Poster No:
1365
Submission Type:
Abstract Submission
Authors:
Norman Scheel1, Tracey Covassin1, Randolph Pearson1, Jeffrey Monroe1, Sally Nogle1, David Kaufman1, David Zhu2
Institutions:
1Michigan State University, East Lansing, MI, 2Albert Einstein College of Medicine, Bronx, NY
First Author:
Co-Author(s):
David Zhu
Albert Einstein College of Medicine
Bronx, NY
Introduction:
Multiple studies have found Default-Mode-Network (DMN) connectivity to be affected by concussion (Bouchard et al., 2024; Zhu et al., 2015). In addition, the Salience Network (SN) has recently gained attention in concussion studies (Churchill et al., 2021; Healey et al., 2022; Kawas et al., 2024). Therefore, we re-analyzed our data investigating the SN. We also introduced dimensional complexity (DC) (Scheel et al., 2018) to analyze brain network changes following concussion. While functional connectivity typically averages voxel time courses for each network region before correlation, DC is calculated via the entropy of the Eigenvalue decomposition of all voxel time courses without averaging. DC, here measured through Omega entropy (Wackermann, 1996), can be interpreted as the coherence of brain activity, where a high entropy represents diffuse activity and low entropy a more coherent activity. Thus, DC might be able to quantify the level of post-concussive brain network disintegration.
Methods:
Eight concussed Division I collegiate football student-athletes and 11 control subjects participated in this study. The Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) was administered over the course of recovery. Anatomical T1-weighted and resting-state functional magnetic resonance imaging (rs-fMRI) scans were collected within 24 hours, 7±1 days, and 30±1 days after concussion. The rs-fMRI data were preprocessed using updated procedures, incl. distortion correction (Yu et al., 2023) and AROMA de-noising (Pruim et al., 2015). Resting-State Network regions were extracted based on Shirer et al., 2012. Pearson correlation coefficients were Fisher-Z transformed prior to averaging and extracted for the dorsal DMN and anterior SN. Omega entropy is derived for the combined dorsal/ventral DMN, the combined anterior/posterior SN, as well as all regions (global). Due to the anti-correlative nature of network activity, sub-networks were not combined for connectivity analyses. Two-way mixed measure ANOVAs investigate differences between concussed athletes and controls. All reported p values are corrected for multiple comparisons using the Bonferroni method, with significance determined at the corrected p<0.05 level.
Results:
Cognitive recovery occurred within 6.0 ± 2.4 days (ImPACT).
While dorsal DMN and anterior SN connectivity showed significant group effects (DMN: F=7.93, p=0.024; SN: F=17.12, p=0.001), their group/time interactions were not significant (DMN: F=1.07, p=0.7; SN: F=1.57, p=0.45), Fig.1.
Both DMN and SN DC showed significant group/time interactions (DMN: F=4.49, p=0.037; SN: F=4.44, p=0.039) and group effects (DMN: F=6.79, p=0.036; SN: F=6.49, p=0.042), with post-hoc T-tests significant at 1 week (p=0.008 for DMN and SN), Fig.2a,b. Global DC showed a significant group effect (F=5.08, p=0.038) but no significant group/time interaction (F=0.5, p=1), Fig.2c.

·Fig1: Changes in functional connectivity for a) dorsal DMN, b) anterior SN, in control (green/left) vs. concussed subjects (red/right), within 24h, 1 week, and 1 month after concussion.

·Fig2: Changes in Omega entropy for a) DMN, b) SN, c) global (all Shirer ROIs) in control (green/left) vs. concussed subjects (red/right), within 24h, 1 week, and 1 month after concussion.
Conclusions:
Consistent with our prior findings, these analyses suggest a longer recovery period than ImPACT scores imply. Significant group differences of functional connectivity in the SN were found, in addition to the DMN, with controls showing higher connectivity. Qualitatively Fig. 1 shows DMN and SN connectivity decreasing in concussed athletes during the first week, and increasing afterward, not quite reaching the level of controls after a month.
Omega entropies of DMN and SN show significant changes post-concussion, corroborating our connectivity findings. After one week DMN and SN entropy are significantly higher in concussed athletes, demonstrating less coherent brain activity even though ImPACT scores indicate full recovery. Qualitatively after one month DMN and SN entropy recovers, but not to the level of controls (Fig. 2a,b).
