The skin-brain connection and pleasant touch as supportive care for psychocutaneous disorders.

Psychodermatology is a subdiscipline of dermatology at the intersection of dermatology, psychiatry, and psychology. In dermatology clinical practice, patients may present with skin disease that affects their mental health, or skin disorders induced or worsened by psychological/psychiatric problems so there is a need for specialised education of dermatologists, as well as multidisciplinary teams, to achieve better management of these patients. Understanding the interaction between the central nervous system and the skin underlying psychocutaneous disorders could help identify alternative therapies that may improve patient well-being. The concept of pleasurable touch has received increasing attention following the discovery of C-tactile (CT) fibres. While afferent C-fibre stimulation is usually associated with pain, temperature, or itch, CT-fibres are stimulated optimally by a stimulus not in the nociceptor range but by a gentle, low-force stroking. As this affective touch may counteract unpleasurable sensations, such as pain and itch, and elicit positive feelings, the potential benefits of gentle touch and massage are interesting for dermatological, especially psychocutaneous, disorders. Here we provide an overview of the skin-brain connection to help understand the benefits of touch and massage, as illustrated with studies on atopic dermatitis and burns, as an adjunct to dermatological treatment for improving patient well-being and optimising treatment outcomes.

Role of medial prefrontal cortex and primary somatosensory cortex in self and other-directed vicarious social touch: a TMS study.

Conflicting evidence points to the contribution of several key nodes of the 'social brain' to the processing of both discriminatory and affective qualities of interpersonal touch. Whether the primary somatosensory cortex (S1) and the medial prefrontal cortex (mPFC), two brain areas vital for tactile mirroring and affective mentalizing, play a functional role in shared representations of C-tactile (CT) targeted affective touch is still a matter of debate. Here, we used offline continuous theta-burst transcranial magnetic stimulation (cTBS) to mPFC, S1 and vertex (control) prior to participants providing ratings of vicarious touch pleasantness for self and others delivered across several body sites at CT-targeted velocities. We found that S1-cTBS led to a significant increase in touch ratings to the self, with this effect being positively associated to levels of interoceptive awareness. Conversely, mPFC-cTBS reduced pleasantness ratings for touch to another person. These effects were not specific for CT-optimal (slow) stroking velocities, but rather they applied to all types of social touch. Overall, our findings challenge the causal role of the S1 and mPFC in vicarious affective touch and suggest that self- vs other-directed vicarious touch responses might crucially depend on the specific involvement of key social networks in gentle tactile interactions.

Touch localization after nerve repair in the hand: insights from a new measurement tool.

Errors of touch localization after hand nerve injuries are common, and their measurement is important for evaluating functional recovery. Available empirical accounts have significant methodological limitations, however, and a quantitatively rigorous and detailed description of touch localization in nerve injury is lacking. Here, we develop a new method of measuring touch localization and evaluate its value for use in nerve injury. Eighteen patients with transection injuries to the median/ulnar nerves and 33 healthy controls were examined. The hand was blocked from the participant's view and points were marked on the volar surface using an ultraviolet (UV) pen. These points served as targets for touch stimulation. Two photographs were taken, one with and one without UV lighting, rendering targets seen and unseen, respectively. The experimenter used the photograph with visible targets to register their locations, and participants reported the felt position of each stimulation on the photograph with unseen targets. The error of localization and its directional components were measured, separate from misreferrals-errors made across digits, or from a digit to the palm. Nerve injury was found to significantly increase the error of localization. These effects were specific to the territory of the repaired nerve and showed considerable variability at the individual level, with some patients showing no evidence of impairment. A few patients also made abnormally high numbers of misreferrals, and the pattern of misreferrals in patients differed from that observed in healthy controls.NEW & NOTEWORTHY We provide a more rigorous and comprehensive account of touch localization in nerve injury than previously available. Our results show that touch localization is significantly impaired following median/ulnar nerve transection injuries and that these impairments are specific to the territory of the repaired nerve(s), vary considerably between patients, and can involve frequent errors spanning between digits.

Topography and relationship-specific social touching in individuals displaying body image disturbances.

Interpersonal touch is intimately related to the emotional bond between the touch giver and the touch receiver. Which bodily regions we touch in those individuals in our social network is relationship specific. Perception of interpersonal touch is altered in psychiatric disorders characterised by body image disturbances (BIDs). Here, we examined whether the 'imagined' experience of social touch in individuals with BIDs is body topography- and relationship-specific. By using an interactive media mobile App, the Virtual Touch Toolkit, high versus low levels of BIDs participants completed heatmaps of full-body virtual avatars, to indicate the body regions they find soothing/unpleasant to be touched by a loved one versus an acquaintance. Self-reports of interoceptive awareness and dysmorphic concerns were also measured. Overall, imagined touch was rated as the most soothing when received from a loved one, and also when this was delivered to 'social' body regions. The importance of the social relationship for the imagined tactile interactions was particularly evident for the high levels of BIDs group, with greater problems with interoceptive awareness predicting higher soothing touch ratings when this was received by a loved one. Despite the evidence that imagined bodily contacts between meaningful people is the most pleasant for socially acceptable bodily regions, our findings may suggest a greater sensitivity to relation-specific bodily patterns of social touch particularly in the high level of BIDs group. Heightened interoceptive awareness may also play a key role in this experience of bodily affective contacts. Future research for body-oriented therapy for BIDs is encouraged to systematically probe the efficacy of imagined social touch interaction protocols which use more plausible, ecological, scenarios where touch is delivered by loved ones and to socially acceptable bodily regions.

Hold me or stroke me? Individual differences in static and dynamic affective touch.

Low-threshold mechanosensory C-fibres, C-tactile afferents (CTs), respond optimally to sensations associated with a human caress. Additionally, CT-stimulation activates brain regions associated with processing affective states. This evidence has led to the social touch hypothesis, that CTs have a key role in encoding the affective properties of social touch. Thus, to date, the affective touch literature has focussed on gentle stroking touch. However, social touch interactions involve many touch types, including static, higher force touch such as hugging and holding. This study aimed to broaden our understanding of the social touch hypothesis by investigating relative preference for static vs dynamic touch and the influence of force on these preferences. Additionally, as recent literature has highlighted individual differences in CT-touch sensitivity, this study investigated the influence of affective touch experiences and attitudes, autistic traits, depressive symptomology and perceived stress on CT-touch sensitivity. Directly experienced, robotic touch responses were obtained through a lab-based study and vicarious touch responses through an online study where participants rated affective touch videos. Individual differences were determined by self-report questionnaire measures. In general, static touch was preferred over CT-non-optimal stroking touch, however, consistent with previous reports, CT-optimal stroking (velocity 1-10 cm/s) was rated most pleasant. However, static and CT-optimal vicarious touch were rated comparably for dorsal hand touch. For all velocities, 0.4N was preferred over 0.05N and 1.5N robotic touch. Participant dynamic touch quadratic terms were calculated for robotic and vicarious touch as a proxy CT-sensitivity measure. Attitudes to intimate touch significantly predict robotic and vicarious quadratic terms, as well as vicarious static dorsal hand touch ratings. Perceived stress negatively predicted robotic static touch ratings. This study has identified individual difference predictors of CT-touch sensitivity. Additionally, it has highlighted the context dependence of affective touch responses and the need to consider static, as well as dynamic affective touch.

Translation, validity, and reliability of the European Portuguese version of the Touch Experiences and Attitudes Questionnaire.

Background: Positive touch experiences have proved to be extremely important throughout our lifespan, with cascading effects on our social life. However, few questionnaires are available to measure attitudes and experiences of touch in the Portuguese population. This study aimed to translate and validate the European Portuguese version of the Touch Experiences and Attitudes Questionnaire (TEAQ), as a reliable and valid instrument to measure different aspects of affective touch experiences and attitudes. Methods: Therefore, an online sample of 384 (299 females and 85 males) participants, aged between 18 and 75 years (M = 24.59; SD = 9.56) was collected. Multidimensional Rasch model and confirmatory factor analysis were carried out, and also reliability and convergent and discriminant validity were determined. In addition, we examined sex differences in attitudes and experiences of touch. Results: Results showed good fit indexes for the 52-item six-factor model structure (friends and family touch, current intimate touch, childhood touch, attitudes to self-care, attitudes to intimate touch, and attitudes to unfamiliar touch). This instrument also showed good reliability and acceptable convergent and discriminant validity. Significant sex differences were found, with female participants reporting more positive touch experiences (including childhood touch, friends and family touch, and current intimate touch) and a more favourable attitude to self-care, with males showing a more positive attitude towards unfamiliar touch. Regarding attitudes towards the intimate touch, scores for both groups were comparable. Conclusion: Overall, the European Portuguese version of the TEAQ presented good psychometric properties and appears to be a reliable and valid self-report measure, being a useful and beneficial instrument in research and clinical settings.

