The effect of unpredictability on the perception of pain: a systematic review and meta-analysis.

ABSTRACT: Despite being widely assumed, the worsening impact of unpredictability on pain perception remains unclear because of conflicting empirical evidence, and a lack of systematic integration of past research findings. To fill this gap, we conducted a systematic review and meta-analysis focusing on the effect of unpredictability on pain perception. We also conducted meta-regression analyses to examine the moderating effect of several moderators associated with pain and unpredictability: stimulus duration, calibrated stimulus pain intensity, pain intensity expectation, controllability, anticipation delay, state and trait negative affectivity, sex/gender and age of the participants, type of unpredictability (intensity, onset, duration, location), and method of pain induction (thermal, electrical, mechanical pressure, mechanical distention). We included 73 experimental studies with adult volunteers manipulating the (un)predictability of painful stimuli and measuring perceived pain intensity and pain unpleasantness in predictable and unpredictable contexts. Because there are insufficient studies with patients, we focused on healthy volunteers. Our results did not reveal any effect of unpredictability on pain perception. However, several significant moderators were found, ie, targeted stimulus pain intensity, expected pain intensity, and state negative affectivity. Trait negative affectivity and uncontrollability showed no significant effect, presumably because of the low number of included studies. Thus, further investigation is necessary to clearly determine their role in unpredictable pain perception.

Expectations underlie the effects of unpredictable pain: a behavioral and electroencephalogram study.

ABSTRACT: Previous studies on the potential effects of unpredictability on pain perception and its neural correlates yielded divergent results. This study examined whether this may be explained by differences in acquired expectations. We presented 41 healthy volunteers with laser heat stimuli of different intensities. The stimuli were preceded either by predictable low, medium, or high cues or by unpredictable low-medium, medium-high, or low-high cues. We recorded self-reports of pain intensity and unpleasantness and laser-evoked potentials (LEPs). Furthermore, we investigated whether dynamic expectations that evolved throughout the experiment based on past trials were better predictors of pain ratings than fixed (nonevolving) expectations. Our results replicate previous findings that unpredictable pain is higher than predictable pain for low-intensity stimuli but lower for high-intensity stimuli. Moreover, we observed higher ratings for the medium-high unpredictable condition than the medium-low unpredictable condition, in line with an effect of expectation. We found significant interactions (N1, N2) for the LEP components between intensity and unpredictability. However, the few significant differences in LEP peak amplitudes between cue conditions did not survive correction for multiple testing. In line with predictive coding perspectives, pain ratings were best predicted by dynamic expectations. Surprisingly, expectations of reduced precision (increased variance) were associated with lower pain ratings. Our findings provide strong evidence that (dynamic) expectations contribute to the opposing effects of unpredictability on pain perception; therefore, we highlight the importance of controlling for them in pain unpredictability manipulations. We also suggest to conceptualize pain expectations more often as dynamic constructs incorporating previous experiences.

Modulation of attention to pain by goal-directed action: a somatosensory evoked potentials approach.

Background: Attentional processes are modulated by current goal pursuit. While pursuing salient cognitive goals, individuals prioritize goal-related information and suppress goal-irrelevant ones. This occurs in the context of pain too, where nonpain cognitive goal pursuit was found to have inhibitory effects on pain-related attention. Crucially, how pursuing nonpain motor goals affects pain-related somatosensory attention is still unknown. The aim of this study was to investigate whether nonpain motor goal pursuit would attenuate pain-related somatosensory attention. Methods: Healthy volunteers (N = 45) performed a robotic arm conditioning task where movements were paired with conflicting (pain and reward), threatening (only pain) or neutral (no pain and no reward) outcomes. To increase the motivational value of pursuing the nonpain motor goal, in the conflicting condition participants could receive a reward for a good motor performance. To examine somatosensory attention during movement, somatosensory evoked potentials (SEPs; N120 and P200) were obtained in response to innocuous tactile stimuli administered on a pain-relevant or pain-irrelevant body location. We expected that the threat of pain would enhance somatosensory attention. Furthermore, we expected that the possibility of getting a reward would inhibit this effect, due to pain-reward interactions. Results: Against our predictions, the amplitude of the N120 did not differ across movement types and locations. Furthermore, the P200 component showed significantly larger SEPs for conflicting and threat movements compared to neutral, suggesting that the threat of pain increased somatosensory attention. However, this effect was not modulated by nonpain motor goal pursuit, as reflected by the lack of modulation of the N120 and P200 in the conflicting condition as compared to the threat condition. This study corroborates the idea that pain-related somatosensory attention is enhanced by threat of pain, even when participants were motivated to move to obtain a reward.

