Longitudinal changes in MEG-based brain network topology of ALS patients with cognitive/behavioural impairment, an exploratory study

Amyotrophic lateral sclerosis (ALS) with only motor impairment (ALS-pure motor) and the behavioural variant of frontotemporal dementia (bvFTD) are hypothesized to represent extreme ends of a disease-spectrum which encompasses ALS with cognitive/behavioural impairment (ALSci/bi). In this longitudinal magnetoencephalography (MEG) study, we investigated changes in brain network topology of ALSci/bi over time as compared to ALS-pure motor and bvFTD patients. Resting-state MEG was recorded in ALS-pure motor (n=9), ALSci/bi (n=16) and bvFTD (n=16) at baseline and 5-month follow-up, projected to source-space. The corrected version of the amplitude envelope correlation was applied to compute frequency-band specific functional connectivity between brain regions, from which the backbone of the functional networks was constructed using the Minimum Spanning Tree (MST) approach. Reference MSTs were computed based on the functional connectivity matrices for ALS-pure motor and bvFTD, against which the networks of ALSci/bi were compared. We showed that, at baseline, networks in the theta band of ALSci/bi patients' were more similar to ALS-pure motor than bvFTD. At follow-up, ALSci/bi patients' beta-band network similarity had moved away from ALS-pure motor and resembled bvFTD.In conclusion, our findings suggest that brain networks of ALSci/bi patients move along the ALS-bvFTD spectrum over time, from ALS-pure motor to bvFTD-like topology.

In this longitudinal magnetoencephalography (MEG) study, we explored changes in brain network topology in amyotrophic lateral sclerosis (ALS) patients with cognitive/behavioural impairment (ALSci/bi), compared to the two extreme ends of the ALS-behavioural variant of frontotemporal dementia (ALS-bvFTD) spectrum (ALS with only motor impairment and bvFTD patients without ALS). We recorded resting-state MEG at baseline and 5-month follow-up, analysing frequency-band specific functional connectivity and constructing the networks’ backbone using the Minimum Spanning Tree (MST). Our findings indicate that at baseline, ALSci/bi networks were more similar to ALS-pure motor than bvFTD in the theta band. At follow-up, ALSci/bi networks shifted towards bvFTD-like topology in the beta band. This suggests that ALSci/bi patients’ brain networks evolve along the ALS-bvFTD spectrum, highlighting potential implications for disease progression.