Neural correlates of cognitive set shifting in amyotrophic lateral sclerosis

Objective: Amyotrophic lateral sclerosis (ALS) has been associated with executive dysfunction, particularly in the domain of cognitive set shifting. In a recent event-related potential (ERP) study, shifting-related cortical activity on a complex set-shifting paradigm was found to be attenuated in patients with ALS. Here, we investigated whether this ERP change could also be observed in a simplified set-shifting task adapted for potential clinical use, and in ALS patients without overt cognitive impairment. Methods: Twenty-six patients and 28 matched healthy controls (HC) completed a set-shifting paradigm involving two task rules and explicit task cues. Cue-locked ERPs were analyzed. Results: ALS patients and HC did not differ in response latency or accuracy. In HC, cues that required shifting task rules elicited more positive parietal ERP waveforms than cues that signaled a rule repetition. This shifting-related amplitude modulation was absent in patients with ALS. The attenuation of ERP activity in ALS patients remained significant when participants with possible cognitive impairment were excluded. Conclusions: Electrophysiological measures can detect ALS-related changes in the neural substrates of set shifting even when these changes do not become apparent in neuropsychological assessment. Significance: These findings illustrate the potential utility of ERPs as indicators of cognitive change in ALS. (C) 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.