Social Touch Reduces Pain Perception-An fMRI Study of Cortical Mechanisms.

Unmyelinated low-threshold mechanoreceptors (C-tactile, CT) in the human skin are important for signaling information about hedonic aspects of touch. We have previously reported that CT-targeted brush stroking by means of a robot reduces experimental mechanical pain. To improve the ecological validity of the stimulation, we developed standardized human-human touch gestures for signaling attention and calming. The attention gesture is characterized by tapping of the skin and is perceived as neither pleasant nor unpleasant, i.e., neutral. The calming gesture is characterized by slow stroking of the skin and is perceived as moderately to very pleasant. Furthermore, the attention (tapping) gesture is ineffective, whereas the calming (stroking) gesture is effective in activating CT-afferents. We conducted an fMRI study (n = 32) and capitalized on the previous development of touch gestures. We also developed an MR compatible stimulator for high-precision mechanical pain stimulation of the thenar region of the hand. Skin-to-skin touching (stroking or tapping) was applied and was followed by low and high pain. When the stroking gesture preceded pain, the pain was rated as less intense. When the tapping gesture preceded the pain, the pain was rated as more intense. Individual pain perception related to insula activation, but the activation was not higher for stroking than for tapping in any brain area during the stimulation period. However, during the evaluation period, stronger activation in the periaqueductal gray matter was observed after calming touch compared to after tapping touch. This finding invites speculation that human-human gentle skin stroking, effective in activating CT-afferents, reduced pain through neural processes involving CT-afferents and the descending pain pathway.

Dynamic touch induces autonomic changes in preterm infants as measured by changes in heart rate variability.

Preterm birth significantly increases the risk of developing various long-term health problems and developmental disabilities. While touch is a crucial component of many perinatal care strategies, the neurobiological underpinnings are rarely considered. C-tactile fibers (CTs) are unmyelinated nerve fibers that are activated by low-force, dynamic touch. Touch directed specifically at CTs activates the posterior insular cortex, consistent with an interoceptive function, and has been shown to reduce heart rate and increase oxygen saturation. The current research compared the effect of five minutes of CT optimal velocity stroking touch versus five minutes of static touch on autonomic markers of preterm infants between 28 and 37 weeks gestational age. CT touch induces a higher increase in heart rate variability metrics related to the parasympathetic system, which persisted for a 5-minute post-touch period. Conversely, there was no such increase in infants receiving static touch. The present findings confirmed that CTs signal the affective quality of nurturing touch, thereby arguing an additional neurobiological substrate for the evident valuable impacts of neonatal tactile interventions and improving the effectiveness of such interventions.

Vicarious ratings of self vs. other-directed social touch in women with and recovered from Anorexia Nervosa.

Anorexia Nervosa (AN) is an eating pathology characterized by restricted eating, body image distortions and impaired socio-cognitive abilities. Altered responses to affective touch-a pleasant interoceptive stimulus hypothesised to involve activation of the C-Tactile (CT) system, may contribute to the aetiology and maintenance of this disorder. Here, we investigated whether third-party social touch vicarious ratings of different body sites at CT-optimal vs. non-CT optimal velocities differed in women with and recovered from AN (RAN) and healthy controls (HCs). Thirty-five HCs, 27 AN and 29 RAN provided pleasantness ratings for two different tasks designed to probe expectations of how touch is perceived by self (self-directed touch) vs. others (other-directed touch). Findings revealed that both clinical groups, compared to HCs, did not differ in their pleasantness ratings to touch for another but when evaluating touch for self, both clinical groups rated CT-optimal touch as less pleasant than HCs. These findings suggest that AN and RAN women demonstrate an atypical vicarious pleasantness response to affective touch involving self, but not others. Novel therapeutic approaches that help anorexics to better interpret or improve tolerance of affective tactile experiences involving the self may be an important addition to current standard treatments.

