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Neonatal Amygdala Functional Connectivity at Rest in Healthy and Preterm Infants and Early Internalizing Symptoms.

ABSTRACT: Alterations in the normal developmental trajectory of amygdala resting state functional connectivity (rs-FC) have been associated with atypical emotional processes and psychopathology. Little is known, however, regarding amygdala rs-FC at birth or its relevance to outcomes. This study examined amygdala rs-FC in healthy, full-term (FT) infants and in very preterm (VPT) infants, and tested whether variability of neonatal amygdala rs-FC predicted internalizing symptoms at age 2 years.Resting state fMRI data were obtained shortly after birth from 65 FT infants (gestational age [GA] ?36 weeks) and 57 VPT infants (GA <30 weeks) at term equivalent. Voxelwise correlation analyses were performed using individual-specific bilateral amygdala regions of interest. Total internalizing symptoms and the behavioral inhibition, depression/withdrawal, general anxiety, and separation distress subdomains were assessed in a subset (n = 44) at age 2 years using the Infant Toddler Social Emotional Assessment.In FT and VPT infants, the amygdala demonstrated positive correlations with subcortical and limbic structures and negative correlations with cortical regions, although magnitudes were decreased in VPT infants. Neonatal amygdala rs-FC predicted internalizing symptoms at age 2 years with regional specificity consistent with known pathophysiology in older populations: connectivity with the anterior insula related to depressive symptoms, with the dorsal anterior cingulate related to generalized anxiety, and with the medial prefrontal cortex related to behavioral inhibition.Amygdala rs-FC is well established in neonates. Variability in regional neonatal amygdala rs-FC predicted internalizing symptoms at 2 years, suggesting that risk for internalizing symptoms may be established in neonatal amygdala functional connectivity patterns.

SUBMITTER: Rogers CE

PROVIDER: S-EPMC5302247 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Neonatal Amygdala Functional Connectivity at Rest in Healthy and Preterm Infants and Early Internalizing Symptoms.

Rogers Cynthia E CE Sylvester Chad M CM Mintz Carrie C Kenley Jeanette K JK Shimony Joshua S JS Barch Deanna M DM Smyser Christopher D CD

Journal of the American Academy of Child and Adolescent Psychiatry 20161125 2

<h4>Objective</h4>Alterations in the normal developmental trajectory of amygdala resting state functional connectivity (rs-FC) have been associated with atypical emotional processes and psychopathology. Little is known, however, regarding amygdala rs-FC at birth or its relevance to outcomes. This study examined amygdala rs-FC in healthy, full-term (FT) infants and in very preterm (VPT) infants, and tested whether variability of neonatal amygdala rs-FC predicted internalizing symptoms at age 2 ye ...[more]

PMID: 28117062

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Project description:Introductionfunctional and structural MRI studies suggest that the orexin (hypocretin) deficiency in the dorso-lateral hypothalamus of narcoleptic patients would influence both brain metabolism and perfusion and would cause reduction in cortical grey matter. Previous fMRI studies have mainly focused on cerebral functioning during emotional processing. The aim of the present study was to explore the hemodynamic behaviour of spontaneous BOLD fluctuation at rest in patients with Narcolepsy type 1 (NT1) close to disease onset.MethodsFifteen drug naïve children/adolescents with NT1 (9 males; mean age 11.7 ± 3 years) and fifteen healthy children/adolescents (9 males; mean age 12.4 ± 2.8 years) participated in an EEG-fMRI study in order to investigate the resting-state functional connectivity of hypothalamus and amygdala. Functional images were acquired on a 3 T system. Seed-based functional connectivity analyses were performed using SPM12. Regions of Interest were the lateral hypothalamus and the amygdala.Resultscompared to controls, NT1 patients showed decreased functional connectivity between the lateral hypothalamus and the left superior parietal lobule, the hippocampus and the parahippocampal gyrus. Decreased functional connectivity was detected between the amygdala and the post-central gyrus and several occipital regions, whereas it was increased between the amygdala and the inferior frontal gyrus, claustrum, insula, and putamen.Conclusionin NT1 patients the abnormal connectivity between the hypothalamus and brain regions involved in memory consolidation during sleep, such as the hippocampus, may be linked to the loss of orexin containing neurons in the dorsolateral hypothalamus. Moreover, also functional connectivity of the amygdala seems to be influenced by the loss of orexin-containing neurons. Therefore, we can hypothesize that dysfunctional interactions between regions subserving the maintenance of arousal, memory and emotional processing may contribute to the main symptom of narcolepsy.

