Introduction
effects.81, hyperalgesia, pain
CORTEX
Literature suggests that attention is a critical cognitive process for pain perception and modulation and may play an important role in placebo and nocebo effects. Here, we investigated how repeated transcranial direct current stimulation (tDCS) applied at the dorsolateral prefrontal cortex (DLPFC) for three consecutive days can modulate the brain functional connectivity (FC) of two networks involved in cognitive control: the frontoparietal network (FPN) and dorsal attention network (DAN), and its association with placebo and nocebo effects.81 healthy subjects were randomized to three groups: anodal, cathodal, and sham tDCS. Resting state fMRI scans were acquired pre- and post- tDCS on the first and third day of tDCS. An Independent Component Analysis (ICA) was performed to identify the FPN and DAN. ANCOVA was applied for group analysis.Compared to sham tDCS, 1) both cathodal and anodal tDCS increased the FC between the DAN and right parietal operculum; cathodal tDCS also increased the FC between the DAN and right postcentral gyrus; 2) anodal tDCS led to an increased FC between the FPN and right parietal operculum, while cathodal tDCS was associated with increased FC between the FPN and left superior parietal lobule/precuneus; 3) the FC increase between the DAN and right parietal operculum was significantly correlated to the placebo analgesia effect in the cathodal group.Our findings suggest that both repeated cathodal and anodal tDCS could modulate the FC of two important cognitive brain networks (DAN and FPN), which may modulate placebo / nocebo effects.In the last few years, brain imaging has been widely used to explore the umderlying mechanisms of placebo and nocebo effects. However, most of the current studies have applied an observational method, investigating the brain networks associated with placebo and nocebo effects. Few studies have explored how the excitability/functional connectivity (FC) changes of certain brain regions could modulate the placebo and nocebo effects.Placebo analgesia and nocebo hyperalgesia are the most well studied placebo/nocebo effects. Literature suggests that pain experience involve multiple brain networks functioning in the sensory, affective, and cognitive aspects of pain signal processing (Multiple brain networks are involved in cognitive control. One of them is the frontoparietal network (FPN) which is involved in perceptual attention, information manipulation in working memory, and goal-directed tasks (Furthermore, literature suggests that the dorsolateral prefrontal cortex (DLPFC), a key region in the FPN, plays a crucial role in pain processing and modulation (With this in mind, we pursued a follow up study investigating how different tDCS treatments (cathodal, anodal, and sham) for three consecutive days can modulate the resting state FC of the FPN and DAN, and the associations between these changes and placebo/nocebo effects. We hypothesize that tDCS at the rDLPFC can modulate the FC of the frontoparietal and dorsal attention networks, and that these functional changes are associated with placebo and nocebo effects. Elucidating the modulation effects of tDCS may help to understand the mechanisms of placebo/nocebo effects and develop new strategies to harness these effects.