of the moderate evidence is related to a single cohort. Future research is required to find out which patients are vulnerable to chronification.

Characterizing biased visuospatial perception in complex regional pain syndrome.

BACKGROUND: Patients suffering from complex regional pain syndrome (CRPS) are increasingly shown to be affected by cognitive difficulties. While these cognitive symptoms were initially described as limited to the perception, representation and use of the body, that is, the somatic space, they were recently shown to also extend to the perception of extra-somatic space. CRPS patients seem indeed to pay less attention to visual stimuli occurring in the same side of space as their affected limb and especially those occurring close to that limb. The aim of the present study was to more precisely characterize these visuospatial biases, by investigating whether they may be dependent on the visually perceived proximity between the visual stimuli and the affected limb. METHODS: Upper-limb CRPS patients and matched control participants performed temporal order judgements on visual stimuli, one presented in either side of space, while they could either see their hands near the visual stimuli or not. RESULTS: Visuospatial biases were not modulated by the availability of visual feedback about the hands. However, secondary analyses revealed that these biases depended on the type of rehabilitation program that the patients followed: whereas patients who did not follow any specific program presented significant biases to the detriment of visual stimuli in the affected side of space, patients who did follow a CRPS-specialized program did not. CONCLUSIONS: Patients' cognitive strategies will be important to consider when studying inter-individual differences in the cognitive symptomatology and associated cognitive-based rehabilitation procedures in CRPS. SIGNIFICANCE: The existence of biases in visuospatial perception in Complex Regional Pain Syndrome has been reported but not always systematically replicated. We show that these biases might depend on the type of general rehabilitation program that the patients follow. Patients' individual cognitive strategies will be important to consider when studying the cognitive symptomatology of CRPS.

Nociceptive steady-state evoked potentials elicited by rapid periodic thermal stimulation of cutaneous nociceptors.

The periodic presentation of a sensory stimulus induces, at certain frequencies of stimulation, a sustained electroencephalographic response known as steady-state evoked potential (SS-EP). In the somatosensory, visual, and auditory modalities, SS-EPs are considered to constitute an electrophysiological correlate of cortical sensory networks resonating at the frequency of stimulation. In the present study, we describe and characterize, for the first time, SS-EPs elicited by the selective activation of skin nociceptors in humans. The stimulation consisted of 2.3-s-long trains of 16 identical infrared laser pulses (frequency, 7 Hz), applied to the dorsum of the left and right hand and foot. Two different stimulation energies were used. The low energy activated only C-nociceptors, whereas the high energy activated both Aδ- and C-nociceptors. Innocuous electrical stimulation of large-diameter Aß-fibers involved in the perception of touch and vibration was used as control. The high-energy nociceptive stimulus elicited a consistent SS-EP, related to the activation of Aδ-nociceptors. Regardless of stimulus location, the scalp topography of this response was maximal at the vertex. This was noticeably different from the scalp topography of the SS-EPs elicited by innocuous vibrotactile stimulation, which displayed a clear maximum over the parietal region contralateral to the stimulated side. Therefore, we hypothesize that the SS-EPs elicited by the rapid periodic thermal activation of nociceptors may reflect the activation of a network that is preferentially involved in processing nociceptive input and may thus provide some important insight into the cortical processes generating painful percepts.

Steady-state evoked potentials to tag specific components of nociceptive cortical processing.

Studies have shown that the periodic repetition of a stimulus induces, at certain stimulation frequencies, a sustained electro-cortical response of corresponding frequency, referred to as steady-state evoked potential (SSEP). Using infrared laser stimulation, we recently showed that SSEPs can be used to explore nociceptive cortical processing. Here, we implemented a novel approach to elicit such responses, using a periodic intra-epidermal electrical stimulation of cutaneous Aδ-nociceptors (Aδ-SSEPs). Using a wide range of frequencies (3-43 Hz), we compared the scalp topographies and temporal dynamics of these Aδ-SSEPs to the Aß-SSEPs elicited by non-nociceptive transcutaneous electrical stimulation, as well as to the transient ERPs elicited by the onsets of the 10-s stimulation trains, applied to the left and right hand. At 3 Hz, we found that the topographies of Aß- and Aδ-SSEPs were both maximal at the scalp vertex, and resembled closely that of the late P2 wave of transient ERPs, suggesting activity originating from the same neuronal populations. The responses also showed marked habituation, suggesting that they were mainly related to unspecific, attention-related processes. In contrast, at frequencies >3 Hz, the topographies of Aß- and Aδ-SSEPs were markedly different. Aß-SSEPs were maximal over the contralateral parietal region, whereas Aδ-SSEPs were maximal over midline frontal regions, thus indicating an entrainment of distinct neuronal populations. Furthermore, the responses showed no habituation, suggesting more obligatory and specific stages of sensory processing. Taken together, our results indicate that Aß- and Aδ-SSEPs offer a unique opportunity to study the cortical representation of nociception and touch.

No evidence for an effect of selective spatial attention on the development of secondary hyperalgesia: A replication study.

