Axonal integrity predicts cortical reorganisation following cervical injury
- Patrick Freund1,2,3,4,
- Claudia A Wheeler-Kingshott5,
- Zoltan Nagy2,
- Nikos Gorgoraptis1,
- Nikolaus Weiskopf2,
- Karl Friston2,
- Alan J Thompson1,
- Chloe Hutton2
- 1Department of Brain Repair & Rehabilitation, UCL Institute of Neurology, UCL, London, UK
- 2Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, UCL, London, UK
- 3Spinal Cord Injury Centre, Royal National Orthopaedic Hospital, UCL, London, UK
- 4Swiss Paraplegic Research, Nottwil, Switzerland
- 5Department of Neuroinflammation, UCL Institute of Neurology, UCL, London, UK
- Correspondence to Dr Patrick Freund, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK;
Contributors PF and CH designed the study, acquired the data, performed statistical analysis and wrote the paper. CW-K, ZN designed the imaging protocol and revised the paper. KF, AJT and NW designed the study, performed statistical analysis and revised the paper.
- Received 22 November 2011
- Accepted 6 March 2012
- Published Online First 6 April 2012
Background Traumatic spinal cord injury (SCI) leads to disruption of axonal architecture and macroscopic tissue loss with impaired information flow between the brain and spinal cord—the presumed basis of ensuing clinical impairment.
Objective The authors used a clinically viable, multimodal MRI protocol to quantify the axonal integrity of the cranial corticospinal tract (CST) and to establish how microstructural white matter changes in the CST are related to cross-sectional spinal cord area and cortical reorganisation of the sensorimotor system in subjects with traumatic SCI.
Methods Nine volunteers with cervical injuries resulting in bilateral motor impairment and 14 control subjects were studied. The authors used diffusion tensor imaging to assess white matter integrity in the CST, T1-weighted imaging to measure cross-sectional spinal cord area and functional MRI to compare motor task-related brain activations. The relationships among microstructural, macrostructural and functional measures were assessed using regression analyses.
Results Diffusion tensor imaging revealed significant differences in the CST of SCI subjects—compared with controls—in the pyramids, the internal capsule, the cerebral peduncle and the hand area. The microstructural white matter changes observed in the left pyramid predicted increased task-related responses in the left M1 leg area, while changes in the cerebral peduncle were predicted by reduced cord area.
Conclusion The observed microstructural changes suggest trauma-related axonal degeneration and demyelination, which are related to cortical motor reorganisation and macrostructure. The extent of these changes may reflect the plasticity of motor pathways associated with cortical reorganisation. This clinically viable multimodal imaging approach is therefore appropriate for monitoring degeneration of central pathways and the evaluation of treatments targeting axonal repair in SCI.
- Spinal cord trauma
- motor cortex
- functional neuroimaging
- functional imaging
- health policy and practice
- multiple sclerosis
Funding This work was supported by the Swiss National Science Foundation (Grant No: PBFR33-120920), Schweizerische Stiftung für medizinische und biologische Stipendien (Grant No: PASMP3-124194), Swiss Paraplegic Research (Nottwil) and the Wellcome Trust. This work was undertaken at UCLH/UCL which received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme.
Competing interests None.
Patient consent The content of this paper does not include any personal information referring to individuals. Therefore we guarantee full anonymity. All participants gave informed, written consent before the study, which was approved by the Joint Ethics Committee of the UCL-Institute of Neurology and the National Hospital for Neurology and Neurosurgery (ref: 08/0243).
Ethics approval Ethics approval was granted by Joint Ethics Committee of the UCL-Institute of Neurology and the National Hospital for Neurology and Neurosurgery (ref: 08/0243).
Provenance and peer review Not commissioned; externally peer reviewed.
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