Functional and microstructural coupling in Appetite-Control Brain Regions in People with MND
Poster No:
102
Submission Type:
Abstract Submission
Authors:
Jeryn Chang1, Thomas Shaw1, Jinglei Lv2, Pamela McCombe1, Robert Henderson1, Diana Lucia1, Christine Guo3, Saskia Bollmann1, Kelly Garner4, Shyuan Ngo1, Frederik Steyn1
Institutions:
1The University of Queensland, Brisbane, Queensland, 2The University of Sydney, Sydney, New South Wales, 3Actigraph LLC, Pensacola, FL, 4The University of New South Wales, Sydney, New South Wales
First Author:
Co-Author(s):
Introduction:
The loss of appetite in people living with Motor Neuron Disease (plwMND; also known as ALS) contributes to weight loss (Sarmet et al., 2022; Shojaie et al., 2024), which is associated with faster disease progression and earlier death (Ngo et al., 2019). Mechanisms that contribute to loss of appetite in MND are poorly understood and may include dysfunction of central neural pathways of energy homeostasis, including those that modulate appetite and reward. We sought to investigate differences in both functional and diffusion MRI-based metrics in plwMND, with and without appetite loss. We examined brain activation of plwMND using fMRI in response to visual stimuli of food items during fasting and fed states, and confirmed our fMRI findings in associated fixel-based tract changes.
Methods:
Forty-two plwMND and twenty-four non-neurodegenerative disease control participants (NCs) were asked to fast overnight prior to fMRI assessment. Functional images were acquired prior to, and following the provision of a liquid meal, and included the random presentation of four blocks of food, and non-food items (TR/TE/Flip Angle/Acquisition Time/Vox=820ms/33ms/53°/11m:12s/2.4x2.4x2.4mm). BOLD signal was extracted by convolving the haemodynamic response function in a voxel-wise general linear model and contrast estimates were extracted using SPM (Penny et al., 2007).
Participants subsequently underwent multiband diffusion scanning (TR/TE/FoV/Acquisition Time/vox=4700ms/84ms/244mm×244mm/2m50s/2x2x2mm) . Images underwent constrained spherical deconvolution to estimate fibre orientation distributions (FODs) (Tournier et al., 2007). A group FOD template was generated using a combination of anatomical and diffusion volumes as inputs (Lv et al., 2023), wherein streamlines and fixels were generated and segmented (Dhollander et al., 2016). Finally, fibre cross-section and densities were tested in a fixel-wise general linear model (Raffelt et al., 2015).
Participants additionally completed assessments on subjective appetite and anthropometric measures.
Participants subsequently underwent multiband diffusion scanning (TR/TE/FoV/Acquisition Time/vox=4700ms/84ms/244mm×244mm/2m50s/2x2x2mm) . Images underwent constrained spherical deconvolution to estimate fibre orientation distributions (FODs) (Tournier et al., 2007). A group FOD template was generated using a combination of anatomical and diffusion volumes as inputs (Lv et al., 2023), wherein streamlines and fixels were generated and segmented (Dhollander et al., 2016). Finally, fibre cross-section and densities were tested in a fixel-wise general linear model (Raffelt et al., 2015).
Participants additionally completed assessments on subjective appetite and anthropometric measures.
Results:
Results showed converging patterns of reduced BOLD activation and reduced fibre cross-section in the cerebellum. Comparing differences in activations between fasted and satiated states when viewing images of high calorie foods, plwMND have reduced activations in the right temporal pole (p=0.043; Fig 1A). Comparisons of appetite measures reveal reductions in appetite in plwMND, as indicated by a significantly lower CNAQ score (p<0.001). Here, CNAQ is associated with reduced activations of the right cerebellar nuclei (p=0.005) in plwMND when shown images of food during a fasted state (Fig 1B).
To confirm the effect of decreased BOLD in the cerebellum, fibre cross-section and density of the nigro-cerebellar tract, a tract that is involved in reward (Washburn et al., 2024), were compared between plwMND and controls (Fig 2A). After family-wise error correction, results show a significant decrease of fibre cross-section in the right cerebellar nuclei of plwMND compared to NND Controls (p<0.05; Fig 2B).
The co-occurrence of BOLD and fibre cross-section reductions in the cerebellum/nigro-cerebellar tract suggests structural-functional coupling in reward pathways, that are jointly impacted in the disease.
To confirm the effect of decreased BOLD in the cerebellum, fibre cross-section and density of the nigro-cerebellar tract, a tract that is involved in reward (Washburn et al., 2024), were compared between plwMND and controls (Fig 2A). After family-wise error correction, results show a significant decrease of fibre cross-section in the right cerebellar nuclei of plwMND compared to NND Controls (p<0.05; Fig 2B).
The co-occurrence of BOLD and fibre cross-section reductions in the cerebellum/nigro-cerebellar tract suggests structural-functional coupling in reward pathways, that are jointly impacted in the disease.
Conclusions:
Overall, these results demonstrate alterations in BOLD activity and microstructure in plwMND in deeply networked brain regions that control motivation, perceptual integration, and socioemotional processing. Multimodal results provide evidence for decreases in fibre cross-section of the nigro-cerebellar tract in plwMND, which might negatively impact appetite functional responses in the cerebellum. Changes in appetite behaviours leading to the loss of weight and fat mass contributes to faster disease progression and earlier death. Results suggest a biological basis for the loss of appetite in plwMND and adds to an evolving understanding of the impact of disease on the cerebellum.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI) 2
Diffusion MRI Modeling and Analysis
Keywords:
Cerebellum
Degenerative Disease
FUNCTIONAL MRI
MRI
Tractography
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
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Provide references using APA citation style.
Lv, J., Zeng, R., Ho, M. P., D'Souza, A., & Calamante, F. (2023). Building a tissue-unbiased brain template of fiber orientation distribution and tractography with multimodal registration. Magn Reson Med, 89(3), 1207-1220. https://doi.org/10.1002/mrm.29496
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Penny, W. D., Friston, K. J., Ashburner, J. T., Kiebel, S. J., & Nichols, T. E. (2007). Statistical parametric mapping: the analysis of functional brain images. Elsevier.
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