Functional thalamocortical connectivity development and alterations in preterm infants during the neonatal period

Cai, Yue; Wu, Xiushuang; Su, Zaiming; Shi, Yuan; Gao, Jia‐Hong

doi:10.1016/j.neuroscience.2017.05.011

Cited by 16 publications

(8 citation statements)

References 51 publications

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“…With our multimodal DTI investigation, we also studied deep gray matter changes associated with prenatal injury as it is known that white and gray matter changes culminate in complex functional deficits (Volpe 2009). Similar to prior pathological and radiological studies of preterm infants (Pierson et al 2007, Kinney 2009, Nagasunder et al 2011, Salvan et al 2014, Cai et al 2017), we found deep gray matter abnormalities are more prominent than cortical changes. Specifically, we found changes in multiple diffusion metrics, including FA, RD and AD in the hippocampus, striatum and thalamus but not sensory cortex.…”

Section: Discussionsupporting

confidence: 90%

“…Indeed, the thalamus appears particularly vulnerable to microstructural changes in preterm neonates and childhood survivors (Nagasunder, Kinney et al 2011, Paquette et al 2015, Menegaux et al 2017). Distinct overlap exists between the evolution of thalamo-cortical and intrahemispheric cortico-cortico connectivity, suggestive of developmental synergy between thalamic morphology and the temporal emergence of cortical networks (Rose et al 2014, Ceschin, Wisnowski et al 2015, Cai, Wu et al 2017, Hwang et al 2017). Importantly, altered functional connectivity is identifiable in preterm infants prior to birth (Thomason et al 2017), emphasizing the contribution of intrauterine insults to early CNS injury.…”

Section: Discussionmentioning

confidence: 99%

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Neonatal erythropoietin mitigates impaired gait, social interaction and diffusion tensor imaging abnormalities in a rat model of prenatal brain injury

Robinson

Corbett

Winer

et al. 2018

Experimental Neurology

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Children who are born preterm are at risk for encephalopathy of prematurity, a leading cause of cerebral palsy, cognitive delay and behavioral disorders. Current interventions are limited and none have been shown to reverse cognitive and behavioral impairments, a primary determinant of poor quality of life for these children. Moreover, the mechanisms of perinatal brain injury that result in functional deficits and imaging abnormalities in the mature brain are poorly defined, limiting the potential to target interventions to those who may benefit most. To determine whether impairments are reversible after a prenatal insult, we investigated a spectrum of functional deficits and diffusion tensor imaging (DTI) abnormalities in young adult animals. We hypothesized that prenatal transient systemic hypoxia-ischemia (TSHI) would induce multiple functional deficits concomitant with reduced microstructural white and gray matter integrity, and tested whether these abnormalities could be ameliorated using postnatal erythropoietin (EPO), an emerging neurorestorative intervention. On embryonic day 18 uterine arteries were transiently occluded for 60min via laparotomy. Shams underwent anesthesia and laparotomy for 60min. Pups were born and TSHI pups were randomized to receive EPO or vehicle via intraperitoneal injection on postnatal days 1 to 5. Gait, social interaction, olfaction and open field testing was performed from postnatal day 25-35 before brains underwent ex vivo DTI to measure fractional anisotropy, axial diffusivity and radial diffusivity. Prenatal TSHI injury causes hyperactivity, impaired gait and poor social interaction in young adult rats that mimic the spectrum of deficits observed in children born preterm. Collectively, these data show for the first time in a model of encephalopathy of prematurity that postnatal EPO treatment mitigates impairments in social interaction, in addition to gait deficits. EPO also normalizes TSHI-induced microstructural abnormalities in fractional anisotropy and radial diffusivity in multiple regions, consistent with improved structural integrity and recovery of myelination. Taken together, these results show behavioral and memory deficits from perinatal brain injury are reversible. Furthermore, resolution of DTI abnormalities may predict responsiveness to emerging interventions, and serve as a biomarker of CNS injury and recovery.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Neonatal erythropoietin mitigates impaired gait, social interaction and diffusion tensor imaging abnormalities in a rat model of prenatal brain injury

Robinson

Corbett

Winer

et al. 2018

Experimental Neurology

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“…For task fMRI, positive BOLD responses were seen contralateral to the side of passive motor task, though in one infant the response was only seen in the injured hemisphere. More recently, Cai and colleagues used rs-fMRI to study 22 preterm infants with ≤10 punctate periventricular white matter lesions identified on T1-and T2-weighted images scanned between 32 and 39 weeks PMA (Cai, Wu, Su, Shi, & Gao, 2017). Findings in these infants were compared with those from a matched group of preterm infants without brain injury.…”

