Training with noninvasive brain-machine interface, tactile feedback, and locomotion to enhance neurological recovery in individuals with complete paraplegia: a randomized pilot study

Abstract

In recent years, our group and others have reported multiple cases of consistent neurological recovery in people with spinal cord injury (SCI) following a protocol that integrates locomotion training with brain machine interfaces (BMI). The primary objective of this pilot study was to compare the neurological outcomes (motor, tactile, nociception, proprioception, and vibration) in both an intensive assisted locomotion training (LOC) and a neurorehabilitation protocol integrating assisted locomotion with a noninvasive brain-machine interface (L + BMI), virtual reality, and tactile feedback. We also investigated whether individuals with chronic-complete SCI could learn to perform leg motor imagery. We ran a parallel two-arm randomized pilot study; the experiments took place in São Paulo, Brazil. Eight adults sensorimotor-complete (AIS A) (all male) with chronic (> 6 months) traumatic spinal SCI participated in the protocol that was organized in two blocks of 14 weeks of training and an 8-week follow-up. The participants were allocated to either the LOC group (n = 4) or L + BMI group (n = 4) using block randomization (blinded outcome assessment). We show three important results: (i) locomotion training alone can induce some level of neurological recovery in sensorimotor-complete SCI, and (ii) the recovery rate is enhanced when such locomotion training is associated with BMI and tactile feedback (∆Mean Lower Extremity Motor score improvement for LOC = + 2.5, L + B = + 3.5; ∆Pinprick score: LOC = + 3.75, L + B = + 4.75 and ∆Tactile score LOC = + 4.75, L + B = + 9.5). (iii) Furthermore, we report that the BMI classifier accuracy was significantly above the chance level for all participants in L + B group. Our study shows potential for sensory and motor improvement in individuals with chronic complete SCI following a protocol with BMIs and locomotion therapy. We report no dropouts nor adverse events in both subgroups participating in the study, opening the possibility for a more definitive clinical trial with a larger cohort of people with SCI.Trial registration: http://www.ensaiosclinicos.gov.br/ identifier RBR-2pb8gq.

Figure 1

Experimental protocol. (A) Training protocol for the Locomotion only (red) and Locomotion + BMI (black) groups. A0 to A4 are clinical assessments. The Pre-training is the period going between the baseline measurement performed by the clinical institution that followed the individual before our protocol began and the onset of our protocol. The training phase contains two blocks of 13–14 weeks of training, and the carry-over phase goes between the end of the protocol and 8 weeks after the training. (B) Both LOC and L + B groups followed the assisted locomotion training, consisting of one Lokomat and one ZeroG training per week. The BMI training consisted of leg motor imagery to control an avatar and sensory feedback provided on subjects’ forearms (C) The 16 EEG electrode placement with the (R)eference and (G)round. (D) Left and right step animation on the avatar were triggered if the output of the linear Classifier (CL) was respectively below or above a certain threshold (− 1, + 1). If the subject did not alternate for 5 s, the avatar moved to an idle state.

Figure 2

BMI scores. (A) EEG classifier accuracy for the calibration sessions. (B) The mean corrected walk distance (CWD) for BMI sessions performed when the subject was seated (empty red bar) or standing position (red filled bar). Both conditions are compared to random (see Supplementary Fig. S1 for description). *P < 0.05, **P < 0.01. Bars are stand deviation (SD) (C) Mean and SD for the CWD for the four study participants that followed the BMI protocol considering both seated and standing sessions and compared to chance level (D) CWD for each block of 6 min of BMI performed seated (empty red circles) or standing (filled red circles), compared to chance level (black line) as measured by the random walk. *P < 0.05, **P < 0.01, P < 0.001, t-test. (E) Mean ± SD time to trigger a step during BMI tasks. (F) The Average coefficients for the first and second CSP component considering the training sessions for the four participants that followed the BMI protocol.

Figure 3

Clinical outcome. (A) Mean ± STD clinical scores (n = 4) for the subjects following the locomotion + BMI training (black circle) and the locomotion only protocol (red triangles). Pinprick's score and tactile score are reported as differences in the baseline assessment at the onset of the protocol (A1); for motor performance, we show the raw lower extremity motor score (LEMS). We also report the lower limb proprioception score and vibration score (max score = 1). The measurement A0 was done (by a different clinical institution) 1–3 years before the onset of the protocol and consisted of only pinprick and motor measurements. (B) Improvement (sensory or LEMS score) measured for participants following the L + B (black circles) or LOC (red triangle) groups for (P)re training (improvement between A0 and A1), (T)raining (improvement between A1 and A3) and (C)arry over (between A3 and A4) (Friedman test, and multiple comparisons with Bonferroni correction, *P < 0.05). (C) AIS grades for all study participants.