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.     

Autistic traits modulate cortical responses to affective but not discriminative touch

The sense of touch is primarily considered a discriminative and exteroceptive sense, facilitating the detection, manipulation and exploration of objects, via an array of low‐threshold mechanoreceptors and fast conducting A‐beta (Aβ) afferents. However, a class of unmyelinated, low‐threshold mechanoreceptors identified in the hairy skin of mammals have been proposed to constitute a second, anatomically distinct system coding the affective qualities of touch. Unlike Aβs, which increase their firing rate linearly with the velocity of a stimulus moving across their receptive field, the response of these C‐tactile afferents (CTs) is described by an inverted ‘U’ curve fit, responding optimally to a skin temperature stimulus moving at between 1 and 10 cm/s. Given the distinct velocity tuning of these fast and slow touch fibres, here we used event‐related potentials to compare the time course of neural responses to 1st (fast) and 2nd (slow) touch systems. We identified a higher amplitude P300 in response to fast, Aβ‐targeted, versus slow CT‐targeted, stroking touch. In contrast, we identified a previously described, C‐fibre specific, ultra‐late potential (ULP) associated with CT‐targeted input. Of special note as regards the function of CTs is that the amplitude of the ULP was negatively correlated with self‐reported levels of autistic traits, which is consistent with the hypothesized affective and social significance of this response. Taken together, these findings provide further support for distinct discriminative and affective touch systems and suggests the temporal resolution of EEG provides an as yet underutilized tool for exploring individual differences in response sensitivity to CT‐targeted touch.     

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.     

Acute tryptophan depletion increases experimental nausea but also induces hunger in healthy female subjects

Background Acute tryptophan depletion (ATD) is an experimental model to reduce central serotonin levels. Methods Thirty‐eight healthy female subjects were randomly assigned to two groups (ATD and control) in a randomized, double‐blinded parallel‐group design. Following a standardized and balanced amino acid diet (including 1.21 g tryptophan) on the first day, they received either a protein drink without tryptophan (but substituted by other amino acids) (ATD condition) or the balanced protein drink with tryptophan (control condition) 24 h later. Four hours after its consumption, they were exposed to a standard rotation procedure. Symptom ratings (SR), ratings of hunger and mood scores were taken prior to rotation, at each break, and 15 and 30 min thereafter, together with saliva cortisol samples. Key Results Five subjects could not tolerate the entire rotation procedure and were excluded from analysis. For the remaining n = 33, SR and hunger ratings were higher during ATD than during control conditions, but mood was unaffected. Cortisol levels rose significantly with rotation but were unaffected by ATD. High baseline cortisol levels were associated with lower SR during rotation. The protective effects of morning cortisol were pronounced during the menstrual and follicular phase of the cycle and not present during ovulation and the luteal phase. Conclusions & Inferences Acute tryptophan depletion is associated with increased symptoms of nausea in healthy female subjects when exposed to body rotation. Acute tryptophan depletion also increases hunger rating. These opposite effects may indicate independent actions of the serotonin on central and peripheral functions.     

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.     

Dynamic touch reduces physiological arousal in preterm infants: A role for c-tactile afferents?

Preterm birth is a significant risk factor for a range of long-term health problems and developmental disabilities. Though touch plays a central role in many perinatal care strategies, the neurobiological basis of these approaches is seldom considered. C-Tactile afferents (CTs) are a class of unmyelinated nerve fibre activated by low force, dynamic touch. Consistent with an interoceptive function, touch specifically targeted to activate CTs activates posterior insular cortex and has been reported to reduce autonomic arousal. The present study compared the effect of 5 min of CT optimal velocity stroking touch to 5 min of static touch on the heart-rate and oxygen saturation levels of preterm infants between 28- & 37-weeks gestational age. CT touch produced a significant decrease in infants’ heart-rates and increase in their blood oxygenation levels, which sustained throughout a 5-min post-touch period. In contrast, there was no significant change in heart-rate or blood oxygenation levels of infants receiving static touch. These findings provide support for the hypothesis that CTs signal the affective quality of nurturing touch, providing a neurobiological substrate for the apparent beneficial effects of neonatal tactile interventions and offering insight for their optimisation.     

