Impaired set-shifting in amyotrophic lateral sclerosis: An event-related potential study of executive function

Executive dysfunctions in patients suffering from amyotrophic lateral sclerosis (ALS) are often described but poorly understood. Specifically, research on patients' ability to flexibly shift between cognitive sets is still scarce and unsystematic. The present study set out to compensate for this lack by providing an in-depth analysis of ALS-related set-shifting impairments.

We first present a quantitative overview of the literature revealing that the Wisconsin Card Sorting Test (WCST) is sensitive to set-shifting impairments in ALS. Moreover, we evaluated patients' performance on a computerized task-switching paradigm modeled after the WCST to elucidate the neurocognitive processes underlying their set-shifting impairments. Twenty-one ALS patients and 21 age- and education-matched controls were required to respond to changing task demands while their EEG was being measured.

Behavioral results revealed significant set-shifting deficits in patients suffering from ALS. Executive deficits were accompanied by substantial alterations of event-related brain activity. While switch cues elicited a more positive posterior event-related potential (ERP) waveform than repeat cues in healthy controls, ERP amplitudes did not vary as a function of switching demand in ALS patients. Individual differences in posterior switch positivity were reliably associated with patients' performance on neuropsychological tests of executive functioning.

The absence of switch-related ERP modulations appears to be a sensitive indicator of executive deficits in ALS patients. Our results suggest that ALS compromises the frontoparietal brain networks involved in anticipatory set-shifting, rendering patients unable to flexibly adapt to changes in environmental contingencies.