RESUMEN
Notable success has been achieved in the study of neurodegenerative conditions using reduction techniques such as principal component analysis (PCA) and sparse inverse covariance estimation (SICE) in positron emission tomography (PET) data despite their widely differing approach. In a recent study of SICE applied to metabolic scans from Parkinson's disease (PD) patients, we showed that by using PCA to prespecify disease-related partition layers, we were able to optimize maps of functional metabolic connectivity within the relevant networks. Here, we show the potential of SICE, enhanced by disease-specific subnetwork partitions, to identify key regional hubs and their connections, and track their associations in PD patients with increasing disease duration. This approach enabled the identification of a core zone that included elements of the striatum, pons, cerebellar vermis, and parietal cortex and provided a deeper understanding of progressive changes in their connectivity. This subnetwork constituted a robust invariant disease feature that was unrelated to phenotype. Mean expression levels for this subnetwork increased steadily in a group of 70 PD patients spanning a range of symptom durations between 1 and 21 years. The findings were confirmed in a validation sample of 69 patients with up to 32 years of symptoms. The common core elements represent possible targets for disease modification, while their connections to external regions may be better suited for symptomatic treatment.
Asunto(s)
Vermis Cerebeloso , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Cuerpo Estriado/diagnóstico por imagen , Progresión de la EnfermedadRESUMEN
In neurodegenerative disorders, a clearer understanding of the underlying aberrant networks facilitates the search for effective therapeutic targets and potential cures. [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging data of brain metabolism reflects the distribution of glucose consumption known to be directly related to neural activity. In FDG PET resting-state metabolic data, characteristic disease-related patterns have been identified in group analysis of various neurodegenerative conditions using principal component analysis of multivariate spatial covariance. Notably, among several parkinsonian syndromes, the identified Parkinson's disease-related pattern (PDRP) has been repeatedly validated as an imaging biomarker of PD in independent groups worldwide. Although the primary nodal associations of this network are known, its connectivity is not fully understood. Here, we describe a novel approach to elucidate functional principal component (PC) network connections by performing graph theoretical sparse network derivation directly within the disease relevant PC partition layer of the whole brain data rather than by searching for associations retrospectively in whole brain sparse representations. Using sparse inverse covariance estimation of each overlapping PC partition layer separately, a single coherent network is detected for each layer in contrast to more spatially modular segmentation in whole brain data analysis. Using this approach, the major nodal hubs of the PD disease network are identified and their characteristic functional pathways are clearly distinguished within the basal ganglia, midbrain and parietal areas. Network associations are further clarified using Laplacian spectral analysis of the adjacency matrices. In addition, the innate discriminative capacity of the eigenvector centrality of the graph derived networks in differentiating PD versus healthy external data provides evidence of their validity.