Characterization of Fetal Cortical Development Using Spectral Analysis of Gyrification (SPANGY)

Abstract

The prenatal period of human brain development is critical for mental health and cognition across the entire lifespan. During this period, the cortex undergoes a dramatic transformation from a smooth lissencephalic surface into an elaborately folded structure, a process whose precise characterization is essential for understanding neurodevelopmental trajectories. This study represents the first application of Spectral Analysis of Gyrification (SPANGY) to a large multi-centric fetal brain MRI dataset (635 subjects, 20-38 weeks gestational age). SPANGY characterizes geometric variations on a surface based on the wavelength of folds, hence, providing a quantitative local description of gyrification at the individual level. Using rigorous normative modeling (GAMLSS) and statistical harmonization (ComBat-GAM), we established age-specific reference trajectories for multi-scale gyrification features (spectral frequency bands). We provide the first ever quantification of the temporally-ordered emergence of cortical folding in successive waves during the entire second half of pregnancy: the earliest-emerging low frequency, deep fissures are progressively superseded by the accelerating expansion of higher frequency folds. The normative curves provide the first step in taking prenatal neurodevelopmental assessment from qualitative inspection into a rigorous statistical inference, creating an objective reference against which deviations from healthy brain growth could be caught earlier.

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BibTeX RIS

BibTeX

@misc{dienye2026characterization,
  title = {{Characterization of Fetal Cortical Development Using Spectral Analysis of Gyrification (SPANGY)}},
  author = {H. Dienye and A. Mihailov and T. Sanchez and G. Marti-Juan and R. Gonzalez Lopez and L. Pomar and J. Sichitiu and V. Dunet and M. Koob and E. Eixarch and A. Manchon and N. Girard and M. MILH and D. Germanaud and M. A. Gonzalez Ballester and O. Camara and G. Piella and M. Bach Cuadra and F. Rousseau and J. Lefevre and O. Coulon and G. AUZIAS},
  howpublished = {bioRxiv},
  year = {2026},
  month = jul,
  doi = {10.64898/2026.07.14.736987},
  url = {https://www.biorxiv.org/content/10.64898/2026.07.14.736987v2},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Characterization of Fetal Cortical Development Using Spectral Analysis of Gyrification (SPANGY)
AU  - H. Dienye
AU  - A. Mihailov
AU  - T. Sanchez
AU  - G. Marti-Juan
AU  - R. Gonzalez Lopez
AU  - L. Pomar
AU  - J. Sichitiu
AU  - V. Dunet
AU  - M. Koob
AU  - E. Eixarch
AU  - A. Manchon
AU  - N. Girard
AU  - M. MILH
AU  - D. Germanaud
AU  - M. A. Gonzalez Ballester
AU  - O. Camara
AU  - G. Piella
AU  - M. Bach Cuadra
AU  - F. Rousseau
AU  - J. Lefevre
AU  - O. Coulon
AU  - G. AUZIAS
PY  - 2026
DA  - 2026/07/14
PB  - bioRxiv
DO  - 10.64898/2026.07.14.736987
UR  - https://www.biorxiv.org/content/10.64898/2026.07.14.736987v2
AB  - The prenatal period of human brain development is critical for mental health and cognition across the entire lifespan. During this period, the cortex undergoes a dramatic transformation from a smooth lissencephalic surface into an elaborately folded structure, a process whose precise characterization is essential for understanding neurodevelopmental trajectories. This study represents the first application of Spectral Analysis of Gyrification (SPANGY) to a large multi-centric fetal brain MRI dataset (635 subjects, 20-38 weeks gestational age). SPANGY characterizes geometric variations on a surface based on the wavelength of folds, hence, providing a quantitative local description of gyrification at the individual level. Using rigorous normative modeling (GAMLSS) and statistical harmonization (ComBat-GAM), we established age-specific reference trajectories for multi-scale gyrification features (spectral frequency bands). We provide the first ever quantification of the temporally-ordered emergence of cortical folding in successive waves during the entire second half of pregnancy: the earliest-emerging low frequency, deep fissures are progressively superseded by the accelerating expansion of higher frequency folds. The normative curves provide the first step in taking prenatal neurodevelopmental assessment from qualitative inspection into a rigorous statistical inference, creating an objective reference against which deviations from healthy brain growth could be caught earlier.
ER  -

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