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Traumatic Brain Injury
TBI is one of the most common causes of neurological disability, affecting 1.7 million per year in the U.S. TBI has two main neuropathologies: focal cortical contusions and diffuse axonal injury (DAI). While the technology for documenting focal cortical contusions is relatively straightforward, this is not the case for DAI, where significant effects may fall below the threshold of standard neuroimaging protocols. The Toronto TBI study has sought to delineate the effects of TBI neuropathology on neuroimaging markers and on behavior. |
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We documented a dose-response relationship between injury severity (as defined by consciousness alteration at the time of injury) and brain volume loss due to DAI as quantified from structural MRI scans. The volume loss was widespread throughout all regions of interest, not just the frontal and temporal regions classically associated with TBI (Levine et al., 2008). Additional studies delineated the relationship of this volume loss to behavior on standard and experimental tests (Levine et al., 2005; Fujiwara et al., 2008; Levine et al., 2013) These include the finding that functional outcome as assessed by self and significant other ratings is related to midline volume loss (Guild & Levine, 2015) and that autobiographical memory recall is related to distributed volume loss centered on the medial temporal lobe hub region (Esopenko & Levine, 2017).
The behavioural effects of DAI, including executive and prefrontal dysfunction, slowing, and reduced performance stability, can be associated with significant real-life disability beyond that documented by standard neuropsychological assessment. We were among the first to document increased brain activation (using H2150 Positron Emission Tomography) associated with memory task performance in patients with TBI, suggesting reduced efficiency of information processing (Levine et al., 2002). Later work using fMRI scanning during performance of a working memory task (Turner et al., 2008) has used multivariate brain-behavior analysis (Partial Least Squares; PLS) to demonstrate that recovery in TBI is associated with engagement of latent but functionally intact networks that already exist in healthy adults (Turner et al., 2011; Raja Beharelle et al., 2011). We were also one of the first groups to document changes in brain noise or complexity of brain signals (as assessed with Magnetoencephalography or MEG) in chronic TBI (Raja Beharelle et al., 2012). In all of the above studies, findings were attributable to DAI (and not focal lesions) owing to the application of the structural neuroimage analyses as described above, whereby atrophy due to DAI was documented in the absence of large focal lesions. We are currently applying similar structural and functional neuroimage analysis techniques in patients with multiple sclerosis and cerebral small vessel disease, which also cause diffuse brain changes.
Baycrest Brain Health in Professional Athletes Study
We are investigating neurocognitive aging longitudinally in former professional and university hockey players on an extensive battery of measures including neuropsychological and psychosocial tests, structural and functional brain imaging with simultaneous fMRI/EEG, genetics, neurological exam, cerebrospinal fluid analysis, and brain donation.
Selected Publications
1. Taghdiri, F., Multani, N., Tarazi, A., Naeimi, S.A., Khodadadi, M., Espoenko, C., Green, R., Colella, B., Wennberg, R., Mikulis, D., Davis, K.D., Goswami, R., Tator, C., Levine, B., & Tartaglia, M.C. (2019). Elevated cerebrospinal fluid total tau in former professional athletes with multiple concussions. Neurology. 92(23):e2717-e2726. DOI: 10.1212/WNL.0000000000007608
2. Richard, N.M., O’ Connor, C., Dey, A., Robertson, I. H., & Levine, B. (2018). External modulation of the sustained attention network in traumatic brain injury. Neuropsychology. 32(5):541-553. DOI: 10.1037/neu0000442
3. Esopenko, C., Chow, T.C., Tartaglia, M.C., Bacopulos, A., Kumar, P., Binns, M.A., Kennedy, J.L., Müeller, D.J., & Levine, B. (2017). Cognitive and Psychosocial Function in Retired Professional Hockey Players. Journal of Neurology, Neurosurgery, and Psychiatry. DOI:http://dx.doi.org/10.1136/jnnp-2016-315260
4. Esopenko, C. & Levine, B. (2017). Autobiographical memory and structural brain changes in chronic phase TBI. Cortex. DOI: http://dx.doi.org/10.1016/j.cortex.2017.01.007
5. Guild, E.B., & Levine, B. (2015). Functional Correlates of Midline Volume Loss in Chronic Traumatic Brain Injury. Journal of the International Neuropsychological Society. DOI: 10.1017/S1355617715000600.
6. Esopenko, C., & Levine, B. (2014). Aging, neurodegenerative disease and traumatic brain injury: the role of neuroimaging. Journal of Neurotrauma.
7. Levine, B., Kovacevic, N., Nica, E.I., Gao, F., Schwartz, M.L., & Black, S.E. (2013). Quantified MRI and cognition in TBI with diffuse and focal damage. Neuroimage: Clinical, 2, 534-541.
8. Raja Beharelle, A., Kovacevic, N., McIntosh, A. R., & Levine, B. (2012). Brain signal variability relates to stability of behavior after recovery from diffuse brain injury. NeuroImage, 60(2), 1528-1537.
9. Raja Beharelle, A., Tisserand, D., McIntosh, A.R., Levine, B. (2011) Brain activity patterns uniquely supporting visual feature integration after traumatic brain injury. Frontiers in Human Neuroscience, 5, 164. DOI: 10.3389/fnhum.2011.00164.
10. Turner, G.R., McIntosh, A.R., & Levine, B. (2011). Prefrontal compensatory engagement in TBI is due to altered functional engagement of existing networks and not functional reorganization. Frontiers in Systems Neuroscience, 5:9. doi: 10.3389/fnsys.2011.00009.
