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Patients were divided in Treatment as Usual (TaU) and mindfulness added to TaU (TaU+MIND) groups.  Patients underwent a neuroimaging and clinical assessment before the treatment and after one year. Longitudinal comparisons of DMN, SN, and FPN connectivity were performed between groups and correlated with clinical changes. Vertex-wise analysis was performed to assess cortical thickness changes. \r\n\r\nResults. 177 CM-MOH patients were randomized to either TaU group or TaU+MIND group. Thirty-four patients, divided in 17 TaU and 17 TaU+MIND, completed the neuroimaging follow-up. At the follow-up, both groups showed an improvement in most clinical variables, whereas only TaU+MIND patients showed a significant headache frequency reduction (p = 0.028). After one year, TaU+MIND patients showed greater SN functional connectivity with the left posterior insula (p-FWE = 0.007) and sensorimotor cortex (p-FWE = 0.026). In TaU+MIND patients only, greater SN-insular connectivity was associated with improved depression scores (r = -0.51, p = 0.038). A longitudinal increase in cortical thickness was observed in the insular cluster in these patients (p = 0.015). Increased anterior cingulate cortex thickness was also reported in TaU+MIND group (p-FWE = 0.02).  \r\n\r\nConclusions. Increased SN-insular connectivity might modulate chronic pain perception and the management of negative emotions. Enhanced SN-sensorimotor connectivity could reflect improved body-awareness of painful sensations. Expanded cingulate cortex thickness might sustain improved cognitive processing of nociceptive information. 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