The impact of the social context on the development of secondary hyperalgesia: an experimental study.

ABSTRACT: Social support has been shown to reduce pain ratings and physiological responses to acute pain stimuli. Furthermore, this relationship is moderated by adult attachment styles. However, these effects have not been characterized in experimentally induced symptoms of chronic pain, such as secondary hyperalgesia (SH) which is characterized by an increased sensitivity of the skin surrounding an injury. We aimed to examine whether social support by handholding from a romantic partner can attenuate the development of experimentally induced SH. Thirty-seven women, along with their partners, participated in 2 experimental sessions 1 week apart. In both sessions, SH was induced using an electrical stimulation protocol. In the support condition, the partner was seated across from the participant holding the participant's hand during the electrical stimulation, whereas in the alone condition, the participant went through the stimulation alone. Heart rate variability was measured for both the participant as well as the partner before, during, and after the stimulation. We found that the width of the area of hyperalgesia was significantly smaller in the support condition. Attachment styles did not moderate this effect of social support on the area width. Increasing attachment avoidance was associated with both a smaller width of hyperalgesia and a smaller increase in the sensitivity on the stimulated arm. For the first time, we show that social support can attenuate the development of secondary hyperalgesia and that attachment avoidance may be associated with an attenuated development of secondary hyperalgesia.

No Evidence That Working Memory Modulates the Plasticity of the Nociceptive System, as Measured by Secondary Mechanical Hypersensitivity.

The effect of cognition on the plasticity of the nociceptive system remains controversial. In this study, we examined whether working memory can buffer against the development of secondary hypersensitivity. Thirty-five healthy women participated in 3 experimental conditions. In each condition, they underwent electrical stimulation of the skin for 2 minutes (middle-frequency electrical stimulation [MFS]), which induces secondary hypersensitivity. During MFS, participants executed either an individually tailored and rewarded n-back task (working memory condition), a rewarded reaction-time task (non-working memory condition), or no task at all (control condition). Before and after MFS, participants rated the self-reported intensity and unpleasantness of mechanical pinprick stimuli. Fear of MFS was also assessed. Heart rate variability was measured to examine potential differences between the 3 conditions and steady-state evoked potentials to the electrical stimulation were recorded to investigate differences in cortical responses. We report no significant difference in hypersensitivity between the 3 conditions. Moreover, engaging in the cognitive tasks did not affect the heart rate variability or the steady-state evoked potentials. Interestingly, higher fear of MFS predicted greater hypersensitivity. In conclusion, we found no evidence that working memory affects the plasticity of the nociceptive system, yet pain-related fear plays a role. PERSPECTIVE: This study shows that the execution of a cognitive task, irrespective of cognitive load or working memory, does not significantly modulate the development of secondary hypersensitivity, heart rate variability, or steady-state evoked potentials. However, higher pain-related fear seems to contribute to greater hypersensitivity.

The effect of high versus low cognitive load on the development of nociceptive hypersensitivity: The roles of sympathetic arousal, sex and pain-related fear.

