Abnormal Functional Connectivity Density in Amyotrophic Lateral Sclerosis

Abstract

Purpose: Amyotrophic lateral sclerosis (ALS) is a motor neuro-degenerative disorder that also damages extra-motor neural pathways. A significant proportion of existing evidence describe alterations in the strengths of functional connectivity, whereas the changes in the density of these functional connections have not been explored. Therefore, our study seeks to identify ALS-induced alternations in the resting-state functional connectivity density (FCD).Methods: Two groups comprising of 38 ALS patients and 35 healthy participants (age and gender matched) were subjected to the resting-state functional magnetic resonance imaging (MRI) scanning. An ultra-fast graph theory method known as FCD mapping was utilized to calculate the voxel-wise short- and long-range FCD values of the brain for each participant. FCD values of patients and controls were compared based on voxels in order to discern cerebral regions that possessed significant FCD alterations. For areas demonstrating a group effect of atypical FCD in ALS, seed-based functional connectivity analysis was then investigated. Partial correlation analyses were carried out between aberrant FCDs and several clinical variables, controlling for age, gender, and total intracranial volume.Results: Patients with ALS were found to have decreased short-range FCD in the primary motor cortex and increased long-range FCD in the premotor cortex. Extra-motor areas that also displayed extensive FCD alterations encompassed the temporal cortex, insula, cingulate gyrus, occipital cortex, and inferior parietal lobule. Seed-based correlation analysis further demonstrated that these regions also possessed disrupted functional connectivity. However, no significant correlations were identified between aberrant FCDs and clinical variables.Conclusion: FCD changes in the regions identified represent communication deficits and impaired functional brain dynamics, which might underlie the motor, motor control, language, visuoperceptual and high-order cognitive deficits in ALS. These findings support the fact that ALS is a disorder affecting multiple systems. We gain a deeper insight of the neural mechanisms underlying ALS.

Precentral degeneration and cerebellar compensation in amyotrophic lateral sclerosis: A multimodal MRI analysis

“…These results were consistent with previous studies reporting decreased interhemispheric FC of the primary motor cortex (Fang et al, 2016;Zhang et al, 2017), and were supported by the findings of decreased degree centrality and FC density in the primary motor cortex in patients with ALS (Li et al, 2018;Zhou et al, 2016). Likewise, the ROI-based FC analysis also showed a lower FC between the precentral ROI and the right cerebellar ROI in patients with ALS.…”

“…Likewise, the ROI-based FC analysis also showed a lower FC between the precentral ROI and the right cerebellar ROI in patients with ALS. These results were consistent with previous studies reporting decreased interhemispheric FC of the primary motor cortex (Fang et al, 2016;Zhang et al, 2017), and were supported by the findings of decreased degree centrality and FC density in the primary motor cortex in patients with ALS (Li et al, 2018;Zhou et al, 2016). Notably, however, there also existed some fMRI studies showing increased FC or activation of the primary motor cortex in patients with ALS Menke et al, 2016).…”

A new parameter to discriminate amyotrophic lateral sclerosis patients from healthy participants by motor cortical excitability changes

“…Abnormal functional connectivity has been demonstrated in patients with ALS. Li et al demonstrated that patients with ALS were found to have decreased resting state short‐range functional connectivity density in the primary motor cortex and increased long‐range functional connectivity density in the premotor cortex. Impaired motor cortical subnetwork with reduced white matter connectivity was also detected in ALS and became more prominent over time .…”

Peer Review #1 of "Static and dynamic alterations in the amplitude of low-frequency fluctuation in patients with amyotrophic lateral sclerosis (v0.1)"

“…The brain areas with static ALFF differences in patients with ALS are consistent with previous reports (Luo et al 2012;Ma et al 2016), except that the right inferior temporal gyrus had increased ALFF. The temporal lobe with aberrant activation and connection in patients with ALS was discovered in preceding rs-fMRI articles (Li et al 2018b;Loewe et al 2017;Zhou et al 2016). Besides, the thinning of cerebral cortex in the right inferior temporal gyrus is related to rapid clinical progression in ALS (Verstraete et al 2012).…”

“…Dysfunction of the right lingual gyrus in ALS was documented, including metabolic difference (Verma et al 2013) and functional connectivity (Li et al 2018b). The lingual gyrus is an important area in the visual system (Yang et al 2015), and 24.13% of Chinese ALS population are considered with visuospatial disability (Wei et al 2015).…”