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Introduction
Successful behavior, especially in challenging conditions, requires both the top-down guidance of perception and action in accordance with current goals and successful bottom-up processing of the incoming stimuli relevant to those goals. Imagine driving in an unfamiliar neighborhood, trying to find the house of a colleague who has invited you to a dinner party. You will likely devote more attention and cognitive control to your task if a thunderstorm breaks out than if it is a bright and sunny day, perhaps even turning off the radio or stopping conversation to do so. Regardless of the weather or how focused you are on finding that address, you will have better success if your host’s house number is indicated by a large black sign with white numbers hanging below the mailbox than if it is indicated by small white numbers painted on the silver-colored metal of the mailbox itself - especially if you’re not wearing your glasses. While attention to our goals is important for guiding behavior, so is our ability to efficiently process stimuli relevant to those goals. The present study leverages individual variation in the denervation of cortical and thalamic cholinergic pathways in patients with Parkinson’s disease (PD) to examine the contributions of those pathways to goal-driven (top-down) versus stimulus-driven (bottom-up) processing.
The progressive decline of dopaminergic neurons in the striatum leading to motor symptoms is a defining feature of PD. However, there is increasing recognition that declines in other neuromodulatory systems likely underlie many of the non-motor symptoms that are not remediated by dopaminergic treatments (see Brichta et al., 2013; Müller and Bohnen, 2013 recent reviews). In the cognitive domain, the dual-syndrome hypothesis of cognitive impairment in PD suggests that dopaminergic denervation primarily leads to executive deficits, and cholinergic decline leads to visuospatial deficits and dementia (Kehagia et al., 2013). However, cortical cholinergic deficits have been shown to predict reduced executive, attention, and verbal learning scores in PD patients without dementia (Bohnen et al., 2012, 2015), suggesting that cholinergic denervation may be associated with PD-related executive deficits more directly. An additional subset of PD patients also has denervation of brainstem-thalamic cholinergic nerve terminals. In contrast to the cognitive deficits seen with cortical cholinergic denervation, thalamic cholinergic denervation does...