Altered brain metabolic connectivity at multiscale level in early Parkinson’s disease

Abstract

To explore the effects of PD pathology on brain connectivity, we characterized with an emergent computational approach the brain metabolic connectome using [18F]FDG-PET in early idiopathic PD patients. We applied whole-brain and pathology-based connectivity analyses, using sparse-inverse covariance estimation in thirty-four cognitively normal PD cases and thirty-four age-matched healthy subjects for comparisons. Further, we assessed high-order resting state networks by interregional correlation analysis. Whole-brain analysis revealed altered metabolic connectivity in PD, with local decreases in frontolateral cortex and cerebellum and increases in the basal ganglia. Widespread long-distance decreases were present within the frontolateral cortex as opposed to connectivity increases in posterior cortical regions, all suggestive of a global-scale connectivity reconfiguration. The pathology-based analyses revealed significant connectivity impairment in the nigrostriatal dopaminergic pathway and in the regions early affected by α-synuclein pathology. Notably, significant connectivity changes were present in several resting state networks especially in frontal regions. These findings expand previous imaging evidence of altered connectivity in cognitively stable PD patients by showing pathology-based connectivity changes and disease-specific metabolic architecture reconfiguration at multiple scale levels, from the earliest PD phases. These alterations go well beyond the known striato-cortical connectivity derangement supporting in vivo an extended neural vulnerability in the PD synucleinopathy.

Emergent Functional Network Effects in Parkinson Disease

“…Thus, the most prominent network disruptions in our nondemented PD sample, of cortical sensorimotor systems as well as the cerebellum and thalamus, suggest that these disruptions reflect remote, downstream effects since synucleinopathy does not develop in these areas until late stages. This finding is consistent with previous PET blood flow and metabolism studies, which also suggest downstream consequences of neuropathology (Wooten et al 1982;Perlmutter and Raichle 1985;Eidelberg 1998;Hershey et al 1998;Sala et al 2017). In support of this idea, previous studies have demonstrated that proteinopathy may influence sensorimotor network function, suggesting that reduced FC arises as a downstream consequence of pathology in other regions.…”

Vulnerability of multiple large‐scale brain networks in dementia with Lewy bodies

“…Building on the core principle that brain regions whose metabolism is correlated at rest are functionally interconnected (Horwitz, Duara, & Rapoport, ), we applied a voxelwise seed‐based interregional correlation analysis (Lee et al, ). This method was previously validated for [18F]FDG–PET data (Horwitz et al, ; Lee et al, ) and allows to derive resting‐state metabolic networks starting from proper seed regions (Ballarini et al, ; Iaccarino et al, ; Perani et al, ; Sala et al, ; Tomasi et al, ; see also Sala & Perani, for a recent review).…”

Fe-Cr-Nb-B ferromagnetic particles with shape anisotropy for cancer cell destruction by magneto-mechanical actuation

“…Once the destruction effect of moving MPs on tumor cells was demonstrated, the researchers focused their work on finding the most appropriate magnetic materials with larger mechanic torque of MPs under the variable magnetic field action. Thus, magnetite particles 6 , 7 , magnetic-vortex NiFe microdiscs prepared by magnetron sputtering followed by optical lithography 8 , 9 , ultrathin perpendicularly magnetized magnetic particles 10 , 11 , synthetic antiferromagnetic and ferrimagnetic microdiscs 12 with no magnetic remanence 13 , nanowires with various compositions obtained by electrodeposition in aluminum membranes 14 – 16 were studied at large for this purpose. The possibility of using STEM cells as carriers for the MPs to the tumor site, followed by the release of MPs based on magneto-mechanical actuation and destruction of cancer cells was also considered by the scientific world 17 .…”