Aberrant Multimodal Connectivity Pattern Involved in Default Mode Network and Limbic Network in Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that progressively affects bulbar and limb function. Despite increasing recognition of the disease as a multinetwork disorder characterized by aberrant structural and functional connectivity, its integrity agreement and its predictive value for disease diagnosis remain to be fully elucidated. In this study, we recruited 37 ALS patients and 25 healthy controls (HCs). High-resolution 3D T1-weighted imaging and resting-state functional magnetic resonance imaging were, respectively, applied to construct multimodal connectomes. Following strict neuroimaging selection criteria, 18 ALS and 25 HC patients were included. Network-based statistic (NBS) and the coupling of grey matter structural–functional connectivity (SC–FC coupling) were performed. Finally, the support vector machine (SVM) method was used to distinguish the ALS patients from HCs. Results showed that, compared with HCs, ALS individuals exhibited a significantly increased functional network, predominantly encompassing the connections between the default mode network (DMN) and the frontoparietal network (FPN). The increased structural connections predominantly involved the inter-regional connections between the limbic network (LN) and the DMN, the salience/ventral attention network (SVAN) and FPN, while the decreased structural connections mainly involved connections between the LN and the subcortical network (SN). We also found increased SC–FC coupling in DMN-related brain regions and decoupling in LN-related brain regions in ALS, which could differentiate ALS from HCs with promising capacity based on SVM. Our findings highlight that DMN and LN may play a vital role in the pathophysiological mechanism of ALS. Additionally, SC–FC coupling could be regarded as a promising neuroimaging biomarker for ALS and shows important clinical potential for early recognition of ALS individuals.

MRI biomarkers and neuropsychological assessments of hippocampal and parahippocampal regions affected by ALS: A systematic review

“…Our findings were approved by a recent study that used aberrant multimodal connectivity patterns and found the regional-node structural-functional connectivity (SC-FC coupling) of the limbic network (LN)-related brain regions such as the hippocampus, and PhG was significantly altered. 100 Interestingly, some studies reported increased FC in certain regions, such as the PhG, 69,72,78 suggesting that the brain may attempt to compensate for dysfunctional networks by recruiting additional areas. This hypothesis is supported by the findings of Stoppel et al, 74 who reported increased novelty-evoked hippocampal activity across 3 months in ALS patients, potentially reflecting compensatory processes.…”

The Spectrum of Cognitive Dysfunction in Amyotrophic Lateral Sclerosis: An Update

“…The increased structural connec tion involved interregional connections between the limbic network and the DMN, and the salient/ventral attention network and FPN, while the decreased structural connections mainly involved those between the limbic and the subcortical network. These FC changes are related to cognitive performance and predict the progression of disease [130]. The dysfunction of circuits connecting basal ganglia with the frontal lobe, in particular, sen sorimotor and limbic circuits, contributes to cognition and motivation disorders [129,131] (Figure 1).…”