Abstract
Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback allows learning voluntary control over specific brain areas by means of operant conditioning and has been shown to decrease pain perception. To further increase the effect of rt-fMRI neurofeedback on pain, we directly compared two different target regions of the pain network, notably the anterior insular cortex (AIC) and the anterior cingulate cortex (ACC). Participants for this prospective study were randomly assigned to two age-matched groups of 14 participants each (7 females per group) for AIC and ACC feedback. First, a functional localizer using block-design heat pain stimulation was performed to define the pain-sensitive target region within the AIC or ACC. Second, subjects were asked to down-regulate the BOLD activation in four neurofeedback runs during identical pain stimulation. Data analysis included task-related and functional connectivity analysis. At the behavioral level, pain ratings significantly decreased during feedback vs. localizer runs, but there was no difference between AIC and ACC groups. Concerning neuroimaging, ACC and AIC showed consistent involvement of the caudate nucleus for subjects that learned down-regulation (17/28) in both task-related and functional connectivity analysis. The functional connectivity toward the caudate nucleus is stronger for the ACC while the AIC is more heavily connected to the ventrolateral prefrontal cortex. Consequently, the ACC and AIC are suitable targets for real-time fMRI neurofeedback during pain perception as they both affect the caudate nucleus, although functional connectivity indicates that the direct connection seems to be stronger with the ACC. Additionally, the caudate, an important area involved in pain perception and suppression, could be a good rt-fMRI target itself. Future studies are needed to identify parameters characterizing successful regulators and to assess the effect of repeated rt-fMRI neurofeedback on pain perception.
Highlights
Pain perception has a great impact on individual emotional health as pain is associated with anxiety (Asmundson and Katz, 2009), anger (Trost et al, 2012), fear (Leeuw et al, 2007a,b; Vlaeyen and Linton, 2012), and worry (Eccleston and Crombez, 2007; Linton, 2013)
Not surprisingly, chronic pain increases the risk of depression and suicide (Turk et al, 1995; Geisser et al, Abbreviations: ACC, anterior cingulate cortex; AIC, anterior insular cortex; aMCC, anterior mid-cingulate cortex; ANOVA, analysis of variance; blood oxygen level dependent (BOLD), blood oxygenation level dependent; fMRI, functional magnetic resonance imaging; GLM, general linear model; ICA, independent component analysis; MELODIC, multivariate exploratory linear optimized decomposition into independent components; MPRAGE, magnetization prepared rapid gradient echo; NRS, numeric rating scale; PIC, posterior insular cortex; PFC, prefrontal cortex; ROI, region of interest; real-time functional magnetic resonance imaging (rt-fMRI), real-time fMRI; SEM, standard error of the mean. 2000; Bair et al, 2003; Ilgen et al, 2008; Denkinger et al, 2014)
EFFECT OF NEUROFEEDBACK ON PAIN RATINGS Pain ratings were lower in the neurofeedback runs compared to the localizer run [non-parametric, p(AIC group) < 0.001; p(ACC) < 0.01] in both groups, but did not show any significant differences between neurofeedback runs
Summary
Pain perception has a great impact on individual emotional health as pain is associated with anxiety (Asmundson and Katz, 2009), anger (Trost et al, 2012), fear (Leeuw et al, 2007a,b; Vlaeyen and Linton, 2012), and worry (Eccleston and Crombez, 2007; Linton, 2013). One novel technique that shows potential in the treatment of chronic pain is real-time functional magnetic resonance imaging (rt-fMRI), which allows volitionally influencing activation of a targeted brain area by means of operant conditioning when being supplied with a corresponding feedback signal. This technique could be employed to reduce brain activation in pain network target areas with the aim to decrease the subjective pain perception
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