Testing different methods for deriving functional connectivity of the locus coeruleus region
Poster No:
1423
Submission Type:
Abstract Submission
Authors:
Kimberly Rogge-Obando1, Kamalpreet Kaur2, Ethan Edwards3, Yeo-Jin Yi4,5, Haatef Pourmotabbed6, Paula Trujillo7, Catie Chang8
Institutions:
1Vanderbilt, Nashville, TN, 2Vanderbilt, Nashville, Tennessee, 3University of Tenessee -Knoxville, Knoxville, TN, 4Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University, Magdeburg,, Magdeburg, Saxony-Anhalt, 5German Center for Neurodegenerative Diseases (DZNE),, Magdeburg, Germany, 6Vanderbilt University, Nashville, TN, 7Vanderbilt University - Medical Center, Nashville, TN, 8Department of Electrical and Computer Engineering, Vanderbilt University, Nashville, TN
First Author:
Co-Author(s):
Yeo-Jin Yi
Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University, Magdeburg,|German Center for Neurodegenerative Diseases (DZNE),
Magdeburg, Saxony-Anhalt|Magdeburg, Germany
Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University, Magdeburg,|German Center for Neurodegenerative Diseases (DZNE),
Magdeburg, Saxony-Anhalt|Magdeburg, Germany
Introduction:
The locus coeruleus (LC) is increasingly recognized as a critical target for early intervention in conditions such as epilepsy, Alzheimer's, and schizophrenia (Fornai, 2011; Chen, 2022; Suttkus, 2021). Investigating LC function using fMRI in both healthy and clinical populations is essential but challenging due to its small size (~1 mm x 14 mm) and discrepancies among published LC masks (Fernandes, 2012). Typical whole-brain fMRI resolution (>2 mm) and variability in mask definitions complicate LC connectivity studies. In this study, we examined whether the BOLD signal derived from two different LC masks – the LC "meta-mask" (Dahl et al., 2022), and the LC region of the Harvard Ascending Arousal Network (AAN) atlas (Edlow,2012) – differ in terms of their whole-brain functional connectivity. Additionally, since published LC masks are typically provided in high-resolution format (e.g., 0.5mm isotropic resolution), they are typically resampled to match the resolution of the fMRI data for time course extraction. Therefore, we also investigate the impact of using LC masks resampled to 1 mm or 2 mm isotropic resolution on the derived LC region time courses.
Methods:
Resting-state fMRI (rsfMRI) scans from 10 healthy controls from the HCP Early Psychosis dataset (TR=0.8s; resolution=2*2*2mm; duration=5min) were processed using motion correction, FIX ICA, nonlinear registration to the MNI152-2009 template (1mm and 2mm), and spatial blurring to 3mm FWHM, followed by regression of motion parameters, white matter, and CSF time courses. The LC meta-mask from (Dahl, 2022) and the LC mask from the AAN atlas (Eldow, 2012) were transformed to 1mm-resolution MNI space, and the resulting masks were additionally resampled to 2mm resolution, yielding 1mm and 2mm versions of both LC masks. LC-region BOLD signals were derived using either the 1mm- or 2mm-resolution versions of each LC mask. Once the signal was retrieved, it was correlated on a voxel-wise basis to the 2mm rsfMRI data to derive the LC-region correlation map. A voxel-wise repeated ANOVA was conducted to test for a main effect of LC mask version (AAN or meta-mask) and resampled resolution (1mm or 2mm) on the resulting whole-brain connectivity maps. Correction for multiple correction was carried out, examining both FDR and clustering-based thresholding.
Results:
After FDR correction, there was a significant difference in whole brain connectivity maps between at least two LC mask comparisons. The significant regions were found surrounding the LC. Post-hoc results indicate that 2mm-resolution versions of the meta-mask and AAN mask show the most significant difference. The comparison between both masks at 1mm resolution, and between the 1mm vs 2mm versions of the meta-mask, also had significant differences. In contrast, the comparison between 1mm vs 2mm AAN masks shows no significant differences. Similarly, after cluster-based thresholding (F (3,27) =2.96, p <0.05), where the F-stat reported here is the minimum threshold to be to have a significant p-value, the main differences were centered around the LC-region with some sparse small clusters around the cortex, insula, and thalamus. (Figure 1)
Conclusions:
Connectivity patterns varied significantly based on LC mask type, with greater variability for the meta-mask than the AAN mask when comparing resolutions. Differences were most prominent near the LC. This work highlights the critical influence of methodological choices in LC fMRI studies, underscoring the need for standardized approaches to improve the reliability and reproducibility of LC connectivity research. Such improved and refined approaches could help us better capture LC-associated connectivity to psychiatric and neurological conditions. Future work will include testing the impact of using a study-derived template, expanding the sample size, and examining early psychosis patients to explore behavioral correlations and the sensitivity of LC connectivity results to methodological differences.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 2
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling 1
Keywords:
FUNCTIONAL MRI
Psychiatric Disorders
1|2Indicates the priority used for review
·Figure 1) Shows the voxel-wise F-statistic map results after cluster threshold correction. These clusters indicate regions that are significantly different between LC mask comparisons.
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Provide references using APA citation style.
Dahl et al., (2022). Locus coeruleus integrity is related to tau burden and memory loss in autosomal-dominant Alzheimer's disease. Neurobiol Aging.
Edlow et al., (2012). Neuroanatomic connectivity of the human ascending arousal system critical to consciousness and its disorders. J Neuropathol Exp Neurol.
Fernandes et al., (2012). The human locus coeruleus 3-D stereotactic anatomy. Surg. Radiol. Anat
Fornai et al., (2011). The role of locus coeruleus in the antiepileptic activity induced by vagus nerve stimulation. European Journal of Neuroscience
Suttkus et al., (2021). Working memory in schizophrenia: The role of the locus coeruleus and its relation to functional brain networks. Brain Behav.