RT Journal Article
SR Electronic
T1 Cognitive Deterioration and Functional Compensation in ALS Measured with fMRI Using an Inhibitory Task
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 14260
OP 14271
DO 10.1523/JNEUROSCI.1111-14.2014
VO 34
IS 43
A1 Kelsey Witiuk
A1 Juan Fernandez-Ruiz
A1 Ryan McKee
A1 Nadia Alahyane
A1 Brian C. Coe
A1 Michel Melanson
A1 Douglas P. Munoz
YR 2014
UL http://www.jneurosci.org/content/34/43/14260.abstract
AB 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.