11. Levine, B., Kovacevic, N., Nica, E.I., Gao, F., Schwartz, M.L., & Black, S.E. The Toronto traumatic brain injury study: injury severity and quantified MRI. (2008). Neurology, 70, 771-778.
12. Turner, G.R. and Levine, B. (2008). Augmented neural activity during executive control processing following diffuse axonal injury. Neurology, 71, 812-18.
13. Fujiwara, E., Schwartz, M. L., Gao, F., Black, S. E., & Levine, B. (2008). Ventral frontal cortex functions and quantified MRI in traumatic brain injury. Neuropsychologia, 46, 461-474.
14. Levine, B., Fujiwara, E., O'Connor, C., Richard, N., Kovacevic, N., Mandic, M., Restagno, A., Easdon, C., Robertson, I. H., Graham, S. J., Cheung, G., Gao, F., Schwartz, M. L., & Black, S. E. (2006). In vivo characterization of traumatic brain injury neuropathology with structural and functional neuroimaging. J Neurotrauma, 23, 1396-411.
15. Levine, B., Black, S.E., Cheung, G., A., Campbell, A., O’Toole, C.M., & Schwartz, M.L. (2005). Gambling Task performance in traumatic brain injury: relationships to injury severity, atrophy, lesion location, and cognitive and psychosocial outcome. Cognitive and Behavioral Neurology, 18, 45-54.
16. Levine, B., Cabeza, R, McIntosh, A.R., Black, S.E., Grady, C.L., & Stuss, D.T. (2002). Functional reorganization of memory following traumatic brain injury: A study with H2150 PET. Journal of Neurology, Neurosurgery, & Psychiatry, 73, 173-181.
2. Richard, N.M., O’ Connor, C., Dey, A., Robertson, I. H., & Levine, B. (2018). External modulation of the sustained attention network in traumatic brain injury. Neuropsychology. 32(5):541-553. DOI: 10.1037/neu0000442
3. Esopenko, C., Chow, T.C., Tartaglia, M.C., Bacopulos, A., Kumar, P., Binns, M.A., Kennedy, J.L., Müeller, D.J., & Levine, B. (2017). Cognitive and Psychosocial Function in Retired Professional Hockey Players. Journal of Neurology, Neurosurgery, and Psychiatry. DOI:http://dx.doi.org/10.1136/jnnp-2016-315260
4. Esopenko, C. & Levine, B. (2017). Autobiographical memory and structural brain changes in chronic phase TBI. Cortex. DOI: http://dx.doi.org/10.1016/j.cortex.2017.01.007
5. Guild, E.B., & Levine, B. (2015). Functional Correlates of Midline Volume Loss in Chronic Traumatic Brain Injury. Journal of the International Neuropsychological Society. DOI: 10.1017/S1355617715000600.
6. Esopenko, C., & Levine, B. (2014). Aging, neurodegenerative disease and traumatic brain injury: the role of neuroimaging. Journal of Neurotrauma.
7. Levine, B., Kovacevic, N., Nica, E.I., Gao, F., Schwartz, M.L., & Black, S.E. (2013). Quantified MRI and cognition in TBI with diffuse and focal damage. Neuroimage: Clinical, 2, 534-541.
8. Raja Beharelle, A., Kovacevic, N., McIntosh, A. R., & Levine, B. (2012). Brain signal variability relates to stability of behavior after recovery from diffuse brain injury. NeuroImage, 60(2), 1528-1537.
9. Raja Beharelle, A., Tisserand, D., McIntosh, A.R., Levine, B. (2011) Brain activity patterns uniquely supporting visual feature integration after traumatic brain injury. Frontiers in Human Neuroscience, 5, 164. DOI: 10.3389/fnhum.2011.00164.
10. Turner, G.R., McIntosh, A.R., & Levine, B. (2011). Prefrontal compensatory engagement in TBI is due to altered functional engagement of existing networks and not functional reorganization. Frontiers in Systems Neuroscience, 5:9. doi: 10.3389/fnsys.2011.00009.
11. Levine, B., Kovacevic, N., Nica, E.I., Gao, F., Schwartz, M.L., & Black, S.E. The Toronto traumatic brain injury study: injury severity and quantified MRI. (2008). Neurology, 70, 771-778.
12. Turner, G.R. and Levine, B. (2008). Augmented neural activity during executive control processing following diffuse axonal injury. Neurology, 71, 812-18.
13. Fujiwara, E., Schwartz, M. L., Gao, F., Black, S. E., & Levine, B. (2008). Ventral frontal cortex functions and quantified MRI in traumatic brain injury. Neuropsychologia, 46, 461-474.
14. Levine, B., Fujiwara, E., O'Connor, C., Richard, N., Kovacevic, N., Mandic, M., Restagno, A., Easdon, C., Robertson, I. H., Graham, S. J., Cheung, G., Gao, F., Schwartz, M. L., & Black, S. E. (2006). In vivo characterization of traumatic brain injury neuropathology with structural and functional neuroimaging. J Neurotrauma, 23, 1396-411.
15. Levine, B., Black, S.E., Cheung, G., A., Campbell, A., O’Toole, C.M., & Schwartz, M.L. (2005). Gambling Task performance in traumatic brain injury: relationships to injury severity, atrophy, lesion location, and cognitive and psychosocial outcome. Cognitive and Behavioral Neurology, 18, 45-54.
16. Levine, B., Cabeza, R, McIntosh, A.R., Black, S.E., Grady, C.L., & Stuss, D.T. (2002). Functional reorganization of memory following traumatic brain injury: A study with H2150 PET. Journal of Neurology, Neurosurgery, & Psychiatry, 73, 173-181.