Anti-correlated networks, global signal regression, and the effects of caffeine in resting-state functional MRI

Abstract

Resting-state functional connectivity magnetic resonance imaging is proving to be an essential tool for the characterization of functional networks in the brain. Two of the major networks that have been identified are the default mode network (DMN) and the task positive network (TPN). Although prior work indicates that these two networks are anti-correlated, the findings are controversial because the anti-correlations are often found only after the application of a pre-processing step, known as global signal regression, that can produce artifactual anti-correlations. In this paper, we show that, for subjects studied in an eyes-closed rest state, caffeine can significantly enhance the detection of anti-correlations between the DMN and TPN without the need for global signal regression. In line with these findings, we find that caffeine also leads to widespread decreases in connectivity and global signal amplitude. Using a recently introduced geometric model of global signal effects, we demonstrate that these decreases are consistent with the removal of an additive global signal confound. In contrast to the effects observed in the eyes-closed rest state, caffeine did not lead to significant changes in global functional connectivity in the eyes-open rest state.

Acute caffeine administration impact on working memory-related brain activation and functional connectivity in the elderly: A BOLD and perfusion MRI study

“…Given the absence of activation paradigm in these studies, it is hard to compare these data with those obtained in the present experimental setting. Another recent study showed that caffeine significantly enhances the detection of the known anti-correlations between the default mode network (DMN) and the task positive network (TPN) (Wong et al, 2012). Subsequently, the WM-load related an increase in functional connectivity after caffeine intake observed here cannot be attributed to a nonspecific effect of this substance.…”

“…Several functional magnetic resonance imaging (fMRI) studies documented the decrease of connectivity and global signal amplitude in various cortical areas at resting states (Rack-Gomer et al, 2009;Rack-Gomer and Liu, 2012;Wong et al, 2012). The rare fMRI activation studies used simple perceptual tasks (i.e.…”

“…Two fMRI activation studies using a placebo-controlled design and working memory (WM) activation paradigms showed a caffeine-induced blood oxygen leveldependent (BOLD) increase in fronto-parietal areas and a decrease in the thalamus (Koppelstaetter et al, 2008;Klaassen et al, 2013) in young to middle-aged volunteers ranging from 25 to 61 years. Previous functional connectivity studies assessed young adults (Rack-Gomer et al, 2009;Rack-Gomer and Liu, 2012;Wong et al, 2012). To date, no study explored the effects of caffeine on brain activation patterns during highly demanding cognitive tasks in elderly cohorts.…”

Structural and functional hyperconnectivity within the sensorimotor system in xenomelia

“…No mean global signal regression has been performed due to an ongoing dispute related to negative correlations observed after mean global signal regression (Qing, Dong, Li, Zang, & Liu, 2015; Wong, Olafsson, Tal, & Liu, 2012; Yeh, Tseng, Lin, Tsai, & Huang, 2015). (10) Data were filtered in the range between 0.01 and 0.1 Hz.…”

Time related effects on functional brain connectivity after serotonergic and cholinergic neuromodulation

“…Currently, no accepted methods are available to include individual drug concentrations in the network analysis. Further, fMRI effects, especially in pharmacological research, are potentially the result of vasodilation, and hence to changes in neurovascular coupling instead of true neural activity [Rack‐Gomer and Liu, 2012; Wong et al, 2012]. Although SSRIs do not typically alter the hemodynamic response [Feczko et al, 2012], AChEIs could increase vessel tone by contraction of the smooth muscles of blood vessels [Rosengarten et al, 2009; Stephenson and Kolka, 1990].…”