Abnormal Resting-State Functional Connectivity Between the Dorsal Anterior Cingulate Cortex and the Limbic System Contributes to Pain and Emotion Regulation Impairment in Fibromyalgia Patients

Abstract

Objectives: The subdivisions of the anterior cingulate cortex (ACC) are involved in distinct functions in the processing of chronic pain and regulation of emotions. However, the specific impact of each ACC subdivision on fibromyalgia (FM) remains unclear. This study aimed to systematically investigate the abnormal resting-state functional connectivity (rsFC) patterns between the ACC (and its subregions) and other chronic-pain-related limbic cortices and subcortical nuclei in patients with FM. Methods: Resting-state functional magnetic resonance imaging (fMRI) was conducted in 31 patients diagnosed with fibromyalgia (FM) and 32 demographically matched healthy controls (HCs). Using subdivisions of the anterior cingulate cortex (ACC) as regions of interest, we employed a seed-based resting-state functional connectivity (rsFC) approach to identify alterations in connectivity between limbic cortex and subcortical nuclei. A two-sample t-test was applied to compare functional connectivity differences between the two groups. Additionally, Pearson correlation analysis was performed to examine the relationships between rsFC alterations and measures of executive function and clinical symptom severity. Results: Patients with FM demonstrated aberrant rsFC of the dorsal ACC (dACC) with the limbic system, notably the amygdala (t = 2.840, SE = 0.942, p = 0.007), parahippocampal gyrus (t = 2.340, SE = 0.905, p = 0.024), and insula (t = 2.159, SE = 0.835, p = 0.036). Subregion analyses further revealed heightened connectivity of the anterior midcingulate cortex (aMCC) with the parahippocampal gyrus (t = 2.737, SE = 1.064, p = 0.009), and increased connectivity of the superior anterior cingulate cortex (supACC) with the insula (t = 2.596, SE = 0.706, p = 0.013) and amygdala (t = 2.398, SE = 0.812, p = 0.021), which were significantly associated with pain severity and depressive symptoms in FM. Conclusion: This study revealed specific abnormalities in the rsFC between the dACC and the limbic cortices and subcortical nuclei in FM patients. The heightened connectivity of the aMCC with the parahippocampal gyrus and of the supACC with the insula and amygdala was closely associated with the regulation of emotion and processing of chronic pain.