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Bilateral corticospinal tract asymmetry predicts motor recovery after transcranial direct current stimulation in subacute stroke patients
Bing-Fong Lin1, Wei Yang1, Shih-Pin Hsu2,3, I-Hui Lee2,3, and Chia-Feng Lu1
1National Yang Ming Chiao Tung University, Taipei, Taiwan, 2Division of Cerebrovascular Diseases, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, 3Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan

Synopsis

Keywords: Stroke, Diffusion Tensor Imaging

Motivation: A reliable neuroimaging biomarker to predict motor improvement after neuromodulation is lacking.

Goal(s): We compared the integrity of bilateral corticospinal tracts and evaluated the asymmetry before tDCS. The association between the motor improvement and pretreatment integrity of the CST was identified to predict motor recovery in subacute stroke patients.

Approach: We calculated the asymmetry and fractional anisotropy between bilateral CST.
The linear regression analysis was conducted to predict the motor recovery.

Results: The patients with more severe motor impairment have higher asymmetry in CST. The tDCS regression models achieved an R2=0.796 and 0.624 for predicting FMA at three months after stroke onset.

Impact: The ischemic stroke patients with higher degree of right white matter integrity have better response to neural modulation effects of tDCS treatment. The identified DTI predictors could be the basis for optimizing the treatment protocols of tDCS in stroke patient.

Background and Purpose

Stroke is one of the leading causes of mortality and disability worldwide, and the upper extremity (UE) is the most commonly affected area in subacute stroke patients. Only 5% to 20% of patients achieved full recovery of the affected upper limb within six months [1]. Transcranial direct current stimulation (tDCS) showed a promising efficacy in improving motor recovery in subacute stroke [2]. Fugl-Meyer Assessment of Upper Extremity (FMA-UE) improvements after tDCS were associated with bilateral intrahemispheric functional connectivity and integrity of the corticospinal tract (CST) [3]. The early changes of white matter integrity after stroke onset is related to stroke recovery [4]. However, the association between pretreatment CST integrity and motor recovery was less explored. In this study, we hypothesized that the pretreatment integrity of the CST could predict the motor recovery in subacute stroke patients after tDCS treatment.

Materials and Methods

This study was approved by the local Institutional Review Board, and the written informed consent was provided by each participant. Thirty-one patients with ischemic stroke at subcortical regions and baseline FMA-UE score between 2 and 56 (moderate-to-severe) were recruited. The enrolled patients were randomly allocated into one of the study groups and either treated with real (ipsilesional primary motor cortex (M1) anode and contralesional M1 cathode) or sham tDCS for 20 sessions (two session per day from Monday to Friday for 2 consecutive weeks). During the intervention, the participants simultaneously practiced occupational therapist-led UE tasks following the principles of task-oriented therapy [5]. The FMA, including upper extremity (66 points in total) and lower extremity (34 points in total), was assessed at three timepoints: pre-treatment baseline (T1), post-treatment (T2), and three months post-stroke (T3). We further defined the patients with FMA-UE larger than 30 as mild to moderate UE impairment and FMA-UE less than 30 as severe UE impairment.
MRI data includes multiplanar T1-weighted BRAVO images (TR/TE: 12.2/5.2 ms; voxel size: 1.0x1.0x1.0 mm3) and diffusion-tensor images (DTI, TR/TE: 9500/89.1 ms; voxel size: 1.0x1.0x2.0 mm3; b value: 1000 s/mm2). These data were acquired on a 3T MRI scanner (GE Discovery MR750, 8-channel head coil) before the tDCS treatment. The probabilistic tractography was performed on the MRtrix3 software [6]. The asymmetry index (AI) between ipsilesional and contralesional CST was calculated using the equation below:
CST - AI =(Contralesional CST FA-Ipsilesional CST FA)/(Contralesional CST FA+Ipsilesional CST FA)

We calculated the fractional anisotropy (FA) of bilateral CST, which was separated into ten segments (Figure 2) [7]. A two-sample t-test with the correction of multiple comparisons was used for statistical analysis to compare the integrity of bilateral CST in the tDCS group. The linear regression analysis was conducted using the bilateral middle eight segments as variables to predict the motor recovery (T3 FMA – T1 FMA, change score). The performance of regression models was evaluated by the goodness-of-fit (R-square, R2) and F statistic versus a constant model (with p < 0.05 as significance).

