Biological Underpinnings of Socio-emotional Regulation in Preterm Infants and Healthy Controls

Preterm infants (PT) often need to spend their first weeks of life in the Neonatal Intensive Care Unit (NICU) where they are exposed to several adverse conditions. Whereas a consistent number of studies suggest that NICU-related experiences may have effects on infant development including long-term impairments in emotional regulation, the underlying mechanisms remain partially unexplored. Spectral analysis of EEG signal has demonstrated that frontal alpha-band asymmetry represents a reliable biomarker of social-emotional functioning. In the literature, higher right frontal activation has been associated with worse emotional regulation but no study has measured this value during a condition of social-emotional stress such as the Still Face paradigm. Our hypothesis is that higher alpha activity will be recorded in right frontal areas in premature infants compared to healthy controls and that this activation will be associated with higher negative emotionality (i.e., worse socio-emotional regulation) expressed during the Still Face paradigm. Moreover, despite several changes in epigenetic patterns have already been reported in association with prematurity and early adverse experiences, the relationship between epigenetic changes and electroencephalographic patterns (i.e. frontal alpha asymmetry) remains unexplored. The investigators therefore expect to find associations between increased methylation levels of socio-emotional and stress related genes (i.e. SLC6A4, NR3C1, OXTR, Piezo1, Piezo2, TRPV1 and TRPM8) with spontaneous oscillations of neural activity at frontal sites measured by EEG (i.e. frontal alpha asymmetry). Finally, there is ample evidence that infant's socio-emotional regulation abilities are highly dependent on the behaviors of their caregivers. More recent studies have shown that behavior can be influenced by interoceptive awareness, i.e., the ability to perceive the physiological condition of one's body in this way and to represent one's internal states. Better interoceptive awareness is associated with better recognition of others' needs, more empathetic behaviors, and better emotional regulation. Therefore, with the present exploratory study, the investigators will compare the interceptive awareness of mothers of preterm infants with that of mothers of full-term infants by exploring possible associations of this dimension with the socio-emotional responses of preterm infants and healthy controls. The investigators expect that better socio-emotional regulation of infants is predicted by a higher level of interoceptive awareness in mothers, regardless of prematurity condition.

The main objective of the present study is to:

1. explore frontal and parietal alpha EEG signal asymmetry in association with social-emotional regulation in a group of preterm infants aged 6-12 months (age corrected, CA).

   Secondary aims are:
2. the investigation of epigenetic correlates (methylation of target genes:(i.e. SLC6A4, NR3C1, OXTR, Piezo1, Piezo2, TRPV1 and TRPM8) associated with social-emotional regulation
3. the contribution of mother's interoceptive awareness (Heartbeat Counting Task index) in social-emotional regulation in a sample of premature infants aged 6-12 months (CA).

The study involves the following procedures:

* EEG signal recording and analysis (frontal alpha rhythm asymmetry; FAA) in PT and FT infants
* Video recording of mother-child interaction in accordance with a modified version of the Still Face paradigm.
* Collection of biological material (DNA)
* Assessment of mothers' interoceptive awareness via Heartbeat Counting Task

Significance and innovation:

To the best of our knowledge, no study has evaluated the association between (1) EEG signal asymmetry, (2) methylation patterns of candidate genes, (3) mothers' interoceptive awareness (Heartbeat Counting Task index), and socio-emotional regulation in premature infants during the first months of life.

The present study will integrate several biomarkers and observational data to better elucidate the role of electroencephalographic activation patterns, epigenetic variations, and mothers' interoceptive awareness in the socio-emotional regulation abilities of infants born prematurely. In addition, a particularly novel aspect of this study is the application of EEG signal recording during the Still Face paradigm. The measurement of the EEG signal during this paradigm could increase our knowledge with respect to the brain mechanisms underlying socio-emotional regulation in premature infants and in healthy control.

Moreover, the focus on parental bodily states might provide a new perspective suggesting that enteroceptive awareness may contribute to support caregiver's ability to understand (and respond to) the infant's signals and emotional states.

Impact:

This study is warranted to provide relevant insights for the biochemical and neurological underpinnings of socio-emotional development in preterm infants and will provide new evidence-base information for improving the quality of supportive interventions for preterm infants and caregivers in and outside the NICU. In addition, the identification of potential electroencephalographic patterns associated with emotional regulation in premature and term infants may prove to be a novel biomarker for the early detection of children at risk for emotional and behavioral problems.

Eligibility Criteria:
Inclusion Criteria:

Inclusion criteria for PT infants are:

• gestational age\< 37weeks;

Inclusion criteria for FT infants are:

• gestational age ≥ 37weeks;

Inclusion criteria for mothers are:

* mothers of Italian nationality;
* mother over 18 years of age;
* mother with absence of manifest psychiatric and/or cognitive pathologies (must be previously diagnosed major psychiatric pathologies);
* non-addicted/no habitual use of psychotropic medications, drugs, alcohol no smoking;
* non-single-parent families.

Exclusion Criteria: refer to inclusion criteria

-