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

Abstract

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.

Dorsal raphe oxytocin receptors regulate the neurobehavioral consequences of social touch

“…OTR knockdown increased the number of perineuronal nets in the S1 (Figs 4I-K), while it decreased the number of perineuronal nets in the lOFC (Fig 4Q). These effects of OTR knockdown may have been driven by serotonin’s potentiation of cortical inhibition 68,78 , with serotonin release associated with decreased activity of the S1 in response to tactile stimulation in both female rats 79,80 and women 68 . Perineuronal nets are generated in response to neural activity 73 , so greater S1 activity and lower lOFC activity could have led to the higher and lower number of perineuronal nets in the S1 and lOFC, respectively (Figs 4I-K, 4Q).…”

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

“…In humans, evidence for the specific rewarding value of CT activating touch comes from a range of fMRI studies which consistently shown that gentle stroking applied to hairy but not palmar skin at CT optimal velocity, reliably produces neural activation in affective and reward related brain regions (Gordon et al, 2013;McGlone et al, 2012;Olausson et al, 2002;Trotter et al, 2016). These areas form key nodes of neural networks with an established role in guiding aspects of social perception, cognition and behaviour (Adolphs, 2003).…”

Effects of MDMA on attention to positive social cues and pleasantness of affective touch

“…CT-preferred stimulation activates dorsal posterior insula and orbitofrontal cortex and is related to the pleasurableness of the experience (Björnsdotter and Olausson, 2011;Francis et al, 1999;McGlone et al, 2014;Olausson et al, 2002;Olausson et al, 2010;Perini and Olausson, 2015). The pleasantness of CT-optimal touch has been proposed to be related to increased levels of serotonin and oxytocin (Trotter et al, 2016;Uvnäs-Moberg, 1998;Walker and McGlone, 2013;Walker and McGlone, 2017a), both of which are influenced by MDMA. Interestingly, recreational MDMA users report that MDMA increases the pleasantness of social touch (Klein et al, 2009).…”