title: Interaction between aging and neurodegeneration in amyotrophic lateral sclerosis.
abstract: We assessed the spontaneous blood-oxygen-level-dependent signal fluctuations in the resting-state brain networks of amyotrophic lateral sclerosis patients and their relation to physiologically sensitive and disease modified functional magnetic resonance imaging parameters. Resting-state functional magnetic resonance imaging was performed at 3 Tesla on 20 amyotrophic lateral sclerosis patients with minimal frontal cognitive dysfunction and 20 age- and sex-matched healthy volunteers. Resting-state network maps were extracted with independent component analysis and group-level statistical analyses were performed to detect disease and disease-by-age interaction effects. Whole-brain global and regional atrophy measures were obtained from same-session structural scans. The sensori-motor network showed significant disease effects, with signals suppressed in patients bilaterally in the primary motor cortex. The default-mode network showed a significant disease-by-age interaction in the posterior cingulate cortex, where signals correlated with age positively in patients and negatively in controls. Both disease and disease-by-age interaction effects were detected in the right fronto-parietal network. Although global atrophy did not show significant differences, regions of reduced gray matter volume were detected in patients compared with controls adjacent to regions of reduced functional connectivity. Our results confirm that resting-state functional magnetic resonance imaging signals in the sensori-motor network are suppressed in amyotrophic lateral sclerosis. A similar suppression is evident in the right fronto-parietal network, possibly reflecting the patients' frontal dysfunction and right-lateralized patterns of regional atrophy. The interaction between disease and aging in the default-mode network unravels a possible mechanism of compensation between motor and extramotor systems emerging as a supplementary functional push to help motor disturbances.
authors.affiliation: Department of Neurological Sciences, Second University of Naples, Naples, Italy. hermitage3t@libero.it
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Tedeschi
authors.forename: Francesca
authors.initials: F
authors.lastname: Trojsi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tessitore
authors.forename: Daniele
authors.initials: D
authors.lastname: Corbo
authors.forename: Anna
authors.initials: A
authors.lastname: Sagnelli
authors.forename: Antonella
authors.initials: A
authors.lastname: Paccone
authors.forename: Alessandro
authors.initials: A
authors.lastname: D'Ambrosio
authors.forename: Giovanni
authors.initials: G
authors.lastname: Piccirillo
authors.forename: Mario
authors.initials: M
authors.lastname: Cirillo
authors.forename: Sossio
authors.initials: S
authors.lastname: Cirillo
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Monsurrò
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Esposito
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology* / Q000502:physiology*; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology