Nociceptive-Evoked Potentials Are Sensitive to Behaviorally Relevant Stimulus Displacements in Egocentric Coordinates.

Feature selection has been extensively studied in the context of goal-directed behavior, where it is heavily driven by top-down factors. A more primitive version of this function is the detection of bottom-up changes in stimulus features in the environment. Indeed, the nervous system is tuned to detect fast-rising, intense stimuli that are likely to reflect threats, such as nociceptive somatosensory stimuli. These stimuli elicit large brain potentials maximal at the scalp vertex. When elicited by nociceptive laser stimuli, these responses are labeled laser-evoked potentials (LEPs). Although it has been shown that changes in stimulus modality and increases in stimulus intensity evoke large LEPs, it has yet to be determined whether stimulus displacements affect the amplitude of the main LEP waves (N1, N2, and P2). Here, in three experiments, we identified a set of rules that the human nervous system obeys to identify changes in the spatial location of a nociceptive stimulus. We showed that the N2 wave is sensitive to: (1) large displacements between consecutive stimuli in egocentric, but not somatotopic coordinates; and (2) displacements that entail a behaviorally relevant change in the stimulus location. These findings indicate that nociceptive-evoked vertex potentials are sensitive to behaviorally relevant changes in the location of a nociceptive stimulus with respect to the body, and that the hand is a particularly behaviorally important site

Fine-grained nociceptive maps in primary somatosensory cortex

Topographic maps of the receptive surface are a fundamental feature of neural organization in many sensory systems. While touch is finely mapped in the cerebral cortex, it remains controversial how precise any cortical nociceptive map may be. Given that nociceptive innervation density is relatively low on distal skin regions such as the digits, one might conclude that the nociceptive system lacks fine representation of these regions. Indeed, only gross spatial organization of nociceptive maps has been reported so far. However, here we reveal the existence of fine-grained somatotopy for nociceptive inputs to the digits in human primary somatosensory cortex (SI). Using painful nociceptive-selective laser stimuli to the hand, and phase-encoded fMRI analysis methods, we observed somatotopic maps of the digits in contralateral SI. These nociceptive maps were highly aligned with maps of non-painful tactile stimuli, suggesting comparable cortical representations for, and possible interactions between, mechanoreceptive and nociceptive signals. Our findings may also be valuable for future studies tracking the timecourse and the spatial pattern of plastic changes in cortical organization involved in chronic pain

Pain-motor integration in the primary motor cortex in Parkinson's disease

In Parkinson's disease (PD), the influence of chronic pain on motor features has never been investigated. We have recently designed a technique that combines nociceptive system activation by laser stimuli and primary motor cortex (M1) activation through transcranial magnetic stimulation (TMS), in a laser-paired associative stimulation design (Laser-PAS). In controls, Laser-PAS induces long-term changes in motor evoked potentials reflecting M1 long-term potentiation-like plasticity, arising from pain-motor integration

The pain matrix reloaded: a salience detection system for the body

Neuroimaging and neurophysiological studies have shown that nociceptive stimuli elia salience detection system for the bodycit responses in an extensive cortical network including somatosensory, insular and cingulate areas, as well as frontal and parietal areas. This network, often referred to as the "pain matrix", is viewed as representing the activity by which the intensity and unpleasantness of the perception elicited by a nociceptive stimulus are represented. However, recent experiments have reported (i) that pain intensity can be dissociated from the magnitude of responses in the "pain matrix", (ii) that the responses in the "pain matrix" are strongly influenced by the context within which the nociceptive stimuli appear, and (iii) that non-nociceptive stimuli can elicit cortical responses with a spatial configuration similar to that of the "pain matrix". For these reasons, we propose an alternative view of the functional significance of this cortical network, in which it reflects a system involved in detecting, orienting attention towards, and reacting to the occurrence of salient sensory events. This cortical network might represent a basic mechanism through which significant events for the body's integrity are detected, regardless of the sensory channel through which these events are conveyed. This function would involve the construction of a multimodal cortical representation of the body and nearby space. Under the assumption that this network acts as a defensive system signaling potentially damaging threats for the body, emphasis is no longer on the quality of the sensation elicited by noxious stimuli but on the action prompted by the occurrence of potential threats

Controlling attention to nociceptive stimuli with working memory

Background: Because pain often signals the occurrence of potential tissue damage, a nociceptive stimulus has the capacity to involuntarily capture attention and take priority over other sensory inputs. Whether distraction by nociception actually occurs may depend upon the cognitive characteristics of the ongoing activities. The present study tested the role of working memory in controlling the attentional capture by nociception. Methodology and Principal Findings: Participants performed visual discrimination and matching tasks in which visual targets were shortly preceded by a tactile distracter. The two tasks were chosen because of the different effects the involvement of working memory produces on performance, in order to dissociate the specific role of working memory in the control of attention from the effect of general resource demands. Occasionally (i.e. 17% of the trials), tactile distracters were replaced by a novel nociceptive stimulus in order to distract participants from the visual tasks. Indeed, in the control conditions (no working memory), reaction times to visual targets were increased when the target was preceded by a novel nociceptive distracter as compared to the target preceded by a frequent tactile distracter, suggesting attentional capture by the novel nociceptive stimulus. However, when the task required an active rehearsal of the visual target in working memory, the novel nociceptive stimulus no longer induced a lengthening of reaction times to visual targets, indicating a reduction of the distraction produced by the novel nociceptive stimulus. This effect was independent of the overall task demands. Conclusion and Significance: Loading working memory with pain-unrelated information may reduce the ability of nociceptive input to involuntarily capture attention, and shields cognitive processing from nociceptive distraction. An efficient control of attention over pain is best guaranteed by the ability to maintain active goal priorities during achievement of cognitive activities and to keep pain-related information out of task settings

