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With the increasing success of mapping brain networks and availability of multiple MR- and PET-based connectivity measures, the need for novel methodologies to unravel the structure and function of the brain at multiple spatial and temporal scales is emerging. Therefore, in this work, we used hybrid PET-MR data of healthy volunteers (n = 67) to identify multiplex core nodes in the human brain. First, monoplex networks of structural, functional and metabolic connectivity were constructed, and consequently combined into a multiplex SC-FC-MC network by linking the same nodes categorically across layers. Taking into account the multiplex nature using a tensorial approach, we identified a set of core nodes in this multiplex network based on a combination of eigentensor centrality and overlapping degree. We introduced a coreness coefficient, which mitigates the effect of modeling parameters to obtain robust results. The proposed methodology was applied onto young and elderly healthy volunteers, where differences observed in the monoplex networks persisted in the multiplex as well. The multiplex core showed a decreased contribution to the default mode and salience network, while an increased contribution to the dorsal attention and somatosensory network was observed in the elderly population. Moreover, a clear distinction in eigentensor centrality was found between young and elderly healthy volunteers.

Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of upper and lower motor neurons. In 10% of patients, the disorder runs in the family. Our aim was to study the impact of ALS-causing gene mutations on cerebral glucose metabolism. Between October 2010 and October 2022, 538 patients underwent genetic testing for mutations with strong evidence of causality for ALS and 18F-2-fluoro-2-deoxy-D-glucose-PET (FDG PET), at University Hospitals Leuven. We identified 48 C9orf72-ALS and 22 SOD1-ALS patients. After propensity score matching, two cohorts of 48 and 21 matched sporadic ALS patients, as well as 20 healthy controls were included. FDG PET images were assessed using a voxel-based and volume-of-interest approach. We observed widespread frontotemporal involvement in all ALS groups, in comparison to healthy controls. The degree of relative glucose metabolism in SOD1-ALS in motor and extra-motor regions did not differ significantly from matched sporadic ALS patients. In C9orf72-ALS, we found more pronounced hypometabolism in the peri-rolandic region and thalamus, and hypermetabolism in the medulla extending to the pons, in comparison to matched sporadic ALS patients. Our study revealed C9orf72-dependent differences in glucose metabolism in the peri-rolandic region, thalamus, and brainstem (i.e., medulla, extending to the pons) in relation to matched sporadic ALS patients.