Project description:Functional connectivity between the amygdala and the prefrontal cortex is critical for socioemotional processing, particularly during face processing. Though processing others' emotions is important for a myriad of complex social behaviors, more research is needed to understand how different types of emotional facial expressions differentially elicit connectivity of the amygdala with widespread neural regions. Moreover, though prior studies have reported cross-sectional associations between altered amygdala-prefrontal cortex functional connectivity and internalizing symptoms (e.g., depression, anxiety), few studies have examined whether amygdala functional connectivity is prospectively related to changes in these symptoms, with little work focusing on low-income men living in stressful contexts. The current study used psycho-physiological interaction analyses at the within-subjects level to examine how amygdala connectivity differed while participants viewed fearful, angry, and neutral faces. We used structural equation modeling at the between-subjects level, using extracted parameter estimates, to test whether amygdala connectivity during face processing predicted increases in internalizing psychopathology over time, controlling for earlier symptoms. An urban sample of 167 young men from low-income families was employed. Results indicated that negative connectivity between the amygdala and prefrontal regions was modulated by emotional face type. Neuronal activity in the cingulate and frontal cortices was connected to amygdala reactivity during fearful and neutral, but not angry, face processing. Moreover, weaker left amygdala-left middle frontal gyrus negative connectivity when viewing fearful faces and stronger right amygdala-left inferior frontal gyrus negative connectivity when viewing neutral faces at age 20 both predicted increases in internalizing behaviors from age 20 to age 22. Our findings show that amygdala-prefrontal cortex connectivity can predict the persistence of internalizing symptoms among high-risk participants over time but suggest that these patterns may differ depending on the emotional stimuli examined.

Project description:Ecological stress during adolescent development may increase the sensitivity to negative emotional processes that can contribute to the onset and progression of internalizing behaviors during preadolescence. Although a small number of studies have considered the link among the relations between ecological stress, amygdala reactivity, and internalizing symptoms in childhood and adolescence, these studies have largely been small, cross-sectional, and often do not consider unique roles of parenting or sex. In the current study, we evaluated the interrelations between ecological stress, amygdala reactivity, subsequent internalizing symptoms, and the moderating roles of parenting and sex among 9- and 10-year-old preadolescents from the Adolescent Brain Cognitive Development (ABCD) Study ®. A subset of participants who met a priori quality control criteria for bilateral amygdala activation during the EN-back faces versus places contrast (N = 7,385; Mean Age = 120 months, SD = 7.52; 49.5% Female) were included in the study. A confirmatory factor analysis was performed to create a latent variable of ecological stress, and multiple structural equation models were tested to evaluate the association among baseline ecological stress and internalizing symptoms one year later, the mediating role of amygdala reactivity, and moderating effects of parental acceptance and sex. The results revealed a significant association between ecological stress and subsequent internalizing symptoms, which was greater in males than females. There was no association between amygdala reactivity during the Faces versus Places contrast and ecological stress or subsequent internalizing symptoms, and no mediating role of amygdala or moderating effect of parental acceptance on the association between ecological stress and internalizing symptoms. An alternative mediation model was tested which revealed that there was a small mediating effect of parental acceptance on the association between ecological stress and internalizing symptoms, demonstrating lower internalizing symptoms among preadolescents one year later. Given the lack of association in brain function, ecological stress and internalizing symptoms in preadolescents in this registered report, effects from comparable small studies should be reconsidered in larger samples.

Dataset Information

Neonatal Amygdala Functional Connectivity at Rest in Healthy and Preterm Infants and Early Internalizing Symptoms.

Publications

Neonatal Amygdala Functional Connectivity at Rest in Healthy and Preterm Infants and Early Internalizing Symptoms.

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