Individualized Cerebellar Damage Predicts the Behavioral Disorders in Children with Brainstem Tumors
Poster No:
283
Submission Type:
Abstract Submission
Authors:
Heyuan Jia1, Kaikai Wang2, Peng Zhang3, Lingzhong Fan4, Liwei Zhang1
Institutions:
1Beijing Tiantan Hospital, Beijing, Beijing, 2Brainnetome Center, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Aca, Beijing, Beijing, 3Beijing Tiantan Hospital, Beijing, China, 4Brainnetome Center, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Aca, Beijing, China
First Author:
Co-Author(s):
Kaikai Wang
Brainnetome Center, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Aca
Beijing, Beijing
Brainnetome Center, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Aca
Beijing, Beijing
Lingzhong Fan
Brainnetome Center, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Aca
Beijing, China
Brainnetome Center, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Aca
Beijing, China
Introduction:
Brainstem tumors, comprising 15% of pediatric brain tumors, primarily affect the medulla oblongata, pons, and midbrain, with diffuse intrinsic pontine gliomas (DIPG) making up 80% of these cases. DIPG is linked to poor prognosis and complex neurological dysfunction. While the brainstem was once thought not to contribute to higher cognitive functions, recent studies show that brainstem tumor patients experience cognitive and behavioral disorders, such as attention deficits, irritability, and emotional disturbances, often persisting after surgery. The cerebellum, closely connected to the brainstem, plays a role in these behaviors. Cerebellar atrophy is commonly seen in brainstem tumor patients, suggesting disruption in cerebellar function. The posterior cerebellum, involved in social cognition and executive function, may contribute to the behavioral impairments observed. Using ACAPULCO for cerebellar segmentation and a normative model based on healthy controls, we aimed to quantify cerebellar damage and link deviations to specific behavioral outcomes in brainstem tumor patients.
Methods:
Participants: 147 pediatric patients with brainstem tumors diagnosed at Beijing Tiantan Hospital (April 2019–December 2022). Healthy control data from 849 children in public databases. All participants' MRI scans were accquited by a 3.0 T scanner with a 3D T1-weighted sequence. First, cerebellar segmentation was done using ACAPULCO, excluding the brainstem with MRIcroGL. Quality was reviewed and manually corrected by two specialists. Volumes for 26 regions were analyzed. Sencond, data harmonization was performed using the Combat method. A normative model was built using Gaussian Process Regression (GPR) with 10-fold cross-validation on control data. Z-scores for patients were generated, with deviations beyond ±1.96 considered significant. Finally, ridge regression predicted behavioral outcomes from cerebellar volume deviations. The total outlier count (tOC) was calculated for regions with Z-scores < -1.96. Ridge regression with fivefold cross-validation (5F-CV) evaluated tOC's predictive power for social problems and withdrawal. 101 repetitions of 5F-CV were performed, and permutation testing (1000 iterations) assessed significance. Additionally, multiple linear regression explored associations between tOC and clinical variables, with a p-value threshold of 0.05.
Results:
Our study identified significant deviations in cerebellar volumes in patients with brainstem tumors, with the majority of patients showing lower-than-normal values. Female patients exhibited a higher prevalence of extreme negative deviations. Multiple regression analysis revealed that tumor volume was positively associated with tOC (p<0.0001), while other clinical factors had no significant impact. tOC was significantly correlated with social problems (r = 0.31, p = 0.001) and withdrawal behaviors (r = 0.28, p = 0.001), indicating that greater cerebellar damage is linked to more severe behavioral symptoms. Ridge regression further confirmed that cerebellar volume deviations predicted social problems (r = 0.27, p = 0.007) and withdrawal behaviors (r = 0.25, p = 0.015). Negative feature weights in regions such as Right X, Left V, and Vermis VIII were linked to these behaviors, emphasizing the role of cerebellar damage in behavioral dysfunction.
·Normative model and the analysis of deviations
·Behavioral prediction models using individualized tOC and cerebellar volumes
Conclusions:
Our study revealed cerebellar damage patterns in brainstem tumor patients, emphasizing the role of both anterior and posterior cerebellar lobes in social problems and withdrawal behaviors. Neuroanatomical deviations were linked to these behavioral disorders, highlighting the importance of the cerebro-brainstem-cerebellar circuits in complex behavioral issues. Early recognition of these cognitive and behavioral changes could improve intervention and surgical strategies, though further research is needed to validate these findings in clinical practice.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Novel Imaging Acquisition Methods:
Anatomical MRI 2
Keywords:
Brainstem
Cerebellar Syndromes
Cerebellum
Cognition
Development
DISORDERS
Machine Learning
MRI
Pediatric Disorders
1|2Indicates the priority used for review
Abstract Information
By submitting your proposal, you grant permission for the Organization for Human Brain Mapping (OHBM) to distribute your work in any format, including video, audio print and electronic text through OHBM OnDemand, social media channels, the OHBM website, or other electronic publications and media.
The Open Science Special Interest Group (OSSIG) is introducing a reproducibility challenge for OHBM 2025. This new initiative aims to enhance the reproducibility of scientific results and foster collaborations between labs. Teams will consist of a “source” party and a “reproducing” party, and will be evaluated on the success of their replication, the openness of the source work, and additional deliverables. Click here for more information. Propose your OHBM abstract(s) as source work for future OHBM meetings by selecting one of the following options:
Please indicate below if your study was a "resting state" or "task-activation” study.
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.
Please indicate which methods were used in your research:
For human MRI, what field strength scanner do you use?
Which processing packages did you use for your study?
Provide references using APA citation style.
Brossard-Racine, M. (2015). Developmental cerebellar cognitive affective syndrome in ex-preterm
survivors following cerebellar injury. Cerebellum, 14(2), 151-164.
Bushara, K. O. (2001). Multiple tactile maps in the human cerebellum. Neuroreport, 12(11), 2483-2486.
Carta, I. (2019). Cerebellar modulation of the reward circuitry and social behavior. Science, 363(6424).
Chao, O. Y. (2021). Functional Convergence of Motor and Social Processes in Lobule IV/V of the Mouse Cerebellum. Cerebellum, 20(6), 836-852.
Cui, Z. X. (2022). Linking Individual Differences in Personalized Functional Network Topography to Psychopathology in Youth. Biological Psychiatry, 92(12), 973-983.
D'Aes, T. (2015). Cognitive and affective disturbances following focal brainstem lesions: a review and report of three cases. Cerebellum, 14(3), 317-340.
Frazier, M. R. (2022). A missing link in affect regulation: the cerebellum. Social Cognitive and Affective Neuroscience, 17(12), 1068-1081.
Han, S. (2020). Automatic cerebellum anatomical parcellation using U-Net with locally constrained optimization. Neuroimage, 218, 116819.
Ike, K. G. O. (2020). Social withdrawal: An initially adaptive behavior that becomes maladaptive when expressed excessively. Neuroscience and Biobehavioral Reviews, 116, 251-267.
Limperopoulos, C. (2007). Does Cerebellar Injury in Premature Infants Contribute to the High Prevalence of Long-term Cognitive, Learning, and Behavioral Disability in Survivors? Pediatrics, 120(3), 584-59.