Altered Functional Networks during Gain Anticipation in Fibromyalgia

Abstract

Reward motivation is essential in shaping human behavior and cognition. Previous studies have shown altered reward motivation and reward brain circuitry in chronic pain conditions, including fibromyalgia. Fibromyalgia is a chronic disorder characterized by widespread musculoskeletal pain, fatigue, cognitive problems, and mood-related symptoms. In this study, we analyzed brain reward networks in patients with fibromyalgia by using a data-driven approach with task-based fMRI data. fMRI data from 24 patients with fibromyalgia and 24 healthy controls were acquired while subjects performed a monetary incentive delay (MID) reward task. Functional networks were derived using independent component analysis (ICA) focused on the gain anticipation phase of the reward task. Functional activity in the motor, value-driven attention, and basal ganglia networks was evaluated during gain anticipation in both patient and healthy control groups. Compared to controls, the motor network was more engaged during gain anticipation in patients with fibromyalgia. Our findings suggest that reward motivation may lead to hyperactivity in the motor network, possibly related to altered motor processing, such as restricted movement or dysregulated motor planning in fibromyalgia. As an exploratory analysis, we compared levels of motor network engagement during early and late timepoints of the gain anticipation phase. Both groups showed greater motor network engagement during the late timepoint (i.e., closer to response), which reflected motor preparation prior to target response. Importantly, compared to controls and consistent with the initial findings described above, patients exhibited greater engagement of the motor network during both early and late timepoints. In summary, by using a novel data-driven ICA approach to analyze task-based fMRI data, we identified elevated motor network engagement during gain anticipation in fibromyalgia.

Keywords: chronic pain; fibromyalgia; gain anticipation; monetary incentive delay (MID) task; motor network.

Figure 1.

Gain trials of the monetary incentive delay (MID) task. Each trial consisted of an anticipation phase and an outcome phase of gain trials (loss and neutral trials were not analyzed in this study). Each trial (TR-locked; TR=2 seconds) consisted of 4 TRs with each TR corresponding to the cue, fixation, target, and outcome. After each trial was a variable-duration inter-trial interval for 5~7 TRs. Cues were either circles (potential gain trials) or squares (potential loss trials; not described in this figure). Cues were presented with monetary values (for gain trials: +$1 and +$5). Note: Other monetary values were presented during the task but were not used in this study (for loss trials: −$1 and −$5; neutral trials $0). After a fixation period, a target period began. A triangle was presented for a variable duration (~250 ms) during the target period; the duration of triangle “target” presentation was determined on prior response accuracy and adjusted throughout the task to obtain an average 66% hit rate. During the outcome phase, hit or miss (i.e., win or no win) feedback was given. After the feedback, a black screen was presented with a pseudo-randomized inter-trial interval period of 1-3 TRs (2, 4, or 6 s duration).

Figure 2.

Example pipelines for the analyses of functional network activation during gain anticipation. (A) Gain anticipation task timecourses constructed by convolving the timecourse of the MID task anticipation phases with the hemodynamic response function. (B) Functional ICA network timecourses resulting from the ICA analysis. Correlations were evaluated between the task timecourse (A) and each of the 3 network timecourses for the main analysis (B) at the individual-level. Then, individual correlation values were averaged for each group to evaluate group differences. Abbreviation: FM, fibromyalgia; HC, healthy control; r, Pearson correlation coefficient.

Figure 3.

Functional networks extracted during MID task performance. Functional networks are shown at peak activation with MNI coordinates. (A) The left motor network includes the left superior and middle frontal gyrus and the left pre- and post-central gyrus. (B) The value-driven attention network includes the early visual cortex, lateral occipital cortex, intraparietal sulcus, and caudate tail. (C) The basal-ganglia network includes a large portion of subcortical brain regions such as the NAcc, thalamus, caudate, pallidum, hippocampus, amygdala, and putamen. Abbreviation: MID, monetary incentive delay; MNI, Montreal Neurological Institute; NAcc, nucleus accumbens.

Figure 4.

Correlation between gain anticipation task presentation and activation in (A) left motor network, (B) value-driven attention network and (C) basal ganglia network. Bar line colors are matched with the brain image color in Figure 3.

Figure 5.

Group differences in functional network – gain anticipation correlation coefficients during early vs. late timepoints. (A) For the left motor network, patients showed higher correlations with the task timecourse than controls at both early and late timepoints of gain anticipation. In addition, the correlations were higher during the late timepoint in both groups. (B) As only trend-level effects, for the value-driven attention network, correlations with the task timecourse were stronger (not significant) during the early timepoint of gain anticipation than during the late timepoint, and the correlation was stronger (not significant) in the control group than in the patient group. (C) For the basal ganglia network, the correlation with the task timecourse was stronger during the late timepoint than during the early timepoint in both groups. Bar line colors are matched with the brain image color in Figure 3.