Reduced brain activity for sensory and motor tasks after treatment in pediatric medulloblastoma
Poster No:
342
Submission Type:
Abstract Submission
Authors:
Jesyin Lai1, Ping Zou Stinnett1, Robert Ogg1, Thomas Merchant1, Heather Conklin1, Amar Gajjar1, Ranganatha Sitaram1
Institutions:
1St. Jude Children's Research Hospital, Memphis, TN
First Author:
Co-Author(s):
Introduction:
Medulloblastoma is the most common malignant childhood brain tumor. Contemporary therapy consists of maximal surgical resection, craniospinal radiotherapy (RT), and chemotherapy. Current protocols stratify patients into high, average, and low risk groups by the presence or absence of metastatic or post-operative residual disease and molecular features. This has effectively improved cure rates and reduced the risk of craniospinal radiation for individuals with more favorable prognoses. However, many pediatric survivors still suffer late effects including long-term neurotoxicity, ototoxicity and endocrinopathies. Since patients in different therapeutic strata receive different RT doses and chemotherapy regimens, late effects may be disparate in these patients. As auditory, visual, and motor functions play vital roles in daily living, identifying, and tracing changes in brain activation in regions responsible for these functions provide useful information to develop interventions for cognitive rehabilitation.
Methods:
Fifty-seven pediatric patients with medulloblastoma (WNT & Non-WNT/Non-SHH) were involved in this study. They were assigned to W+N1 and N2+N3 therapeutic strata based on the extent of disease and molecular classification. They received RT plus 4 (W+N1) or 7 (N2+N3) cycles of chemotherapy. To longitudinally trace their auditory, visual, and motor functions, functional magnetic resonance imaging (fMRI) data were acquired during a sensory survey task at three different time points (TP): pre-RT (TP0), post-RT/pre-chemotherapy (TP1), and post-chemotherapy (TP2: 9/12 months post-enrollment for W+N1/N2+N3). Participants aged 5-23 years (11.25 ± 4.3) at their first fMRI exams. Participants were asked to tap their right fingers actively during simultaneous auditory (dissonant ascending/descending pure tones) and visual (flashing checkboards) presentation (20s stimuli + 20s gap) in 3 blocks. Task-related brain activation patterns were analyzed using SPM software, and subsequent analysis was performed using custom Python code. To identify regions of interest (ROIs) with changes in brain activation, we used k-nearest-neighbors-based searchlight analysis to classify blood oxygenation-level dependent (BOLD) signals into TP0 vs. TP1 or TP0 vs. TP2 separately for the two strata. ROIs were identified using cut-off thresholds of 0.6-0.68 f1-score and 20 cluster-size based on the AAL atlas. Medians of BOLD signals in ROIs were computed for comparisons across TPs. Response times and frequencies (RFs = response no./stimulus duration) were calculated to assess behavior performance.
Results:
Through searchlight-pattern classifications in W+N1, changes in BOLD signals across TPs were identified in the L cerebellum, L superior temporal gyrus, L thalamus, L supplementary motor area (SMA), etc. Median BOLD amplitudes were reduced across TPs in the L superior temporal gyrus, L SMA, and L thalamus. In addition, via similar analysis in N2+N3, changes in BOLD signals across TPs were identified in the R cerebellum, superior occipital gyrus, L postcentral gyrus, L calcarine cortex, etc. Decreased median BOLD amplitudes across TPs were found in the superior occipital gyri, L postcentral gyrus, and L calcarine cortex. When behavior performance was analyzed, there was a trend of RF reduction across TPs and response times were similar across TPs in W+N1. Both RFs and response times were similar across TPs in N2+N3.
·Reduced brain activity during sensory and motor processing as a function of time point in pediatric participants of medulloblastoma. * p < 0.10 (paired t-test)
·Response time and response frequency across time points of the sensory survey task in pediatric participants of medulloblastoma.
Conclusions:
For W+N1, reduced BOLD signals were observed in ROIs responsible for auditory and sensory processing and movement control. For N2+N3, decreased BOLD signals were found in ROIs responsible for object recognition, sensory perception, and visuospatial processing. These observations suggest disparate deficit profiles in auditory, visual, and motor processing in the different strata, probably related to differences in disease extent and the impact of surgery, RT and chemotherapy.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Higher Cognitive Functions:
Higher Cognitive Functions Other
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI)
Classification and Predictive Modeling
Perception, Attention and Motor Behavior:
Perception: Multisensory and Crossmodal 2
Keywords:
FUNCTIONAL MRI
Motor
Pediatric Disorders
Perception
Treatment
1|2Indicates the priority used for review
Provide references using author date format
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