Investigating the neural correlates of the left thalamus in women with fibromyalgia: A Granger causality and voxel-based morphometry approach

Abstract

Background: Fibromyalgia is a chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, and psychological distress. Despite its high prevalence, the neurobiological mechanisms underlying fibromyalgia remain poorly understood. This study aims to investigate the structural and functional correlates of the left thalamus in fibromyalgia patients using a combined Granger causality and voxel-based morphometry approach.

Methods: We analyzed functional and structural magnetic resonance imaging data from 20 female fibromyalgia patients and 20 female age-matched healthy controls. Voxel-based morphometry was employed to evaluate grey matter volume differences, while Granger causality analysis explored effective connectivity between the left thalamus and other brain regions. Psychological metrics, including pain intensity, pain self-perception, anxiety, depression, and pain catastrophizing, were assessed to determine correlations with neuroimaging findings.

Results: Our analysis revealed significantly increased grey matter volume in the left thalamus among fibromyalgia patients compared to controls, alongside a decrease in the right amygdala. Correlation analyses indicated strong associations between increased thalamic volume and pain intensity, pain catastrophizing, and anxiety. Granger causality analysis demonstrated decreased outflow from the left thalamus to key regions involved in pain processing, including bilateral caudate, right fusiform, and right hippocampus, as well as increased inflow from areas associated with visual and cognitive processing, including right inferior occipital cortex, right middle frontal cortex, and right inferior parietal cortex, suggesting a complex interplay between structural changes and psychological factors in pain processing.

Conclusions: This study provides novel insights into the neurobiological underpinnings of fibromyalgia, highlighting the role of the left thalamus in both pain perception and emotional regulation. Our findings underscore the necessity for a multi-faceted understanding of fibromyalgia that integrates neuroimaging, psychological assessments, and their implications for future therapeutic interventions. Further research is warranted to explore the longitudinal effects of treatment on structural and functional brain changes in fibromyalgia.

Keywords: Fibromyalgia; Granger causality; grey matter volume; neuroimaging; psychological distress; voxel-based morphometry.

Figure 1.

Regions showing significant GMV differences between FM and HC subjects. Hot (red) color represents increased GMV in FM and blue color represents decreased GMV in FM. FWE corrected p < 0.05. FM: fibromyalgia; HC: healthy control; GMV: grey matter volume; few: family-wise error rate.

Figure 2.

Scatter plots of the partial correlation analysis. (a) Positive correlation between the left thalamus volume and pain catastrophizing. (b) Positive correlation between the left thalamus volume and pain intensity. (c) Positive correlation between the left thalamus volume and rumination. (d) Positive correlation between the left thalamus volume and STAI. L: left; STAI: state-trait anxiety inventory.

Figure 3.

Regions showing significant causal connectivity to and from the left thalamus between FM and HC subjects (a) Causal effect from the left thalamus to whole-brain (Outflow). (b) Causal effects from whole-brain to the left thalamus (Inflow). The arrows indicate the direction of causality. p < 0.05, FWE corrected. FM: fibromyalgia; HC: healthy control; FWE: family-wise error rate.