Results and Discussion

Table 1 lists the demographic data, pretreatment and change score of FMA. The recruited patients with tDCS treatment showed significant improvement (positive values of change score, p<0.016) of the FM-UE, and FM-LE. In the baseline (T1), the patients with mild to moderate UE impairment (FM-UE>30 points) showed a higher CST-AI compared to severe UE impairment (FM-UE ≤30 points) (p=0.045) (Table 2). Figure 1 shows the correlation between CST-AI and FM-UL at baseline. The patients with more severe motor impairment tend to have higher asymmetry in CST among all the patients, though no significance was observed. CST was initially separated into ten segments, from the M1 to the brainstem (Figure 2). We calculated the mean FA for each segment in both ipsilesional and contralesional CST. The results revealed that the contralesional FA in segments 1 to 8 were significantly higher than that of the ipsilesional CST. In the tDCS group, the linear regression models using bilateral FA of CST as predictors achieved an R2 = 0.796, and p = 0.001 for predicting FMA-UE (Figure 3a), and R2 = 0.624, and p = 0.036 for predicting FMA-LE (Figure 3c) at three months after stroke onset. All the proposed regression models showed the significance of correlation coefficients in the tDCS group, but not in the sham group (Figure 3b and 3d).

Conclusions

This study reported that the patients with more severe motor impairment may have higher asymmetry in CST. Furthermore, motor recovery induced by tDCS can be predicted based on the pre-treatment microstructural integrity of CST.

Acknowledgements

This work was supported by Veterans General Hospitals and University System of Taiwan Joint Research Program (VGHUST112-G1-3-3), National Science and Technology Council (NSTC 112-2314-B-A49-060), Taiwan Ministry of Science and Technology (110-2320-B-075-002, 111-2320-B-075-010), the Taipei Veterans General Hospital (V110C-124, V111C-213, V112C-036), and the National Yang Ming Chiao Tung University (111W32408, 112W32101) from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Taiwan Ministry of Education.

References

  1. Kwakkel, G. and B.J. Kollen, Predicting activities after stroke: what is clinically relevant? Int J Stroke, 2013. 8(1): p. 25-32. 2.
  2. Bolognini, N., et al., Bi-hemispheric transcranial direct current stimulation for upper-limb hemiparesis in acute stroke: a randomized, double-blind, sham-controlled trial. Eur J Neurol, 2020. 27(12): p. 2473-2482. 3.
  3. Hsu, S.-P., et al., Effects of bihemispheric transcranial direct current stimulation on motor recovery in subacute stroke patients: a double-blind, randomized sham-controlled trial. Journal of NeuroEngineering and Rehabilitation, 2023. 20(1): p. 27. 4.
  4. Pinter, D., et al., Early Progressive Changes in White Matter Integrity Are Associated with Stroke Recovery. Transl Stroke Res, 2020. 11(6): p. 1264-1272. 5.
  5. Hubbard, I.J., et al., Task‐specific training: evidence for and translation to clinical practice. Occupational therapy international, 2009. 16(3‐4): p. 175-189. 6.
  6. Tournier, J.-D., et al., MRtrix3: A fast, flexible and open software framework for medical image processing and visualisation. Neuroimage, 2019. 202: p. 116137. 7.
  7. Lin, B.F., et al., Right Arcuate Fasciculus as Outcome Predictor after Low‐Frequency Repetitive Transcranial Magnetic Stimulation in Nonfluent Aphasic Stroke. European Journal of Neurology, 2023.

Figures

Table 1. Baseline characteristics of early subacute stroke participants. UE Upper Extremity, LE Lower Extremity

Table 2. According Fugl-Meyer-Upper Extremity (FM-UE) score classify patients into mild-moderate and severe upper extremity impairment.

Figure 1. Correlation analysis between baseline CST-AI and baseline FM-UL

Figure 2. The mean FA values for each segment in the ipsilesional and contralesional CST. * The difference is significant at the 0.005 level (multiple comparison).

Figure 3. Linear regression between pre-tDCS integrity of CST and motor recovery (T3 FMA-T1 FMA). The horizontal axes represent the predicted ΔFMA (change score) based on the DTI microstructural indices of CST, and the vertical axes represent the measured/actual ΔFMA. The dashed diagonal lines indicate the perfect match between the predicted and measured values.

Proc. Intl. Soc. Mag. Reson. Med. 32 (2024)
0078
DOI: https://doi.org/10.58530/2024/0078