Functional organization and restoration of the brain motor-execution network after stroke and rehabilitation

Abstract

Multiple cortical areas of the human brain motor system interact coherently in the low frequency range (<0.1 Hz), even in the absence of explicit tasks. Following stroke, cortical interactions are functionally disturbed. How these interactions are affected and how the functional organization is regained from rehabilitative treatments as people begin to recover motor behaviors has not been systematically studied. We recorded the intrinsic functional magnetic resonance imaging (fMRI) signals from 30 participants: 17 young healthy controls and 13 aged stroke survivors. Stroke participants underwent mental practice (MP) or both mental practice and physical therapy (MP+PT) within 14-51 days following stroke. We investigated the network activity of five core areas in the motor-execution network, consisting of the left primary motor area (LM1), the right primary motor area (RM1), the left pre-motor cortex (LPMC), the right pre-motor cortex (RPMC) and the supplementary motor area (SMA). We discovered that (i) the network activity dominated in the frequency range 0.06-0.08 Hz for all the regions, and for both able-bodied and stroke participants (ii) the causal information flow between the regions: LM1 and SMA, RPMC and SMA, RPMC and LM1, SMA and RM1, SMA and LPMC, was reduced significantly for stroke survivors (iii) the flow did not increase significantly after MP alone and (iv) the flow among the regions during MP+PT increased significantly. We also found that sensation and motor scores were significantly higher and correlated with directed functional connectivity measures when the stroke-survivors underwent MP+PT but not MP alone. The findings provide evidence that a combination of mental practice and physical therapy can be an effective means of treatment for stroke survivors to recover or regain the strength of motor behaviors, and that the spectra of causal information flow can be used as a reliable biomarker for evaluating rehabilitation in stroke survivors.

Keywords: brain network activity; functional magnetic resonance imaging; low-frequency oscillations; spectral Granger causality; stroke recovery.

Figure 1

Power spectra and peak power. (A) Peak of power spectra for SMA occurs within the frequency band 0.06–0.08 Hz for able-bodied participants (blue colored plot), stroke survivors who underwent MP+PT (green colored plot), stroke survivors who underwent MP only (red colored plot) and for stroke survivors before intervention (black colored plot). (B) Peak power and the associated standard error of the mean for each ROI in each condition is shown.

Figure 2

Granger causality (GC) spectra. Young able bodied vs. aged stroke survivors before and after intervention. Average GC spectra for all the possible connections among five ROIs (LM1, RM1, LPMC, RPMC, and SMA) were computed. Seven connections (A–G) were found which were significantly stronger for AB condition (blue colored plots) whereas none of the connections was significantly stronger for stroke survivors following stroke (black colored plots) as well as following MP (red colored plots). Here black colored dashed horizontal line represents the significance level (p < 0.01, sample size = 26) calculated using random permutation test. Three connections (A,D,F) were significantly stronger for participants who underwent MP+PT (green colored plots). Peak of GC spectra for all the ROIs under all the conditions was also found in the frequency range 0.06–0.08 Hz.

Figure 3

Integrated causal flow. Young able bodied vs. aged stroke survivors before and after intervention. Integrated causal flow for frequency band 0.04–0.1 Hz is calculated for all the seven connections (B–G). Here ^*represents significant causal flow values. Three connections: (A) LM1 to SMA, (B) SMA to LM1, and (G) SMA to LPMC showed significant causal flow values for stroke survivors after MP+PT whereas none of the causal influences for stroke survivors are significant before and after MP treatments.

Figure 4

Percent difference and modulation. Compared to (A) able-bodied participants, percent decrease of the causal flow ranged from −21 to −97% for aged stroke patients as shown in (B), whereas compared to these stroke patients, there was a percent modulation ranging from −77 to 65% for stroke patients who underwent MP as shown in (C) and from −45 to 94% for stroke patients who underwent MP+PT as shown in (D). Percent decrease and percent modulations are shown with red and black colored dots respectively. Width of the arrows represents corresponding strength of connections on an arbitrary scale. Wider the arrows, stronger are the connections.

Figure 5

Network activity comparison. Considering the causal influences for all significant connections, stronger network activity (***p = 10⁻⁵) was observed for able-bodied participants than stroke-survivors. No significant difference between integrated causal flow values was found between stroke survivors before and after mental practice (MP) (p = 0.75) whereas network activity was significantly higher when they underwent combined session of mental practice and physical therapy (MP+PT) (*p = 0.02). We also found that the network activity was significantly higher following MP+PT than following MP only (**p = 0.01).

Figure 6

Brain and behavioral correlation. The Fugl-Meyer Motor Assessment (FMA) scores for stroke-survivors: (A) before intervention (blue bars) and after MP (red bars), and (B) before intervention (blue bars) and after MP+PT (red bars) are plotted. We also observed that for connection: (C) from SMA to LPMC, the correlation coefficient (r) between differences in FMA scores (ΔFMA) and GC-values (ΔGC) before and after MP+PT intervention showed a trend toward statistical significance.