Gentle touch perception: From early childhood to adolescence

Affective touch plays an important role in children’s social interaction and is involved in shaping the development of the social brain. The positive affective component of touch is thought to be conveyed via a group of unmyelinated, low-threshold mechanoreceptive afferents, known as C-tactile fibers that are optimally activated by gentle, slow, stroking touch. Touch targeting these C-tactile fibers has been shown to decrease the heart rate in infants. The current study investigated the relationship between age and psychophysical ratings in response to affective touch. A total of n = 43 participants (early childhood: aged 5–8 years, 9 girls, 12 boys; late childhood: aged 9–12 years, 12 girls, 10 boys) were presented with C-tactile optimal and sub-optimal stroking velocities and rated touch pleasantness on an affective pictorial scale. For both age groups, we found that children preferred C-tactile-targeted stimulation. A comparison with previously published data showed that the children’s preference for C-tactile-targeted stimulation was similar to those obtained in adolescents and adults. We speculate that the effect of C-tactile-targeted touch, which is linked with pleasantness, shapes the children’s preference for C-tactile over non-C-tactile-targeted stimulation, and that C-tactile afferent stimulation is important for social development.     

Serotonergic function, substance craving, and psychopathology in detoxified alcohol-addicted males undergoing tryptophan depletion

Alcohol addiction is associated with alterations of central nervous dopaminergic and serotonergic functions. Acute tryptophan depletion has not yet been applied in detoxified alcohol-addicted patients in order to investigate its impact on psychopathology, psychoneuroendocrinology, and substance craving behaviour. 25 alcohol-addicted males randomly either received a tryptophan-free or tryptophan-containing amino acid drink and 7 days later the respective other drink. Anxiety, depression, and craving were assessed before and 5 h after the drink. Tryptophan, 5-HIAA, dopamine, norepinephrine, epinephrine, and HVA in serum were measured before and after both treatments. Nocturnal urinary cortisol measurements and genotyping for the HTTLPR polymorphism of the SLC6A4 gene were performed. Tryptophan depletion resulted in a significant reduction of total and free serum tryptophan while the tryptophan-rich drink increased serum levels. Both treatments caused a significant increase of serum serotonin levels, however, serum 5-HIAA was decreased after depletion but increased after sham depletion. Dopamine and norepinephrine were elevated after tryptophan depletion and sham. Depletion increased depression scores (MADRS), while the full amino acid drink improved state and trait anxiety ratings (STAI) and substance craving. Urinary cortisol excretion was not affected by both treatments. Patients with the ll genotype of the serotonin transporter gene displayed lower baseline tryptophan levels compared to patients with the heterozygous genotype. Results suggest an impaired serotonergic function in alcohol-addicted males.     

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.     

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.     

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.     

Infant brain response to affective and discriminative touch: A longitudinal study using fNIRS

ABSTRACT

The affective-motivational component of touch has been shown to consistently activate the social- brain network in children, adolescents and adults, including the posterior superior temporal sulcus (pSTS). However, very little is known about the neural mechanisms of affective touch processing during the first year of life. The objective of the present study was to analyze brain response to affective and discriminative touch in a sample of seven-month-old infants (N = 35) who were followed longitudinally at 12 months of age (N = 25). Infants were given affective and discriminative touch to the bare forearm while their brain response was recorded using functional near-spectroscopy (fNIRS). Seven-month-olds presented brain activation for affective and discriminative stimuli in channels placed over the somatosensory region, but no activation was recorded in channels placed in the temporal region for affective touch. At 12 months of age, infants presented a significant increase in hemodynamic activity in channels placed over the temporal region for affective touch, compared to seven-month-olds. Our study presents evidence of a developmental trajectory for distinct aspects of touch brain processing in the first year of life, with the recruitment of the temporal region for the affective component of touch, maturing in the second semester of life.     

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.     

Clinical and neurochemical effect of acute tryptophan depletion in unaffected relatives of patients with bipolar affective disorder.

BACKGROUND: The lowering of mood induced by an acute tryptophan depletion (ATD) has been proposed as a candidate endophenotype for the vulnerability to manic-depressive illness. This study tests this hypothesis in relatives of probands from well-characterized multiplex families affected with bipolar affective disorder (BAD). METHODS: In a double-blind, crossover design, 20 unaffected relatives (URs) and 19 control subjects received either a 100-g amino acid (AA) drink devoid of tryptophan or a placebo, respectively. Clinical and biochemical effects of ATD were compared between unaffected relatives of BAD probands and age- and sex-matched control subjects. RESULTS: At 5 hours after AA drink ingestion, relative to the placebo, ATD resulted in 74% and 84% decreases in total plasma tryptophan concentrations in control subjects and relatives of patients with BAD, respectively. Unlike control subjects unaffected relatives experienced a lowering of mood during ATD but not with the placebo. Furthermore, URs tended to show increased impulsivity in the ATD condition. Measurements obtained before ingestion of the AA drink indicated that, relative to control subjects URs exhibited lower serotonin platelet concentrations, lower affinity, and fewer binding sites of the serotonin transporter for imipramine; these differences were unaffected by ATD. CONCLUSION: These results replicate and extend previous findings suggesting that URs of patients with BAD are more susceptible to low tryptophan availability. This finding may bear significance in the purported role of serotonergic mechanisms in the vulnerability to depressive syndrome and/or illness.     

