Platform Session – Electromyography: Neural correlates of cognitive set shifting in amyotrophic lateral sclerosis

Abstract

Introduction Neurodegeneration in amyotrophic lateral sclerosis (ALS) has traditionally been thought to be restricted to motor pathways. Over the last decades, it became increasingly recognized that functional impairment in ALS also extends to the cognitive domain. For example, accumulating neuropsychological evidence suggests that up to 50% of patients with ALS show impairments in executive functioning. Executive dysfunctions impose a severe burden on both patients with ALS and their caregivers. The neuropsychological assessment of ALS-related changes in executive functioning can provide diagnostic information of high clinical importance. However, standard neuropsychological testing in ALS is often complicated by patients’ motor symptoms. The recording of event-related potential (ERP) correlates of executive functions offers an opportunity to overcome this limitation. Methods I will describe two ERP studies that focused on cognitive set shifting as a specific domain of executive functioning. In both studies, patients with ALS and healthy control participants completed computerized set-shifting tasks while their EEG was being measured. Participants were required to sort cards according to changing task rules. When the valid task rule changed, a cue informed participants that they should shift to another sorting criterion. On the level of ERPs, such shift cues typically elicit a sustained positivity over parietal electrode sites. This so-called posterior switch positivity (PSP) is commonly regarded as an ERP indicator of set-shifting processes. Our studies examined the utility of the PSP as an indicator of executive dysfunctions in patients with ALS. Results In Study 1, we found the amplitude of the PSP to be significantly attenuated in patients with ALS in comparison to healthy controls. In addition, the individual extent of PSP-amplitude attenuation was significantly associated with patients’ performance on neuropsychological tests of executive functioning. Study 2 replicated this pattern of reduced PSP amplitudes in an independent sample of patients with ALS while using a considerably simplified set-shifting task. Attenuated PSP amplitudes were also observed in patients who did not show any signs of cognitive impairment in neuropsychological assessment. Conclusion ALS seems to be associated with a robust attenuation of PSP amplitudes that is not bound to a particular set-shifting paradigm. This ERP change can be detected in the absence of overt executive dysfunctions. Attenuated PSP amplitudes in ALS may thus reflect subtle changes in cognitive set shifting before these changes can be detected with neuropsychological tests. If longitudinal studies can corroborate the prognostic value of PSP amplitudes in ALS patients, PSP recordings might complement the neuropsychological assessment of executive dysfunctions in ALS.