title: Cognitive deterioration and functional compensation in ALS measured with fMRI using an inhibitory task.
abstract: Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons, resulting in progressive weakness and muscle atrophy. Recent studies suggest that nondemented ALS patients can show selective cognitive impairments, predominantly executive dysfunction, but little is known about the neural basis of these impairments. Oculomotor studies in ALS have described deficits in antisaccade execution, which requires the implementation of a task set that includes inhibition of automatic responses followed by generation of a voluntary action. It has been suggested that the dorsolateral prefrontal cortex (DLPFC) contributes in this process. Thus, we investigated whether deterioration of executive functions in ALS patients, such as the ability to implement flexible behavior during the antisaccade task, is related to DLPFC dysfunction. While undergoing an fMRI scan, 12 ALS patients and 12 age-matched controls performed an antisaccade task with concurrent eye tracking. We hypothesized that DLPFC deficits would appear during the antisaccade preparation stage, when the task set is being established. ALS patients made more antisaccade direction errors and showed significant reductions in DLPFC activation. In contrast, regions, such as supplementary eye fields and frontal eye fields, showed increased activation that was anticorrelated with the number of errors. The ALS group also showed reduced saccadic latencies that correlated with increased activation across the oculomotor saccade system. These findings suggest that ALS results in deficits in the inhibition of automatic responses that are related to impaired DLPFC activation. However, they also suggest that ALS patients undergo functional changes that partially compensate the neurological impairment.
authors.affiliation: Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Witiuk
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Distrito Federal 04510, México.
authors.forename: Juan
authors.identifier: http://orcid.org/0000-0002-4038-0904
authors.initials: J
authors.lastname: Fernandez-Ruiz
authors.affiliation: Department of Medicine, Division of Neurology, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Ryan
authors.initials: R
authors.lastname: McKee
authors.affiliation: Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Nadia
authors.initials: N
authors.lastname: Alahyane
authors.affiliation: Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Coe
authors.affiliation: Department of Medicine, Division of Neurology, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Melanson
authors.affiliation: Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada, Department of Medicine, Division of Neurology, Queen's University, Kingston, Ontario K7L 3N6, Canada, Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario K7L 3N6, Canada, and Department of Psychology, Queen's University, Kingston, Ontario K7L 3N6, Canada doug.munoz@queensu.ca.
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Munoz
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology; D003072:Cognition Disorders / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology; D010775:Photic Stimulation / Q000379:methods*; D011597:Psychomotor Performance / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology; D012438:Saccades / Q000502:physiology
keywords: amyotrophic lateral sclerosis; antisaccade; cognitive control; fMRI; prefrontal cortex; task set