The neurophysiology of unmyelinated tactile afferents

CT (C tactile) afferents are a distinct type of unmyelinated, low-threshold mechanoreceptive units existing in the hairy but not glabrous skin of humans and other mammals. Evidence from patients lacking myelinated tactile afferents indicates that signaling in these fibers activate the insular cortex. Since this system is poor in encoding discriminative aspects of touch, but well-suited to encoding slow, gentle touch, CT fibers in hairy skin may be part of a system for processing pleasant and socially relevant aspects of touch. CT fiber activation may also have a role in pain inhibition. This review outlines the growing evidence for unique properties and pathways of CT afferents.     

Unmyelinated tactile afferents underpin detection of low-force monofilaments

Human hairy but not glabrous skin has unmyelinated (C) tactile (CT) afferents that project to insular cortex. We studied two subjects with the rare sensory neuronopathy syndrome who lack A-beta fibers but have relatively preserved C-fiber function. Weak monofilaments were detected on hairy skin alone. Hence, the ability to detect light touch does not depend entirely on the A-beta somatosensory system; CT afferents may contribute to the detection of weak monofilaments.     

Gentle stroking elicits somatosensory ERP that differentiates between hairy and glabrous skin

Here we asked whether, similar to visual and auditory event-related potentials (ERPs), somatosensory ERPs reflect affect. Participants were stroked on hairy or glabrous skin at five stroking velocities (0.5, 1, 3, 10 and 20 cm/s). For stroking of hairy skin, pleasantness ratings related to velocity in an inverted u-shaped manner. ERPs showed a negativity at 400 ms following touch onset over somatosensory cortex contra-lateral to the stimulation site. This negativity, referred to as sN400, was larger for intermediate than for faster and slower velocities and positively predicted pleasantness ratings. For stroking of glabrous skin, pleasantness showed again an inverted u-shaped relation with velocity and, additionally, increased linearly with faster stroking. The sN400 revealed no quadratic effect and instead was larger for faster velocities. Its amplitude failed to significantly predict pleasantness. In sum, as was reported for other senses, a touch’s affective value modulates the somatosensory ERP. Notably, however, this ERP and associated subjective pleasantness dissociate between hairy and glabrous skin underscoring functional differences between the skin with which we typically receive touch and the skin with which we typically reach out to touch.     

Effects of acute tryptophan depletion on central processing of CT‐targeted and discriminatory touch in humans

C‐tactile afferents (CTs) are slowly conducting nerve fibres, present only in hairy skin. They are optimally activated by slow, gentle stroking touch, such as those experienced during a caress. CT stimulation activates affective processing brain regions, alluding to their role in affective touch perception. We tested a theory that CT‐activating touch engages the pro‐social functions of serotonin, by determining whether reducing serotonin, through acute tryptophan depletion, diminishes subjective pleasantness and affective brain responses to gentle touch. A tryptophan depleting amino acid drink was administered to 16 healthy females, with a further 14 receiving a control drink. After 4 h, participants underwent an fMRI scan, during which time CT‐innervated forearm skin and CT non‐innervated finger skin was stroked with three brushes of differing texture, at CT‐optimal force and velocity. Pleasantness ratings were obtained post scanning. The control group showed a greater response in ipsilateral orbitofrontal cortex to CT‐activating forearm touch compared to touch to the finger where CTs are absent. This differential response was not present in the tryptophan depleted group. This interaction effect was significant. In addition, control participants showed a differential primary somatosensory cortex response to brush texture applied to the finger, a purely discriminatory touch response, which was not observed in the tryptophan depleted group. This interaction effect was also significant. Pleasantness ratings were similar across treatment groups. These results implicate serotonin in the differentiation between CT‐activating and purely discriminatory touch responses. Such effects could contribute to some of the social abnormalities seen in psychiatric disorders associated with abnormal serotonin function.     

Neural correlates of gentle skin stroking in early infancy

Physical expressions of affection play a foundational role in early brain development, but the neural correlates of affective touch processing in infancy remain unclear. We examined brain responses to gentle skin stroking, a type of tactile stimulus associated with affectionate touch, in young infants. Thirteen term-born infants aged 11–36 days, recruited through the FinnBrain Birth Cohort Study, were included in the study. Soft brush strokes, which activate brain regions linked to somatosensory as well as socio-affective processing in children and adults, were applied to the skin of the right leg during functional magnetic resonance imaging. We examined infant brain responses in two regions-of-interest (ROIs) known to process gentle skin stroking – the postcentral gyrus and posterior insular cortex – and found significant responses in both ROIs. These results suggest that the neonate brain is responsive to gentle skin stroking within the first weeks of age, and that regions linked to primary somatosensory as well as socio-affective processing are activated. Our findings support the notion that social touch may play an important role in early life sensory processing. Future research will elucidate the significance of these findings for human brain development.     

