Additional file 1 of Gamma-aminobutyric acid and glutamate/glutamine levels in the dentate nucleus and periaqueductal gray with episodic and chronic migraine: a proton magnetic resonance spectroscopy study

Additional file 1: Fig. S1. Associations between headache frequency and neurochemical levels. (A) and (B) show the correlation between headache frequency and the GABA level in the PAG. (C) and (D) show the correlation between headache frequency and the Glx level in the PAG. (E) and (F) show the correlation between headache frequency and the GABA level in the DN. (G) and (H) show the correlation between headache frequency and the Glx level in the DN. Dots represent participants with migraine. The black regression line represents Pearson’s correlation coefficient (r). Gray shading represents the 95% confidence intervals of the partial correlations. PAG, periaqueductal gray; DN, dentate nucleus; GABA, gamma-aminobutyric acid; Glx, glutamate/glutamine. Fig. S2. Associations between disease duration and neurochemical levels. (A) and (B) show the correlation between disease duration and the GABA level in the PAG. (C) and (D) show the correlation between disease duration and the Glx level in the PAG. (E) and (F) show the correlation between disease duration and the GABA level in the DN. (G) and (H) show the correlation between disease duration and the Glx level in the DN. Dots represent participants with migraine. The black regression line represents Pearson’s correlation coefficient (r). Gray shading represents the 95% confidence intervals of the partial correlations. PAG, periaqueductal gray; DN, dentate nucleus; GABA, gamma-aminobutyric acid; Glx, glutamate/glutamine. Fig. S3. Associations between the MIDAS score and neurochemical levels. (A) and (B) show the correlation between the MIDAS score and GABA level in the PAG. (C) and (D) show the correlation between the MIDAS score and Glx level in the PAG. (E) and (F) show the correlation between the MIDAS score and GABA level in the DN. (G) and (H) show the correlation between the MIDAS score and Glx level in the DN. Dots represent participants with migraine. The black regression line represents Pearson’s correlation coefficient (r). Gray shading represents the 95% confidence intervals of the partial correlations. MIDAS, migraine disability assessment scale; PAG, periaqueductal gray; DN, dentate nucleus; GABA, gamma-aminobutyric acid; Glx, glutamate/glutamine. Fig. S4. Associations between the HIT-6 score and neurochemical levels. (A) and (B) show the correlation between the HIT-6 score and GABA level in the PAG. (C) and (D) show the correlation between the HIT-6 score and Glx level in the PAG. (E) and (F) show the correlation between the HIT-6 score and GABA level in the DN. (G) and (H) show the correlation between the HIT-6 score and Glx level in the DN. Dots represent participants with migraine. The black regression