Table 2.

Summary of all included studies.

References	Intervention(s)	Sample size	Age (years)	Intervention duration (sessions/weeks)	Area of treatment	Comparison and outcome measure	Results	Adverse effects	Duration migraine	Evidence level*
Migraine
Cao et al. (2021), China	G1; taVNS = NR; 20-Hz. G2; taVNS = NR 1 Hz;	N = 24	31.33 ± 1.55	taVNS stimulation lasted about 8 min. Unique session	Left concha (cymba and cavum)	VAS, MSQ, SDS, SAS, number migraines fMRI G1 vs. G2	G2; taVNS (1Hz) improved FC in PAG, bilateral MCC, right precuneus/posterior cingulate cortex, left MFG, left cuneus, left insula, ACC. Number migraines better with 1Hz ta-VNS. NS VAS, MSQ, SDS, SAS	None	8.68 ± 1.47 y.	2
Wei et al. (2022), China	G1; EA G2; healthy people	N = 30	32.285 ± 6.41	2Hz, 1 mA for 8 min until the end of fMRI scan	GB 8	HRSD-17 & HRSA-14	G1 could inprove (GB8) FC between the right insula subregions and parietal lobe, namely, the right dAI and right postcentral gyrus, and the right PI and left precuneus	None	16.20 ± 8.19	3
Sacca et al. (2022), USA	G1; taVNS =; 1-Hz. G2; taVNS = 20 Hz	N = 20	31.33 ± 1.55 y	taVNS stimulation 1Hz, 8 minutes, 4 mA, 2 session with fMRI scan	Left concha (cymba and cavum)	Migraine duration, number of migraine attacks, VAS, Migraine Specific Quality of Life Questionnaire, fMRI	G1 Improved NTS/LC–occipital cortex sFC and a decrease of NTS-thalamus sFC, greater LC precuneus and LC–inferior parietal cortex sFC than G2. G1 decreased NTS–postcentral gyrus dFC than G2. G2 compared with baseline increase of the LC–anterior cingulate cortex (ACC) sFC.	None		2
Zhang et al. (2021), China	G1; taVNS = 33, 1Hz, 0.2ms G2; Sham group = 26	N = 70	NR	30 min of 12 treatment sessions in total during the 4 week treatment	Left cymba concha	VAS MSQ Migraine attack times SAS fMRI G1 vs. G2	G1 SF number of migraine days (p = 0.024) G1 SF (p = 0.008), migraine attack times (p = 0.015) NS MSQ, SAS, SDS fMRI G1; FC, occipital' thalamic seed and the bilateral PoG reduction of the migraine days (p = 0.016) G2; NS	None	4.0 (1.9) days 4.0 (3.2) days	1
Luo et al. (2020), China	G1; taVNS 1Hz, 0.2ms. G2s; tVNS Sham.	N = 27	29.85 ± 8.09	Unique session of MRI scan, total of six 20-min fMRI runs and 8 min ta-VNS	CO11 and CO14, left cymba concha	VAS, MSQ, SAS, SDS, fMRI G1 vs. G2	G1; FC Improved, left amygdala, left MFG, right SMA, left dorsolateral superior frontal gyrus, bilateral paracentral lobules, bilateral postcingulum gyrus, and right frontal superior medial gyrus. Left FC and right SMA in frequency/time in migraine in 4 weeks.	None	NR; NR	2
Zhang et al. (2021), China	G1; ta-VNS, 1Hz, 0.2ms. G2; Sham ta-VNS	N = 26	32.50 ± 7.57	MRI session of 30 minutes	Left cymba concha	VAS, MSQ, SDS, SAS, fMRI G1 vs. G2	G1 greater deactivation at the bilateral LC. rsFC the right temporoparietal junction and left secondary somatosensory cortex (S2) SF increased vs. G2	None	7.15 ± 2.87 Y. 3.23 ± 1.58 mo	3
Straube et al. (2015), Germany	G1; taVNS 25 Hz, 250 μs, cycle: 30s on, 30 s off G2; ta-VNS 1 Hz; 250 μs, cycle: 30s on, 30 s off	N = 46 N = 24 N = 22	41,55 ± 11,95	4 h per day during 12 weeks	Concha of the outer ear	Pain Imtensity (NRS), MIDAS, HIT-6, BDI G1 vs. G2	G2 SF headache days, (p = 0.035). HIT-6 & MIDAS SF G1 & G2	Only 3 of 46 patients (7%) dropped out due to side effects of t-VNS.	20.4 ± 12.1 years 27.1 ± 13.0 years	2
Yang et al. (2014), China	G1; AG; G2; SAG; G3; MG	N = 30	33.28 ± 8.03	30 min of unique session 30 min Sham acupucnture 40 min rest	TE8, TE19, GB33	VAS PET-CT	G1 & G2 VAS SF (P < 0.05) MG NS(P = 0.047) AG vs. MG middle frontal gyrus, postcentral gyrus, the precuneus, parahippocampus, cerebellum and middle cingulate cortex (MCC), and decreased in the left hemisphere of (MTC) SAG vs. MG posterior cingulate cortex (PCC), insula, inferior temporal gyrus, MTC, superior temporal gyrus, postcentral gyrus, fusiform gyrus, inferior parietal lobe, superior parietal lobe, supramarginal gyrus, middle occipital lobe, angular and precuneus cerebellum, parahippocampus	None	NR NR	2
Vijayalakshmi et al. (2014), India	G1; Electro acupuncture; G2; Drug therapy	N = 60 N = 30 each group	NR	10 sessions for 30 days (0.5 mA; 10-20 Hz) flunarizine 20 mg OD and tab. paracetamol 500 mg SOS for 30 days	DU 20, P.6, St.36, GB.41, GB.14, EM, LI.4, LI.10, ST.44, Ear points: Ear shenmen and Ear stomach (16)	MIDAS WHO QOL BREF	G1 SF (P = 0.005–0.000) in all outcomes.	None	NR NR	2

VAS, visual analog scale; MSQ, Migraine Specific Quality of Life; SDS, Self-rating Depression Scale; SAS, Self-rating Anxiety Scale; NVS, transcutaneous auricular-Nerve Vagus stimulation; fMRI, functional Magnetic Resonance Image; AG, Electro-acupuncture group; SAG, Sham Acupunture Group; MG, Migraineur Wait-List control Group; WHO QOL BREF.

^*Levels of Evidence based on the Quality Rating Scheme for Studies and Other Evidence modified from the Oxford Centre for Evidence-Based Medicine for rating of individual studies; available online at https://www.cebm.net/2016/05/ocebm-levels-of-evidence/.RCT.

NR, Not reported; LC, locus coeruleus; rsFC, Resting state functional connectivity; SF, Significance; EA, Electro-acupuncture; PCC, Posterior cingulate cortex; MTC, Middle Temporal Cortex; SMA, supplementary motor area; MFG, middle frontal gyrus; MFC, Middle Frontal Cortex.