Does Nice or Nasty Matter? The Intensity of Touch Modulates the Rubber Hand Illusion.

Our sense of body ownership results from the ongoing integration of perceptual information coming from the different senses (i.e., multisensory integration). The Rubber Hand Illusion (RHI) has been extensively studied to investigate the malleability of body ownership through contrasting multisensory information. Indeed, during the RHI, stroking a visible rubber hand synchronously to participants' hand hidden from sight generates the illusion of ownership of the rubber hand (embodiment) and the mis-location of participants' hand as closer to the rubber hand (proprioceptive drift). It is well known that the RHI is optimally evoked by a pleasant stroking (affective) touch, but what of an unpleasant (painful) stroking touch - does hedonic valence matter? To this aim, participants repeated the RHI while receiving different types of touch: pleasant, painful, and neutral. Results showed, for the first time, that the subjective intensity of the tactile stimulation experienced across the different conditions modulates the strength of the proprioceptive drift. Notably, participants reported a stronger RHI (mis-placed body ownership) from stimulation rated as more intense and involving an interoceptive activation (pain and pleasantness vs. neutral). We propose that interoceptive information, regardless of the valence of the stimuli (positive or negative), are perceived as more intense and enhance, through the activation of the limbic system, multisensory integration. In the context of the RHI, this translates to a stronger illusion in terms of proprioceptive drift.

A psychophysical and neuroimaging analysis of genital hedonic sensation in men.

Current understanding of human genital-brain interactions relates primarily to neuroendocrine and autonomic control, whereas interactions during sexual stimulation remain largely unexplored. Here we present a systematic approach towards identifying how the human brain encodes sensory genital information. Using a validated affective touch paradigm and functional magnetic resonance imaging, we found that hedonic responses to discriminatory versus affective tactile stimulation were distinctly different for both penile shaft and forearm. This suggests that, as with other body sites, genital skin contains small diameter mechanoreceptive nerve fibres that signal pleasant touch. In the brain, secondary somatosensory cortex (S2) distinguished between affective and discriminative touch for the penile shaft, but not for the forearm. Frenulum stimulation induced the greatest reports of subjective pleasure and led to the greatest deactivation of the default-mode network. This study represents a first pass at investigating, in humans, the relationship between innervation of genital surfaces, hedonic feelings, and brain mechanisms, in a systematic way.

Acute tryptophan depletion alters affective touch perception.

RATIONALE: Affiliative tactile interactions help regulate physiological arousal and confer resilience to acute and chronic stress. C-tactile afferents (CTs) are a population of unmyelinated, low threshold mechanosensitive cutaneous nerve fibres which respond optimally to a low force stimulus, moving at between 1 and 10 cm/s. As CT firing frequencies correlate positively with subjective ratings of touch pleasantness, they are hypothesised to form the first stage of encoding affiliative tactile interactions. Serotonin is a key modulator of social responses with known effects on bonding. OBJECTIVES: The aim of the present study was to determine the effect of acutely lowering central serotonin levels on perceptions of CT-targeted affective touch. METHODS: In a double blind, placebo-controlled design, the effect of acute tryptophan depletion (ATD) on 25 female participants' ratings of directly and vicariously experienced touch was investigated. Psychophysical techniques were used to deliver dynamic tactile stimuli; some velocities were targeted to optimally activate CTs (1-10 cm/s), whereas other, faster and slower strokes fell outside the CT optimal range. Discriminative tactile function, cold pain threshold and tolerance were also measured. RESULTS: ATD significantly increased pleasantness ratings of both directly and vicariously experienced affective touch, increasing discrimination of the specific hedonic value of CT targeted velocities. While ATD had no effect on either tactile or cold pain thresholds, there was a trend for reduced tolerance to cold pain. CONCLUSIONS: These findings are consistent with previous reports that depletion of central serotonin levels modulates neural and behavioural responsiveness to appetitive sensory signals.

From Skin Mechanics to Tactile Neural Coding: Predicting Afferent Neural Dynamics During Active Touch and Perception.