Autonomic pain responses during sleep: a study of heart rate variability

The autonomic nervous system (ANS) reacts to nociceptive stimulation during sleep, but whether this reaction is contingent to cortical arousal, and whether one of the autonomic arms (sympathetic/parasympathetic) predominates over the other remains unknown. We assessed ANS reactivity to nociceptive stimulation during all sleep stages through heart rate variability, and correlated the results with the presence of cortical arousal measured in concomitant 32-channel EEG. Fourteen healthy volunteers underwent whole-night polysomnography during which nociceptive laser stimuli were applied over the hand. RR intervals (RR) and spectral analysis by wavelet transform were performed to assess parasympathetic (HF(WV)) and sympathetic (LF(WV) and LF(WV)/HF(WV) ratio) reactivity. During all sleep stages, RR significantly decreased in reaction to nociceptive stimulations, reaching a level similar to that of wakefulness, at the 3rd beat post-stimulus and returning to baseline after seven beats. This RR decrease was associated with an increase in sympathetic LF(WV) and LF(WV)/HF(WV) ratio without any parasympathetic HF(WV) change. Albeit RR decrease existed even in the absence of arousals, it was significantly higher when an arousal followed the noxious stimulus. These results suggest that the sympathetic-dependent cardiac activation induced by nociceptive stimuli is modulated by a sleep dependent phenomenon related to cortical activation and not by sleep itself, since it reaches a same intensity whatever the state of vigilance

Linking pain and the body: neural correlates of visually induced analgesia

The visual context of seeing the body can reduce the experience of acute pain, producing a multisensory analgesia. Here we investigated the neural correlates of this “visually induced analgesia” using fMRI. We induced acute pain with an infrared laser while human participants looked either at their stimulated right hand or at another object. Behavioral results confirmed the expected analgesic effect of seeing the body, while fMRI results revealed an associated reduction of laser-induced activity in ipsilateral primary somatosensory cortex (SI) and contralateral operculoinsular cortex during the visual context of seeing the body. We further identified two known cortical networks activated by sensory stimulation: (1) a set of brain areas consistently activated by painful stimuli (the so-called “pain matrix”), and (2) an extensive set of posterior brain areas activated by the visual perception of the body (“visual body network”). Connectivity analyses via psychophysiological interactions revealed that the visual context of seeing the body increased effective connectivity (i.e., functional coupling) between posterior parietal nodes of the visual body network and the purported pain matrix. Increased connectivity with these posterior parietal nodes was seen for several pain-related regions, including somatosensory area SII, anterior and posterior insula, and anterior cingulate cortex. These findings suggest that visually induced analgesia does not involve an overall reduction of the cortical response elicited by laser stimulation, but is consequent to the interplay between the brain's pain network and a posterior network for body perception, resulting in modulation of the experience of pain

Pain perception and migraine

Background: It is well-known that both inter-and intra-individual differences exist in the perception of pain; this is especially true in migraine, an elusive pain disorder of the head. Although electrophysiology and neuroimaging techniques have greatly contributed to a better understanding of the mechanisms involved in migraine during recent decades, the exact characteristics of pain threshold and pain intensity perception remain to be determined, and continue to be a matter of debate.Objective: The aim of this review is to provide a comprehensive overview of clinical, electrophysiological, and functional neuroimaging studies investigating changes during various phases of the so-called "migraine cycle" and in different migraine phenotypes, using pain threshold and pain intensity perception assessments.Methods: A systematic search for qualitative studies was conducted using search terms "migraine," "pain," "headache," "temporal summation," "quantitative sensory testing," and "threshold," alone and in combination (subject headings and keywords). The literature search was updated using the additional keywords "pain intensity," and "neuroimaging"to identify full-text papers written in English and published in peer-reviewed journals, using PubMed and Google Scholar databases. In addition, we manually searched the reference lists of all research articles and review articles.Conclusion: Consistent data indicate that pain threshold is lower during the ictal phase than during the interictal phase of migraine or healthy controls in response to pressure, cold and heat stimuli. There is evidence for preictal sub-allodynia, whereas interictal results are conflicting due to either reduced or no observed difference in pain threshold. On the other hand, despite methodological limitations, converging observations support the concept that migraine attacks may be characterized by an increased pain intensity perception, which normalizes between episodes. Nevertheless, future studies are required to longitudinally evaluate a large group of patients before and after pharmacological and non-pharmacological interventions to investigate phases of the migraine cycle, clinical parameters of disease severity and chronic medication usage

A supramodal representation of the body surface

The ability to accurately localize both tactile and painful sensations on the body is one of the most important functions of the somatosensory system. Most accounts of localization refer to the systematic spatial relation between skin receptors and cortical neurons. The topographic organization of somatosensory neurons in the brain provides a map of the sensory surface. However, systematic distortions in perceptual localization tasks suggest that localizing a somatosensory stimulus involves more than simply identifying specific active neural populations within a somatotopic map. Thus, perceptual localization may depend on both afferent inputs and other unknown factors. In four experiments, we investigated whether localization biases vary according to the specific skin regions and subset of afferent fibers stimulated. We represented localization errors as a ‘perceptual map’ of skin locations. We compared the perceptual maps of stimuli that activate Aβ (innocuous touch), Aδ (pinprick pain), and C fibers (non-painful heat) on both the hairy and glabrous skin of the left hand. Perceptual maps exhibited systematic distortions that strongly depended on the skin region stimulated. We found systematic distal and radial (i.e., towards the thumb) biases in localization of touch, pain, and heat on the hand dorsum. A less consistent proximal bias was found on the palm. These distortions were independent of the population of afferent fibers stimulated, and also independent of the response modality used to report localization. We argue that these biases are likely to have a central origin, and result from a supramodal representation of the body surface