BACKGROUND: According to limited-capacity theories of attention, less attentional resources remain available when engaging in a high- versus a low-demanding cognitive task. This may reduce the perceived intensity and the evoked cortical responses of concomitant nociceptive stimuli. Whether and how the competition for limited attentional resources between a cognitive task and pain impacts the development of long-lasting hypersensitivity is unclear. METHODS: Eighty-four healthy participants were randomized into a low or high cognitive load group. Low-frequency electrical stimulation (LFS) of the skin was used to induce secondary hypersensitivity. We hypothesized that performing the high-load task during LFS would reduce the development of hypersensitivity. We examined whether painfulness, nonpain-related sympathetic arousal, or sex related to hypersensitivity, by assessing intensity and unpleasantness of mechanical pinprick stimulation. During task execution, we recorded steady-state evoked potentials evoked by LFS and skin conductance level for sympathetic arousal. Afterwards, participants reported task difficulty and LFS-related fear. For the primary outcomes, we used mixed analysis of variances. RESULTS: The results confirmed the difference in cognitive load. Although LFS successfully induced hypersensitivity, the high-load task did not reduce its development. Next, the steady-state evoked potentials did not differ between groups. Hypersensitivity correlated positively with pain-related fear and negatively with skin conductance level before LFS, despite the lack of group differences in skin conductance level. We did not find any sex differences in hypersensitivity. CONCLUSIONS: These results do not confirm that high cognitive load or sex modulate hypersensitivity, but show associations with pain-related fear and non-pain-related sympathetic arousal. SIGNIFICANCE: Previous research has mainly focused on cognitive load effects on the perception of acute painful stimuli. Yet this study extends our understanding by investigating cognitive load effects on the development of long-lasting secondary hypersensitivity, a common aspect in numerous persistent pain conditions. As cognitive tasks are presented during a painful procedure inducing secondary hypersensitivity, we test the long-lasting effects of cognitive load. Additionally, we used psychophysiological measurements to explored potential underlying mechanisms involving limited attentional resources and sympathetic arousal.

The Effect of Observing High or Low Pain on the Development of Central Sensitization.

It is unknown whether watching other people in high pain increases mechanical hypersensitivity induced by pain. We applied high-frequency electrical stimulation (HFS) on the skin of healthy volunteers to induce pinprick mechanical hypersensitivity. Before HFS participants were randomly allocated to 2 groups: in the low pain group, which was the control condition, they watched a model expressing and reporting lower pain scores, in the high pain group the model expressed and reported higher scores. The 2 videos were selected on the basis of a pilot/observational study that had been conducted before. We tested the differences in perceived intensity of the HFS procedure, in the development of hypersensitivity and the role of fear and empathy. The high pain group reported on average higher pain ratings during HFS. The perceived intensity of hypersensitivity, but not the unpleasantness or the length of the area was higher in the high pain group. Our results suggest that watching a person expressing more pain during HFS increases one's own pain ratings during HFS and may weakly facilitate the development of secondary mechanical hypersensitivity, although this latter result needs replication. PERSPECTIVE: Observing a person in high pain can influence the perceived pain intensity of a procedure leading to secondary mechanical hypersensitivity, and has a weak effect on hypersensitivity itself. The role of fear remains to be elucidated.

The effect of unpredictability on the perception of breathlessness: a narrative review.

Breathlessness is an aversive bodily sensation impacting millions of people worldwide. It is often highly detrimental for patients and can lead to profound distress and suffering. Notably, unpredictable breathlessness episodes are often reported as being more severe and unpleasant than predictable episodes, but the underlying reasons have not yet been firmly established in experimental studies. This review aimed to summarize the available empirical evidence about the perception of unpredictable breathlessness in the adult population. Specifically, we examined: (1) effects of unpredictable relative to predictable episodes of breathlessness on their perceived intensity and unpleasantness, (2) potentially associated neural and psychophysiological correlates, (3) potentially related factors such as state and trait negative affectivity. Nine studies were identified and integrated in this review, all of them conducted in healthy adult participants. The main finding across studies suggested that unpredictable compared to predictable, breathlessness elicits more frequently states of high fear and distress, which may contribute to amplify the perception of unpredictable breathlessness, especially its unpleasantness. Trait negative affectivity did not seem to directly affect the perception of unpredictable breathlessness. However, it seemed to reinforce state fear and anxiety, hence possible indirect modulatory pathways through these affective states. Studies investigating neural correlates of breathlessness perception and psychophysiological measures did not show clear associations with unpredictability. We discuss the implication of these results for future research and clinical applications, which necessitate further investigations, especially in clinical samples suffering from breathlessness.

