Longitudinal assessment of local and global functional connectivity following sports-related concussion
- 698 Downloads
Growing evidence suggests that sports-related concussions (SRC) may lead to acute changes in intrinsic functional connectivity, although most studies to date have been cross-sectional in nature with relatively modest sample sizes. We longitudinally assessed changes in local and global resting state functional connectivity using metrics that do not require a priori seed or network selection (regional homogeneity; ReHo and global brain connectivity; GBC, respectively). A large sample of collegiate athletes (N = 43) was assessed approximately one day (1.74 days post-injury, N = 34), one week (8.44 days, N = 34), and one month post-concussion (32.47 days, N = 30). Healthy contact sport-athletes served as controls (N = 51). Concussed athletes showed improvement in mood symptoms at each time point (p’s < 0.05), but had significantly higher mood scores than healthy athletes at every time point (p’s < 0.05). In contrast, self-reported symptoms and cognitive deficits improved over time following concussion (p’s < 0.001), returning to healthy levels by one week post-concussion. ReHo in sensorimotor, visual, and temporal cortices increased over time post-concussion, and was greatest at one month post-injury. Conversely, ReHo in the frontal cortex decreased over time following SRC, with the greatest decrease evident at one month post-concussion. Differences in ReHo relative to healthy athletes were primarily observed at one month post-concussion rather than the more acute time points. Contrary to our hypothesis, no significant cross-sectional or longitudinal differences in GBC were observed. These results are suggestive of a delayed onset of local connectivity changes following SRC.
KeywordsfMRI Mild traumatic brain injury Regional homogeneity Resting state
This research was conducted using internal funds from the Laureate Institute for Brain Research, which is supported by The William K. Warren Foundation. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. Dr. Meier had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors thank the psychiatric assessment team, the MRI technicians, and Dr. Rashmi Singh at the Laureate Institute for Brain Research for their assistance in data collection and Christopher Nerio, David Polanski, Dr. Thomas Allen, and Dr. Lamont Cavanagh for athlete referral and injury oversight.
Compliance with ethical standards
Disclosures and informed consent
The authors declare that they have no conflict of interest. This article was prepared while Dr. Bellgowan was employed at The National Institute of Neurological Disorders and Stroke. The opinions expressed in this article are the author’s own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. All procedures performed were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
- Abbas, K., Shenk, T. E., Poole, V. N., Breedlove, E. L., Leverenz, L. J., Nauman, E. A., et al. (2015). Alteration of default mode network in high school football athletes due to repetitive subconcussive mild traumatic brain injury: a resting-state functional magnetic resonance imaging study. Brain Connectivity, 5(2), 91–101. doi: 10.1089/brain.2014.0279.CrossRefPubMedGoogle Scholar
- Buckner, R. L., Sepulcre, J., Talukdar, T., Krienen, F. M., Liu, H., Hedden, T., et al. (2009). Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer's disease. The Journal of Neuroscience, 29(6), 1860–1873. doi: 10.1523/JNEUROSCI.5062-08.2009.CrossRefPubMedPubMedCentralGoogle Scholar
- Cernich, A., Reeves, D., Sun, W., & Bleiberg, J. (2007). Automated neuropsychological assessment metrics sports medicine battery. Arch Clin Neuropsychol, 22 Suppl 1, S101-114. doi: 10.1016/j.acn.2006.10.008.
- Czerniak, S.M., Sikoglu, E.M., Liso Navarro, A.A., McCafferty, J., Eisenstock, J., Stevenson, J. H., et al. (2015). A resting state functional magnetic resonance imaging study of concussion in collegiate athletes. Brain Imaging and Behavior, 9(2), 323–332. doi: 10.1007/s11682-014-9312-1.
- Dettwiler, A., Murugavel, M., Putukian, M., Cubon, V., Furtado, J., & Osherson, D. (2014). Persistent differences in patterns of brain activation after sports-related concussion: a longitudinal functional magnetic resonance imaging study. Journal of Neurotrauma, 31(2), 180–188. doi: 10.1089/neu.2013.2983.CrossRefPubMedPubMedCentralGoogle Scholar
- Giza, C. C., & Hovda, D. A. (2014). The new neurometabolic cascade of concussion. Neurosurgery, 75 Suppl 4, S24-33. doi: 10.1227/NEU.0000000000000505.
