BOLD Activation Changes in Silent Verb Generation after Radiotherapy for Medulloblastoma
Poster No:
824
Submission Type:
Abstract Submission
Authors:
Josue Luiz Dalboni da Rocha1, Ping Zou Stinnett2, Robert Ogg2, Thomas Merchant2, Giles Robinson2, Amar Gajjar,2, Heather Conklin2, Ranganatha Sitaram1
Institutions:
1St. Jude Children’s Research Hospital, Memphis, TN, 2St Jude Children Hospital, Memphis, TN
First Author:
Co-Author(s):
Introduction:
Medulloblastoma is the most common malignant pediatric brain tumor (Carta, 2020). While post-operative radiotherapy significantly improves survival rates, it is often associated with neurocognitive deficits, particularly affecting language and executive functions. Functional MRI (fMRI) during language tasks can detect alterations in brain activation patterns related to these deficits (Dalboni da Rocha, 2024). This study investigates changes in Blood Oxygenation Level-Dependent (BOLD) activation during a silent verb generation task in medulloblastoma patients before and after radiation therapy. This task engages language production and cognitive control networks, providing insight into functional activation during language processing (Price, 2012).
Methods:
Thirty-one medulloblastoma patients (11F/20M, mean age: 10.2 ± 5.0 years) underwent fMRI scans during a silent verb generation task pre- and post-irradiation. The silent verb generation task involved presenting patients with a series of nouns, presented visually in one session and auditorily in another. Patients were instructed to silently think of an appropriate verb associated with each noun without vocalizing their response. Preprocessing steps, including realignment, co-registration, normalization, brain and surgical void segmentation, and smoothing, were performed using SPM12 (Penny, 2011). In this study, activation scores were defined as voxel-wise t-values derived from task-versus-rest comparisons for each individual patient visit. A group-level t-test between pre- and post-irradiation scans identified voxels with significant activation decrease over time. Voxels with family-wise error corrected p < 0.05 and cluster size ≥50 voxels were selected. Cluster-averaged activation scores within each cluster were extracted for each patient at each time point. A leave-one-patient-out cross-validation (Dalboni da Rocha, 2020) was conducted using a linear Support Vector Machine (SVM) (Vapnik, 1963) to classify fMRI data as pre- or post-irradiation based on these cluster-averaged activation scores as features.
Results:
Nine clusters showed decreased activation scores after radiotherapy, primarily in the cerebellum, inferior frontal gyrus, middle temporal gyrus, anterior cingulate cortex, and supplementary motor area (Figure 1). These decreases suggest reduced task-related neural activation. The SVM classifier achieved 70.97% accuracy (sensitivity: 74.19%; specificity: 67.74%). The decreased activation scores in cerebellar regions and language-related cortical areas suggests that post-operative radiotherapy impacts neural circuits involved in language production and cognitive control. Mean activation scores consistently decreased across clusters post-radiotherapy (Figure 2).
·Figure 1. Brain regions with decreased BOLD activation post-radiotherapy during silent verb generation. Thresholds applied: Family-wise error-corrected p < 0.5; minimum cluster size ≥50 voxels.
·Figure 2. Comparison of mean activation scores across patients, within the selected clusters, according to the brain region where they are located. Blue: pre-radiotherapy. Red: post-radiotherapy.
Conclusions:
The observed decrease in BOLD activation in key language and cognitive regions may reflect radiation-induced neurotoxicity affecting neuronal function and connectivity. While historically associated with motor control, the cerebellum plays a significant role in language processing and cognitive functions (McAfee, 2022). Decreased activation in the inferior frontal gyrus and supplementary motor area aligns with potential impairments in language generation and motor planning (Hickok, 2007; Hertrich, 2016). The successful classification of pre- versus post-irradiation scans indicates that these activation patterns could be biomarkers for monitoring treatment-related neurocognitive changes. Radiotherapy in medulloblastoma patients is associated with decreased activation in cerebellar and cortical regions during silent verb generation, indicating potential neural mechanisms underlying post-treatment cognitive deficits. These findings underscore the importance of monitoring brain function in survivors and may inform interventions to mitigate cognitive impairments resulting from post-operative radiotherapy.
Language:
Speech Production 1
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI) 2
Keywords:
Language
Machine Learning
PEDIATRIC
Other - Cancer
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?
Are you Internal Review Board (IRB) certified? Please note: Failure to have IRB, if applicable will lead to automatic rejection of abstract.
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.
Dalboni da Rocha, J. L. (2020). Multilevel diffusion tensor imaging classification technique for characterizing neurobehavioral disorders. Brain Imaging and Behavior, 14, 641–652.
Dalboni da Rocha, J. L. (2024). Functional MRI assessment of brain activity patterns associated with reading in medulloblastoma survivors. Brain Sciences, 14(9), 904. https://doi.org/10.3390/brainsci14090904
Hertrich, I. (2016). The role of the supplementary motor area for speech and language processing. Neuroscience and Biobehavioral Reviews, 68, 602–610.
Hickok, G. (2007). The cortical organization of speech processing. Nature Reviews Neuroscience, 8, 393–402. https://doi.org/10.1038/nrn2113
McAfee, S. S. (2022). Cerebellar coordination of neuronal communication in cerebral cortex. Frontiers in Systems Neuroscience, 15, 781527.
Penny, W. D. (2011). Statistical parametric mapping: The analysis of functional brain images. Elsevier.
Price, C. J. (2012). A review and synthesis of the first 20 years of PET and fMRI studies of heard speech, spoken language, and reading. NeuroImage, 62(2), 816–847.
Vapnik, V. (1963). Pattern recognition using generalized portrait method. Automation and Remote Control, 24, 774–780.