Visual perception of the arm manipulates the experienced pleasantness of touch

Touch, such as a caress, can be interpreted as very pleasant. The emotional valence assigned to touch is likely related to certain bottom-up factors, such as optimal activation of C-tactile (CT) afferents. It is however unclear if besides somatosensory input, contextual factors related to the own body also play a role in the perceived pleasantness of touch. To test this, we manipulated visual appearance of the participant’s arm (veridical vision, no vision, pixelated moving statistic projected onto the arm (i.e. crawling skin)). We used slow velocity stroking (CT optimal stroking) with a soft brush to induce pleasant touch, and fast velocity stroking as a control condition. After each visual condition we asked participants (N = 23) to rate the emotional valence of the stroking they felt. After slow velocity stroking ratings on perceived pleasantness (but not on perceived unpleasantness) were modulated by visual condition, with veridical vision of the arm resulting in higher pleasantness ratings than both no vision and pixelated vision. We conclude that contextual processes affect the perceived pleasantness of touch. These findings shed a new light on the underlying mechanisms of how humans experience pleasant touch and show that pleasant touch not solely dependents on bottom up information.     

Processing of affective and emotionally neutral tactile stimuli in the insular cortex

The insula is important for the processing of pleasant aspects of touch whereas its role in the processing of emotionally neutral touch has been less explored. Here, we used a network approach to investigate the insular processing of pleasant stroking touch and emotionally neutral vibratory touch, analysing functional magnetic resonance imaging data from 23 healthy adult participants. Vibration and skin stroking activated areas in the posterior, middle and anterior insula. Psychophysiological interaction analyses suggested that skin stroking increased functional connectivity between the posterior and ventral anterior insula. Vibration instead increased functional connectivity between the posterior and dorsal anterior insula, and induced a stronger decrease of the default mode network activity compared to stroking. These results confirmed findings from previous studies showing that the posterior insula processes affective touch information. We suggest that this is accomplished by relaying tactile information from the posterior insula to ventral anterior insula, an area tightly connected to the emotional parts of the brain. However, our results also suggested that the insula processes tactile information with less emotional valence. A central hub in this processing seemed to be the right dorsal anterior insula.     

The perception of affective touch in Parkinson's disease and its relation to small fibre neuropathy

Affective touch sensation is conducted by a sub‐class of C‐fibres in hairy skin known as C‐Tactile (CT) afferents. CT afferents respond maximally to gentle skin stroking at velocities between 1 and 10 cm/s. Parkinson's disease (PD) is characterised by markedly reduced cutaneous C‐fibres. It is not known if affective touch perception is influenced by C‐fibre density and if affective touch is impaired in PD compared to healthy controls. We predicted that perceived pleasantness to gentle stroking in PD would correlate with C‐afferent density and that affective touch perception would be impaired in PD compared to healthy controls. Twenty‐four PD patients and 27 control subjects rated the pleasantness of brush stroking at an optimum CT stimulation velocity (3 cm/s) and two sub‐optimal velocities (0.3 and 30 cm/s). PD patients underwent quantification of C‐fibre density using skin biopsies and corneal confocal microscopy. All participants rated a stroking velocity of 3 cm/s as the most pleasant with significantly lower ratings for 0.3 and 30 cm/s. There was a significant positive correlation between C‐fibre density and pleasantness ratings at 3 and 30 cm/s but not 0.3 cm/s. Mean pleasantness ratings were consistently higher in PD patients compared to control subjects across all three velocities. This study shows that perceived pleasantness to gentle touch correlates significantly with C‐fibre density in PD. The higher perceived pleasantness in PD patients compared to controls suggests central sensitisation to peripheral inputs, which may have been enhanced by dopamine therapy.     

C-tactile afferents: Cutaneous mediators of oxytocin release during affiliative tactile interactions?

Low intensity, non-noxious, stimulation of cutaneous somatosensory nerves has been shown to trigger oxytocin release and is associated with increased social motivation, plus reduced physiological and behavioural reactivity to stressors. However, to date, little attention has been paid to the specific nature of the mechanosensory nerves which mediate these effects. In recent years, the neuroscientific study of human skin nerves (microneurography studies on single peripheral nerve fibres) has led to the identification and characterisation of a class of touch sensitive nerve fibres named C-tactile afferents. Neither itch nor pain receptive, these unmyelinated, low threshold mechanoreceptors, found only in hairy skin, respond optimally to low force/velocity stroking touch. Notably, the speed of stroking which C-tactile afferents fire most strongly to is also that which people perceive to be most pleasant. The social touch hypothesis posits that this system of nerves has evolved in mammals to signal the rewarding value of physical contact in nurturing and social interactions. In support of this hypothesis, we review the evidence that cutaneous stimulation directly targeted to optimally activate C-tactile afferents reduces physiological arousal, carries a positive affective value and, under healthy conditions, inhibits responses to painful stimuli. These effects mirror those, we also review, which have been reported following endogenous release and exogenous administration of oxytocin. Taken together this suggests C-tactile afferent stimulation may mediate oxytocin release during affiliative tactile interactions.     

