Table 3.

Summary of discussed studies examining EEG correlates and predictors of rTMS outcomes

Study	Study Design	Sample (N)	EEG Metrics	EEG Timing	rTMS Parameters	Findings
Arns et al, 2012	Open label, multi-site	MDD (n=86) or Dysthymia (n=4)	Individual alpha peak frequency Theta power Cordance P300	Prior to initiation of rTMS	Left DLPFC 10Hz, 110% MT, 1500 pulses per session –OR– Right DLPFC 1Hz, 110% MT, 1200 pulses per session (if presence of focal left beta spindles during EEG) Average 20.7 sessions	Relative to responders, at baseline non-responders had: ↑Frontal-central theta power Slower anterior individual alpha peak frequency Larger P300 amplitude ↓Pre-frontal delta and beta cordance
Bailey et al. 2019	Open label outpatient treatment	MDD (n=42); Controls (n=21; received only baseline EEG and no rTMS)	Alpha power, theta power, theta cordance, individualized alpha peak frequency, alpha connectivity, theta connectivity	Baseline and after 1 week of treatment	Left DLPFC, 10Hz, 2000 pulses per session, 110%MT 5–8 weeks of treatment	Larger theta connectivity at baseline and at 1 week in responders compared to non-responders. No other baseline EEG measures differed between responders and non-responders.
Bares et al. 2014	Randomized, blinded, sham controlled	MDD (n=60; inpatients)	Prefrontal theta cordance	Baseline and after 1 week of treatment	Right DLPFC, 1-Hz, 600 pulses per session, 100% MT, for 20 consecutive working days	Decrease of cordance after 1 week of treatment predicted response. Compared to baseline, theta cordance at week 1 was significantly decreased in responders, but not in nonresponders to rTMS.
Corlier et al. 2019 paper in press	Open label outpatient treatment	MDD (n=147)	Individual alpha frequency Absolute difference between IAF and 10Hz (i.e., |IAF – 10Hz|)	Pre-treatment	Initial: 10Hz left DLPFC ≥80% MTIf not tolerating or subtherapeutic, changed to either: Simultaneous bilateral stimulation w/ 1Hz on right DLPFC Continued unilateral left DLPFC at 5Hz	There was no correlation between either IAF or |IAF-10Hz| values and clinical outcome in the overall sample. Significant correlations were found for both IAF and |IAF-10Hz| and the 10Hz group’s clinical outcome. No such relationship was found in the simultaneous bilateral or 5Hz sub-groups. Clinical outcomes of top IAF quartile of the 10Hz group were significantly better as compared to the bottom quartile.
Hunter et al. 2017	Open label outpatient treatment	MDD (n=18; outpatient)	Change in theta cordance	Baseline and after 1 week of treatment	Left DLPFC, 10Hz, 3000 pulses per session, 120%MT for 5 days per week over 6 weeks.	Change in central regional cordance after 1 week was associated with improvement after 6 weeks of treatment.
Jin et al. 2014	Randomized, sham controlled, double-blinded trial 3 arms: active synchronized TMS with fixed frequency set at individualized alpha frequency, active synchronized TMS with random frequency from 8–13Hz, and sham TMS.	MDD (n=52)	Individual alpha frequency	Prior to rTMS to determine individual alpha frequency	Experimental synchronized TMS device: cylindrical magnets positioned sagitally along midline with axis of rotation perpendicular to midline. Compared to standard rTMS devices, magnetic waveforms are sinusoidal with energy of magnetic field <1% of standard	Statistically significant clinical improvement was seen in the active group compared to sham, but not between the random frequency and fixed individualized alpha frequency groups.
Krepel et al, 2018	Open label, multi-site	MDD or Dysthymia (n=106 Total)	Individual alpha peak frequency Theta power P300	Prior to initiation of rTMS	Left DLPFC 10Hz –OR– Right DLPFC 1Hz	No difference between responders and nonresponders for individual alpha peak frequency, theta power, or P300 prior to initiation of rTMS.
Leuchter et al, 2015	Randomized, double-blinded, sham controlled trial (synchronized rTMS with fixed frequency set at individualized alpha frequency vs. sham)	MDD (n=202)	Individual alpha frequency	Prior to rTMS to determine individual Alpha Frequency	Same experimental synchronized TMS device as above (Jin et al., 2014)	No statistical significance with ITT analysis. Significantly lower HAM-D score in the active treatment group with PP analysis (n=120, 59 active and 61 sham)
Petrosino et al, 2018	Open Label	MDD+PTSD (n=21)	Intrinsic alpha frequency	Baseline and post-treatment	Left DLPFC, 5Hz, 120% MT, 3000–4000 pulses/session, up to 40 sessions	No IAF changes were found between baseline and follow-up. There was not a significant relation between baseline IAF and clinical outcome.
Shalbaf et al. 2018	Data from 2 single-blind randomized, controlled trials	MDD (n=51) and Healthy Comparison (n=25)	Permutation entropy intrinsic mode function index Relative power of delta, theta, alpha, beta, gamma band	Pre-treatment	120%MT, either high frequency TMS (n=25) or theta burst TMS (n=26) over left DLPFC	Responders had higher permutation entropy intrinsic mode function index relative to non-responders, particularly at left frontal locations. Permutation entropy intrinsic mode function index was a superior predictor of treatment response than relative power of frequency bands

IAF = individual alpha frequency; ITT = intent to treat, PP = per protocol, MDD = major depressive disorder, DLPFC = dorsolateral prefrontal cortex