Localization of Brain Networks Engaged by the Sustained Attention to Response Task Provides Quantitative Markers of Executive Impairment in Amyotrophic Lateral Sclerosis

Abstract

Objective: To identify cortical regions engaged during the sustained attention to response task (SART) and characterize changes in their activity associated with the neurodegenerative condition amyotrophic lateral sclerosis (ALS). Methods: High-density electroencephalography (EEG) was recorded from 33 controls and 23 ALS patients during a SART paradigm. Differences in associated event-related potential peaks were measured for Go and NoGo trials. Sources active during these peaks were localized, and ALS-associated differences were quantified. Results: Go and NoGo N2 and P3 peak sources were localized to the left primary motor cortex, bilateral dorsolateral prefrontal cortex (DLPFC), and lateral posterior parietal cortex (PPC). NoGo trials evoked greater bilateral medial PPC activity during N2 and lesser left insular, PPC and DLPFC activity during P3. Widespread cortical hyperactivity was identified in ALS during P3. Changes in the inferior parietal lobule and insular activity provided very good discrimination (AUROC > 0.75) between patients and controls. Activation of the right precuneus during P3 related to greater executive function in ALS, indicative of a compensatory role. Interpretation: The SART engages numerous frontal and parietal cortical structures. SART–EEG measures correlate with specific cognitive impairments that can be localized to specific structures, aiding in differential diagnosis.

Event‐related potentials associated with attentional networks evidence changes in executive and arousal vigilance

“…For executive vigilance, ERPs of overall responses were compared as a function of hits or misses in executive vigilance trials and ERPs across time‐on‐task were analyzed as a function of hits in the initial and last period of the task. Epochs were target‐locked (from 200 ms before to 1000 ms after) in executive vigilance trials and ERPs of interest were analyzed by paired t tests in channels based on previous research with signal‐detection tasks (Bonnefond et al, 2010; Groot et al, 2021; Lara et al, 2018; McMackin et al, 2020; Reteig et al, 2019), in particular: P1 (100–200 ms), N1 (140–230 ms), and P3 (350–650 ms) at Pz and SP (500–800 ms) at Cz and adjacent channels. Given that clear peaks were not observed in P1 and N1 in executive vigilance contrasts, ERPs for executive vigilance contrasts were analyzed as a function of adaptive mean amplitude (Martín‐Arévalo et al, 2015).…”

“…ERP studies measuring executive vigilance via signal‐detection tasks have found differences in early and late ERPs associated with hits on infrequent signals and correct rejections in the absence of infrequent signals (Karamacoska et al, 2019; McMackin et al, 2020; Reteig et al, 2019). Nonetheless, evidence is both scarce and inconsistent regarding whether the decrease in hits is accompanied by a change in ERPs across time‐on‐task.…”

Sustained attention to response task-related beta oscillations relate to performance and provide a functional biomarker in ALS

“…We have recently demonstrated this cortical activation through the combination of quantitative electroencephalography (EEG) and source analysis, which provides excellent temporal resolution with good spatial resolution. We have also demonstrated that disease-related abnormalities in cortical network activation can be interrogated individually using spatially and temporally specific measures to determine the nature of underlying network disruption, even in the absence of impaired task performance [3].…”

Resting-state EEG reveals four subphenotypes of amyotrophic lateral sclerosis

“… 21 Using this approach with task-based paradigms, we have shown changes implicating dysfunction of the frontoparietal network. 9 , 23 , 24 Furthermore, we have shown that resting-state EEG, which can provide distinct measures that reflect different processes in the brain, 25 can quantitatively capture both motor and cognitive networks affected in ALS. More specifically, using sensor-space analysis, we have found resting-state EEG changes that are correlated with structural changes in MRI 10 and in line with other EEG studies.…”