Table 1.
Healthy subject's fMRI activation/deactivation results after taVNS compared to sham (or to baseline) following anatomical order; brainstem, subcortical areas, and cortical areas.
| Studies | Kraus et al. (79) | Dietrich et al. (81) | Kraus et al. (80) | Frangos et al. (82) | Yakunina et al. (83) | Badran et al. (84) | Sclocco et al. (85) | Sclocco et al. (86) |
|---|---|---|---|---|---|---|---|---|
| Objective of the study | Feasibility | Feasibility | Compare stim sites |
Compare to sham |
Compare stim sites |
Compare to sham |
Brainstem evaluation | Compare frequencies |
| Number of subjects | 8 | 4 | 8/8 | 12 | 37 | 17 | 16 | 30 |
| Age (mean ± SD) years | Range 20–37 |
30.0 ± 2.7 | Range 20–37 |
32.6 ± 13.8 | 30.9 ± 8.2 | 25.8 ± 7.6 | 27.0 ± 6.6 | 29.0 ± 9.8 |
| Gender (ratio F:M) | 6:2 | 0:4 | U | 9:3 | 19:18 | 8:9 | 9:7 | 17:13 |
| Design | Parallel | Crossover | Parallel | Crossover | Crossover | Crossover | Crossover | Crossover |
| Blinding | Single | None | Single | Single | Single | Single | Single | Single |
| Devices | TENS EMP2 | Custom | TENS EMP2 | NEMOS® | Custom | Custom | Custom | Custom |
| Stimulation site | Inner tragus L | Inner tragus L |
Inner tragus L |
Cymba conchae L |
Cymba conchae L |
Tragus L |
Cymba conchae L |
Cymba conchae L |
| Comparative | ||||||||
| Sham location | – | – | Lobe L |
Lobe L |
Lobe L |
Lobe L |
Lobe L |
Cymba conchae L (no current) |
| Baseline | No stim | Resting-state | Resting-state | Resting-state | Resting-state | – | Resting-state | |
| Frequency (Hz) | 8 | 25 | 8 | 25 | 25 | 25 | 25 | 2, 10, 25, 100 |
| Pulse width (μs) | 20 | 250 | 20 | 250 | 500 | 500 | 450 | 300 |
| Intensity (mA) | Low: 4 ± 1.0 High: 5 ± 1.0 |
4.0–8.0 | 4.0–5.0 under pain threshold |
0.3–0.8 | 0.2–1.8 0.1 under pain threshold |
0.1–5.1 200% sensation threshold | 1.6 ± 2.4 4–5 on a 0–10 pain scale | Vary with fq 2: 7.2 ± 1.0 10: 6.5 ± 1.3 25: 5.9 ± 1.2 100: 5.6 ± 1.2 |
| Duration | 2 min off – 30 s on−60 s off X 4 |
100 s off - 50 s on X 4 – 100 s off |
2 min off – 30 s on−1 min off X 4 |
2 min off – 7 min on−11 min off |
30 s on−60 s off X 4 |
30 s off – 60 s on−60 s off X 2 – 60 s on−30 s off |
Match the breathing cycle for a total of 8 min |
Match the breathing cycle for a total of 8.5 min |
| fMRI technique | 1.5 T | 1.5 T | 1.5 T | 3.0 T 12-Channel head coil |
3.0 T 32-Channel head coil |
3.0 T 32-Channel head coil |
7.0 T 32-Channel and birdcage transmit coil |
3.0 T 64-Channel head/neck coil |
| Brainstem areas | ||||||||
| Spinal trigeminal nucleus | – | – | – | ↑ bilat | – | nd* | ↑ ipsi | ↑ ipsi |
| Nucleus of the tractus solitarius | – | – | ↓ | ↑ ipsi | ↑ bilat | nd* | ↑ ipsi | ↑ ipsi |
| Locus coeruleus | – | ↑ ipsi | ↓ | ↑ bilat | ↑ bilat | nd* | ↑ cont |
↑ cont (2 Hz) ↑ bilat (100 Hz) |
| Raphe nuclei | – | – | – | ↑ bilat | – | nd* | ↑ cont | ↑ bilat (2,100) |
| Subcortical areas | ||||||||
| Thalamus | (↑c) | ↑ ipsi > cont | nd | ↑ bilat | ↑ bilat | nd | – | – |
| Caudate | (nd) | nd | – | ?(↑c) | ↑ bilat | ↑ cont | – | – |
| Nucleus accumbens | (nd) | ↓ cont | – | ↑ cont (↑b) | – | nd | – | – |
| Putamen | (nd) | nd | – | ?(↑c) | nd (nd) | nd | – | – |
| Amygdala | (↓ b) | nd | – | ↑ cont | nd (↓b) | nd | – | – |
| Hippocam-pus | (↓ i) | nd | – | ↓ bilat | nd (↓b) | nd | – | – |
| Parahippocampus | (↓ b) | nd | ↓ ipsi (↓i) | ↓ bilat | nd (↓b) | nd | – | – |
| Insula | (↑ b) | ↑ ipsi | ↑ ipsi (↑i) | ↑ bilat | nd (↓i) | nd (↑b) | – | – |
| Hypotha-lamus | (nd) | nd | – | ↓ bilat | nd (nd) | nd | – | – |
| Cerebellum | (nd) | ↓ cont | – | ↑ bilat | ↑ bilat | ↑ bilat (↑i) | – | – |
| Cortical areas | ||||||||
| mPFC | (↓b) | ↑ ipsi | ↑ bilat (↑b) | – | nd (↓b) | ↑ ipsi | – | – |
| Orbitofron-tal cortex | (nd) | nd | – | ↑ cont | – | nd | – | – |
| Lateral Frontal cortex |
(↑i) | – | – | – | nd (↓c) | nd (↑b) | – | – |
| ACC | (↑c) | nd | nd (↑c) | ↑ bilat | nd (↓b) | ↑ cont | – | – |
| Pre-central gyrus | (↑b) | nd | – | – | nd (↓b) | nd | – | – |
| Post-central gyrus | ↑ bilat | – | ↑ bilat | nd (↓b) | nd (↑c) | – | – | |
| Paracentral lobule | (↓b) | – | ↑ bilat | – | nd | – | – | |
| PCC/precuneus | (↓b) | ↑ ipsi | nd (↓i) | ↑ bilat | nd (↓b) | nd | – | – |
| Parietal cortex | (nd) | nd | nd (↑c) | – | nd (nd) | nd | – | – |
| Temporal middle | (↓b) | – | – | – | nd (↓b) | nd | – | – |
| Occipital lobe | (nd) | nd | – | – | nd (↓i>c) | nd | – | – |
ACC, anterior cingulate cortex; Bilat/b, bilateral; Cont/c, contralateral to the stimulated ear; fq, frequency; Ipsi/i, ipsilateral to the stimulated ear; L, left; mPFC, medial prefrontal cortex; min, minutes; nd, not detected; PCC, posterior cingulate cortex; s, seconds; stim, stimulation; ?, unknown; ↑, activation; ↓, deactivation; (), results between parentheses are taVNS vs baseline; results out of parentheses are taVNS vs sham; –, not analyzed; *, lack of results in the brainstem results may be biased due to the methodological approach used (not accurate for the brainstem).