Error Processing and Pain: A New Perspective.

Errors put organisms in danger. Upon error commission, error processing allows for the updating of behavior that proved ineffective in light of the current context and goals, and for the activation of behavioral defensive systems. Pain, on the other hand, signals actual or potential danger to one's physical integrity and, likewise, motivates protective behavior. These parallels suggest the existence of cross-links between pain and error processing but so far their relationship remains elusive. In this review, we tie together findings from the field of pain research with those from electroencephalography studies on error processing [specifically the Error Related Negativity (ERN) and Positivity (Pe)]. More precisely, we discuss 3 plausible associations: Firstly, pain may enhance error processing as it increases error salience. Secondly, persons fearful of pain may be particularly vigilant towards painful errors and thus show a stronger neural response to them. Thirdly, the ERN as a component of the neural response to error commission is considered an endophenotype of threat sensitivity. As high sensitivity to pain threats is known to incite avoidance behavior, this raises the intriguing possibility that neural signatures of error processing predict pain-related protective behaviors, such as avoidance. We propose an integration of these findings into a common framework to inspire future research. PERSPECTIVE: Inspired by research in anxiety disorders, we discuss the potential bi-directional relationships between error processing and pain, and identify future directions to examine the neural and psychological processes involved in acute and chronic pain and respective avoidance behavior.

The effects of unpredictability and negative affect on perception and neural gating in different interoceptive modalities.

Breathlessness and pain frequently co-occur in chronic conditions, and their unpredictability is often reported to amplify perception and negative affect (NA), however any common neural mechanisms remain largely unexplored. This study examined the effects of (unpredictable) bodily threat on perception and neural gating of respiratory and somatosensory stimuli. Healthy adults (N = 51) experienced brief paired inspiratory occlusions and electrocutaneous stimuli, with their neural activity monitored via electroencephalography. Neural gating was measured as a ratio of the N1 response to the second relative to the first stimulus in a pair. In 4/6 blocks, threatening stimulation, in form of additional loaded breaths or electrocutaneous pulses, was presented predictably or unpredictably. Participants reported: perceived intensity and unpleasantness of all stimuli, fear, trait NA and intolerance of uncertainty (IU). Threatening stimulation increased perception, fear, and N1 amplitudes, without affecting neural gating. There was no group effect of unpredictability, though interactions were found with NA and IU. Cross-modal correlations revealed significant baseline relationships in neural gating and perception, though not in their modulation by threat. The present findings demonstrate that respiratory and somatosensory modalities relate in baseline perception and neural gating, and exhibit similar modulation effects by unpleasant stimulation. Further research is encouraged to elucidate the underlying mechanisms of these relationships, and the potential interactions with stimulus unpredictability.

The breathing brain: The potential of neural oscillations for the understanding of respiratory perception in health and disease.

Dyspnea or breathlessness is a symptom occurring in multiple acute and chronic illnesses, however, the understanding of the neural mechanisms underlying its subjective experience is limited. In this topical review, we propose neural oscillatory dynamics and cross-frequency coupling as viable candidates for a neural mechanism underlying respiratory perception, and a technique warranting more attention in respiration research. With the evidence for the potential of neural oscillations in the study of normal and disordered breathing coming from disparate research fields with a limited history of interdisciplinary collaboration, the main objective of the review was to converge the existing research and suggest future directions. The existing findings show that distinct limbic and cortical activations, as measured by hemodynamic responses, underlie dyspnea, however, the time-scale of these activations is not well understood. The recent findings of oscillatory neural activity coupled with the respiratory rhythm could provide the solution to this problem, however, more research with a focus on dyspnea is needed. We also touch on the findings of distinct spectral patterns underlying the changes in breathing due to experimental manipulations, meditation and disease. Subsequently, we suggest general research directions and specific research designs to supplement the current knowledge using neural oscillation techniques. We argue for the benefits of interdisciplinary collaboration and the converging of neuroimaging and behavioral methods to best explain the emergence of the subjective and aversive individual experience of dyspnea.

