The cortical cholinergic system contributes to the top-down control of distraction: Evidence from patients with Parkinson's disease.

Past animal and human studies robustly report that the cholinergic system plays an essential role in both top-down and bottom-up attentional control, as well as other aspects of cognition (see Ballinger et al., 2016 for a recent review). However, current understanding of how two major cholinergic pathways in the human brain (the basal forebrain-cortical pathway, and the brainstem pedunculopontine-thalamic pathway) contribute to specific cognitive functions remains somewhat limited. To address this issue, we examine how individual variation in the integrity of striatal-dopaminergic, thalamic-cholinergic, and cortical-cholinergic pathways (measured using Positron Emission Tomography in patients with Parkinson's disease) was associated with individual variation in the initial goal-directed focus of attention, the ability to sustain attentional performance over time, and the ability to avoid distraction from a highly-salient, but irrelevant, environmental stimulus. Compared to healthy controls, PD patients performed similarly in the precision of attention-dependent judgments of duration, and in sustaining attention over time. However, PD patients' performance was strikingly more impaired by the distractor. More critically, regression analyses indicated that only cortical-cholinergic integrity, not thalamic-cholinergic or striatal-dopaminergic integrity, made a specific contribution to the ability to resist distraction after controlling for the other variables. These results demonstrate that the basal forebrain cortical cholinergic system serves a specific role in executing top-down control to resist external distraction.