Normative references of corpus callosum across lifespan and application in neurological and neuroimmunological disorders
11 affiliations
- 1Department of Radiology, Beijing Tiantan Hospital, Capital Medical University
- 2Centre for Cognitive and Brain Sciences and Department of Psychology, University of Macau
- 3Department of Radiology, The First Affiliated Hospital of USTC, University of Science and Technology of China
- 4Department of Neurology, Beijing Tiantan Hospital, Capital Medical University
- 5Philips (China) Investment Co., Ltd.
- 6Institute of Research and Clinical Innovations, Neusoft Medical Systems Co., Ltd.
- 7China National Clinical Research Center for Neurological Diseases
- 8Centre for Medical Image Computing, University College London
- 9Dementia Research Centre, Queen Square Institute of Neurology, University College London
- 10Faculty of Health Sciences, University of Macau
- 11Qinghai University Affiliated Hospital
Abstract
Background: The corpus callosum (CC) is the largest white matter structure and is often affected in neurological and neuroimmunological disorders. However, previous studies mainly used group-level comparisons. This limits patient-level magnetic resonance imaging (MRI) assessment.
Methods: In this multicenter retrospective study, 3D T ₁ -weighted MRI data from 24,305 healthy controls aged 4–85 years were used to construct age-,sex-, and estimated total intracranial volume (eTIV)- adjusted normative references for the whole CC and five subregions. Deviation scores were calculated and applied to 4,081 patients with multiple sclerosis (MS, n = 573), neuromyelitis optica spectrum disorder (NMOSD, n = 389), mild cognitive impairment (MCI, n = 308), Alzheimer’s disease (AD, n = 623), Parkinson’s disease (PD, n = 1,285), and cerebral small vessel disease (CSVD, n = 903). Classification, clinical correlation, and prognostic analyses were performed as exploratory applications.
Results: The volume of CC subregions peaked from early adulthood (central, 26.0 years) to midlife (posterior, 47.2 years; anterior, 47.5 years), forming a “centre-to-periphery” pattern. MS showed negative deviations mainly in central and mid-anterior regions (Cohen’s d = −0.28 to −0.30, p FDR<0.001), while CSVD and AD showed widespread negative deviations ( d = −0.13 to −0.49). NMOSD, MCI, and PD showed relatively small or regionally limited deviations. Deviation score based classification performance ranged from AUC = 0.598–0.775. Exploratory analyses identified weak correlations between deviation scores and processing speed in MS (Spearman’s ρ up to 0.22, p < 0.05) and cognition in CSVD ( ρ = 0.12–0.19, p < 0.05) and AD ( ρ = 0.10–0.16, p < 0.05). None survived FDR correction. Baseline deviation-based risk groups stratified subsequent relapse and disability outcomes in MS and NMOSD ( p < 0.001). An exploratory comparison suggested a nominal difference in baseline CC deviation burden between MCI converters and non-converters to AD.
Conclusion: Lifespan normative references of the CC provide a quantitative framework for characterizing individual structural deviations across neurological and neuroimmunological disorders. Exploratory clinical analyses suggest potential applications that require further validation.
Related
- Age- and sex-specific normative references and performance zones for core muscular endurance in adolescents aged 12–16 years: a cross-sectional study
- Clinical Significance and Distribution of Cerebrospinal Fluid Type IV Oligoclonal Band Pattern in Neurological Disorders: A Retrospective Analysis
- Glymphatic Dysfunction Across Neurological Disorders: Links to Neurodegeneration, Inflammaging, Gut–Brain Signaling, and Physiological Modulators
- Temporal Clustering of Acute Neurological Disorders: Testing the Clinical Impression of Diagnostic 'Theme Shifts'
- Lifespan EEG reference charts disentangle alpha-band alterations in neurological and neuropsychiatric disorders
BibTeX
@article{luo2026normative,
title = {{Normative references of corpus callosum across lifespan and application in neurological and neuroimmunological disorders}},
author = {Yuqi Luo and Li Chai and Kun Chen and Xiaozhou Du and Tianyu Gao and Yuerong Lizhu and Jun Qiu and Decai Tian and Jinyuan Weng and Jun Xu and Siyao Xu and Xiaolu Xu and Renlong Zhang and Yunyun Duan and James Cole and Zhen Yuan and Haiyan Wu and Zhizheng Zhuo and Yaou Liu and CHART Investigators},
journal = {Frontiers in Neurology},
year = {2026},
month = nov,
doi = {10.3389/fneur.2026.1970514},
url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1970514/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Normative references of corpus callosum across lifespan and application in neurological and neuroimmunological disorders
AU - Yuqi Luo
AU - Li Chai
AU - Kun Chen
AU - Xiaozhou Du
AU - Tianyu Gao
AU - Yuerong Lizhu
AU - Jun Qiu
AU - Decai Tian
AU - Jinyuan Weng
AU - Jun Xu
AU - Siyao Xu
AU - Xiaolu Xu
AU - Renlong Zhang
AU - Yunyun Duan
AU - James Cole
AU - Zhen Yuan
AU - Haiyan Wu
AU - Zhizheng Zhuo
AU - Yaou Liu
AU - CHART Investigators
PY - 2026
DA - 2026/11/02
JO - Frontiers in Neurology
DO - 10.3389/fneur.2026.1970514
UR - https://www.frontiersin.org/articles/10.3389/fneur.2026.1970514/full
AB - Background: The corpus callosum (CC) is the largest white matter structure and is often affected in neurological and neuroimmunological disorders. However, previous studies mainly used group-level comparisons. This limits patient-level magnetic resonance imaging (MRI) assessment. Methods: In this multicenter retrospective study, 3D T ₁ -weighted MRI data from 24,305 healthy controls aged 4–85 years were used to construct age-,sex-, and estimated total intracranial volume (eTIV)- adjusted normative references for the whole CC and five subregions. Deviation scores were calculated and applied to 4,081 patients with multiple sclerosis (MS, n = 573), neuromyelitis optica spectrum disorder (NMOSD, n = 389), mild cognitive impairment (MCI, n = 308), Alzheimer’s disease (AD, n = 623), Parkinson’s disease (PD, n = 1,285), and cerebral small vessel disease (CSVD, n = 903). Classification, clinical correlation, and prognostic analyses were performed as exploratory applications. Results: The volume of CC subregions peaked from early adulthood (central, 26.0 years) to midlife (posterior, 47.2 years; anterior, 47.5 years), forming a “centre-to-periphery” pattern. MS showed negative deviations mainly in central and mid-anterior regions (Cohen’s d = −0.28 to −0.30, p FDR<0.001), while CSVD and AD showed widespread negative deviations ( d = −0.13 to −0.49). NMOSD, MCI, and PD showed relatively small or regionally limited deviations. Deviation score based classification performance ranged from AUC = 0.598–0.775. Exploratory analyses identified weak correlations between deviation scores and processing speed in MS (Spearman’s ρ up to 0.22, p < 0.05) and cognition in CSVD ( ρ = 0.12–0.19, p < 0.05) and AD ( ρ = 0.10–0.16, p < 0.05). None survived FDR correction. Baseline deviation-based risk groups stratified subsequent relapse and disability outcomes in MS and NMOSD ( p < 0.001). An exploratory comparison suggested a nominal difference in baseline CC deviation burden between MCI converters and non-converters to AD. Conclusion: Lifespan normative references of the CC provide a quantitative framework for characterizing individual structural deviations across neurological and neuroimmunological disorders. Exploratory clinical analyses suggest potential applications that require further validation.
SN - 1664-2295
ER -