After the pre-processing in part 1 Pre Processing (n = 280). We start to build the SuStaIn model.

1. ROI selection

In the Table, we present only the ROIs that showed significant differences between cases (GDM exposure, n = 666) and controls (non-GDM exposure with healthy BMI, n = 6,149), both before and after FDR correction. Regions previously reported as significant are highlighted in yellow. Average thickness (n = 280)

In the Plot, we display only the ROIs with significant case–control differences in z-scores after FDR correction.

2. Parameter Setting

Z_val = 1, Z_max = 1.5 ( determined roughly by the 95 percentile of the distribution)

The linear z-score model describes a subtype progression pattern as the linear evolution of biomarkers between different z-scores. Each stage corresponds to a biomarker reaching a new z-score from the set of z-scores for each biomarker, Z_vals. Each biomarker starts with a minimum value of 0 at stage 0 and reaches a maximum of Z_max at the final stage of the progression. The number of stages is determined by the number of biomarkers and z-scores in Z_vals.

3. Results

Subtype 1: Frontal-first, then posterior spread

rostral middle frontal → pars triangularis → superior frontal → pars orbitalis → pars opercularis → superior temporal → middle temporal → precuneus → superior parietal → fusiform → postcentral → transverse temporal → lateral occipital → cuneus → lingual

Subtype 2: Posterior-first, then anterior spread

lingual → cuneus → lateral occipital → fusiform → precuneus → superior parietal → postcentral → transverse temporal → middle temporal → superior temporal → superior frontal → pars opercularis → rostral middle frontal → pars triangularis → pars orbitalis

Interpretation from GPT, still need more research…

🔎 Subtype 1: Frontal-first, then posterior spread

• Starts in frontal association cortex: rostral middle frontal, pars triangularis, superior frontal, orbitalis, opercularis.
  • These are executive/language-related prefrontal regions.
  • Could reflect early disruption in higher-order cognitive control networks, possibly due to subtle metabolic/neurodevelopmental insults.
• Then progresses to temporal and parietal association cortex (superior/middle temporal, precuneus, superior parietal, fusiform).
  • Suggests a spread to language, memory, visuospatial regions.
• Ends in posterior occipital/lingual regions.
  • That would indicate visual cortex changes are late.

👉 Interpretation: This subtype might represent a “top-down” developmental vulnerability, where higher-order executive/language areas (prefrontal) are more sensitive to prenatal metabolic exposure, and changes cascade posteriorly with development.

🔎 Subtype 2: Posterior-first, then anterior spread