Association between hippocampal subfield development and socio-emotional outcomes in preterm infants

2150 

Abstract Submission 

Camille Heguy^1,2, Sarah Palmis^1,2, Bradley Karat³, Guillaume Gilbert⁴, Christine Saint-Martin⁵, Wissam Shalish^6,7, Emma Duerden^8,9,10, Marie Brossard-Racine^1,2,11

¹Advances in Brain&Child Development Laboratory, Research Institute of the MUHC, Montreal, Quebec, Canada, ²Department of Neurology & Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, Canada, ³Robarts Research Institute, University of Western Ontario, London, Ontario, Canada, ⁴MR Clinical Science, Philips Healthcare, Mississauga, Ontario, Canada, ⁵Department of Medical Imaging, Division of Pediatric Radiology, Montreal Children's Hospital, MUHC, Montreal, Quebec, Canada, ⁶Department of Pediatrics, Division of Neonatology, Montreal Children’s Hospital, Montreal, Quebec, Canada, ⁷Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada, ⁸Faculty of Education, Western University, London, Ontario, Canada, ⁹Western Institute for Neuroscience, Western University, London, Ontario, Canada, ¹⁰Pediatrics, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada, ¹¹School of Physical & Occupational Therapy, McGill University, Montreal, Quebec, Canada

Camille Heguy, BSc  
Advances in Brain&Child Development Laboratory, Research Institute of the MUHC|Department of Neurology & Neurosurgery, Faculty of Medicine, McGill University
Montreal, Quebec, Canada|Montreal, Quebec, Canada

Sarah Palmis, PhD  
Advances in Brain&Child Development Laboratory, Research Institute of the MUHC|Department of Neurology & Neurosurgery, Faculty of Medicine, McGill University
Montreal, Quebec, Canada|Montreal, Quebec, Canada

Bradley Karat  
Robarts Research Institute, University of Western Ontario
London, Ontario, Canada

Guillaume Gilbert, PhD  
MR Clinical Science, Philips Healthcare
Mississauga, Ontario, Canada

Christine Saint-Martin, MD  
Department of Medical Imaging, Division of Pediatric Radiology, Montreal Children's Hospital, MUHC
Montreal, Quebec, Canada

Wissam Shalish, MD PhD  
Department of Pediatrics, Division of Neonatology, Montreal Children’s Hospital|Department of Medicine, Division of Experimental Medicine, McGill University
Montreal, Quebec, Canada|Montreal, Quebec, Canada

Emma Duerden, PhD  
Faculty of Education, Western University|Western Institute for Neuroscience, Western University|Pediatrics, Schulich School of Medicine & Dentistry, Western University
London, Ontario, Canada|London, Ontario, Canada|London, Ontario, Canada

Marie Brossard-Racine, PhD  
Advances in Brain&Child Development Laboratory, Research Institute of the MUHC|Department of Neurology & Neurosurgery, Faculty of Medicine, McGill University|School of Physical & Occupational Therapy, McGill University
Montreal, Quebec, Canada|Montreal, Quebec, Canada|Montreal, Quebec, Canada

Each year, more than 1 in 10 neonates are born prematurely (<36 weeks gestational age [GA]) worldwide¹. Premature birth carries long-term consequences, including an increased risk of socio-emotional difficulties during childhood². The hippocampus is a crucial brain region for socio-emotional abilities as it conducts functions such as the flexible manipulation of relational memories which is essential for understanding social interactions and behaviour regulation³. Prior studies showed that children born very preterm (<32 weeks GA; [VPT]) exhibit reduced total hippocampal volumes compared to their term-born peers at school-age⁴ and that volume reduction is associated with impaired memory functions⁵. Recent studies in healthy adults have suggested that the hippocampus functional topography may be region-specific⁶. However, investigations of early hippocampal subfield development and how they may relate to functional outcomes are sparse in VPT infants. With the recent refinement of Hippunfold, a validated automatic magnetic resonance imaging [MRI]-based hippocampal subfield segmentation pipeline⁷, we may now have the tools to fill this gap in knowledge. Therefore, this ongoing study aims to 1) quantify total and subfield hippocampal volumes at term-equivalent age [TEA] in VPT infants and 2) explore the relationships between volumes at TEA and socio-emotional competencies at 12 months corrected age.

Enrolled VPT infants completed a brain MRI under natural sleep at TEA on a 3.0 Tesla MRI system (Achieva X-Series, Philips Healthcare) using a 32-channel head coil. High-resolution (1 mm isotropic) T1-weighted images were acquired and pre-processed using Hippunfold. Pre-processing steps included N4 bias field correction, resampling to a 0.3mm isotropic subvolume, linear registration to an age-appropriate template, cropping to coronal-oblique subvolumes and left-right flipping of the left hippocampi sub-volumes. Automatic segmentation of the hippocampi and 7 subfields (subiculum, cornu ammonis [CA] 1-4, dentate gyrus [DG] and Stratum Radiatum, Lacunosum, and Moleculare [SRLM]) was also performed in Hippunfold. Lastly, manual correction was performed when necessary. At 12 months corrected age, parents completed the Brief Infant-Toddler Social and Emotional Assessment (BITSEA)⁸, which yielded results divided into two subscales: Problem, (e.g., anxiety, aggression and defiance) and Competence (e.g., prosocial behaviors, empathy and compliance). Partial correlation analyses were performed to determine the relationships between each hippocampal subfield volume and both socio-emotional subscales while controlling for GA at birth and sex. Correction for multiple comparisons was performed using the False Discovery Rate (FDR).

In this ongoing study, the hippocampi and subfields of 40 VPT infants were successfully segmented using Hippunfold (Table 1 and Fig. 2). Of those, 17 (43%) infants had an available BITSEA at 12 months corrected age. The results of the BITSEA showed that 29% of VPT infants had deficits on the Problem and 41% on the Competence subscales. The left CA4/DG volume at TEA was significantly negatively associated with the Problem score (r=-0.55; p=0.03) and positively associated with the Competence score (r=0.53, p=0.04) at 12 months corrected age. However, these associations did not remain significant after FDR correction. No other significant associations were found.

In this study, we found significant associations between left CA4/DG volumes at TEA and socio-emotional development at 12 months in VPT infants. Upcoming analyses in a larger sample size will allow the addition of more clinical variables in our models to better understand these complex associations. We hope that these results will enhance our comprehension of the role of hippocampal subfield development in the socio-emotional well-being of VPT infants.

Social Interaction

Emotion and Motivation Other

Early life, Adolescence, Aging ²

Subcortical Structures ¹

Emotions

Segmentation

Social Interactions

STRUCTURAL MRI

Sub-Cortical