Is it a painful error? The effect of unpredictability and intensity of punishment on the error-related negativity, and somatosensory evoked potentials.

We examined how predictable and unpredictable punishment intensity contingent on error commission modulated ERN amplitudes. We recorded the ERN in 35 healthy volunteers performing the Eriksen flanker task. Errors were punished with predictable nonpainful, painful or unpredictable electrical stimulation. Furthermore, we investigated trait anxiety. We observed that ERN amplitudes did not differ across conditions, nor were there significant effects of anxiety. In contrast, we found that predictable painful punishments led to smaller Error Positivity (Pe). The effects of predictability and intensity were present in Somatosensory Evoked Potentials elicited by the punishments. N1 amplitudes were increased for painful compared to nonpainful stimulation, and P2/P3 amplitudes for painful compared to nonpainful, and for unpredictable compared to predictable stimulation. We suggest that unpredictability and increased painfulness of punishments enhance the potential motivational significance of the errors, but do not potentiate ERN amplitudes beyond the ones elicited by errors punished with predictable nonpainful stimulation.

High-frequency electrical stimulation of cutaneous nociceptors differentially affects pain perception elicited by homotopic and heterotopic electrical stimuli.

Animal studies have shown that high-frequency electrical stimulation (HFS) of peripheral C-fiber nociceptors induces both homosynaptic and heterosynaptic long-term potentiation (LTP) within spinal nociceptive pathways. In humans, when HFS is applied onto the skin to activate nociceptors, single electrical stimuli are perceived more intense at the HFS site compared with a control site, a finding that was interpreted as a perceptual correlate of homosynaptic LTP. The present study aimed to investigate if after HFS the pain elicited by electrical stimuli delivered at the skin next to the HFS site is perceived as more intense compared with the pain at a control site (contralateral arm). To test this, HFS was applied to one of the two ventral forearms of 24 healthy participants. Before and after HFS, single electrical stimuli were delivered through the HFS electrode, through an identical electrode next to the HFS electrode and an identical electrode at the contralateral arm. After HFS, the pain elicited by the single electrical stimuli was reduced at all three sites, with the largest reduction at the HFS site. Nevertheless, electrical stimuli delivered to the skin next to the HFS site were perceived as more intense than control stimuli. This result indicates that higher pain ratings to electrical stimuli after HFS at the HFS site cannot solely be interpreted as a perceptual correlate of homosynaptic changes. Furthermore, we show for the first time, in humans, that HFS can reduce pain elicited by single electrical stimuli delivered through the same electrode.NEW & NOTEWORTHY High-frequency electrical stimulation (HFS) of cutaneous nociceptors can reduce pain perception to single electrical stimuli delivered through the same electrode. Moreover, single electrical stimuli delivered to the skin next to the site at which HFS was applied are perceived as more intense compared with that at the contralateral control site, indicating the presence of heterosynaptic effects for electrical stimuli.

Motor action changes pain perception: a sensory attenuation paradigm in the context of pain.

