Identifying the spatial location of touch on the skin surface is a fundamental function of our somatosensory system. Despite the fact that stimulation of even single mechanoreceptive afferent fibres is sufficient to produce clearly localised percepts, tactile localisation can be modulated also by higher level processes such as body posture. This suggests that tactile events are coded using multiple representations using different coordinate systems. Recent reports provide evidence for systematic biases on tactile localisation task, which are thought to result from a supramodal representation of the skin surface. While the influence of non-informative vision of the body and gaze direction on tactile discrimination tasks has been extensively studied, their effects on tactile localisation tasks remain largely unexplored. To address this question, participants performed a tactile localization task on their left hand under different visual conditions by means of a mirror box; in the mirror condition, a single stimulus was delivered on participants' hand, while the reflexion of the right hand was seen through the mirror; in the object condition, participants looked at a box through the mirror, and in the right hand condition, participants looked directly at their right hand. Participants reported the location of the tactile stimuli using a silhouette of a hand. Results showed a shift in the localization of the touches towards the tip of the fingers (distal bias) and the thumb (radial biases) across conditions. Critically, distal biases were reduced when participants looked towards the mirror compared to when they looked at their right hand suggesting that gaze direction reduces the typical proximo-distal biases in tactile localization. Moreover, vision of the hand modulates the internal configuration of points' locations, by elongating it, in the radio-ulnar axis.

There are bi-directional interactions between the autonomic nervous system (ANS) and pain. This is likely underpinned by a substantial overlap between brain areas of the central autonomic network and areas involved in pain processing and modulation. To date, however, relatively little is known about the neuronal substrates of the ANS-pain association. Here, we acquired resting state fMRI scans in 21 healthy subjects at rest and during tonic noxious cold stimulation. As indicators of autonomic function, we examined how heart rate variability (HRV) frequency measures were influenced by tonic noxious stimulation and how these variables related to participants’ pain perception and to brain functional connectivity in regions known to play a role in both ANS regulation and pain perception, namely the right dorsal anterior cingulate cortex (dACC) and periaqueductal gray (PAG). Our findings support a role of the cardiac ANS in brain connectivity during pain, linking functional connections of the dACC and PAG with measurements of low frequency (LF)-HRV. In particular, we identified a three-way relationship between the ANS, cortical brain networks known to underpin pain processing, and participants’ subjectively reported pain experiences. LF-HRV both at rest and during pain correlated with functional connectivity between the seed regions and other cortical areas including the right dorsolateral prefrontal cortex (dlPFC), left anterior insula (AI), and the precuneus. Our findings link cardiovascular autonomic parameters to brain activity changes involved in the elaboration of nociceptive information, thus beginning to elucidate underlying brain mechanisms associated with the reciprocal relationship between autonomic and pain-related systems.

There is a strict interaction between the autonomic nervous system (ANS) and pain, which might involve descending pain modulatory mechanisms. The periaqueductal grey (PAG) is involved both in descending pain modulation and ANS, but its role in mediating this relationship has not yet been explored. Here, we sought to determine brain regions mediating ANS and descending pain control associations. Thirty participants underwent conditioned pain modulation (CPM) assessments, in which they rated painful pressure stimuli applied to their thumbnail, either alone or with a painful cold contralateral stimulation. Differences in pain ratings between ‘pressure‐only’ and ‘pressure + cold’ stimuli provided a measure of descending pain control. In 18 of the 30 participants, structural scans and two functional MRI assessments, one pain‐free and one during cold‐pain were acquired. Heart rate variability (HRV) was simultaneously recorded. Normalised low‐frequency HRV (LF‐HRVnu) and the CPM score were negatively correlated; individuals with higher LF‐HRVnu during pain reported reductions in pain during CPM. PAG‐ventro‐medial prefrontal cortex (vmPFC) and PAG‐rostral ventromedial medulla (RVM) functional connectivity correlated negatively with the CPM. Importantly, PAG‐vmPFC functional connectivity mediated the strength of the LF‐HRVnu‐CPM association. CPM response magnitude was also negatively correlated with vmPFC GM volume. Our multi‐modal approach, using behavioural, physiological and MRI measures, provides important new evidence of interactions between ANS and descending pain mechanisms. ANS dysregulation and dysfunctional descending pain modulation are characteristics of chronic pain. We suggest that further investigation of body‐brain interactions in chronic pain patients may catalyse the development of new treatments. Key points Heart rate variability (HRV) is associated with descending pain modulation as measured by the conditioned pain modulation protocol (CPM). There is an association between CPM scores and the functional connectivity between the periaqueductal grey (PAG) and ventro‐medial prefrontal cortex (vmPFC). CPM scores are also associated with vmPFC grey matter volume. The strength of functional connectivity between the PAG and vmPFC mediates the association between HRV and CPM. Our data provide new evidence of interactions between the autonomic nervous system and descending pain mechanisms.

Background Functional connectivity (FC) perturbations have been reported in multiple chronic pain phenotypes, but the nature of reported changes varies between cohorts and may relate to the consequences of living with chronic‐pain related comorbidities, such as anxiety and depression. Healthy volunteer studies provide opportunities to study the effects of tonic noxious stimulation independently of these sequelae. Connectivity changes in task negative and positive networks, for example, the default mode and salience networks (DMN/SN), respectively, have been described, but how these and other connectivity networks, for example, those governing descending pain control are affected by the presence of tonic, noxious stimulation in healthy, pain‐free individuals, remains unknown. Method In 20 healthy volunteers, we assessed FC prior to, during, and following tonic cold painful stimulation in the ventromedial prefrontal cortex (vmPFC), rostral anterior insula (rAI), subgenual anterior cingulate cortex (ACC) and periaqueductal grey (PAG). We also recorded subjectively reported pain using a computerised visual analogue scale. Results We saw DMN FC changes during painful stimulation and that inter‐network connectivity between the rAI with the vmPFC increased during pain, whereas PAG‐precuneus FC decreased. Pain‐induced FC alterations persisted following noxious stimulation. FC changes related to the magnitude of individuals' subjectively reported pain. Conclusions We demonstrate FC changes during and following tonic cold‐pain in healthy participants. Similarities between our findings and reports of patients with chronic pain suggest that some FC changes observed in these patients may relate to the presence of an ongoing afferent nociceptive drive. Significance How pain‐related resting state networks are affected by tonic cold‐pain remains unknown. We investigated functional connectivity alterations during and following tonic cold pain in healthy volunteers. Cold pain perturbed the functional connectivity of the ventro‐medial prefrontal cortex, anterior insula, and the periacquaductal grey area. These connectivity changes were associated with the magnitude of individuals’ reported pain. We suggest that some connectivity changes described in chronic pain patients may be due to an ongoing afferent peripheral drive.

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