Postoperative limbic functional connectivity predicts 5-year BMI in children with craniopharyngioma
Poster No:
1494
Submission Type:
Abstract Submission
Authors:
Jennapher Lingo VanGilder1, Paul VanGilder1, Nicholas Phillips1, Jinsoo Uh1, Thomas Merchant1
Institutions:
1St. Jude Children's Research Hospital, Memphis, TN
First Author:
Co-Author(s):
Introduction:
Children treated for craniopharyngioma, a brain tumor associated with the hypothalamic-pituitary axis, are at-risk for developing severe obesity. Studies have shown that the extent of hypothalamic involvement by tumor is linked to body mass index (BMI) (Klages et al. 2022), and our preliminary work suggests that the integrity of the fornix, a white matter tract that emerges from the hypothalamus, is associated with BMI in children five years after treatment. Functional MRI studies report that obesity is associated with abnormal activation of prefrontal (i.e., inhibitory control) and limbic (i.e., reward processing) cortices (Berridge et al. 2010). These reports implicate limbic structure and function in BMI regulation, yet the neural substrate underlying poor BMI trajectories in children treated for craniopharyngioma remains unknown. The purpose of this study was to evaluate the extent that postoperative fornix integrity impacts neural networks associated with long-term BMI. We hypothesized that greater functional connectivity between limbic and prefrontal brain regions would predict lower BMI at a 5-year follow-up visit.
Methods:
Thirty-eight children (mean±SD age=12.99±3.54 years, female=18) underwent MRI after surgery but prior to radiotherapy (54 Gy [RBE]). DWI data were collected using a 1.5T Siemens scanner: b-value = 1 ms/µm2 with 12 directions and one b=0 image; four scans were collected to increase the signal-to-noise ratio. Raw images were preprocessed to reduce noise and the DTI model was applied to quantify FA in each voxel. A region of interest (ROI) approach was used to quantify fornix FA for each patient. Resting state fMRI images were acquired on a Siemens 3T scanner: TR=2.01 s, TE=30 ms, flip angle=90°, slice thickness=3.5 mm, and nslice=32. We performed a functional connectivity (FC) analysis using a seed-based approach with the CONN toolbox. Whole-brain correlation maps for each patient were calculated between 166 ROIs using the AAL atlas 3 (Rolls et al. 2020). A general linear model assessed whether ROI-ROI connectivity strength was correlated with the fornix FA value for each patient (FDR-corrected p<0.05). BMI was collected 5 years after radiotherapy and the age- and sex-specific z-score was calculated using normative values. Simple linear regression evaluated the relationship between 5-year BMI z-score and FC values for ROI pairs that were significantly correlated with fornix integrity.
Results:
Whole-brain analyses revealed that the connectivity between 31 ROI pairs were associated with fornix FA after FDR-correction. Among these, the FC between three pairs of brain regions were negatively associated with 5-year BMI z-scores, i.e., greater connectivity predicted lower BMI at 5-year follow-up. The connectivity pairs were the right putamen and middle cingulate (β=-1.58, p=0.05), the right supplementary motor area and pallidum (β=-1.94, p=0.02), and the right supplementary motor area and putamen (β=-1.50, p=0.02) (Fig. 1). A schematic of the connectivity between prefrontal and limbic brain regions associated with fornix integrity and BMI at 5-year follow-up is shown in Fig. 2.
Conclusions:
Our findings suggest that children with better postoperative fornix integrity have greater connectivity between neural regions in the prefrontal (i.e., cognitive control) and limbic (i.e., reward processing) networks. These findings align with previous literature that report greater activation of brain regions associated with cognitive control (e.g., the cingulate and supplementary motor area (Aron 2011)), are linked to suppressed activation of brain regions associated with reward processing (e.g., pallidum and putamen (Berridge 2010)), and regulation of food consumption (Farr et al. 2016). Our results suggest that conservative treatment approaches should be considered to preserve the integrity of limbic anatomy to reduce the risk of developing obesity later in life. Future work will evaluate if surgical approach impacts postoperative limbic anatomy.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism)
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 1
Diffusion MRI Modeling and Analysis 2
Task-Independent and Resting-State Analysis
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Subcortical Structures
Keywords:
Limbic Systems
PEDIATRIC
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
·The connectivity between limbic and prefrontal networks is associated with fornix fractional anisotropy (FA, in gray) and five-year BMI z-score (in red). SMA=supplementary motor area.
·Right, coronal, and axial glass brain views of connectivity between prefrontal and limbic brain regions associated with fornix integrity and BMI 5 years after treatment. SMA=supplementary motor area
Provide references using author date format
Berridge K.C. (2010), 'The tempted brain eats: Pleasure and desire circuits in obesity and eating disorders', Brain Research, vol. 1350, pp. 43-64
Farr, O.M. (2016), 'Central nervous system regulation of eating: Insights from human brain imaging', Metabolism, vol. 65, no. 5, pp. 699-713
Klages K.L. (2022), 'Health-related quality of life, obesity, fragmented sleep, fatigue, and psychosocial problems among youth with craniopharyngioma', Psycho-Oncology, vol. 31, no. 5, pp. 779-787
Rolls E.T. (2020), 'Automated anatomical labelling atlas 3', NeuroImage, vol. 206, no. 116189, pp. 1053-8119