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Use of In vivo Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates
Published on: July 6, 2013
Long-term neurobiological consequences of early postnatal hCMV-infection in former preterms: a functional MRI study
Maik Dorn1, Karen Lidzba, Andrea Bevot
1Department of Pediatric Neurology and Developmental Medicine, Children's Hospital, University Hospital, Eberhard Karls University, Tübingen, Germany; Experimental Pediatric Neuroimaging, Children's Hospital, University Hospital, Eberhard Karls University, Tübingen, Germany; Department of Neuroradiology, University Hospital, Eberhard Karls University, Tübingen, Germany.
Abstract:
Early postnatal infection with human cytomegalovirus (hCMV) may contribute to an adverse cognitive outcome in early preterm-born children (PT). We here set out to explore whether long-term neurobiological consequences of such an infection are detectable using fMRI in children and adolescents who were born very preterm and who either did (PThCMV+ ) or did not (PT(hCMV-)) suffer from an early postnatal hCMV-infection, when compared with typically developing healthy control (HC) subjects. Overall, data from 71 children and adolescents could be included, 34 PT (of which 15 were PT(hCMV+) and 19 were PT(hCMV-)) and 37 HC. Using a recently established "dual use" fMRI task, we investigated language and visuospatial functions. There were significant activation differences in the left hippocampus (PT > HC and PT(hCMV+) > HC), and in the right anterior cingulate cortex (PT(hCMV-) > PT(hCMV+)) when performing the language task. Surprisingly, only a small region in the occipital cortex showed a significant activation difference (HC > PT(HCMV-)) when performing the visuospatial task. Targeted analyses revealed differences in gray matter volume, but not density, in several brain regions. Our results suggest that long-term neurobiological consequences of an early postnatal hCMV infection are detectable even in older children and adolescents formerly born very preterm, compatible with a higher effort when performing a cognitive task. This suggests that measures to prevent such an infection are warranted. Furthermore, an interrelation of brain structure and function was detected that may constitute a severe confound when using fMRI to compare structurally differing groups.
Insights
Early human cytomegalovirus (hCMV) infection in preterm infants can lead to detectable long-term neurobiological changes. These findings in children and adolescents suggest increased cognitive effort and highlight the need for infection prevention.
Area of Science:
- Neuroscience
- Pediatrics
- Infectious Diseases
Background:
- Early postnatal infection with human cytomegalovirus (hCMV) is a potential risk factor for adverse cognitive outcomes in preterm-born children.
- Long-term neurobiological effects of hCMV infection in very preterm children are not well understood, particularly in older age groups.
- Functional magnetic resonance imaging (fMRI) offers a potential tool to investigate these subtle, long-term consequences.
Purpose of the Study:
- To determine if long-term neurobiological consequences of early postnatal hCMV infection are detectable using fMRI in children and adolescents.
- To compare brain function and structure between very preterm children with and without early hCMV infection and healthy controls.
- To investigate the impact of hCMV infection on language and visuospatial processing.
Main Methods:
- A cohort of 71 children and adolescents (34 preterm, 37 healthy controls) was studied.
- Preterm participants included those with (PT(hCMV+)) and without (PT(hCMV-)) early postnatal hCMV infection.
- A dual-use fMRI task assessed language and visuospatial functions, alongside targeted analyses of gray matter volume.
Main Results:
- Significant activation differences were observed in the left hippocampus and right anterior cingulate cortex during language tasks.
- Preterm children (PT) and those with hCMV infection (PT(hCMV+)) showed altered hippocampal activation compared to controls (HC).
- Gray matter volume differences were found in several brain regions, but not gray matter density.
- Visuospatial task revealed minimal activation differences, primarily in the occipital cortex (HC > PT(HCMV-)).
Conclusions:
- Early postnatal hCMV infection has detectable long-term neurobiological consequences in very preterm children and adolescents.
- These findings suggest increased cognitive effort during tasks, underscoring the importance of preventive measures against hCMV.
- An interplay between brain structure and function was identified, potentially confounding fMRI-based group comparisons.