The affective and cognitive processing of touch, oral texture, and temperature in the brain

Some of the principles of the representation of affective touch in the brain are described. Positively affective touch and temperature are represented in parts of the orbitofrontal and pregenual cingulate cortex. The orbitofrontal cortex is implicated in some of the affective aspects of touch that may be mediated through C fibre touch afferents, in that it is activated more by light touch to the forearm (a source of C-tactile (CT) afferents) than by light touch to the glabrous skin of the hand. Oral somatosensory afferents implicated in sensing the texture of food including fat in the mouth also activate the orbitofrontal and pregenual cingulate cortex, as well as the insular taste cortex. Top-down cognitive modulation of the representation of affective touch produced by word labels is found in parietal cortex area 7, the insula and ventral striatum. The cognitive labels also influence activations to the sight of touch and also the correlations with pleasantness in the pregenual cingulate/orbitofrontal cortex and ventral striatum.     

Brain mechanisms for processing affective touch

Despite the crucial role of touch in social development, there is very little functional magnetic resonance imaging (fMRI) research on brain mechanisms underlying social touch processing. The “skin as a social organ” hypothesis is supported by the discovery of C‐tactile (CT) nerves that are present in hairy skin and project to the insular cortex. CT‐fibers respond specifically well to slow, gentle touch such as that which occurs during close social interactions. Given the social significance of such touch researchers have proposed that the CT‐system represents an evolutionarily conserved mechanism important for normative social development. However, it is currently unknown whether brain regions other than the insula are involved in processing CT‐targeted touch. In the current fMRI study, we sought to characterize the brain regions involved in the perception of CT‐supported affective touch. Twenty‐two healthy adults received manual brush strokes to either the arm or palm. A direct contrast of the blood‐oxygenation‐level‐dependent (BOLD) response to gentle brushing of the arm and palm revealed the involvement of a network of brain regions, in addition to the posterior insula, during CT‐targeted affective touch to the arm. This network included areas known to be involved in social perception and social cognition, including the right posterior superior temporal sulcus and the medial prefrontal cortex (mPFC)/dorso anterior cingulate cortex (dACC). Connectivity analyses with an mPFC/dACC seed revealed coactivation with the left insula and amygdala during arm touch. These findings characterize a network of brain regions beyond the insula involved in coding CT‐targeted affective touch. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Cognitive influences on the affective representation of touch and the sight of touch in the human brain

We show that the affective experience of touch and the sight of touch can be modulated by cognition, and investigate in an fMRI study where top-down cognitive modulations of bottom-up somatosensory and visual processing of touch and its affective value occur in the human brain. The cognitive modulation was produced by word labels, ‘Rich moisturizing cream’ or ‘Basic cream’, while cream was being applied to the forearm, or was seen being applied to a forearm. The subjective pleasantness and richness were modulated by the word labels, as were the fMRI activations to touch in parietal cortex area 7, the insula and ventral striatum. The cognitive labels influenced the activations to the sight of touch and also the correlations with pleasantness in the pregenual cingulate/orbitofrontal cortex and ventral striatum. Further evidence of how the orbitofrontal cortex is involved in affective aspects of touch was that touch to the forearm [which has C fiber Touch (CT) afferents sensitive to light touch] compared with touch to the glabrous skin of the hand (which does not) revealed activation in the mid-orbitofrontal cortex. This is of interest as previous studies have suggested that the CT system is important in affiliative caress-like touch between individuals.     

Within‐limb somatotopic representation of acute muscle pain in the human contralateral dorsal posterior insula

It is well established that the insular cortex processes noxious information. We have previously shown that noxious inputs from the arm and leg are coarsely organized somatotopically within the dorsal posterior insula. The same has been shown for inputs from C tactile afferents, which mediate affective touch, and it has been suggested that the insula may be responsible for the localization of some somatosensory stimuli. Knowing the degree of spatial detail may have significant implications for the potential role of the dorsal posterior insula in the processing of noxious stimuli. Using high‐resolution functional magnetic resonance imaging (fMRI), we compared insula activation patterns in 13 subjects during muscle pain induced by injection of hypertonic saline (5%) into three muscles within the same limb: shoulder (deltoid), forearm (flexor carpi radialis), and hand (first dorsal interosseous). Mapping the maximally activated voxels within the contralateral dorsal posterior insula in each individual subject during each pain stimulus revealed a clear somatotopy of activation within the contralateral dorsal posterior insula. Shoulder pain was represented anterior to forearm pain and medial to hand pain. This fine somatotopic organization may be crucial for pain localization or other aspects of the pain experience that differ depending on stimulation site. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Exposure shapes the perception of affective touch