ABSTRACT: A large body of evidence indicates how pain affects motor control, yet the way the motor system influences pain perception remains unclear. We present 2 experiments that investigated sensory attenuation of pain implementing a 2-alternative forced choice paradigm. Particularly, healthy participants received painful stimuli on a moving and nonmoving hand during the execution or the preparation of reaching motor actions. At the end of each trial, they indicated on which hand they perceived the stimulus stronger. The point of subjective equality was obtained to measure sensory attenuation. The intensity (experiment 1) and the threat value (experiment 2) of the pain stimuli were manipulated between-subjects to examine their impact on sensory attenuation. Results of experiment 1 (N = 68) revealed that executing a motor action attenuates pain processing in the moving hand. Sensory attenuation during motor preparation alone occurred with stronger stimulus intensities. Sensory attenuation was not affected by the intensity of the pain stimuli. Results of experiment 2 (N = 79) replicated the phenomenon of sensory attenuation of pain during motor action execution. However, sensory attenuation was not affected by the threat value of pain. Together these findings indicate that executing, but not preparing, a motor action affects pain processing in that body part. No significant associations were found between sensory attenuation indices and inhibitory control abilities or pain catastrophizing, vigilance and rumination. These results provide insight into the inhibitory effects of motor actions on pain processing, suggesting that pain perception is a dynamic experience susceptible to individuals' actions in the environment.

Cross-modal relationships of neural gating with the subjective perception of respiratory and somatosensory sensations.

Neural gating is a phenomenon whereby the response to a stimulus in the electroencephalogram (EEG) is attenuated when preceded by an identical stimulus. Attenuation of paired auditory clicks has repeatedly been shown to be affected in mental disorders, for example, schizophrenia. Neural gating has also been measured for respiratory and somatosensory sensations, however the attenuation of bodily relevant stimuli has not yet been systematically related to the subjective perception of bodily sensations. This research direction is potentially relevant to explaining disease trajectories in psychosomatic conditions characterized by chronic breathlessness and/or pain. In the present study, we recorded high-density EEG from 85 healthy young adults while they experienced brief paired respiratory occlusions and brief paired electrocutaneous stimulation of the wrist. The event-related potential N1 was measured centro-laterally in response to the second relative to the first stimulus to quantify neural gating in both sensory domains. Participants experienced resistive loaded breaths and electrocutaneous stimuli of various intensities, rated their perceived intensity and unpleasantness, and performed magnitude estimation. Relationships of respiratory and somatosensory neural gating to the subjective intensity and unpleasantness of sensations, as well as the ability to discriminate sensations of varying intensities, were investigated intra-modally and cross-modally. We report significant relationships of the somatosensory neural gating to perceived intensity and unpleasantness of respiratory and somatosensory sensations, with the stronger neural gating relating to a stronger subjective intensity and unpleasantness. We discuss these unexpected findings through the lens of individual differences and different theoretical accounts on the origins of cortical attenuation of repetitive stimuli.

Rating the Intensity of a Laser Stimulus, but Not Attending to Changes in Its Location or Intensity Modulates the Laser-Evoked Cortical Activity.

Top-down attention towards nociceptive stimuli can be modulated by asking participants to pay attention to specific features of a stimulus, or to provide a rating about its intensity/unpleasantness. Whether and how these different top-down processes may lead to different modulations of the cortical response to nociceptive stimuli remains an open question. We recorded electroencephalographic (EEG) responses to brief nociceptive laser stimuli in 24 healthy participants while they performed a task in which they had to compare two subsequent stimuli on their Spatial location (Location task) or Intensity (Intensity Task). In two additional blocks (Location + Ratings, and Intensity + Ratings) participants had to further provide a rating of the perceived intensity of the stimulus. Such a design allowed us to investigate whether focusing on spatial or intensity features of a nociceptive stimulus and rating its intensity would exert different effects on the EEG responses. We did not find statistical evidence for an effect on the signal while participants were focusing on different features of the signal. We only observed a significant cluster difference in frontoparietal leads at approximately 300-500 ms post-stimulus between the magnitude of the signal in the Intensity and Intensity + Rating conditions, with a less negative response in the Intensity + Rating condition in frontal electrodes, and a less positive amplitude in parietal leads. We speculatively propose that activity in those electrodes and time window reflects magnitude estimation processes. Moreover, the smaller frontal amplitude in the Intensity + Rating condition can be explained by greater working memory engagement known to reduce the magnitude of the EEG signal. We conclude that different top-down attentional processes modulate responses to nociceptive laser stimuli at different electrodes and time windows depending on the underlying processes that are engaged.

