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Dysconnectivity of neurocognitive networks at rest in very-preterm born adults.

ABSTRACT: Advances in neonatal medicine have resulted in a larger proportion of preterm-born individuals reaching adulthood. Their increased liability to psychiatric illness and impairments of cognition and behaviour intimate lasting cerebral consequences; however, the central physiological disturbances remain unclear. Of fundamental importance to efficient brain function is the coordination and contextually-relevant recruitment of neural networks. Large-scale distributed networks emerge perinatally and increase in hierarchical complexity through development. Preterm-born individuals exhibit systematic reductions in correlation strength within these networks during infancy. Here, we investigate resting-state functional connectivity in functional magnetic resonance imaging data from 29 very-preterm (VPT)-born adults and 23 term-born controls. Neurocognitive networks were identified with spatial independent component analysis conducted using the Infomax algorithm and employing Icasso procedures to enhance component robustness. Network spatial focus and spectral power were not generally significantly affected by preterm birth. By contrast, Granger-causality analysis of the time courses of network activity revealed widespread reductions in between-network connectivity in the preterm group, particularly along paths including salience-network features. The potential clinical relevance of these Granger-causal measurements was suggested by linear discriminant analysis of topological representations of connection strength, which classified individuals by group with a maximal accuracy of 86%. Functional connections from the striatal salience network to the posterior default mode network informed this classification most powerfully. In the VPT-born group it was additionally found that perinatal factors significantly moderated the relationship between executive function (which was reduced in the VPT-born as compared with the term-born group) and generalised partial directed coherence. Together these findings show that resting-state functional connectivity of preterm-born individuals remains compromised in adulthood; and present consistent evidence that the striatal salience network is preferentially affected. Therapeutic practices directed at strengthening within-network cohesion and fine-tuning between-network inter-relations may have the potential to mitigate the cognitive, behavioural and psychiatric repercussions of preterm birth.

SUBMITTER: White TP

PROVIDER: S-EPMC3930099 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Very preterm birth (VPT; ≤32 weeks' gestation) is associated with altered brain development and cognitive and behavioral difficulties across the lifespan. However, heterogeneity in outcomes among individuals born VPT makes it challenging to identify those most vulnerable to neurodevelopmental sequelae. Here, we aimed to stratify VPT children into distinct behavioral subgroups and explore between-subgroup differences in neonatal brain structure and function. 198 VPT children (98 females) previously enrolled in the Evaluation of Preterm Imaging Study (EudraCT 2009-011602-42) underwent Magnetic Resonance Imaging at term-equivalent age and neuropsychological assessments at 4-7 years. Using an integrative clustering approach, we combined neonatal socio-demographic, clinical factors and childhood socio-emotional and executive function outcomes, to identify distinct subgroups of children based on their similarity profiles in a multidimensional space. We characterized resultant subgroups using domain-specific outcomes (temperament, psychopathology, IQ and cognitively stimulating home environment) and explored between-subgroup differences in neonatal brain volumes (voxel-wise Tensor-Based-Morphometry), functional connectivity (voxel-wise degree centrality) and structural connectivity (Tract-Based-Spatial-Statistics). Results showed two- and three-cluster data-driven solutions. The two-cluster solution comprised a 'resilient' subgroup (lower psychopathology and higher IQ, executive function and socio-emotional scores) and an 'at-risk' subgroup (poorer behavioral and cognitive outcomes). No neuroimaging differences between the resilient and at-risk subgroups were found. The three-cluster solution showed an additional third 'intermediate' subgroup, displaying behavioral and cognitive outcomes intermediate between the resilient and at-risk subgroups. The resilient subgroup had the most cognitively stimulating home environment and the at-risk subgroup showed the highest neonatal clinical risk, while the intermediate subgroup showed the lowest clinical, but the highest socio-demographic risk. Compared to the intermediate subgroup, the resilient subgroup displayed larger neonatal insular and orbitofrontal volumes and stronger orbitofrontal functional connectivity, while the at-risk group showed widespread white matter microstructural alterations. These findings suggest that risk stratification following VPT birth is feasible and could be used translationally to guide personalized interventions aimed at promoting children's resilience.

Project description:Introduction: Adults Born Very Preterm (ABP) are an underperceived but steadily increasing patient population. It has been shown that they face multiple physical, mental and emotional health problems as they age. Very little is known about their specific health care needs beyond childhood and adolescence. This article focuses on their personal perspectives: it explores how they feel embedded in established health care structures and points to health care-related barriers they face. Methods: We conducted 20 individual in-depth interviews with adults born preterm aged 20-54 years with a gestational age (GA) below 33 weeks at birth and birth weights ranging from 870-1,950 g. Qualitative content analysis of the narrative interview data was conducted to identify themes related to self-perceived health, health care satisfaction, and social well-being. Results: The majority (85%) of the study participants reported that their former prematurity is still of concern in their everyday lives as adults. The prevalence of self-reported physical (65%) and mental (45%) long-term sequelae of prematurity was high. Most participants expressed dissatisfaction with health care services regarding their former prematurity. Lack of consideration for their prematurity status by adult health care providers and the invisibility of the often subtle impairments they face were named as main barriers to receiving adequate health care. Age and burden of disease were important factors influencing participants' perception of their own health and their health care satisfaction. All participants expressed great interest in the provision of specialized, custom-tailored health-care services, taking the individual history of prematurity into account. Discussion: Adults born preterm are a patient population underperceived by the health care system. Longterm effects of very preterm birth, affecting various domains of life, may become a substantial burden of disease in a subgroup of formerly preterm individuals and should therefore be taken into consideration by adult health care providers.

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Dysconnectivity of neurocognitive networks at rest in very-preterm born adults.

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