Glutamatergic system and TMS plasticity protocols
| Study | Design (n) | Age, yr* | Male, % | Protocol | Drug (dose) | TMS target | Mechanism of action | Effect |
|---|---|---|---|---|---|---|---|---|
| Healthy participants | ||||||||
| Stefan et al. (56) | C/O (6) | 27 ± 6 | 78.5 | PAS25 | Dextromethorphan (150 mg) | M1 | NMDAR antagonist | Blocked LTP-like |
| Weise et al. (57) | C/O (11) | 21.8 ± 3.1 | 45.5 | PAS25 | Dextromethorphan (120 mg) | M1 | NMDAR antagonist | Blocked LTP-like |
| C/O (13) | 22.3 ± 3.3 | 53.85 | PAS25 | Dextromethorphan (120 mg) + nimodipine (30 mg) | M1 | NMDAR antagonist + L-type VGCC blocker | Increased LTP-like | |
| Wolters et al. (42) | C/O (10) | 27.8 ± 5.7 | 55.9 | PAS10 | Dextromethorphan (150 mg) | M1 | NMDAR antagonist | Blocked LTD-like |
| Suppa et al. (58) | C/O (8) | 27 ± 3 | 41.2 | Laser-PAS50 | Memantine (10 mg) | M1 | NMDAR antagonist | Blocked LTP-like |
| Wankerl et al. (54) | C/O (15) | 26.5 ± 3.7 | 40 | cTBS300 | Dextromethorphan (120 mg) | M1 | NMDAR antagonist | Blocked cTBS-LTP; blocked cTBS + nimodipine-LTD |
| Huang et al. (53) | C/O (6) | 29 ± 67 | 16.67 | iTBS cTBS | Memantine (10 mg) | M1 | NMDAR antagonist | Blocked LTP-like and LTD-like |
| Colnaghi et al. (55) | Parallel (30) | 27.3 ± 5.35 | 50 | cTBS | Memantine (10 mg) | Cerebellum | NMDAR antagonist | Blocked occulomotor metrics of plasticity |
| Teo et al. (60) | C/O (6) | NR | 66.7 | iTBS | D-cycloserine (100 mg) | M1 | NMDAR partial agonist | Switched LTP-like to LTD-like |
| Selby et al. (61) | C/O (12) | 29.66 ± 6.37 | 41.7 | iTBS | D-cycloserine (100 mg) | M1 | NMDAR partial agonist | Blocked early LTP-like followed by enhanced LTP-like after 60 min; blocked 16-hr SRC rightward shift |
| Wrightson et al. (62) | C/O (20) | 33.7 | 60 | Repeat iTBS (2 × 60 min apart) | D-cycloserine (100 mg) | M1 | NMDAR partial agonist | Increased LTP-like after both tetani |
| Brown et al. (35) | C/O (10) | 26–37 | 60 | 10 Hz rTMS | D-cycloserine (100 mg) | M1 | NMDAR partial agonist | Increased LTP-like |
| Brown et al. (36) | C/O (10) | 26–37 | 60 | 10 Hz rTMS | D-cycloserine (100 mg) | M1 | NMDAR partial agonist | Decreased ICF and increased ICI |
| Kweon et al. (59) | C/O (10) | 28 ± 6 | 40 | 10 Hz rTMS | D-cycloserine (100 mg) | M1 | NMDAR partial agonist | No effect on MEP amplitude post-10 Hz; decreased SRC intercept |
| MDD | ||||||||
| Cole et al. (64) | C/O (12 MDD, 12 HC) | 35.8 ± 15.3 | 58.3 | iTBS | D-cycloserine (100 mg) | M1 | NMDAR partial agonist | Normalized SRC shift in MDD and stabilized LTP-like |
| Cole et al. (11) | Parallel (50) | 40.8 ± 13.4 | 38 | iTBS (20 sessions) | D-cycloserine (100 mg) | Left DLPFC | NMDAR partial agonist | Improved antidepressant effects |
C/O = crossover; cTBS = continuous theta-burst stimulation; DLPFC = dorsolateral prefrontal cortex; HC = healthy controls; ICF = intracortical facilitation; ICI = intracortical inhibition; iTBS = intermittent theta-burst stimulation; LTD = long-term depression; LTP = long-term potentiation; M1 = motor cortex; MDD = major depressive disorder; MEP = motor-evoked potential; NMDAR = N-methyl-d-aspartate receptor; NR = not reported; PAS = paired associative stimulation; rTMS = repetitive transcranial magnetic stimulation; SRC = stimulus response curve; TBS = theta-burst simulation; TMS = transcranial magnetic stimulation; VGCC = voltage-gated Ca2+ channel.
↵* Data are presented as mean ± standard deviation.