Department of Exercise Sciences


Relationships between functional and structural corticospinal tract integrity and walking post stroke

Gowri Jayaram, Charlotte J. Stagg, Patrick Esser, Udo Kischka, James Stinear, Heidi Johansen-Berg Published in Clinical Neurophysiol (2012)

Introduction

Stroke rehabilitation therapies may be more effective if they are tailored to an individual patient’s surviving anatomical and physiological substrates. However, development of such strategies first requires identification of functional and structural measures that are associated with clinical status that could in future be tested as predictors of outcomes. Studies on upper limb recovery following stroke have highlighted the importance of the structural and functional integrity of the corticospinal tract (CST) in determining clinical outcomes. However, such relationships have not been fully explored for the lower limb. There is some evidence of increased activity in the ipsilateral (contralesional) motor cortex during paretic lower limb movements in more severely impaired patients but the functional and clinical significance of such activity is unclear.

Aim

We aimed to test whether variation in walking impairment was associated with variation in structural or functional integrity of the CST. We used transcranial magnetic stimulation (TMS) to directly assess functional connectivity from the motor cortex of each hemisphere to both lower limbs in chronic stroke patients with persistent paresis of their lower limb. We used diffusion tensor imaging (DTI) to assess the structural integrity of the CST in each hemisphere. We hypothesized that patients with a higher degree of structural damage to the CST in the lesioned hemisphere would have greater relative functional connectivity from the contralesional motor cortex to the ipsilateral paretic limb, and greater walking impairment.

Method

  • Participants: Nine individuals with persistent hemiparesis due to chronic stroke (≥ 6 months) were recruited. Patients were screened for contradictions to MRI and TMS.
  • Each participant’s overall impairment was assessed using the lower-limb section of the Fugl-Meyer (FM) scale, with higher scores reflecting greater function. 
  • TMS was used to stimulate each motor cortex while EMG recordings were taken from the vastus lateralis (VL) bilaterally. 
  • These EMG measures were used to calculate both ipsilateral and contralateral recruitment curves for each lower limb. 
  • The slope of these recruitment curves was used to examine the strength of functional connectivity from the motor cortex in each hemisphere to the lower limbs in chronic stroke patients and to calculate a ratio between ipsilateral and contralateral outputs referred to as the functional connectivity ratio (FCR). 
  • The structural integrity of the CST was assessed during diffusion tensor MRI to measure the asymmetry in fractional anisotropy (FA) of the internal capsule. 
  • Lower limb impairment and walking speed were also measured.

Results

  • The FCR for the paretic leg correlated with walking impairment, such that greater relative ipsilateral connectivity was associated with slower walking speeds (Fig. 2). 
  • Asymmetrical FA values, reflecting reduced structural integrity of the lesioned CST, were associated with greater walking impairment. 
  • FCR and FA asymmetry were strongly positively correlated with each other (Fig. 3B). 
Jayaram 2012 Fig 2 (insert after results)
Jayaram 2012 Fig 3 (insert after results and figure 2)

Interpretation

This study investigated the iner-relationship between the structural integrity and functional connectivity of the CST and the extent of lower limb impairment in chronic stroke patients. Patients with relatively greater ipsilateral connectivity between the contralesional motor cortex and the paretic lower limb were more behaviourally impaired and had greater structural damage to their ipsilesional hemisphere CST.

The relationships between functional and structural measures of the corticospinal tract and behavioural outcomes presented here further our understanding of the factors that may influence walking recovery post stroke and demonstrate the complimentary nature of neurophysiological and imaging techniques in characterizing a patient’s residual anatomical and physiological substrates.

In the future, such measures may inform the selection of therapeutic strategies, moving towards more individualized treatments that will optimize a patient’s potential for recovery.

Acknowledgements

This work was supported by Wellcome Trust; NIHR Biomedical Research Centre, Oxford; Whitaker Foundation.