- Guskiewicz, K. M., McCrea, M., Marshall, S. W., Cantu, R. C., Randolph, C., Barr, W., et al. (2003). Cumulative effects associated with recurrent concussion in collegiate football players: the NCAA concussion study. JAMA, 290(19), 2549–2555. doi: 10.1001/jama.290.19.2549.CrossRefPubMedGoogle Scholar
- Jiang, L., Xu, T., He, Y., Hou, X. H., Wang, J., Cao, X. Y., et al. (2015). Toward neurobiological characterization of functional homogeneity in the human cortex: regional variation, morphological association and functional covariance network organization. Brain Structure & Function, 220(5), 2485–2507. doi: 10.1007/s00429-014-0795-8.CrossRefGoogle Scholar
- Johnson, B., Zhang, K., Gay, M., Horovitz, S., Hallett, M., Sebastianelli, W., et al. (2012). Alteration of brain default network in subacute phase of injury in concussed individuals: resting-state fMRI study. NeuroImage, 59(1), 511–518. doi: 10.1016/j.neuroimage.2011.07.081.CrossRefPubMedGoogle Scholar
- Johnson, B., Neuberger, T., Gay, M., Hallett, M., & Slobounov, S. (2014). Effects of subconcussive head trauma on the default mode network of the brain. Journal of Neurotrauma, 31(23), 1907–1913. doi: 10.1089/neu.2014.3415.
- Jones, T. B., Bandettini, P. A., Kenworthy, L., Case, L. K., Milleville, S. C., Martin, A., et al. (2010). Sources of group differences in functional connectivity: an investigation applied to autism spectrum disorder. NeuroImage, 49(1), 401–414. doi: 10.1016/j.neuroimage.2009.07.051.CrossRefPubMedGoogle Scholar
- Kasahara, M., Menon, D. K., Salmond, C. H., Outtrim, J. G., Taylor Tavares, J. V., Carpenter, T. A., et al. (2010). Altered functional connectivity in the motor network after traumatic brain injury. Neurology, 75(2), 168–176. doi: 10.1212/WNL.0b013e3181e7ca58.CrossRefPubMedPubMedCentralGoogle Scholar
- Lew, H. L., Pogoda, T. K., Baker, E., Stolzmann, K. L., Meterko, M., Cifu, D. X., et al. (2011). Prevalence of dual sensory impairment and its association with traumatic brain injury and blast exposure in OEF/OIF veterans. The Journal of Head Trauma Rehabilitation, 26(6), 489–496. doi: 10.1097/HTR.0b013e318204e54b.CrossRefPubMedGoogle Scholar
- Mayer, A. R., Hanlon, F. M., Dodd, A. B., Ling, J. M., Klimaj, S. D., & Meier, T. B. (2015b). A functional magnetic resonance imaging study of cognitive control and neurosensory deficits in mild traumatic brain injury. Human Brain Mapping, 36(11), 4394–4406. doi: 10.1002/hbm.22930.CrossRefPubMedPubMedCentralGoogle Scholar
- McCrory, P., Meeuwisse, W. H., Aubry, M., Cantu, B., Dvorak, J., Echemendia, R. J., et al. (2013). Consensus statement on concussion in sport: the 4th international conference on concussion in sport held in Zurich, November 2012. British Journal of Sports Medicine, 47(5), 250–258. doi: 10.1136/bjsports-2013-092313.CrossRefPubMedGoogle Scholar
- Militana, A. R., Donahue, M. J., Sills, A. K., Solomon, G. S., Gregory, A. J., Strother, M. K., et al. (2015). Alterations in default-mode network connectivity may be influenced by cerebrovascular changes within 1 week of sports related concussion in college varsity athletes: a pilot study. Brain Imaging and Behavior. doi: 10.1007/s11682-015-9407-3.Google Scholar
- Park, E., Bell, J. D., Siddiq, I. P., & Baker, A. J. (2009). An analysis of regional microvascular loss and recovery following two grades of fluid percussion trauma: a role for hypoxia-inducible factors in traumatic brain injury. Journal of Cerebral Blood Flow and Metabolism, 29(3), 575–584. doi: 10.1038/jcbfm.2008.151.CrossRefPubMedGoogle Scholar
