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. 2025 Jun 26:19:1576932.
doi: 10.3389/fnins.2025.1576932. eCollection 2025.

The clinical relevance of healthy neurodevelopmental connectivity in childhood and adolescence: a meta-analysis of resting-state fMRI

Merida Galilea Tapia Medina  1   2   3 , Raquel Cosío-Guirado  1   2   3 , Maribel Peró-Cebollero  1   2   3 , Cristina Cañete-Massé  1 , Erwin Rogelio Villuendas-González  4 , Joan Guàrdia-Olmos  1   2   3
Affiliations

The clinical relevance of healthy neurodevelopmental connectivity in childhood and adolescence: a meta-analysis of resting-state fMRI

Merida Galilea Tapia Medina et al. Front Neurosci. .

Abstract

Background: In recent years, interest has grown in brain connectivity during infancy and adolescence, particularly in understanding neurodevelopment. Research is focusing on how brain network complexity evolves, providing insight into developmental neural connectivity. While some studies highlight key periods of brain maturation, findings remain inconsistent, leaving the neural correlates of typical development uncertain. This meta-analysis aims to identify brain regions and functional connectivity networks that show age-related activation patterns. Our goal is to clarify how neural wiring and complexity change with age, using seed-based d mapping (SDM) to analyze resting-state functional connectivity.

Methods: We reviewed studies employing resting-state functional magnetic resonance imaging (rs-fMRI) to examine brain connectivity in typically developing children and adolescents. After thoroughly application of the rigorous inclusion criteria, five studies published between 2013 and 2024 remained selected for this analysis. While this is a small number, this limitation reflects our unwavering commitment to methodological rigor and the current scarcity of available literature, ensuring that only high-quality studies were considered.

Results: Consistent increases in seed-based connectivity involving the left frontal and prefrontal cortices were observed, particularly the left superior frontal gyrus and bilateral anterior cingulate cortex. These areas showed increased connectivity in older compared to younger participants.

Conclusion: The left frontal and prefrontal cortices, which are critical for executive function, attention, and intelligence, appear to strengthen their connectivity during childhood and adolescence. These observations provide a preliminary glimpse into typical brain maturation. However, due to the small number of studies and heterogeneity in age comparisons. No clinical implications can be drawn at this stage, and further research is required to confirm these developmental trends.

Keywords: brain connectivity; fMRI; healthy neurodevelopment; meta-analysis; resting-state.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of the meta-analysis search conducted.
Figure 2
Figure 2
Representation of the positive and negative peak coordinates obtained in the different studies included in the meta-analysis. Blue color represents the minimum peaks and green color represents the maximum peak. The size of every node is proportioned to the Cohen’s d calculated through the meta-analysis. (1) Dai et al. (2019), (2) Içer (2019), (3) Liuzzi et al. (2023), (4) Xiao et al. (2016a), (5) Xiao et al. (2016b).
Figure 3
Figure 3
Forest plot of the negative effect size. The effect size (Cohen’s d; blue circle) is shown with the 95% confidence interval.
Figure 4
Figure 4
Representation of the most significant coordinates that show activation in older participants compared with younger participants. The left superior frontal gyrus, medial, is shown in blue; the left anterior cingulate/paracingulate gyri is shown in yellow; the right anterior cingulate/paracingulate gyri is shown in red.
See this image and copyright information in PMC

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