Section: Intraventricular Hemorrhage and Periventricular Leukomalaciamentioning

confidence: 99%

Neonatal brain injury and aberrant connectivity

et al. 2019

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Brain injury sustained during the neonatal period may disrupt development of critical structural and functional connectivity networks leading to subsequent neurodevelopmental impairment in affected children. These networks can be characterized using structural (via diffusion MRI) and functional (via resting state-functional MRI) neuroimaging techniques. Advances in neuroimaging have led to expanded application of these approaches to study term- and prematurely-born infants, providing improved understanding of cerebral development and the deleterious effects of early brain injury. Across both modalities, neuroimaging data are conducive to analyses ranging from characterization of individual white matter tracts and/or resting state networks through advanced 'connectome-style' approaches capable of identifying highly connected network hubs and investigating metrics of network topology such as modularity and small-worldness. We begin this review by summarizing the literature detailing structural and functional connectivity findings in healthy term and preterm infants without brain injury during the postnatal period, including discussion of early connectome development. We then detail common forms of brain injury in term- and prematurely-born infants. In this context, we next review the emerging body of literature detailing studies employing diffusion MRI, resting state-functional MRI and other complementary neuroimaging modalities to characterize structural and functional connectivity development in infants with brain injury. We conclude by reviewing technical challenges associated with neonatal neuroimaging, highlighting those most relevant to studying infants with brain injury and emphasizing the need for further targeted study in this high-risk population.

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“…However, to date the characteristics of the neonatal structural connectome and the development across the perioperative period in CHD neonates in comparison to healthy controls are not well studied. Furthermore, while there is evidence that WMI can disrupt the structural and functional connectome in preterm born infants (Ceschin et al 2015, Cai et al 2017, how the specific emergent properties of the whole-brain network are affected by WMI in neonates with CHD remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Delayed maturation of the structural brain connectome in neonates with congenital heart disease

Feldmann

Guo

Miller

et al. 2020

Preprint

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There is emerging evidence for delayed brain development in neonates with congenital heart disease (CHD). We hypothesize that the perioperative development of the structural brain connectome is a proxy to such delays. Therefore, we set out to quantify the alterations and longitudinal pre- to postoperative changes in the connectome in CHD neonates and assess risk factors for disturbed perioperative network development relative to healthy term newborns. In this prospective cohort study, 114 term neonates with CHD underwent cardiac surgery at the University Children’s Hospital Zurich. Forty-six healthy term newborns were included as controls. Pre- and postoperative structural connectomes were derived from mean fractional anisotropy values of fibre pathways traced using diffusion tractography. Graph theory parameters calculated across a range of proportional cost thresholds were compared between groups by multi-threshold permutation correction adjusting for con-founders. Network based statistic was calculated for edgewise network comparison. White matter injury (WMI) volume was quantified on 3D T1-weighted images. Random coefficient mixed models with interaction terms of (i) CHD subtype and (ii) WMI volume with postmenstrual age at MRI respectively were built to assess modifying effects on network development. Pre- and postoperatively, at the global level, efficiency, indicative of network integration, was higher in controls compared to CHD neonates. In contrast, local efficiency and transitivity, indicative of network segregation, were higher in CHD neonates compared to controls (all p<0.025 for one-sided t-tests). Preoperatively these group differences were also found across multiple widespread nodes (all p<0.025, accounting for multiple comparison), whereas postoperatively nodal differences were not evident. At the edge-level, the majority of weaker connections in CHD neonates compared to controls involved interhemispheric connections (66.7% preoperatively; 54.5% postoperatively). A trend showing a more rapid pre- to postoperative decrease in local efficiency was found in class I CHD neonates compared to controls. In CHD neonates, larger WMI volume was associated with lower strength (p=0.0026) and global efficiency (p=0.0097). The maturation of the structural connectome is delayed in neonates with CHD, with a pattern of lower structural integration and higher segregation compared to healthy controls. Trend-level evidence indicated that normalized postoperative cardiac physiology in class I CHD neonates might improve structural network topology. In contrast, the degree of WMI burden negatively impacts network strength and integration. Further research is needed to elucidate how aberrant structural network development in CHD represents neural correlates of later neurodevelopmental impairments.

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Functional thalamocortical connectivity development and alterations in preterm infants during the neonatal period

Cited by 16 publications

References 51 publications

Neonatal erythropoietin mitigates impaired gait, social interaction and diffusion tensor imaging abnormalities in a rat model of prenatal brain injury

Neonatal erythropoietin mitigates impaired gait, social interaction and diffusion tensor imaging abnormalities in a rat model of prenatal brain injury

Neonatal brain injury and aberrant connectivity

Delayed maturation of the structural brain connectome in neonates with congenital heart disease

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