- Pogoda, T. K., Hendricks, A. M., Iverson, K. M., Stolzmann, K. L., Krengel, M. H., Baker, E., et al. (2012). Multisensory impairment reported by veterans with and without mild traumatic brain injury history. Journal of Rehabilitation Research and Development, 49(7), 971–984.CrossRefPubMedGoogle Scholar
- Roebuck-Spencer, T. M., Vincent, A. S., Gilliland, K., Johnson, D. R., & Cooper, D. B. (2013). Initial clinical validation of an embedded performance validity measure within the automated neuropsychological metrics (ANAM). Archives of Clinical Neuropsychology, 28(7), 700–710. doi: 10.1093/arclin/act055.CrossRefPubMedGoogle Scholar
- Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., et al. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. The Journal of Neuroscience, 27(9), 2349–2356. doi: 10.1523/JNEUROSCI.5587-06.2007.CrossRefPubMedPubMedCentralGoogle Scholar
- Seichepine, D. R., Stamm, J. M., Daneshvar, D. H., Riley, D. O., Baugh, C. M., Gavett, B. E., et al. (2013). Profile of self-reported problems with executive functioning in college and professional football players. Journal of Neurotrauma, 30(14), 1299–1304. doi: 10.1089/neu.2012.2690.CrossRefPubMedPubMedCentralGoogle Scholar
- Sheline, Y. I., Barch, D. M., Price, J. L., Rundle, M. M., Vaishnavi, S. N., Snyder, A. Z., et al. (2009). The default mode network and self-referential processes in depression. Proceedings of the National Academy of Sciences of the United States of America, 106(6), 1942–1947. doi: 10.1073/pnas.0812686106.CrossRefPubMedPubMedCentralGoogle Scholar
- Singh, R., Savitz, J., Teague, T. K., Polanski, D. W., Mayer, A. R., Bellgowan, P. S., et al. (2015). Mood symptoms correlate with kynurenine pathway metabolites following sports-related concussion. Journal of Neurology, Neurosurgery, and Psychiatry. doi: 10.1136/jnnp-2015-311369.PubMedGoogle Scholar
- Slobounov, S. M., Gay, M., Zhang, K., Johnson, B., Pennell, D., Sebastianelli, W., et al. (2011). Alteration of brain functional network at rest and in response to YMCA physical stress test in concussed athletes: RsFMRI study. NeuroImage, 55(4), 1716–1727. doi: 10.1016/j.neuroimage.2011.01.024.CrossRefPubMedPubMedCentralGoogle Scholar
- Urban, K. J., Barlow, K. M., Jimenez, J. J., Goodyear, B. G., & Dunn, J. F. (2015). Functional near-infrared spectroscopy reveals reduced interhemispheric cortical communication after pediatric concussion. Journal of Neurotrauma, 32(11), 833–840. doi: 10.1089/neu.2014.3577.CrossRefPubMedPubMedCentralGoogle Scholar
- Yeo, B. T., Krienen, F. M., Sepulcre, J., Sabuncu, M. R., Lashkari, D., Hollinshead, M., et al. (2011). The organization of the human cerebral cortex estimated by intrinsic functional connectivity. Journal of Neurophysiology, 106(3), 1125–1165. doi: 10.1152/jn.00338.2011.CrossRefPubMedGoogle Scholar
- Zhan, J., Gao, L., Zhou, F., Kuang, H., Zhao, J., Wang, S., et al. (2015). Decreased regional homogeneity in patients with acute mild traumatic brain injury: a resting-state fMRI study. The Journal of Nervous and Mental Disease, 203(10), 786–791. doi: 10.1097/NMD.0000000000000368.CrossRefPubMedGoogle Scholar
- Zhu, D. C., Covassin, T., Nogle, S., Doyle, S., Russell, D., Pearson, R. L., et al. (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, 32(5), 327–341. doi: 10.1089/neu.2014.3413.CrossRefPubMedGoogle Scholar
- Zuo, X. N., Xu, T., Jiang, L., Yang, Z., Cao, X. Y., He, Y., et al. (2013). Toward reliable characterization of functional homogeneity in the human brain: preprocessing, scan duration, imaging resolution and computational space. NeuroImage, 65, 374–386. doi: 10.1016/j.neuroimage.2012.10.017.CrossRefPubMedGoogle Scholar