Investigating Default Mode and Sensorimotor Network Connectivity in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by degeneration of upper motor neurons (UMN) arising from the motor cortex in the brain and lower motor neurons (LMN) in the brainstem and spinal cord. Cerebral changes create differences in brain activity captured by functional magnetic resonance imaging (fMRI), including the spontaneous and simultaneous activity occurring between regions known as the resting state networks (RSNs). Progressive neurodegeneration as observed in ALS may lead to a disruption of RSNs which could provide insights into the disease process. Previous studies have reported conflicting findings of increased, decreased, or unaltered RSN functional connectivity in ALS and do not report the contribution of UMN changes to RSN connectivity. We aimed to bridge this gap by exploring two networks, the default mode network (DMN) and the sensorimotor network (SMN), in 21 ALS patients and 40 age-matched healthy volunteers. An UMN score dichotomized patients into UMN+ and UMN- groups. Subjects underwent resting state fMRI scan on a high field MRI operating at 4.7 tesla. The DMN and SMN changes between subject groups were compared. Correlations between connectivity and clinical measures such as the ALS Functional Rating Scale-Revised (ALSFRS-R), disease progression rate, symptom duration, UMN score and finger tapping were assessed. Significant group differences in resting state networks between patients and controls were absent, as was the dependence on degree of UMN burden. However, DMN connectivity was increased in patients with greater disability and faster progression rate, and SMN connectivity was reduced in those with greater motor impairment. These patterns of association are in line with literature supporting loss of inhibitory interneurons.