From localized to long-range: functional connectivity alterations in mild to moderate chronic low back pain patients

Mild pain can influence brain function, yet its central neurobiological mechanisms in chronic low back pain (CLBP) remain insufficiently defined. This study aimed to quantitatively evaluate localized and long-range functional connectivity (FC) alterations in patients with mild to moderate CLBP using static/dynamic regional homogeneity (sReHo/dReHo) and seed-based FC, and to assess their statistical relationships with clinical pain and psychological metrics.

A total of 55 mild to moderate CLBP patients and 39 healthy controls (HCs) underwent 3.0 T resting-state functional magnetic resonance imaging (rs-fMRI) and clinical assessments, including Visual Analogue Scale (VAS), Short-Form of the McGill Pain Questionnaire (SF-MPQ), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Pittsburgh Sleep Quality Index (PSQI). sReHo and dReHo (sliding window =50 TRs, step size =5 TRs) maps were computed to identify abnormal localized brain regions. Brain regions showing significant group differences were selected as seeds (6-mm spherical regions of interest, ROIs) for whole-brain FC analysis. Statistical comparisons were corrected using Gaussian random field (GRF) theory (voxel-level P<0.005, cluster-level P<0.05). Partial correlation analyses were used to control for age, sex, education, and head motion (Bonferroni-corrected threshold P<0.007).

Compared with HCs, patients exhibited significantly reduced sReHo in the third cerebellar vermis (peak t=-4.253, GRF P<0.05), alongside reduced dReHo in the right parahippocampal gyrus (t=-4.796, GRF P<0.05) and left inferior temporal gyrus (t=-3.935, GRF P<0.05). Seed-based FC analysis revealed decreased connectivity between the third cerebellar vermis and right hippocampus (t=-4.678, GRF P<0.05), and increased connectivity between the left inferior temporal gyrus and left pallidus (t=4.441, GRF P<0.05). Patients showed significantly higher SAS anxiety scores (25.15±5.01 vs. 23.08±2.18, P=0.008). Correlation analyses demonstrated that sReHo in the third cerebellar vermis was negatively correlated with SAS scores (r=-0.384, P=0.005), whereas FC between the left inferior temporal gyrus and left pallidus was positively correlated with SF-MPQ sensory (r=0.381, P=0.006), affective (r=0.386, P=0.005), and total scores (r=0.445, P=0.001).

Patients with mild to moderate CLBP exhibit distinct localized and long-range FC alterations within cerebello-hippocampal and cortico-basal ganglia pathways. These neurofunctional changes may contribute to the integration of subjective pain dimensions and comorbid anxiety. Combining static/dynamic ReHo with seed-based FC provides complementary neurobiological insight into how low-intensity chronic pain may affect the central nervous system and highlights the importance of early clinical recognition.