Table 4.
TMS and neuroimaging techniques used in the study
| Technique | Experiment/Protocol | Purpose/proposed neurophysiology | Targeted CNS Structure | Primary Reason for Collecting |
|---|---|---|---|---|
| rTMS (TBS) | iTBS | Promotes LTP-like neuromodulation (i.e., excitatory-inducing) | Left DLPFC | Treatment Intervention |
| cTBS | Promotes LTD-like neuromodulation (i.e., inhibitory-inducing) | Right DLPFC | Treatment Intervention | |
| Single and Paired-Pulse TMS | RMT | Assesses cortical excitability via indirect activation of cortical interneurons (I-wave) | M1 (bilaterally) | Used to normalize the following TMS experiments (e.g., % of RMT) |
| AMT | Cortical excitability via direct activation of corticospinal tract neurons (D-wave) | M1 (bilaterally) | Used to normalize the TBS treatment intensity (e.g., % of AMT) | |
| MEP Amplitude | Capacity of the corticospinal tract in recruiting neurons from faster temporospatial summation at cortico-motoneuronal synapses. Reflects glutamatergic (NMDA- and AMPA-receptor) activity | Left M1 | Used as unconditioned MEP (i.e., test MEP), to calculate degree of inhibition during paired-pulse experiments (e.g., degree of inhibition = conditioned/unconditioned MEP) | |
| SICI | Short-interval intracortical inhibition primarily influenced by GABAA-receptor activity | Left M1 | To investigate TMS biomarkers of treatment response examined with correlation analysis between baseline TMS and pre-post changes in clinical measures | |
| LICI | Long-interval intracortical inhibition primarily influenced by GABAB-receptor activity | Left M1 | ||
| ICF | Intracortical facilitation primarily influenced by glutamatergic (NMDA- and AMPA-receptor) activity | Left M1 | ||
| TMS-EEG | TEP and ERSP | Assesses trans-synaptic activation of local and distal cortical networks mediated by excitatory and inhibitory cortical circuitry | TMS performed on the left and right DLPFC (120% of RMT) and TEP/ERSP are recorded from the DLPFC (primarily) and whole brain (exploratorily) | To investigate TMS-EEG biomarkers of treatment response, examined with correlation analysis between baseline TEPs/ERSPs and pre-post changes in clinical measures. To investigate cortical changes from treatment, examined with repeated-measures analysis [pre- vs post initial treatment (week 4, or week 6 for non-remitters), vs post maintenance phase (e.g., final week (week 24)] |
| MRI | Structural MRI | Assesses anatomy and morphology of CNS structures | Whole brain | To be uploaded into the neuronavigation software to assist with the location and targeting of the M1 and DLPFC during TMS assessments and TBS treatment, respectively (MRI-assisted TMS) |
| MRS | Availability of neurotransmitters within the CNS (GABA and Glutamate) | Bilateral ACC | To investigate biomarkers of treatment response, examined with correlation analysis between baseline values and pre-post changes in clinical measures | |
| Functional MRI | Resting state connectivity between CNS structures | Bilateral DLPFC and ACC |
ACC Anterior cingulate cortex, AMT Active motor threshold, cTBS Continuous TBS, CNS Central nervous system, DLPFC Dorsolateral prefrontal cortex, EEG Electroencephalogram, ERSP Event related spectral perturbation, ICF Intracortical facilitation, iTBS Continuous TBS, LICI Long-interval intracortical inhibition, LTD Long-term depression, LTP Long-term potentiation, M1 Motor cortex, MEP Motor evoked potential, MRI Magnetic resonance imaging, MRS Magnetic resonance spectroscopy, RMT Resting motor threshold, rTMS repetitive transcranial magnetic stimulation, SICI Short-interval intracortical inhibition, TBS Theta burst stimulation, TES TMS-evoked potential, TMS Transcranial magnetic stimulation