Growing Together and Growing Apart: Regional and Sex Differences in the Lifespan Developmental Trajectories of Functional Homotopy

TLDR

Functional homotopy, the strong synchrony between geometrically corresponding interhemispheric regions, is a core feature of brain architecture but its lifespan development has rarely been directly examined. This study aimed to map age‑related changes in homotopic resting‑state functional connectivity across the human lifespan. The authors assessed homotopic RSFC in 214 healthy participants aged 7 to 85 years using fMRI. They found region‑specific developmental trajectories: sensorimotor areas showed increasing homotopic connectivity, higher‑order regions decreased, some regions followed quadratic or cubic patterns, and sex differences emerged in dorsolateral prefrontal cortex and amygdala, underscoring robust lifespan effects that warrant further mechanistic investigation in disease.

Abstract

Functional homotopy, the high degree of synchrony in spontaneous activity between geometrically corresponding interhemispheric (i.e., homotopic) regions, is a fundamental characteristic of the intrinsic functional architecture of the brain. However, despite its prominence, the lifespan development of the homotopic resting-state functional connectivity (RSFC) of the human brain is rarely directly examined in functional magnetic resonance imaging studies. Here, we systematically investigated age-related changes in homotopic RSFC in 214 healthy individuals ranging in age from 7 to 85 years. We observed marked age-related changes in homotopic RSFC with regionally specific developmental trajectories of varying levels of complexity. Sensorimotor regions tended to show increasing homotopic RSFC, whereas higher-order processing regions showed decreasing connectivity (i.e., increasing segregation) with age. More complex maturational curves were also detected, with regions such as the insula and lingual gyrus exhibiting quadratic trajectories and the superior frontal gyrus and putamen exhibiting cubic trajectories. Sex-related differences in the developmental trajectory of functional homotopy were detected within dorsolateral prefrontal cortex (Brodmann areas 9 and 46) and amygdala. Evidence of robust developmental effects in homotopic RSFC across the lifespan should serve to motivate studies of the physiological mechanisms underlying functional homotopy in neurodegenerative and psychiatric disorders.