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February 9, 2026Tomography0 citationsOpen Access

Comprehensive Morphometric MRI Assessment in Children with Breath-Holding Spells: Integration of Automated (Vol2Brain) and Semi-Automated (3D Slicer) Segmentation Methods

AAAdil AytaçBalıkesir UniversityHAHilal AydınBalıkesir University

Key Result

Children with breath-holding spells showed significantly reduced bilateral amygdala volumes (left: p=0.011, g=0.52; right: p=0.007, g=0.56), decreased right anterior insula thickness (p=0.014, g=0.49) and volume (p=0.021, g=0.41), reduced cortical thickness in bilateral anterior cingulate cortices (left: p=0.019, g=0.43; right: p=0.017, g=0.45), right medial frontal cortex (p=0.009, g=0.52), and decreased volumes in right cerebellar lobule VI (p=0.007, g=0.50), left lobule VIIA crus I (p=0.012, g=0.44), and vermis IX–X (p=0.010, g=0.47) compared to controls.

Key Points

  • The aim is to evaluate anatomical brain differences in children with breath-holding spells compared to a control group using advanced MRI techniques.
  • Analyzed 3D T1-weighted cranial MRI data from 48 children with breath-holding spells and 50 control children.
  • Examined 135 brain regions for volumetric, surface area, and cortical thickness measures.
  • Used analysis of covariance to control for age, sex, and total intracranial volume.
  • Children with breath-holding spells showed reduced amygdala volumes bilaterally.
  • Cortical thickness and volume were lower in the right anterior insula.
  • Cortical thickness decreased in the bilateral anterior cingulate and right medial frontal cortex.
  • Subregional cerebellar analysis revealed volume reductions in specific lobules.

Study Design

Type

Cross-Sectional (n=98)

Multicenter

No

Structured PICO

Do children with breath-holding spells exhibit regional anatomical differences in brain volume, surface area, and cortical thickness compared to healthy controls?

P
Population
98 children, comprising 48 with breath-holding spells (BHSs) and 50 control children
I
Intervention
Three-dimensional T1-weighted cranial MRI with morphometric analysis (automated Vol2Brain and semi-automated 3D Slicer segmentation methods)
C
Comparator
Control children
O
Outcome
Regional anatomical differences in brain volume, surface area, and cortical thickness across 135 brain regionssurrogate

Children with breath-holding spells demonstrate measurable morphometric reductions in brain regions involved in autonomic and emotional regulation, such as the amygdala and anterior insula.

Main Result

Effect estimate: Cohen's d (Hedges' g) ranging from 0.41 to 0.56 for significantly different regions

Limitations

  • Retrospective, cross-sectional design limits causal inference
  • Relatively small sample size may limit generalizability
  • Single-center study conducted in Turkey may limit global applicability
  • Potential confounding factors such as nutritional and iron status were not controlled
  • No longitudinal follow-up to assess progression or reversibility of morphometric changes
  • Imaging conducted without sedation may have limitations in image quality despite motion artifact exclusion

Abstract

Objectives: To evaluate regional anatomical differences in brain volume, surface area, and cortical thickness between children with breath-holding spells (BHSs) and a control group using morphometric MRI analyses. Methods: Three-dimensional T1-weighted cranial MRI data from 48 children with BHSs and 50 control children were retrospectively analyzed, yielding volumetric, surface area, and cortical thickness measures for 135 brain regions. All measurements were assessed relative to total intracranial volume (ICV). Group comparisons were performed using analysis of covariance with age, sex, and ICV as covariates, followed by Benjamini–Hochberg false discovery rate correction (q < 0.05). Results: The BHS group exhibited reduced bilateral amygdala volumes (left: q = 0.042; right: q = 0.038). Both cortical thickness and volume were reduced in the right anterior insula (thickness: q = 0.046; volume: q = 0.049). In addition, cortical thickness was reduced in the bilateral anterior cingulate cortices (left: p = 0.019, q = 0.045; right: p = 0.017, q = 0.043) as well as in the right medial frontal cortex (p = 0.009, q = 0.036). Subregional cerebellar analysis demonstrated volume reductions in the right lobule VI (q = 0.031), left lobule VIIA (Crus I) (q = 0.043), and vermis IX–X (q = 0.039). Conclusions: Detecting measurable morphometric changes in brain regions involved in autonomic and emotional regulation in children with BHSs will contribute to understanding the neurobiological characteristics associated with BHSs.

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Cite This Study

Aytaç et al. (2026) conducted a cross-sectional in Children aged 6 months to 6 years with clinically diagnosed breath-holding spells (BHSs), normal neurodevelopment, and normal brain MRI compared to age-matched controls with normal brain MRI and no neurological disorders (n=98). Children with breath-holding spells showed significantly reduced bilateral amygdala volumes (left: p=0.011, g=0.52; right: p=0.007, g=0.56), decreased right anterior insula thickness (p=0.014, g=0.49) and volume (p=0.021, g=0.41), reduced cortical thickness in bilateral anterior cingulate cortices (left: p=0.019, g=0.43; right: p=0.017, g=0.45), right medial frontal cortex (p=0.009, g=0.52), and decreased volumes in right cerebellar lobule VI (p=0.007, g=0.50), left lobule VIIA crus I (p=0.012, g=0.44), and vermis IX–X (p=0.010, g=0.47) compared to controls.

synapsesocial.com/papers/698979a6f0ec2af6756e770bhttps://doi.org/10.3390/tomography12020021
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