Amygdala subnuclei volumes, functional connectivity, and social–emotional outcomes in children born very preterm

Abstract

Children born very preterm can demonstrate social-cognitive impairments, which may result from limbic system dysfunction. Altered development of the subnuclei of the amygdala, stress-sensitive regions involved in emotional processing, may be a key predictor of social-skill development. In a prospective cohort study, 7-year-old children born very preterm underwent neurodevelopmental testing and brain MRI. The Child Behavioral Checklist (CBCL) was used to assess social–emotional outcomes. Subnuclei volumes were extracted automatically from structural scans (n = 69) and functional connectivity (n = 66) was examined. General Linear Models were employed to examine the relationships between amygdala subnuclei volumes and functional connectivity values and social–emotional outcomes. Sex was a significant predictor of all social–emotional outcomes (P < 0.05), with boys having poorer social–emotional outcomes. Smaller right basal nuclei volumes (B = -0.043, P = 0.014), smaller right cortical volumes (B = -0.242, P = 0.02) and larger right central nuclei volumes (B = 0.85, P = 0.049) were associated with increased social problems. Decreased connectivity strength between thalamic and amygdala networks and smaller right basal volumes were significant predictors of greater social problems (both, P < 0.02), effects which were only observed in girls (P = 0.025). Dysregulated maturation of the amygdala subnuclei, along with altered connectivity strength in stress-sensitive regions, may reflect stress-induced dysfunction and can be predictive of social–emotional outcomes.

Exploring functional connectivity in clinical and data-driven groups of preterm and term adults

“…Very preterm birth (VPT; i.e., at <33 weeks' gestation) occurs during a rapid stage of brain development, making those born VPT vulnerable to neurological insult (Volpe, 2009) and long-lasting difficulties in attention, executive function, and socio-emotional processing (Anderson et al, 2021;Johnson and Marlow, 2011;Kroll et al, 2017). Functional connectivity alterations in brain regions and networks important for cognitive and affective processing have also been reported in VPT samples across the lifespan, and have been studied amongst the possible biological mechanisms underlying the behavioural difficulties associated with VPT birth (Bäuml et al, 2015;Kanel et al, 2022;Mueller et al, 2022;Papini et al, 2016;Ramphal et al, 2020;Rogers et al, 2017;Siffredi et al, 2022;Sylvester et al, 2018). It is important to highlight, however, that not only have previous studies identified brain changes associated with behavioural difficulties in those born VPT, but have also characterised neural adaptions which support domain-specific performance (Daamen et al, 2014;Finke et al, 2015;Nosarti et al, 2006Nosarti et al, , 2009Schafer et al, 2009).…”

Impact of a mindfulness‐based intervention on neurobehavioral functioning and its association with large‐scale brain networks in preterm young adolescents

“…9 In VPT children and adults, increased and decreased FC of the amygdala with other brain regions including posterior cingulate cortex, precuneus, and superior temporal areas and thalamus have been associated with the capacity to recognize facial expression of anger and with social problems. 7,10,11 Similarly, static FC studies using whole-brain datadriven approaches have found atypical resting-state networks associated with prematurity across the lifespan, especially FC of the salience, default mode, and frontal networks. 6,12 In VPT children, Mossad et al 13 showed that increased connectivity in the default mode network at the age of 6 was linked to social and working memory difficulties by the age of 8.…”

“…In VPT infants, overall cognitive scores at 6 months were predicted by medial prefrontal cortex‐executive control connectivity strength 9 . In VPT children and adults, increased and decreased FC of the amygdala with other brain regions including posterior cingulate cortex, precuneus, and superior temporal areas and thalamus have been associated with the capacity to recognize facial expression of anger and with social problems 7,10,11 . Similarly, static FC studies using whole‐brain data‐driven approaches have found atypical resting‐state networks associated with prematurity across the lifespan, especially FC of the salience, default mode, and frontal networks 6,12 .…”

Amygdala structure and function and its associations with social-emotional outcomes in a low-risk preterm sample

“…Changes in the function of this circuit seem to have an effect on how emotions are regulated and increase the risk of psychiatric disorders (VanTieghem and Tottenham 2018 ). For instance, greater exposure to pain-related stress in infants born low-risk preterm has been linked to disrupted developmental scores (Morag et al 2017 ).…”