Touch is a common occurrence in our lives, where affective and inter-personal aspects of touch are important for our well-being. We investigated whether touch exposure affects hedonic and discriminative aspects of tactile perception. The perceived pleasantness and intensity of gentle forearm stroking, over different velocities, was assessed in individuals reporting to seldom receive inter-personal touch, and in controls who received touch often. The groups did not differ in their stroking intensity judgements, nor in tactile discrimination sensitivity; however, individuals with low touch exposure evaluated the pleasantness of touch differently. These individuals did not differentiate pleasantness over the stroking velocities in the same way as the control group. The pleasantness curve for the low touch exposure group was significantly flatter and they rated 3 cm/s stroking as significantly less pleasant. Other physiological and questionnaire measures were obtained and the appreciation of touch from familiar persons was positively related to the pleasantness of touch in controls, but this was not found in low touch exposure individuals. This suggests that the association of human caresses from well-known individuals, with the pleasure derived, may depend on continued exposure to it.     

Tactile Perception in Adults with Autism: a Multidimensional Psychophysical Study

Although sensory problems, including unusual tactile sensitivity, are heavily associated with autism, there is a dearth of rigorous psychophysical research. We compared tactile sensation in adults with autism to controls on the palm and forearm, the latter innervated by low-threshold unmyelinated afferents subserving a social/affiliative submodality of somatosensation. At both sites, the groups displayed similar thresholds for detecting light touch and innocuous sensations of warmth and cool, and provided similar hedonic ratings of the pleasantness of textures. In contrast, increased sensitivity to vibration was seen in the autism group on the forearm, along with increased sensitivity to thermal pain at both sites. These findings suggest normal perception along with certain areas of enhanced perception in autism, consistent with previous studies.     

fNIRS detects temporal lobe response to affective touch

Touch plays a crucial role in social–emotional development. Slow, gentle touch applied to hairy skin is processed by C-tactile (CT) nerve fibers. Furthermore, ‘social brain’ regions, such as the posterior superior temporal sulcus (pSTS) have been shown to process CT-targeted touch. Research on the development of these neural mechanisms is scant, yet such knowledge may inform our understanding of the critical role of touch in development and its dysfunction in disorders involving sensory issues, such as autism. The aim of this study was to validate the ability of functional near-infrared spectroscopy (fNIRS), an imaging technique well-suited for use with infants, to measure temporal lobe responses to CT-targeted touch. Healthy adults received brushing to the right forearm (CT) and palm (non-CT) separately, in a block design procedure. We found significant activation in right pSTS and dorsolateral prefrontal cortex to arm > palm touch. In addition, individual differences in autistic traits were related to the magnitude of peak activation within pSTS. These findings demonstrate that fNIRS can detect brain responses to CT-targeted touch and lay the foundation for future work with infant populations that will characterize the development of brain mechanisms for processing CT-targeted touch in typical and atypical populations.     

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.     

Infants discriminate the source of social touch at stroking speeds eliciting maximal firing rates in CT-fibers

The evaluation of interpersonal touch is heavily influenced by its source. For example, a gentle stroke from a loved one is generally more pleasant than the same tactile stimulation from a complete stranger. Our study tested the early ontogenetic roots of humans’ sensitivity to the source of interpersonal touch. We measured the heart rate of three groups of nine-month-olds while their legs were stroked with a brush. The participants were stroked at a different speed in each group (0.3 cm/s, 3 cm/s, 30 cm/s). Depending on the Identity condition (stranger vs. parent), the person who acted as if she was stroking the infant’s leg was either an unfamiliar experimenter or the participant’s caregiver. In fact, the stimulation was always delivered by a second experimenter blind to the Identity condition. Infants’ heart rate decreased more in reaction to strokes when their caregiver rather than a stranger acted as the source of the touch. This effect was found only for tactile stimulations whose velocity (3 cm/s) is known to elicit maximal mean firing rates in a class of afferents named C-tactile fibers (CTs). Thus, the infants’ reaction to touch is modulated not just by its mechanical properties but also by its social source.     

Vision in the palm of your hand

Here we show that pointing movements made to visual targets projected onto the palm of the hand are more precise and accurate than those made to targets projected onto back of the hand. This advantage may be related to the fact that the number of cortical bimodal neurons coding both visual and tactile stimuli increases with tactile receptor density, which is known to be higher in glabrous than in hairy skin.