Skin-to-skin Contact in NICU, Caregiving Touch and Neural Correlates of Slow Stroking Touch Stimulation in Preterm Infants. A MRI Study

Background and rationale One way of operationalizing social touch has been provided by the correspondence between properties of much naturalistic affiliative interpersonal touch and the unique tuning characteristics of low-threshold unmyelinated peripheral afferent fibers. The mechanosensitive C-tactile fibers are activated by gentle skin stroking of the hairy (1-10 cm/s), but not glabrous, skin in adults. In adult, C-tactile fibers activation is correlated with perceived pleasantness. C-tactile fibers are known to mature early and it has been hypothesized that they play a role in encoding socio-affective dimensions of touch. The primary cortical target for C-tactile afferents is thought to be the posterior insular cortex. Importantly, sense of touch develops prior to the 8th week of gestation and insula cortex matures at 27th week of gestation. There is reason to believe that affective touch is already processed during the early stage of development. Recent research on full-term (FT) infants highlighted that the neural correlates of affective touch processing, activated by gentle tactile stimulation are the somatosensory cortex and the insular cortex. However, to our knowledge, no study has examined whether these two regions-of-interest (ROIs), known to process gentle skin stroking, responds to gentle skin stroking in preterm infants (PT).

Moreover, despite, several change were done in the NICU to provide more natural conditions for the PT, these infants often receive very little in terms of early physical contact. Importantly, maternal skin-to-skin contact, has the potential to mitigate some of the adverse consequences of prematurity. A recent Cochrane review reported an average 60% reduction in mortality with this intervention compared to usual care in hospitalized low birth weight infants. The review further showed a 35% relative reduction in nosocomial infections or sepsis, a shorter hospital stay and lower incidence of respiratory infections. Prolonged SSC also provides more effective thermal control, promotes breast feeding, weight gain, shorter hospital stays and stronger neural responses. However, despite the importance of SSC for optimal child development, little is known whether the duration of SSC is associated with the above mentioned ROIs in PT infants.

Finally, In humans, 65% of face-to-face interactions between mothers and infants involve touch communication. Also the quality of the touch matters: gentle stroking touch generates more smiling in infants than static touch. During mother-infant face-to face interactions mothers use touch to engage with their infants, to demonstrate affection. Caregiving touch (CT) reduces infant stress by increasing positive affect19, calms infants in pain and discomfort. Also, CT is associated with sensitive caregiving behavior21, which in turn is associated with better cognitive and behavioral outcomes both in FT and PT children. Importantly, maternal sensitivity predicts infant brain volumes and functional connectivity in 3-6 month-old FT infants. Although CT/sensitive caregiving behavior might contribute to the brain responses in early infancy, the potential link between CT/sensitive caregiving behavior and the above mentioned ROIs response to gentle skin stroking remains to be tested both in PT and FT infants.

Aim 1. To examine differences between PT and FT infants in brain response in somatosensory cortex and the insular cortex (regions-of-interest: ROIs) to skin stroking by gentle brush applied by a trained experimenter during an MRI acquisition.

Experimental Design: FT and PT infants will be scanned around of 2 months of age, corrected age (CA) for prematurity. All infants will undergo an MRI exam with a 3 Tesla Philips Achieva scanner and a 32-channel head coil at the Neuroimaging Lab, Scientific Institute, IRCCS Eugenio Medea. In agreement with Tuulari procedure (Tuulari et al., 2019), during MRI acquisition, a trained experimenter manually will apply gentle brush strokes to infants' right anterior shin region in a proximal to distal direction. The length of the stimulated area will be measured to cover 15 cm, and brush strokes will be applied at a velocity of 5 cm/s for 15s, with randomized inter-stimulus intervals of 10-15 s. The experimenter will be guided by auditory cues delivered through the scanner head phones. At the scanning site, the families will receive by a trained and experienced radiographer and the researchers. Before the scan, the scanning protocol will be revised with the parents and the absence of safety risks will be confirmed by the personnel. All MRI will be performed during natural sleep. All infants will be provided with customized hearing protection. Standard ear muffs will be given to parents, as they will stay in the scanning room throughout the whole scanning session. The scanning will be observed by the personnel from the control room.