Modulation of Functional Connectivity and Low-Frequency Fluctuations After Brain-Computer Interface-Guided Robot Hand Training in Chronic Stroke: A 6-Month Follow-Up Study

Cathy C Y Lau, Kai Yuan, Patrick C M Wong, Winnie C W Chu, Thomas W Leung, Wan-Wa Wong, Raymond K Y Tong, Cathy C Y Lau, Kai Yuan, Patrick C M Wong, Winnie C W Chu, Thomas W Leung, Wan-Wa Wong, Raymond K Y Tong

Abstract

Hand function improvement in stroke survivors in the chronic stage usually plateaus by 6 months. Brain-computer interface (BCI)-guided robot-assisted training has been shown to be effective for facilitating upper-limb motor function recovery in chronic stroke. However, the underlying neuroplasticity change is not well understood. This study aimed to investigate the whole-brain neuroplasticity changes after 20-session BCI-guided robot hand training, and whether the changes could be maintained at the 6-month follow-up. Therefore, the clinical improvement and the neurological changes before, immediately after, and 6 months after training were explored in 14 chronic stroke subjects. The upper-limb motor function was assessed by Action Research Arm Test (ARAT) and Fugl-Meyer Assessment for Upper-Limb (FMA), and the neurological changes were assessed using resting-state functional magnetic resonance imaging. Repeated-measure ANOVAs indicated that long-term motor improvement was found by both FMA (F[2,26] = 6.367, p = 0.006) and ARAT (F[2,26] = 7.230, p = 0.003). Seed-based functional connectivity analysis exhibited that significantly modulated FC was observed between ipsilesional motor regions (primary motor cortex and supplementary motor area) and contralesional areas (supplementary motor area, premotor cortex, and superior parietal lobule), and the effects were sustained after 6 months. The fALFF analysis showed that local neuronal activities significantly increased in central, frontal and parietal regions, and the effects were also sustained after 6 months. Consistent results in FC and fALFF analyses demonstrated the increase of neural activities in sensorimotor and fronto-parietal regions, which were highly involved in the BCI-guided training. Clinical Trial Registration: This study has been registered at ClinicalTrials.gov with clinical trial registration number NCT02323061.

Keywords: brain-computer interface; fractional amplitude low-frequency fluctuations; functional magnet resonance imaging; rehabilatation robotics; stroke.

Conflict of interest statement

RT is one of the inventors of the Hong Kong Polytechnic University-held patent for the hand exoskeleton robot which was used in this study. All authors, however, are of no financial relationship whatsoever for the submitted work with Rehab-Robotics Company Ltd., the company which manufactures the commercial version of the original device under a license agreement with the University.

Copyright © 2021 Lau, Yuan, Wong, Chu, Leung, Wong and Tong.

Figures

Figure 1
Figure 1
The intervention. (A) The sequence of the training paradigm. (B) The average success rate of all training trials across 20 sessions for all subjects. Error bars stand for standard errors. The dark black line stands for the chance level. (C) The average α suppression score of all training trials across 20 sessions for all subjects. Error bars stand for standard errors.
Figure 2
Figure 2
Seed-based whole-brain analysis results. (A) The left panel showed the FC map in the Pre session when the seed was set at iM1. Voxels with z > 2.7 were shown. The iM1 seed was denoted as a green sphere in the figure. The color-coded area illustrates the significant clusters found in Post (contralesional premotor area) and Post6month (contralesional SMA). The white numbers beside the images represent the coordinate in MNI space. (B) The left panel showed the FC map in the Pre session when the seed was set at iSMA. Voxels with z > 2.7 were shown. The iSMA seed was denoted as a green sphere in the figure. The color-coded area illustrates the significant clusters found in Post (bilateral SPL) and Post6month (bilateral SPL). The white numbers beside the images represent the coordinate in MNI space.
Figure 3
Figure 3
fALFF analyses results. (A) Significant increased clusters were observed in the ipsilesional precentral area and contralesional superior parietal lobule when comparing Post and Pre sessions. (B) Significantly increased clusters were observed in the contralesional precentral area and ipsilesional superior frontal area when comparing Post6month and Pre sessions. (C) Significantly increased clusters were observed in bilateral SMA and paracentral lobule when comparing Post6month and Post sessions.

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