First order cutaneous neurons allow object recognition, texture discrimination, and sensorimotor feedback. Their function is well-investigated under passive stimulation while their role during active touch or sensorimotor control is understudied. To understand how human perception and sensorimotor controlling strategy depend on cutaneous neural signals under active tactile exploration, the finite element (FE) hand and Izhikevich neural dynamic model were combined to predict the cutaneous neural dynamics and the resulting perception during a discrimination test. Using in-vivo microneurography generated single afferent recordings, 75% of the data was applied for the model optimization and another 25% was used for validation. By using this integrated numerical model, the predicted tactile neural signals of the single afferent fibers agreed well with the microneurography test results, achieving the out-of-sample values of 0.94 and 0.82 for slowly adapting type I (SAI) and fast adapting type I unit (FAI) respectively. Similar discriminating capability with the human subject was achieved based on this computational model. Comparable performance with the published numerical model on predicting the cutaneous neural response under passive stimuli was also presented, ensuring the potential applicability of this multi-level numerical model in studying the human tactile sensing mechanisms during active touch. The predicted population-level 1st order afferent neural signals under active touch suggest that different coding strategies might be applied to the afferent neural signals elicited from different cutaneous neurons simultaneously.

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.

A topographical and physiological exploration of C-tactile afferents and their response to menthol and histamine.

Unmyelinated tactile (C-tactile or CT) afferents are abundant in arm hairy skin and have been suggested to signal features of social affective touch. Here, we recorded from unmyelinated low-threshold mechanosensitive afferents in the peroneal and radial nerves. The most distal receptive fields were located on the proximal phalanx of the third finger for the superficial branch of the radial nerve and near the lateral malleolus for the peroneal nerve. We found that the physiological properties with regard to conduction velocity and mechanical threshold, as well as their tuning to brush velocity, were similar in CT units across the antebrachial (n = 27), radial (n = 8), and peroneal (n = 4) nerves. Moreover, we found that although CT afferents are readily found during microneurography of the arm nerves, they appear to be much more sparse in the lower leg compared with C-nociceptors. We continued to explore CT afferents with regard to their chemical sensitivity and found that they could not be activated by topical application to their receptive field of either the cooling agent menthol or the pruritogen histamine. In light of previous studies showing the combined effects that temperature and mechanical stimuli have on these neurons, these findings add to the growing body of research suggesting that CT afferents constitute a unique class of sensory afferents with highly specialized mechanisms for transducing gentle touch.NEW & NOTEWORHY Unmyelinated tactile (CT) afferents are abundant in arm hairy skin and are thought to signal features of social affective touch. We show that CTs are also present but are relatively sparse in the lower leg compared with C-nociceptors. CTs display similar physiological properties across the arm and leg nerves. Furthermore, CT afferents do not respond to the cooling agent menthol or the pruritogen histamine, and their mechanical response properties are not altered by these chemicals.

C-low threshold mechanoafferent targeted dynamic touch modulates stress resilience in rats exposed to chronic mild stress.

Affiliative tactile interactions buffer social mammals against neurobiological and behavioral effects of stress. The aim of this study was to investigate the cutaneous mechanisms underlying such beneficial consequences of touch by determining whether daily stroking, specifically targeted to activate a velocity/force tuned class of low-threshold c-fiber mechanoreceptor (CLTM), confers resilience against established markers of chronic unpredictable mild stress (CMS). Adult male Sprague Dawley rats were exposed to 2 weeks of CMS. Throughout the CMS protocol, some rats were stroked daily, either at CLTM optimal velocity (5 cm/s) or outside the CLTM optimal range (30 cm/s). A third CMS exposed group did not receive any tactile stimulation. The effect of CMS on serum corticosterone levels, anxiety- and depressive-like behaviors in these three groups was assessed in comparison to a control group of non-CMS exposed rats. While stroking did not mitigate the effects of CMS on body weight gain, CLTM optimal velocity stroking did significantly reduce CMS-induced elevations in corticosterone following an acute forced-swim. Rats receiving CLTM optimal stroking also showed significantly fewer anxiety-like behaviors (elevated plus-maze) than the other CMS exposed rats. In terms of depressive-like behavior, whereas the same velocity-specific resilience was observed in a forced-swim test and social interaction test both groups of stroked rats spent significantly less time interacting than control rats, though they also spent significantly less time in the corner than non-stroked CMS rats. Together, these findings support the theory CLTMs play a functional role in regulating the physiological condition of the body.

