Motor imagery in amyotrophic lateral Sclerosis: An fMRI study of postural control

Abstract

Background: The functional reorganization of brain networks sustaining gait is poorly characterized in amyotrophic lateral sclerosis (ALS) despite ample evidence of progressive disconnection between brain regions. The main objective of this fMRI study is to assess gait imagery-specific networks in ALS patients using dynamic causal modeling (DCM) complemented by parametric empirical Bayes (PEB) framework.

Method: Seventeen lower motor neuron predominant (LMNp) ALS patients, fourteen upper motor neuron predominant (UMNp) ALS patients and fourteen healthy controls participated in this study. Each subject performed a dual motor imagery task: normal and precision gait. The Movement Imagery Questionnaire (MIQ-rs) and imagery time (IT) were used to evaluate gait imagery in each participant. In a neurobiological computational model, the circuits involved in imagined gait and postural control were investigated by modelling the relationship between normal/precision gait and connection strengths.

Results: Behavioral results showed significant increase in IT in UMNp patients compared to healthy controls (P_corrected < 0.05) and LMNp (P_corrected < 0.05). During precision gait, healthy controls activate the model's circuits involved in the imagined gait and postural control. In UMNp, decreased connectivity (inhibition) from basal ganglia (BG) to supplementary motor area (SMA) and from SMA to posterior parietal cortex (PPC) is observed. Contrary to healthy controls, DCM detects no cerebellar-PPC connectivity in neither UMNp nor LMNp ALS. During precision gait, bilateral connectivity (excitability) between SMA and BG is observed in the LMNp group contrary to UMNp and healthy controls.

Conclusions: Our findings demonstrate the utility of implementing both DCM and PEB to characterize connectivity patterns in specific patient phenotypes. Our approach enables the identification of specific circuits involved in postural deficits, and our findings suggest a putative excitatory-inhibitory imbalance. More broadly, our data demonstrate how clinical manifestations are underpinned by network-specific disconnection phenomena in ALS.

Keywords: ALS; Connectivity; DCM; Motor imagery; Neuroimaging; fMRI.

Fig. 1

The experimental protocol based on the Bakker study (Bakker et al., 2008) Subjects were asked to perform a mental imagery task in either motor (MI) or visual (VI) mode depending on presented visual stimulus (photos). During MI trials, a green square is present at the beginning of the path. During VI trials, a black disc is shown at the beginning of the path. The end of the path was identical irrespective of the imaging task (visual and motor), and was represented by a green pad displayed at a fixed distance of 6 m. (a) The photos show a corridor with a white path in the middle and a green sign positioned on the path. (b) Time-course of the experiment, participants were asked to close their eyes while imagining themselves standing, and to press the button when they started imagining walking on the path and to press the button again at the end of the task. The inter-trial interval was random (4 to 12 sec). The transition to the next test was signaled by the appearance of a large “X” sign in the center of the screen.

Fig. 2

The average strength of endogenous connectivity parameters for Controls (A), LMN (B) and UMN (C). The values (coupling parameters) reflect a rate constant (Hz) at which activity is propagated from one region to another. Values are significant at a posterior probability >95%. SMA = Supplementary motor area; PPC = Posterior parietal cortex; BG = Basal Ganglia.

Fig. 3

Effective connectivity during broad path condition within control (A), LMN (B) and UMN (C). The red line represents increased connectivity and the blue lines represent decreased connectivity.

Fig. 4

Effective connectivity during narrow path condition within control (A), LMN (B) and UMN (C). The red lines represent increased connectivity.