Effects of carbamazepine on dopamine- and serotonin-mediated neuroendocrine responses

Neuroendocrine testing was carried out in seven male volunteers before and at the end of a 10-day course of carbamazepine (up to 700 mg daily). After carbamazepine treatment, the prolactin response to intravenous administration of the serotonin precursor tryptophan (5 g) was significantly enhanced, but there was no change in basal plasma tryptophan level or in tryptophan disposition after infusion. The prolactin response to intravenous protirelin (6.25 micrograms) was unaltered. Carbamazepine treatment also produced an increase in the growth hormone response to subcutaneous administration of the dopamine agonist apomorphine hydrochloride (5 micrograms/kg). These data suggest that carbamazepine may alter brain serotonin and dopamine function in humans. Such effects could be involved in the therapeutic properties of carbamazepine in affective disorder.     

ALE meta‐analysis reveals dissociable networks for affective and discriminative aspects of touch

Emotionally‐laden tactile stimulation—such as a caress on the skin or the feel of velvet—may represent a functionally distinct domain of touch, underpinned by specific cortical pathways. In order to determine whether, and to what extent, cortical functional neuroanatomy supports a distinction between affective and discriminative touch, an activation likelihood estimate (ALE) meta‐analysis was performed. This meta‐analysis statistically mapped reported functional magnetic resonance imaging (fMRI) activations from 17 published affective touch studies in which tactile stimulation was associated with positive subjective evaluation (n = 291, 34 experimental contrasts). A separate ALE meta‐analysis mapped regions most likely to be activated by tactile stimulation during detection and discrimination tasks (n = 1,075, 91 experimental contrasts). These meta‐analyses revealed dissociable regions for affective and discriminative touch, with posterior insula (PI) more likely to be activated for affective touch, and primary somatosensory cortices (SI) more likely to be activated for discriminative touch. Secondary somatosensory cortex had a high likelihood of engagement by both affective and discriminative touch. Further, meta‐analytic connectivity (MCAM) analyses investigated network‐level co‐activation likelihoods independent of task or stimulus, across a range of domains and paradigms. Affective‐related PI and discriminative‐related SI regions co‐activated with different networks, implicated in dissociable functions, but sharing somatosensory co‐activations. Taken together, these meta‐analytic findings suggest that affective and discriminative touch are dissociable both on the regional and network levels. However, their degree of shared activation likelihood in somatosensory cortices indicates that this dissociation reflects functional biases within tactile processing networks, rather than functionally and anatomically distinct pathways. Hum Brain Mapp 37:1308‐1320, 2016. © 2016 Wiley Periodicals, Inc.     

Effect of acute tryptophan depletion on the response to controllable and uncontrollable noise stress.

BACKGROUND: Previous research provides evidence linking serotonin (5-hydroxytryptamine, 5-HT) with stress and depression. The controllable/uncontrollable (C/UC) stress paradigm aims to generate a state/condition, namely a feeling of lack of control in the context of a stressor, which might be an important factor in precipitating a negative mood state. Acute tryptophan depletion (ATD) is a technique that produces a decrease in central 5-HT levels in vivo. This study investigated the role of 5-HT in the behavioral response to a C/UC stress paradigm with ATD. METHODS: Healthy adult volunteers were randomly assigned to receive either a TRP-supplemented (n = 15) or TRP-deficient (n = 13) amino acid drink. At 5 hours postdrink, volunteers were subjected to sessions of controllable and uncontrollable noise stress (100-dB white noise). Subjective ratings of mood were obtained before and after the interventions. RESULTS: Participants who received the tryptophan-depleting drink had greater self-report ratings of negative mood on visual analogue scales and the Profile of Mood States after the uncontrollable stress than did participants who received the balanced drink. CONCLUSIONS: The results suggest that 5-HT might play a role in providing resilience to uncontrollable stress. Additional studies with specific 5-HT pharmacologic probes will further clarify the results.