In your eyes: vision of the body alters touch perception in women with eating disorder symptoms.

We investigated the effects of non-informative vision of the body on exteroceptive multisensory integration and touch perception in participants presenting with different levels of eating disorder (ED) symptoms. The study employed a sample of women reporting low (low ED; n = 31) vs high (high ED; n = 34) levels of subclinical ED symptoms who undertook the Somatic Signal Detection task (SSDT). During the SSDT, participants are required to detect near-threshold tactile stimulation at their fingertip with and without a simultaneous light flash next to the stimulated fingertip. Previous research has found that participants have a tendency to erroneously report touch sensations in the absence of the stimulation, and especially when the light flash is presented. In this study, participants completed the SSDT under two conditions: while their hand was visible (non-informative vision), and while their hand was hidden from sight (no vision). Non-informative vision of the hand was found to have a different effect on SSDT performances according to participants' levels of ED symptoms. High ED participants were better able to correctly detect the touch during the SSDT when their hand was visible. Conversely, for low ED participants, vision of the body was linked to a greater effect of the light in inducing false reports of touch. We suggest that in those with high ED symptoms, vision of the body may exacerbate a predisposition to focusing on external rather than internal bodily information.

The off-line effect of affective touch on multisensory integration and tactile perceptual accuracy during the somatic signal detection task.

Affective touch refers to the emotional and motivational facets of tactile sensation and has been linked to the activation of a specialised system of mechanosensory afferents (the CT system), that respond optimally to slow caress-like touch. Affective touch has been shown to play an important role in the building of the bodily self: the multisensory integrated global awareness of one's own body. Here we investigated the effects of affective touch on subsequent tactile awareness and multisensory integration using the Somatic Signal Detection Task (SSDT). During the SSDT, participants were required to detect near-threshold tactile stimulation on their cheek, in the presence/absence of a concomitant light. Participants repeated the SSDT twice, before and after receiving a touch manipulation. Participants were divided into two groups: one received affective touch (CT optimal; n = 32), and the second received non-affective touch (non-CT optimal; n = 34). Levels of arousal (skin conductance levels, SCLs) and mood changes after the touch manipulation were also measured. Affective touch led to an increase in tactile accuracy, as indicated by less false reports of touch and a trend towards higher tactile sensitivity during the subsequent SSDT. Conversely, non-affective touch was found to induce a partial decrease in the correct detection of touch possibly due to a desensitization of skin mechanoreceptors. Both affective and non-affective touch induced a more positive mood and higher SCLs in participants. The increase in SCLs was greater after affective touch. We conclude that receiving affective touch enhances the sense of bodily self therefore increasing perceptual accuracy and awareness. Higher SCLs are suggested to be a possible mediator linking affective touch to a greater tactile accuracy. Clinical implications are discussed.

The role of maternal touch in the association between SLC6A4 methylation and stress response in very preterm infants.

Very preterm (VPT) infants requiring hospitalization in the Neonatal Intensive Care Unit (NICU) are exposed to several stressful procedural experiences. One consequence of NICU-related stress is a birth-to-discharge increased serotonin transporter gene (SLC6A4) methylation that has been associated with poorer stress regulation at 3 months of age. Maternal touch is thought to support infants' stress response, but its role in moderating the effects of SLC6A4 methylation changes is unknown. The aim of this study was to assess the role of maternal touch in moderating the association between increased SLC6A4 methylation and stress response in 3-month-old VPT infants. Twenty-nine dyads were enrolled and at 3 months (age corrected for prematurity), participated in the Face-to-Face Still-Face paradigm to measure infants' stress response (i.e., negative emotionality) and the amount of maternal touch (i.e., dynamic and static). Results showed that low level of maternal touch is associated with high level of negative emotionality during social stress. Furthermore, during NICU stay SLC6A4 methylation in VPT exposed to low level of maternal touch at 3 months was associated with increased negative emotionality. Thus, low levels of maternal static touch can intensify the negative effects of SLC6A4 epigenetic changes on stress response in 3-month-old VPT infants.