Nutritional supplement induced modulations in the functional connectivity of a porcine brain

ABSTRACT

Background

Functional connectivity (FC) measures statistical dependence between cortical brain regions. Studies of FC facilitate understanding of the brain’s function and architecture that underpin normal cognition, behavior, and changes associated with various factors (e.g. nutritional supplements) at a large scale.

Objective

We aimed to identify modifications in FC patterns and targeted brain anatomies in piglets following perinatal intake of different nutritional diets using a graph theory based approach.

Methods

Forty-four piglets from four groups of pregnant sows, who were treated with nutritional supplements, including control diet, docosahexaenoic acid (DHA), egg yolk (EGG), and DHA + EGG, went through resting-state functional magnetic resonance imaging (rs-fMRI). We introduced the use of differential degree test (DDT) to identify differentially connected edges (DCEs). Simulation studies were first conducted to compare the DDT with permutation test, using three network structures at different noise levels. DDT was then applied to rs-fMRI data acquired from piglets.

Results

In simulations, the DDT showed a greater accuracy in detecting DCEs when compared with the permutation test. For empirical data, we found that the strength of internodal connectivity is significantly increased for more than 6% of edges in the EGG group and more than 8% of edges in the DHA and DHA + EGG groups, all compared to the control group. Moreover, differential wiring diagrams between group comparisons provided means to pinpoint brain hubs affected by nutritional supplements.

Conclusion

DDT showed a greater accuracy of detection of DCEs and demonstrated EGG, DHA, and DHA + EGG supplemented diets lead to an improved internodal connectivity in the developing piglet brain.

KEYWORDS:

• Functional connectivity
• brain development
• graph theory
• docosahexaenoic acid
• egg yolk
• differential degree test
• nutritional supplement
• porcine model

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors declare that data associated with the present paper only are available for Nutritional Neuroscience Journal upon request.

Additional information

Funding

The study was supported by grants from the United States Department of Agriculture, National Institute of Food and Agriculture (#2020-67017-30839) and the American Egg Board, Egg Nutrition Center.

Notes on contributors

Ishfaque Ahmed

Ishfaque Ahmed is a Ph.D. student at the University of Georgia and Lecturer in Physics at University of Sindh. He has completed his B.S. (2010) and M.S. (2016) in Physics. His research interests are related to biomedical imaging, computational biophysics, graph theory and data science.

William D. Reeves

William D. Reeves is a Ph.D. student at the University of Georgia. They have completed their B.S. in Cell and Molecular Biology (2015) and B.S. in Physics (2018). Their interests lie in the application of graph theory to functional MRI, functional connectivity, and computational simulations of functional time series.

Wenwu Sun

Wenwu Sun is a Ph.D. student at the University of Georgia. He completed his B.S (2017) in Physics. His research interest is focused on brain development, functions, connectivity, and magnetic resonance imaging studies.

Stephanie T. Dubrof

Stephanie T. Dubrof is a Ph.D. student at the University of Georgia and a Graduate Assistant Researcher. She is in the Department of Nutritional Science, and her research focuses on maternal nutrition. She uses a translational pig model to elucidate the mechanism of action of bioactive food components on inflammation and neurocognition in offspring following maternal diet intervention.

Jillien G. Zukaitis

Jillien G. Zukaitis completed her B.S. (2021) and M.S. (2022) in Nutrition at the University of Georgia. She is interested in developmental nutrition, and her research focused on maternal supplementation for optimal health and perinatal cognitive development.

Franklin D. West

Franklin D. West is a faculty member in the Regenerative Bioscience Center and a professor in the Animal and Dairy Science Department at the University of Georgia. He completed his B.S. in Biology at Morehouse College in 2004 and his Ph.D. in Stem Cell Biology at the University of Georgia in 2008. His research focuses on traumatic brain injury and stroke and novel regenerative therapies including extracellular vesicles and stem cells.

Hea Jin Park

Hea Jin Park is an Associate professor at the Department of Nutritional Sciences at the University of Georgia. The research conducted in our laboratory aims to identify and define the beneficial role of bioactive food compounds and functional foods on optimal health in humans. We utilize translational large animal models and human cohorts to elucidate the mechanism of action of food components on inflammation and neurocognition.

Qun Zhao

Qun Zhao is a Professor of Physics at the University of Georgia. He obtained his B.S. and Ph.D. all in electrical engineering in 1989 and 1995, respectively. His research interest is focused on brain development, functions, and connectivity, machine learning, graph theory, and magnetic resonance imaging.