Executive function in chronic pain patients and healthy controls: different cortical activation during response inhibition in fibromyalgia

Abstract

The primary symptom of fibromyalgia (FM) is chronic, widespread pain; however, patients report additional symptoms including decreased concentration and memory. Performance-based deficits are seen mainly in tests of working memory and executive function. Neural correlates of executive function were investigated in 18 FM patients and 14 age-matched healthy controls during a simple Go/No-Go task (response inhibition) while they underwent functional magnetic resonance imaging (fMRI). Performance was not different between FM and healthy control, in either reaction time or accuracy. However, fMRI revealed that FM patients had lower activation in the right premotor cortex, supplementary motor area, midcingulate cortex, putamen and, after controlling for anxiety, in the right insular cortex and right inferior frontal gyrus. A hyperactivation in FM patients was seen in the right inferior temporal gyrus/fusiform gyrus. Despite the same reaction times and accuracy, FM patients show less brain activation in cortical structures in the inhibition network (specifically in areas involved in response selection/motor preparation) and the attention network along with increased activation in brain areas not normally part of the inhibition network. We hypothesize that response inhibition and pain perception may rely on partially overlapping networks, and that in chronic pain patients, resources taken up by pain processing may not be available for executive functioning tasks such as response inhibition. Compensatory cortical plasticity may be required to achieve performance on a par with control groups.

Perspective: Neural activation (fMRI) during response inhibition was measured in fibromyalgia patients and controls. FM patients show lower activation in the inhibition and attention networks and increased activation in other areas. Inhibition and pain perception may use overlapping networks: resources taken up by pain processing may be unavailable for other processes.

Figure 1. Go/no-go Reaction Times and False Alarms

Performance measures from the Go/No-Go task for Healthy Controls and individuals with Fibromyalgia, separated by Run. Error bars reflect standard errors. Figure 1A shows reaction times for „Go“ trials: there were no significant differences between FM and HC. Figure 1B shows false alarms (incorrect responses to the „No-Go“ trials): there were no significant differences between FM and HC.

Figure 2. Group differences in brain activation associated with inhibition between fibromyalgia patients and healthy controls

Statistical parametric maps (SPMs) demonstrating differences between groups associated with inhibition (NoGo > Go) superimposed on a template provided by MRIcron. Figure 2a, 2b, 2d: greater activation in HCs (HCs > FM). Figure 2c: greater activation in FM patients (FM > HCs): Figures 2a, 2b and 2c: two sample t-test with age as covariate of no interest. Figure 2d: two sample t-test with age and anxiety scores as covariates of no interest. IC = insular cortex, ITG = inferior temporal gyrus, MCC = mid cingulate cortex, PMC = premotor cortex, SMA = supplementary motor area, L = left, R = right. Figure 2b: the right side of the image ist he right side of the brain; SPMs are corrected for multiple comparisons (p < 0.05 cluster level).

Figure 3. Correlation analysis between BOLD response and percentage body area in pain/ functional connectivity analysis between inhibition associated BOLD response in the right inferior temporal gyrus and medial frontal wall

a. SPM demonstrating a negative correlation between %BR in pain and BOLD response in the brainstem (FM patients). b. greater functional connectivity in fibromyalgia patients (compared to healthy controls) between right inferior temporal/fusiform gyrus (= seed region) and MFG (= medial frontal gyrus), SFG (= superior frontal gyrus), and SMA (= supplementary motor area), L = left, R = right. Figure 2b: the right side of the image is the right side of the brain; SPMs are corrected for multiple comparisons (p < 0.05 cluster level).