Voxel-based statistical analysis of thalamic glucose metabolism in traumatic brain injury: relationship with consciousness and cognition

Objective: To study the relationship between thalamic glucose metabolism and neurological outcome after severe traumatic brain injury (TBI). Methods: Forty-nine patients with severe and closed TBI and 10 healthy control subjects with 18F-FDG PET were studied. Patients were divided into three groups: MCS&VS group (n ¼ 17), patients in a vegetative or a minimally conscious state; In-PTA group (n ¼ 12), patients in a state of post-traumatic amnesia (PTA); and Out-PTA group (n ¼ 20), patients who had emerged from PTA. SPM5 software implemented in MATLAB 7 was used to determine the quantitative differences between patients and controls. FDG-PET images were spatially normalized and an automated thalamic ROI mask was generated. Group differences were analysed with two sample voxel-wise t-tests. Results: Thalamic hypometabolism was the most prominent in patients with low consciousness (MCS&VS group) and the thalamic hypometabolism in the In-PTA group was more prominent than that in the Out-PTA group. Healthy control subjects showed the greatest thalamic metabolism. These differences in metabolism were more pronounced in the internal regions of the thalamus. Conclusions: The results confirm the vulnerability of the thalamus to suffer the effect of the dynamic forces generated during a TBI. Patients with thalamic hypometabolism could represent a sub-set of subjects that are highly vulnerable to neurological disability after TBI.Lull Noguera, N.; Noé, E.; Lull Noguera, JJ.; Garcia Panach, J.; Chirivella, J.; Ferri, J.; López-Aznar, D.... (2010). Voxel-based statistical analysis of thalamic glucose metabolism in traumatic brain injury: relationship with consciousness and cognition. Brain Injury. 24(9):1098-1107. doi:10.3109/02699052.2010.49459210981107249Gallagher, C. N., Hutchinson, P. J., & Pickard, J. D. (2007). Neuroimaging in trauma. Current Opinion in Neurology, 20(4), 403-409. doi:10.1097/wco.0b013e32821b987bWoischneck, D., Klein, S., Rei�berg, S., D�hring, W., Peters, B., & Firsching, R. (2001). Classification of Severe Head Injury Based on Magnetic Resonance Imaging. Acta Neurochirurgica, 143(3), 263-271. doi:10.1007/s007010170106Grados, M. A. (2001). Depth of lesion model in children and adolescents with moderate to severe traumatic brain injury: use of SPGR MRI to predict severity and outcome. Journal of Neurology, Neurosurgery & Psychiatry, 70(3), 350-358. doi:10.1136/jnnp.70.3.350Meythaler, J. M., Peduzzi, J. D., Eleftheriou, E., & Novack, T. A. (2001). Current concepts: Diffuse axonal injury–associated traumatic brain injury. Archives of Physical Medicine and Rehabilitation, 82(10), 1461-1471. doi:10.1053/apmr.2001.25137Scheid, R., Walther, K., Guthke, T., Preul, C., & von Cramon, D. Y. (2006). Cognitive Sequelae of Diffuse Axonal Injury. Archives of Neurology, 63(3), 418. doi:10.1001/archneur.63.3.418Brandstack, N., Kurki, T., Tenovuo, O., & Isoniemi, H. (2006). MR imaging of head trauma: Visibility of contusions and other intraparenchymal injuries in early and late stage. Brain Injury, 20(4), 409-416. doi:10.1080/02699050500487951Xu, J., Rasmussen, I.-A., Lagopoulos, J., & Håberg, A. (2007). Diffuse Axonal Injury in Severe Traumatic Brain Injury Visualized Using High-Resolution Diffusion Tensor Imaging. Journal of Neurotrauma, 24(5), 753-765. doi:10.1089/neu.2006.0208Levine, B., Fujiwara, E., O’connor, C., Richard, N., Kovacevic, N., Mandic, M., … Black, S. E. (2006). In Vivo Characterization of Traumatic Brain Injury Neuropathology with Structural and Functional Neuroimaging. Journal of Neurotrauma, 23(10), 1396-1411. doi:10.1089/neu.2006.23.1396Metting, Z., Rödiger, L. A., De Keyser, J., & van der Naalt, J. (2007). Structural