Unraveling the Miswired Connectome: A Developmental Perspective

Abstract

Summary The vast majority of mental illnesses can be conceptualized as developmental disorders of neural interactions within the connectome, or developmental miswiring. The recent maturation of pediatric in vivo brain imaging is bringing within reach the identification of clinically meaningful brain-based biomarkers of developmental disorders. Even more auspicious, is the ability to study the evolving connectome throughout life, beginning in utero, which promises to move the field from topological phenomenology to etiological nosology. Here, we scope advances in pediatric imaging of the brain connectome as the field faces the challenge of unraveling developmental miswiring. We highlight promises while also providing a pragmatic review of the many obstacles ahead that must be overcome to significantly impact public health.

Differential patterns of age‐related cortical and subcortical functional connectivity in 6‐to‐10 year old children: A connectome‐wide association study

“…Finally, data scrubbing was used to further compensate for motion, removing volumes with excessive movement (i.e., greater than 0.5 mm root mean squared relative motion; Power, Barnes, Snyder, Schlaggar, & Petersen, 2012, 2013) since head motion during scanning can amplify developmental differences in connectivity (Power et al., 2012). This effect is significantly reduced after compensating for movement (Di Martino et al., 2014). …”

“…Mental health in adulthood is highly dependent on brain development beginning in the womb and continuing throughout adolescence and into adulthood. One theory is that the neurobiological underpinnings of mental illnesses are largely driven by atypical brain connectivity originating in childhood (Di Martino et al., 2014; Menon, 2013). Through an understanding of typical connectivity, we can identify aberrant patterns associated with neuropsychiatric disorders.…”

“…In infancy, the brain's short‐range connections are dominant (Gao et al., 2011; Di Martino et al., 2014). Throughout childhood and adolescence, functional connectivity becomes increasingly distributed, with long‐range connections becoming stronger and short‐range connectivity decreasing (Fair et al., 2009; Di Martino et al., 2014; Rubia, 2013).…”

“…In infancy, the brain's short‐range connections are dominant (Gao et al., 2011; Di Martino et al., 2014). Throughout childhood and adolescence, functional connectivity becomes increasingly distributed, with long‐range connections becoming stronger and short‐range connectivity decreasing (Fair et al., 2009; Di Martino et al., 2014; Rubia, 2013). Furthermore, graph theory studies have also demonstrated that while topological features of brain connectivity are mature by age eight, the hierarchical and modularity of global brain networks continues to mature into adulthood (Menon, 2013).…”

“…Development of brain connectivity is increasingly being studied using whole‐brain connectomes derived from resting‐state functional MRI (rs‐fMRI; Di Martino et al., 2014; Rubia, 2013). Connectomes represent brain connectivity between pairs of grey matter ROI's (Bullmore & Sporns, 2009; Rubinov & Sporns, 2010).…”