line represents Pearson’s correlation coefficient (r). Gray shading represents the 95% confidence intervals of the partial correlations. HIT-6, Headache Impact Test; PAG, periaqueductal gray; DN, dentate nucleus; GABA, gamma-aminobutyric acid; Glx, glutamate/glutamine. Fig. S5. Associations between the PHQ-9 score and neurochemical levels. (A) and (B) show the correlation between the PHQ-9 score and GABA level in the PAG. (C) and (D) show the correlation between the PHQ-9 score and Glx level in the PAG. (E) and (F) show the correlation between the PHQ-9 score and GABA level in the DN. (G) and (H) show the correlation between the PHQ-9 score and Glx level in the DN. Dots represent participants with migraine. The black regression line represents Pearson’s correlation coefficient (r). Gray shading represents the 95% confidence intervals of the partial correlations. Patient Health Questionnaire-9; PAG, periaqueductal gray; DN, dentate nucleus; GABA, gamma-aminobutyric acid; Glx, glutamate/glutamine. Fig. S6. Associations between the GAD-7 score and neurochemical levels. (A) and (B) show the correlation between the GAD-7 score and GABA level in the PAG. (C) and (D) show the correlation between the GAD-7 score and Glx level in the PAG. (E) and (F) show the correlation between the GAD-7 score and GABA level in the DN. (G) and (H) show the correlation between the GAD-7 score and Glx level in the DN. Dots represent participants with migraine. The black regression line represents Pearson’s correlation coefficient (r). Gray shading represents the 95% confidence intervals of the partial correlations. Generalized Anxiety Disorder-7; PAG, periaqueductal gray; DN, dentate nucleus; GABA, gamma-aminobutyric acid; Glx, glutamate/glutamine. Fig. S7. Associations between the PSQI score and neurochemical levels. (A) and (B) show the correlation between the PSQI score and GABA level in the PAG. (C) and (D) show the correlation between the PSQI score and Glx level in the PAG. (E) and (F) show the correlation between the PSQI score and GABA level in the DN. (G) and (H) show the correlation between the PSQI score and Glx level in the DN. Dots represent participants with migraine. The black regression line represents Pearson’s correlation coefficient (r). Gray shading represents the 95% confidence intervals of the partial correlations. PSQI, Pittsburgh Sleep Quality Index; PAG, periaqueductal gray; DN, dentate nucleus; GABA, gamma-aminobutyric acid; Glx, glutamate/glutamine. Fig. S8. Associations between the MoCA score and neurochemical levels. (A) and (B) show the correlation between the MoCA score and GABA level in the PAG. (C) and (D) show the correlation between the MoCA score and Glx level in the PAG. (E) and (F) show the correlation between the MoCA score and GABA level in the DN. (G) and (H) show the correlation between the MoCA score and Glx level in the DN. Dots represent participants with migraine. The black regression line represents Pearson’s correlation coefficient (r). Gray shading represents the 95% confidence intervals of the partial correlations. MoCA, Montreal Cognitive Assessment; PAG, periaqueductal gray; DN, dentate nucleus; GABA, gamma-aminobutyric acid; Glx, glutamate/glutamine.