Central sensitization refers to the increased responsiveness of nociceptive neurons in the central nervous system after repeated or sustained peripheral nociceptor activation. It is hypothesized to play a key role in the development of chronic pain. A hallmark of central sensitization is an increased sensitivity to noxious mechanical stimuli extending beyond the injured location, known as secondary hyperalgesia. For its ability to modulate the transmission and the processing of nociceptive inputs, attention could constitute a promising target to prevent central sensitization and the development of chronic pain. It was recently shown that the experimental induction of central sensitization at both forearms of healthy volunteers using bilateral high-frequency electrocutaneous stimulation (HFS), can be modulated by encouraging participants to selectively focus their attention to one arm, to the detriment of the other arm, resulting in a greater secondary hyperalgesia on the attended arm as compared to the unattended one. Given the potential value of the question being addressed, we conducted a preregistered replication study in a well-powered independent sample to assess the robustness of the effect, i.e., the modulatory role of spatial attention on the induction of central sensitization. This hypothesis was tested using a double-blind, within-subject design. Sixty-seven healthy volunteers performed a task that required focusing attention toward one forearm to discriminate innocuous vibrotactile stimuli while HFS was applied on both forearms simultaneously. Our results showed a significant increase in mechanical sensitivity directly and 20 min after HFS. However, in contrast to the previous study, we did not find a significant difference in the development of secondary hyperalgesia between the attended vs. unattended arms. Our results question whether spatial selective attention affects the development of secondary hyperalgesia. Alternatively, the non-replication could be because the bottom-up capture of attention caused by the HFS-mediated sensation was too strong in comparison to the top-down modulation exerted by the attentional task. In other words, the task was not engaging enough and the HFS pulses, including those on the unattended arm, were too salient to allow a selective focus on one arm and modulate nociceptive processing.

The role of spatial attention in attentional control over pain: an experimental investigation.

Distraction is a common method of pain control that is often found to be effective. However, it is still largely unexplored which components of distraction are responsible for its effects. This study investigated the role of the spatial location of task-relevant stimuli in the effectiveness of distraction. Two experiments were performed in which the spatial location of visual stimuli during nociceptive input was manipulated. In a first experiment, we tested whether the reaction to nociceptive information is slower when visual stimuli are presented at a different spatial location than at the same spatial location. In a second experiment, we examined whether the manipulation of spatial location affects the experience of pain. Overall, results indicated that directing attention away from the pain location results in a slower response to painful stimuli and a reduction in pain. It may be concluded that the analgesic effect of distraction is at least partly the result of the spatial location of the distracting information.

Measuring the sensitivity of tactile temporal order judgments in sighted and blind participants using the adaptive psi method.

Spatial locations of somatosensory stimuli are coded according to somatotopic (anatomical distribution of the sensory receptors on the skin surface) and spatiotopic (position of the body parts in external space) reference frames. This was mostly evidenced by means of temporal order judgment (TOJ) tasks in which participants discriminate the temporal order of two tactile stimuli, one applied on each hand. Because crossing the hands generates a conflict between anatomical and spatial responses, TOJ performance is decreased in such posture, except for congenitally blind people, suggesting a role of visual experience in somatosensory perception. In previous TOJ studies, stimuli were generally presented using the method of constant stimuli-that is, the repetition of a predefined sample of stimulus-onset asynchronies (SOA) separating the two stimuli. This method has the disadvantage that a large number of trials is needed to obtain reliable data when aiming at dissociating performances of groups characterized by different cognitive abilities. Indeed, each SOA among a large variety of different SOAs should be presented the same number of times irrespective of the participant's performance. This study aimed to replicate previous tactile TOJ data in sighted and blind participants with the adaptive psi method in order to validate a novel method that adapts the presented SOA according to the participant's performance. This allows to precisely estimate the temporal sensitivity of each participant while the presented stimuli are adapted to the participant's individual discrimination threshold. We successfully replicated previous findings in both sighted and blind participants, corroborating previous data using a more suitable psychophysical tool.

Visuomotor impairments in complex regional pain syndrome during pointing tasks.

ABSTRACT: Complex regional pain syndrome (CRPS) is thought to be characterized by cognitive deficits affecting patients' ability to represent, perceive, and use their affected limb as well as its surrounding space. This has been tested, among others, by straight-ahead tasks testing oneself's egocentric representation, but such experiments lead to inconsistent results. Because spatial cognitive abilities encompass various processes, we completed such evaluations by varying the sensory inputs used to perform the task. Complex regional pain syndrome and matched control participants were asked to assess their own body midline either visually (ie, by means of a moving visual cue) or manually (ie, by straight-ahead pointing with one of their upper limbs) and to reach and point to visual targets at different spatial locations. Although the 2 former tasks only required one single sensory input to be performed (ie, either visual or proprioceptive), the latter task was based on the ability to coordinate perception of the position of one's own limb with visuospatial perception. However, in this latter task, limb position could only be estimated by proprioception, as vision of the limb was prevented. Whereas in the 2 former tasks CRPS participants' performance was not different from that of controls, they made significantly more deviations errors during the visuospatial task, regardless of the limb used to point or the direction of pointing. Results suggest that CRPS patients are not specifically characterized by difficulties in representing their body but, more particularly, in integrating somatic information (ie, proprioception) during visually guided movements of the limb.