Department of Neuroradiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, Milano, Italy.
Department of Medicine and Surgery, University of Parma, Via Volturno 39, Parma, 43125, Italy.
J Headache Pain. 2024 Jun 11;25(1):97. doi: 10.1186/s10194-024-01803-5.
Mindfulness practice has gained interest in the management of Chronic Migraine associated with Medication Overuse Headache (CM-MOH). Mindfulness is characterized by present-moment self-awareness and relies on attention control and emotion regulation, improving headache-related pain management. Mindfulness modulates the Default Mode Network (DMN), Salience Network (SN), and Fronto-Parietal Network (FPN) functional connectivity. However, the neural mechanisms underlying headache-related pain management with mindfulness are still unclear. In this study, we tested neurofunctional changes after mindfulness practice added to pharmacological treatment as usual in CM-MOH patients.
The present study is a longitudinal phase-III single-blind Randomized Controlled Trial (MIND-CM study; NCT03671681). Patients had a diagnosis of CM-MOH, no history of neurological and severe psychiatric comorbidities, and were attending our specialty headache centre. 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.
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).
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. Our findings unveil the therapeutic potential of mindfulness and the underlying neural mechanisms in CM-MOH patients.
Name of Registry; MIND-CM study; Registration Number ClinicalTrials.gov identifier: NCT0367168; Registration Date: 14/09/2018.
正念练习在治疗与药物过度使用性头痛相关的慢性偏头痛（CM-MOH）方面引起了兴趣。正念的特点是当下自我意识，并依赖于注意力控制和情绪调节，从而改善与头痛相关的疼痛管理。正念调节默认模式网络（DMN）、突显网络（SN）和额顶网络（FPN）功能连接。然而，正念治疗头痛相关疼痛的神经机制仍不清楚。在这项研究中，我们测试了正念练习添加到 CM-MOH 患者的药物治疗后神经功能的变化。
本研究为纵向三期单盲随机对照试验（MIND-CM 研究；NCT03671681）。患者患有 CM-MOH，无神经和严重精神共病病史，正在我们的专业头痛中心就诊。患者分为常规治疗组（TaU）和正念添加到常规治疗组（TaU+MIND）。患者在治疗前和一年后进行神经影像学和临床评估。对两组间 DMN、SN 和 FPN 连接进行纵向比较，并与临床变化相关联。还进行了顶点分析以评估皮质厚度变化。
177 例 CM-MOH 患者被随机分配至 TaU 组或 TaU+MIND 组。34 例患者，分为 17 例 TaU 和 17 例 TaU+MIND，完成了神经影像学随访。在随访时，两组的大多数临床变量均有所改善，而只有 TaU+MIND 组头痛频率显著降低（p=0.028）。一年后，TaU+MIND 组患者的 SN 与左侧后岛叶（p-FWE=0.007）和感觉运动皮层（p-FWE=0.026）的功能连接增强。仅在 TaU+MIND 患者中，SN-岛叶连接增强与抑郁评分的改善相关（r=-0.51，p=0.038）。在这些患者中观察到岛叶簇的皮质厚度呈纵向增加（p=0.015）。还报告了 TaU+MIND 组前扣带皮层厚度增加（p-FWE=0.02）。
SN-岛叶连接增强可能调节慢性疼痛感知和负性情绪的管理。增强的 SN-感觉运动连接可能反映出对疼痛感觉的身体意识的改善。扣带皮层厚度的增加可能维持对伤害性信息的认知处理的改善。我们的研究结果揭示了正念治疗 CM-MOH 患者的潜在治疗作用和潜在的神经机制。
注册名称；MIND-CM 研究；注册号ClinicalTrials.gov 标识符：NCT0367168；注册日期：2018 年 9 月 14 日。
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