A highly cognitive demanding working memory task may prevent the development of nociceptive hypersensitivity.

Whether, how, and which cognitive factors modulate the development of secondary hypersensitivity/hyperalgesia after central sensitization is not fully understood. Here, we tested, in 3 subsequent experiments, whether being engaged in non-pain-related cognitive demanding tasks: (1) lessens the amount of hypersensitivity developed after an experimental procedure sensitizing nociceptive pathways; and (2) modulates cortical responses to somatosensory stimuli (measured by electroencephalography, EEG). In the first experiment, we validated a novel model in humans using low-frequency stimulation of the skin and demonstrated that it was able to successfully induce hypersensitivity to mechanical pinprick stimuli in the area surrounding the sensitized site. In the second and third experiments, we engaged participants in tasks of increasing difficulty (the Eriksen Flanker Task in experiment 2, and a modified N-back task in experiment 3). We observed that hypersensitivity to mechanical stimuli still developed in experiment 2, that is, the pinprick stimuli applied on the sensitized arm were perceived as more intense after low-frequency stimulation. By contrast, no statistically significant enhancement of mechanical hypersensitivity was observed in experiment 3, indicating that, at the group level, being engaged in a difficult N-back task may interfere with the development of mechanical hypersensitivity. Contrary to previous studies, which have used different methods to induce sensitization, we did not observe any increase in the cortical response to somatosensory stimuli applied on the sensitized arm. We conclude that (1) the development of pinprick hypersensitivity is modulated by the concomitant execution of a difficult N-back task, and (2) the enhancement of cortical responses to somatosensory stimuli is related to the method used to induce central sensitization.

Error-related negativity relates to the neural processing of brief aversive bodily sensations.

The error-related negativity (ERN) is an event-related potential occurring in the electroencephalogram (EEG) within 100 ms after the commission of an error. The ERN is thought to partially reflect emotionally aversive aspects of error commission, however, it has thus far not been related to the neural processing of other aversive events, such as brief aversive bodily sensations. Therefore, the present study investigated the links between the ERN and the N1 amplitudes of respiratory-related evoked potentials (RREP) and somatosensory evoked potentials (SEP). During the acquisition of high-density EEG, 41 healthy participants performed a Flanker task to evoke the ERN, while RREP and SEP were separately elicited, using inspiratory occlusions and electrocutaneous stimulation of the wrist. Significant positive correlations were observed between the amplitudes of the ERN and the N1 of RREP and SEP, suggesting relationships between the neural processing of different emotionally aversive events, namely errors and bodily sensations.

Intense and sustained pain reduces cortical responses to auditory stimuli: Implications for the interpretation of the effects of heterotopic noxious conditioning stimulation in humans.

Phasic pain stimuli are inhibited when they are applied concomitantly with a conditioning tonic stimulus at another body location (heterotopic noxious conditioning stimulation, HNCS). While the effects of HNCS are thought to rely on a spino-bulbo-spinal mechanism in animals (termed diffuse noxious inhibitory controls, DNIC), the underlying neurophysiology in humans may involve other pathways. In this study, we investigated the role of concomitant supraspinal mechanisms during HNCS by presenting auditory stimuli during a conditioning tonic painful stimulus (the cold pressor test, CPT). Considering that auditory stimuli are not conveyed through the spinal cord, any changes in brain responses to auditory stimuli during HNCS can be ascribed entirely to supraspinal mechanisms. Electroencephalography (EEG) was recorded during HNCS, and auditory stimuli were administered in three blocks, before, during and after HNCS. Nociceptive withdrawal reflexes (NWRs) were recorded at the same time points to investigate spinal processing. Our results showed that AEPs were significantly reduced during HNCS. Moreover, the amplitude of the NWR was significantly diminished during HNCS in most participants. Given that spinal and supraspinal mechanisms operate concomitantly during HNCS, the possibility of isolating their individual contributions in humans is questionable. We conclude that the net effects of HCNS are not independent from attentional/cognitive influences.

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.