Brain connectivity in normally developing children and adolescents

Highlights

• Major events shape the developmental changes in brain connectivity.

• Brain changes coincide with cognitive development.

• Connectivity analysis allows investigation of regional and global brain changes.

Abstract

The developing human brain undergoes an astonishing sequence of events that continuously shape the structural and functional brain connectivity. Distinct regional variations in the timelines of maturational events (synaptogenesis and synaptic pruning) occurring at the synaptic level are reflected in brain measures at macroscopic resolution (cortical thickness and gray matter density). Interestingly, the observed brain changes coincide with cognitive milestones suggesting that the changing scaffold of brain circuits may subserve cognitive development. Recent advances in connectivity analysis propelled by graph theory have allowed, on one hand, the investigation of maturational changes in global organization of structural and functional brain networks; and on the other hand, the exploration of specific networks within the context of global brain networks. An emerging picture from several connectivity studies is a system-level rewiring that constantly refines the connectivity of the developing brain.

Introduction

The structure and function of neural connections are continuously shaped by several events that constitute brain maturation. Our understanding about these major events has largely been derived from animal models and postmortem studies (Huttenlocher, 1979, Huttenlocher, 1984, Huttenlocher, 1990, Huttenlocher et al., 1982a, Huttenlocher et al., 1982b, Becker et al., 1984, Bourgeois, 1997, Bourgeois et al., 1994, Huttenlocher and Dabholkar, 1997). Neuroimaging studies provided a paradigm shift by allowing comprehensive non-invasive investigation of brain structure and function in humans (Giedd et al., 1999, Gogtay et al., 2004, Raznahan et al., 2011, Shaw et al., 2006a, Shaw et al., 2006b, Thompson et al., 2000, Dosenbach et al., 2010, Ameis et al., 2014, Khundrakpam et al., 2015). However, much of the studies to date have focused on focal developmental changes in brain structure and function. As such, detailed description of the developing neural circuitry, especially the changing relationships among disparate brain components, has not been adequately addressed till recently. Recent developments in characterizing brain networks, referred to as the field of ‘connectomics’ (Bassett and Bullmore, 2009, Bullmore and Sporns, 2009, Bullmore and Bassett, 2011, Evans, 2013, He and Evans, 2010, Khundrakpam et al., 2013, Hagmann et al., 2010a, Sporns, 2011, Sporns, 2013), have helped untangle maturational changes in brain connectivity and provide evidence for ‘connectomic’ biomarkers for the detection of neurodevelopmental disorders (Fair et al., 2012, Worbe et al., 2012, Lewis et al., 2013, Lewis et al., 2014, Kaiser, 2013).

In this review, we outline a perspective on connectivity in the developing human brain (with focus on childhood and adolescence) and deliberate on how recent advances in the field of ‘connectomics’ using graph-theoretic approaches have increased our understanding of the maturing brain architecture. We first provide an overview of the major events that occur during normal brain development. Next, we discuss the anatomical and functional MRI studies that have shown focal changes in brain structure and function with development. We then elaborate on traditional approaches (read as, seed-based and region-of-interest (ROI)-based studies) toward understanding brain connectivity in the developing brain. We deliberate on the need for whole-brain connectivity approach and how graph theory provides a valid framework for addressing the same. We then discuss graph-theoretic studies that have been done with several imaging modalities including diffusion tensor imaging (DTI), MRI, and functional MRI (fMRI) in terms of two perspectives: i) whole-brain organizational changes with development as inferred with global topological parameters and ii) system-level changes with development. Lastly, we discuss the mediation of genes and environment in the developing brain.