Interestingly, even global DC displays a significant group effect with higher entropy in concussed athletes. These results suggest DC as an additional valuable biomarker for monitoring and predicting post-concussive recovery and warrant further research.
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
fMRI Connectivity and Network Modeling 1
Multivariate Approaches
Other Methods
Perception, Attention and Motor Behavior:
Consciousness and Awareness
Keywords:
Cognition
Computational Neuroscience
Consciousness
Data analysis
DISORDERS
MRI
Neurological
Trauma
Other - Concussion
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Resting state
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Patients
Was this research conducted in the United States?
Yes
Are you Internal Review Board (IRB) certified?
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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
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Were any animal research approved by the relevant IACUC or other animal research panel?
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Not applicable
Please indicate which methods were used in your research:
Functional MRI
Structural MRI
Neuropsychological testing
Computational modeling
For human MRI, what field strength scanner do you use?
3.0T
Which processing packages did you use for your study?
AFNI
SPM
FSL
Other, Please list
-
AROMA, SynBOLD-DisCo, in-house code
Provide references using APA citation style.
Bouchard, H. C., Higgins, K. L., Amadon, G. K., Laing-Young, J. M., Maerlender, A., Al‑Momani, S., Neta, M., Savage, C. R., & Schultz, D. H. (2024). Concussion-Related Disruptions to Hub Connectivity in the Default Mode Network Are Related to Symptoms and Cognition. Journal of Neurotrauma
Churchill, N. W., Hutchison, M. G., Graham, S. J., & Schweizer, T. A. (2021). Concussion Risk and Resilience: Relationships with Pre-Injury Salience Network Connectivity. Journal of Neurotrauma.
Healey, K., Fang, Z., Smith, A., Zemek, R., & Ledoux, A.-A. (2022). Adolescents with a concussion have altered brain network functional connectivity one month following injury when compared to adolescents with orthopedic injuries. NeuroImage: Clinical
Kawas, M. I., Atcheson, K. M., Flood, W. C., Sheridan, C. A., Barcus, R. A., Flashman, L. A., McAllister, T. W., Lipford, M. E., Kim, J., Urban, J. E., Davenport, E. M., Vaughan, C. G., Sai, K. K. S., Stitzel, J. D., Maldjian, J. A., & Whitlow, C. T. (2024). Cognitive and Salience Network Connectivity Changes following a Single Season of Repetitive Head Impact Exposure in High School Football. American Journal of Neuroradiology
Pruim, R. H. R., Mennes, M., van Rooij, D., Llera, A., Buitelaar, J. K., & Beckmann, C. F. (2015). ICA-AROMA: A robust ICA-based strategy for removing motion artifacts from fMRI data. NeuroImage
Scheel, N., Franke, E., Münte, T. F., & Madany Mamlouk, A. (2018). Dimensional Complexity of the Resting Brain in Healthy Aging, Using a Normalized MPSE. Frontiers in Human Neuroscience
Shirer, W. R., Ryali, S., Rykhlevskaia, E., Menon, V., & Greicius, M. D. (2012). Decoding subject-driven cognitive states with whole-brain connectivity patterns. Cerebral Cortex
Wackermann, J. (1996). Beyond mapping: Estimating complexity of multichannel EEG recordings. Acta Neurobiologiae Experimentalis
Yu, T., Cai, L. Y., Morgan, V. L., Goodale, S. E., Englot, D. J., Chang, C. E., Landman, B. A., & Schilling, K. G. (2023). SynBOLD-DisCo: Synthetic BOLD images for distortion correction of fMRI without additional calibration scans. Medical Imaging 2023: Image Processing
Zhu, D. C., Covassin, T., Nogle, S., Doyle, S., Russell, D., Pearson, R. L., Monroe, J., Liszewski, C. M., DeMarco, J. K., & Kaufman, D. I. (2015). A Potential Biomarker in Sports-Related Concussion: Brain Functional Connectivity Alteration of the Default-Mode Network Measured with Longitudinal Resting-State fMRI over Thirty Days. Journal of Neurotrauma
No