Investigating Default Mode and Sensorimotor Network Connectivity in Amyotrophic Lateral Sclerosis

Abstract

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.

Regional Dynamics of the Resting Brain in Amyotrophic Lateral Sclerosis Using Fractional Amplitude of Low-Frequency Fluctuations and Regional Homogeneity Analyses

“…Decreased fALFF and ReHo in ALS patients were found bilaterally in precentral and postcentral gyrus, as well as the bilateral supplementary motor cortex, all regions considered as part of the SMN. Changes in the connectivity of the SMN are one of the most consistent findings in ALS (Tedeschi et al, 2012;Trojsi et al, 2015;Mohammadi et al, 2009; but see Chenji et al, 2016). In fact, previous studies reported changes in functional and effective connectivity in the SMN of ALS patients (Trojsi et al, 2015;Fang et al, 2016).…”

“…The DMN is associated with internal processing, including manipulation of episodic memory, theory of mind and future thinking, and deactivates when the subject engages in any goaloriented task (Raichle et al, 2001). Changes in functional connectivity of the DMN are often reported in ALS (Trojsi et al, 2015;Heimrath et al, 2014;Mohammadi et al, 2009; but see Chenji et al, 2016) as well as deficits in memory recall (Machts et al, 2014) and theory of mind (van der Hulst et al, 2015). In addition, attentional and verbal fluency impairments are reported in ALS (Abrahams et al, 2000;Goldstein & Abrahams, 2013) and correlated with changes in the DMN (Heimrath et al, 2014).…”

Neuroimaging Endpoints in Amyotrophic Lateral Sclerosis

“…A number of fMRI studies investigating differences between patients with ALS and controls at rest have furthermore revealed functional connectivity abnormalities within the sensorimotor network, although some studies reported reduced functional connectivity in ALS [79–81], others increased motor network coherence [71, 82], and others a mixed picture [83, 84]. These inconsistencies are most likely driven by methodological differences and/or clinical and cognitive heterogeneity of patient samples.…”

Distance canonical correlation analysis with application to an imaging-genetic study

“…SM is related to the coordination of the body when performing motor tasks. 31 DMN is the dominant network when subjects are in resting state, mind-wandering, or not involved in a specific task. Dysfunction within the DMN has been associated with several mental disorders, 32,33 e.g., schizophrenia, depression, autism, etc.…”