and functional neuroimaging in mild-to-moderate head injury. The Lancet Neurology, 6(8), 699-710. doi:10.1016/s1474-4422(07)70191-6Nakayama, N. (2006). Relationship between regional cerebral metabolism and consciousness disturbance in traumatic diffuse brain injury without large focal lesions: an FDG-PET study with statistical parametric mapping analysis. Journal of Neurology, Neurosurgery & Psychiatry, 77(7), 856-862. doi:10.1136/jnnp.2005.080523Nakayama, N. (2006). Evidence for white matter disruption in traumatic brain injury without macroscopic lesions. Journal of Neurology, Neurosurgery & Psychiatry, 77(7), 850-855. doi:10.1136/jnnp.2005.077875O’Leary, D. D. M., Schlaggar, B. L., & Tuttle, R. (1994). Specification of Neocortical Areas and Thalamocortical Connections. Annual Review of Neuroscience, 17(1), 419-439. doi:10.1146/annurev.ne.17.030194.002223Mitelman, S. A., Byne, W., Kemether, E. M., Newmark, R. E., Hazlett, E. A., Haznedar, M. M., & Buchsbaum, M. S. (2006). Metabolic thalamocortical correlations during a verbal learning task and their comparison with correlations among regional volumes. Brain Research, 1114(1), 125-137. doi:10.1016/j.brainres.2006.07.043Laureys, S., Faymonville, M., Luxen, A., Lamy, M., Franck, G., & Maquet, P. (2000). Restoration of thalamocortical connectivity after recovery from persistent vegetative state. The Lancet, 355(9217), 1790-1791. doi:10.1016/s0140-6736(00)02271-6Laureys, S., Goldman, S., Phillips, C., Van Bogaert, P., Aerts, J., Luxen, A., … Maquet, P. (1999). Impaired Effective Cortical Connectivity in Vegetative State: Preliminary Investigation Using PET. NeuroImage, 9(4), 377-382. doi:10.1006/nimg.1998.0414Laureys, S., Owen, A. M., & Schiff, N. D. (2004). Brain function in coma, vegetative state, and related disorders. The Lancet Neurology, 3(9), 537-546. doi:10.1016/s1474-4422(04)00852-xGuye, M., Bartolomei, F., & Ranjeva, J.-P. (2008). Imaging structural and functional connectivity: towards a unified definition of human brain organization? Current Opinion in Neurology, 24(4), 393-403. doi:10.1097/wco.0b013e3283065cfbPrice, C. J., & Friston, K. J. (2002). Functional Imaging Studies of Neuropsychological Patients: Applications and Limitations. Neurocase, 8(5), 345-354. doi:10.1076/neur.8.4.345.16186Kim, J., Avants, B., Patel, S., Whyte, J., Coslett, B. H., Pluta, J., … Gee, J. C. (2008). Structural consequences of diffuse traumatic brain injury: A large deformation tensor-based morphometry study. NeuroImage, 39(3), 1014-1026. doi:10.1016/j.neuroimage.2007.10.005Maxwell, W. L., MacKinnon, M. A., Smith, D. H., McIntosh, T. K., & Graham, D. I. (2006). Thalamic Nuclei After Human Blunt Head Injury. Journal of Neuropathology & Experimental Neurology, 65(5), 478-488. doi:10.1097/01.jnen.0000229241.28619.75SIDAROS, A., SKIMMINGE, A., LIPTROT, M., SIDAROS, K., ENGBERG, A., HERNING, M., … ROSTRUP, E. (2009). Long-term global and regional brain volume changes following severe traumatic brain injury: A longitudinal study with clinical correlates. NeuroImage, 44(1), 1-8. doi:10.1016/j.neuroimage.2008.08.030Ashburner, J., & Friston, K. J. (2000). Voxel-Based Morphometry—The Methods. NeuroImage, 11(6), 805-821. doi:10.1006/nimg.2000.0582Good, C. D., Johnsrude, I. S., Ashburner, J., Henson, R. N. A., Friston, K. J., & Frackowiak, R. S. J. (2001). A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains. NeuroImage, 14(1), 21-36. doi:10.1006/nimg.2001.0786Giacino, J. T., Ashwal, S., Childs, N., Cranford, R., Jennett, B., Katz, D. I., … Zasler, N. D. (2002). The minimally conscious state: Definition and diagnostic criteria. Neurology, 58(3), 349-353. doi:10.1212/wnl.58.3.349Gispert, J. ., Pascau, J., Reig, S., Martínez-Lázaro, R., Molina, V., García-Barreno, P., & Desco, M. (2003). Influence of the normalization template on the outcome of statistical parametric mapping of PET scans. NeuroImage, 19(3), 601-612. doi:10.1016/s1053-8119(03)00072-7Ashburner, J., & Friston, K. J. (1999). Nonlinear spatial normalization using basis functions. Human Brain Mapping, 7(4), 254-266. doi:10.1002/(sici)1097-0193(1999)7:43.0.co;2-gTzourio-Mazoyer, N., Landeau, B., Papathanassiou, D., Crivello, F., Etard, O., Delcroix, N., … Joliot, M. (2002). Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain. NeuroImage, 15(1), 273-289. doi:10.1006/nimg.2001.0978Genovese, C. R., Lazar, N. A., & Nichols, T. (2002). Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate. NeuroImage, 15(4), 870-878. doi:10.1006/nimg.2001.1037LAUREYS, S., LEMAIRE, C., MAQUET, P., PHILLIPS, C., & FRANCK, G. (1999). Cerebral metabolism during vegetative state and after recovery to consciousness. Journal of Neurology, Neurosurgery & Psychiatry, 67(1), 121-122. doi:10.1136/jnnp.67.1.121Tommasino, C., Grana, C., Lucignani, G., Torri, G., & Fazio, F. (1995). Regional Cerebral Metabolism of Glucose in Comatose and Vegetative State Patients. Journal of Neurosurgical Anesthesiology, 7(2), 109-116. doi:10.1097/00008506-199504000-00006ANDERSON, C. V., WOOD, D.-M. G., BIGLER, E. D., & BLATTER, D. D. (1996). Lesion Volume, Injury Severity, and Thalamic Integrity following Head Injury. Journal of Neurotrauma, 13(2), 59-65. doi:10.1089/neu.1996.13.59Ge, Y., Patel, M. B., Chen, Q., Grossman, E. J., Zhang, K., Miles, L., … Grossman, R. I. (2009). Assessment of thalamic perfusion in patients with mild traumatic brain injury by true FISP arterial spin labelling MR imaging at 3T. Brain Injury, 23(7-8), 666-674. doi:10.1080/02699050903014899Uzan, M. (2003). Thalamic proton magnetic resonance spectroscopy in vegetative state induced by traumatic brain injury. Journal of Neurology, Neurosurgery & Psychiatry, 74(1), 33-38. doi:10.1136/jnnp.74.1.33OMMAYA, A. K., & GENNARELLI, T. A. (1974). CEREBRAL CONCUSSION AND TRAUMATIC UNCONSCIOUSNESS. Brain, 97(1), 633-654. doi:10.1093/brain/97.1.633Giacino, J., & Whyte, J. (2005). The Vegetative and Minimally Conscious States. Journal of Head Trauma Rehabilitation, 20(1), 30-50. doi:10.1097/00001199-200501000-00005Zeman, A. (2001). Consciousness. Brain, 124(7), 1263-1289. doi:10.1093/brain/124.7.1263Kinney, H. C., Korein, J., Panigrahy, A., Dikkes, P., & Goode, R. (1994). Neuropathological Findings in the Brain of Karen Ann Quinlan -- The Role of the Thalamus in the Persistent Vegetative State. New England Journal of Medicine, 330(21), 1469-1475. doi:10.1056/nejm199405263302101Saeeduddin Ahmed, Rex Bierley, Java. (2000). Post-traumatic amnesia after closed head injury: a review of the literature and some suggestions for further research. Brain Injury, 14(9), 765-780. doi:10.1080/026990500421886Wilson, J. T., Hadley, D. M., Wiedmann, K. D., & Teasdale, G. M. (1995). Neuropsychological consequences of two patterns of brain damage shown by MRI in survivors of severe head injury. Journal of Neurology, Neurosurgery & Psychiatry, 59(3), 328-331. doi:10.1136/jnnp.59.3.328Wilson, J. T., Teasdale, G. M., Hadley, D. M., Wiedmann, K. D., & Lang, D. (1994). Post-traumatic amnesia: still a valuable yardstick. Journal of Neurology, Neurosurgery & Psychiatry, 57(2), 198-201. doi:10.1136/jnnp.57.2.198Fearing, M. A., Bigler, E. D., Wilde, E. A., Johnson, J. L., Hunter, J. V., Xiaoqi Li, … Levin, H. S. (2008). Morphometric MRI Findings in the Thalamus and Brainstem in Children After Moderate to Severe Traumatic Brain Injury. Journal of Child Neurology, 23(7), 729-737. doi:10.1177/0883073808314159Little, D. M., Kraus, M. F., Joseph, J., Geary, E. K., Susmaras, T., Zhou, X. J., … Gorelick, P. B. (2010). Thalamic integrity underlies executive dysfunction in traumatic brain injury. Neurology, 74(7), 558-564. doi:10.1212/wnl.0b013e3181cff5d