附加文件1：图S1。头痛频率与神经化学水平的关联。(A)与(B)展示了头痛频率与中脑导水管周围灰质（periaqueductal gray, PAG）内γ-氨基丁酸（gamma-aminobutyric acid, GABA）水平的相关性。(C)与(D)展示了头痛频率与PAG内谷氨酸/谷氨酰胺（glutamate/glutamine, Glx）水平的相关性。(E)与(F)展示了头痛频率与齿状核（dentate nucleus, DN）内GABA水平的相关性。(G)与(H)展示了头痛频率与DN内Glx水平的相关性。散点代表偏头痛受试者。黑色回归线代表皮尔逊相关系数（r）。灰色阴影代表偏相关分析的95%置信区间。PAG，中脑导水管周围灰质；DN，齿状核；GABA，γ-氨基丁酸；Glx，谷氨酸/谷氨酰胺。
图S2。疾病病程与神经化学水平的关联。(A)与(B)展示了疾病病程与中脑导水管周围灰质内γ-氨基丁酸水平的相关性。(C)与(D)展示了疾病病程与中脑导水管周围灰质内谷氨酸/谷氨酰胺水平的相关性。(E)与(F)展示了疾病病程与齿状核内γ-氨基丁酸水平的相关性。(G)与(H)展示了疾病病程与齿状核内谷氨酸/谷氨酰胺水平的相关性。散点代表偏头痛受试者。黑色回归线代表皮尔逊相关系数（r）。灰色阴影代表偏相关分析的95%置信区间。PAG，中脑导水管周围灰质；DN，齿状核；GABA，γ-氨基丁酸；Glx，谷氨酸/谷氨酰胺。
图S3。偏头痛残疾评估量表（migraine disability assessment scale, MIDAS）评分与神经化学水平的关联。(A)与(B)展示了MIDAS评分与中脑导水管周围灰质内γ-氨基丁酸水平的相关性。(C)与(D)展示了MIDAS评分与中脑导水管周围灰质内谷氨酸/谷氨酰胺水平的相关性。(E)与(F)展示了MIDAS评分与齿状核内γ-氨基丁酸水平的相关性。(G)与(H)展示了MIDAS评分与齿状核内谷氨酸/谷氨酰胺水平的相关性。散点代表偏头痛受试者。黑色回归线代表皮尔逊相关系数（r）。灰色阴影代表偏相关分析的95%置信区间。MIDAS，偏头痛残疾评估量表；PAG，中脑导水管周围灰质；DN，齿状核；GABA，γ-氨基丁酸；Glx，谷氨酸/谷氨酰胺。
图S4。头痛影响测试（Headache Impact Test, HIT-6）评分与神经化学水平的关联。(A)与(B)展示了HIT-6评分与中脑导水管周围灰质内γ-氨基丁酸水平的相关性。(C)与(D)展示了HIT-6评分与中脑导水管周围灰质内谷氨酸/谷氨酰胺水平的相关性。(E)与(F)展示了HIT-6评分与齿状核内γ-氨基丁酸水平的相关性。(G)与(H)展示了HIT-6评分与齿状核内谷氨酸/谷氨酰胺水平的相关性。散点代表偏头痛受试者。黑色回归线代表皮尔逊相关系数（r）。灰色阴影代表偏相关分析的95%置信区间。HIT-6，头痛影响测试；PAG，中脑导水管周围灰质；DN，齿状核；GABA，γ-氨基丁酸；Glx，谷氨酸/谷氨酰胺。
图S5。患者健康问卷9项（Patient Health Questionnaire-9, PHQ-9）评分与神经化学水平的关联。(A)与(B)展示了PHQ-9评分与中脑导水管周围灰质内γ-氨基丁酸水平的相关性。(C)与(D)展示了PHQ-9评分与中脑导水管周围灰质内谷氨酸/谷氨酰胺水平的相关性。(E)与(F)展示了PHQ-9评分与齿状核内γ-氨基丁酸水平的相关性。(G)与(H)展示了PHQ-9评分与齿状核内谷氨酸/谷氨酰胺水平的相关性。散点代表偏头痛受试者。黑色回归线代表皮尔逊相关系数（r）。灰色阴影代表偏相关分析的95%置信区间。PHQ-9，患者健康问卷9项；PAG，中脑导水管周围灰质；DN，齿状核；GABA，γ-氨基丁酸；Glx，谷氨酸/谷氨酰胺。
图S6。广泛性焦虑障碍7项量表（Generalized Anxiety Disorder-7, GAD-7）评分与神经化学水平的关联。(A)与(B)展示了GAD-7评分与中脑导水管周围灰质内γ-氨基丁酸水平的相关性。(C)与(D)展示了GAD-7评分与中脑导水管周围灰质内谷氨酸/谷氨酰胺水平的相关性。(E)与(F)展示了GAD-7评分与齿状核内γ-氨基丁酸水平的相关性。(G)与(H)展示了GAD-7评分与齿状核内谷氨酸/谷氨酰胺水平的相关性。散点代表偏头痛受试者。黑色回归线代表皮尔逊相关系数（r）。灰色阴影代表偏相关分析的95%置信区间。GAD-7，广泛性焦虑障碍7项量表；PAG，中脑导水管周围灰质；DN，齿状核；GABA，γ-氨基丁酸；Glx，谷氨酸/谷氨酰胺。
图S7。匹兹堡睡眠质量指数（Pittsburgh Sleep Quality Index, PSQI）评分与神经化学水平的关联。(A)与(B)展示了PSQI评分与中脑导水管周围灰质内γ-氨基丁酸水平的相关性。(C)与(D)展示了PSQI评分与中脑导水管周围灰质内谷氨酸/谷氨酰胺水平的相关性。(E)与(F)展示了PSQI评分与齿状核内γ-氨基丁酸水平的相关性。(G)与(H)展示了PSQI评分与齿状核内谷氨酸/谷氨酰胺水平的相关性。散点代表偏头痛受试者。黑色回归线代表皮尔逊相关系数（r）。灰色阴影代表偏相关分析的95%置信区间。PSQI，匹兹堡睡眠质量指数；PAG，中脑导水管周围灰质；DN，齿状核；GABA，γ-氨基丁酸；Glx，谷氨酸/谷氨酰胺。
图S8。蒙特利尔认知评估量表（Montreal Cognitive Assessment, MoCA）评分与神经化学水平的关联。(A)与(B)展示了MoCA评分与中脑导水管周围灰质内γ-氨基丁酸水平的相关性。(C)与(D)展示了MoCA评分与中脑导水管周围灰质内谷氨酸/谷氨酰胺水平的相关性。(E)与(F)展示了MoCA评分与齿状核内γ-氨基丁酸水平的相关性。(G)与(H)展示了MoCA评分与齿状核内谷氨酸/谷氨酰胺水平的相关性。散点代表偏头痛受试者。黑色回归线代表皮尔逊相关系数（r）。灰色阴影代表偏相关分析的95%置信区间。MoCA，蒙特利尔认知评估量表；PAG，中脑导水管周围灰质；DN，齿状核；GABA，γ-氨基丁酸；Glx，谷氨酸/谷氨酰胺。