TMS Mechanisms
The dorsolateral prefrontal cortex (Left or Right DLPFC) has been the primary area of interest for stimulation as many functional imaging studies that indicated depression is associated with this region of the brain, though other studies locate the ventromedial and anterior portions of the Prefrontal Cortex. Some researchers have not only proposed an under-activated Left DLPFC, but suggested an imbalance between frontal regions. For example, the ‘frontal asymmetry hypothesis’ of depression states that in depression there is an imbalance in left vs. right frontal brain activation (Henriques 1992)[iii]. This insight has led to the rise of various approaches to TMS depression treatment.

 

Of all brain regions known to be related to the illness of depression (e.g., prefrontal, cingulate, parietal and temporal cortical regions) the DLPFC is regarded as one of the most accessible sites for treatment with TMS (Wassermann & Lisanby 2011[iv]) and therefore is the most commonly targeted area.

TMS Protocols
The behavioral effects of TMS have been found to depend on the frequency, intensity and duration of stimulation (e.g. O’Reardon et al 2007[v]Bakkera, Shaha et al 2015[vi]).

Progress in the development of technical aspects of TMS devices and advancing insights have led to the continuing development of peer reviewed innovative protocols, such as Theta Burst TMS[vii] which are hoped to be powerful new tools in the TMS Field.

High Frequency (5-20 Hz) TMS (HF-TMS)
Numerous single site studies have applied stimulation frequencies of 10 Hz (10 stimulations/second) to 20 Hz. (O'Reardon et al., 2007[viii]; George et al., 2010). Most of these studies have been performed in treatment resistant patients. It is not yet known which exact frequencies appear to be the most beneficial, as the FDA has approved protocols of both 10 Hz and the protocol of Brainsway which uses 18 Hz frequency.

Low Frequency (1-2 Hz)TMS (LF-TMS)
Several LF-TMS studies have been performed, including Pallanti et al, 2010 [ix]. In the largest controlled study on LF-TMS in depression, 130 patients were initially assigned to a low frequency stimulation protocol of either 1 or 2 Hz  (Fitzgerald et al., 2006)[x]. Of the 130 patients enrolled, approximately 51% could be classified as responders after 10 days of treatment. This treatment consists of 1 pulse per second ( as opposed to 10 or 18 pulses/second) and is often much easier to tolerate.
Although LF-TMS is a more recently developed protocol, it appears to have beneficial effects.  Several studies and meta-analysis studies show similar findings  (Chen, Jianjun, et al)[xi] [xii].

 Deep TMS:
There are occasions when we may decide to have a deeper penetration of magnetic waves than is normally available from a flat figure 8 coil. In these instances, we use a specific coil developed for just this particular approach.

We work with each patient to develop the most appropriate protocol approach. In TMS, more or deep is not necessarily better. We constantly monitor patient progress and adjust protocols as the evidence warrants.

[i] Connolly, K. R., et al. "Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center." The Journal of clinical psychiatry 73.4 (2012): e567-73.

[ii] Dunner, D. L., et al. "A multisite, naturalistic, observational study of transcranial magnetic stimulation for patients with pharmacoresistant major depressive disorder: durability of benefit over a 1-year follow-up period." The Journal of clinical psychiatry 75.12 (2014): 1394-1401.

[iii] Henriques, Jeffrey B., and Richard J. Davidson. "Left frontal hypoactivation in depression." Journal of abnormal psychology 100.4 (1991): 535.

[iv] Wassermann, Eric M., and Sarah H. Lisanby. "Therapeutic application of repetitive transcranial magnetic stimulation: a review." Clinical Neurophysiology 112.8 (2001): 1367-1377.

[v] O’Reardon, John P., et al. "Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial." Biological psychiatry 62.11 (2007): 1208-1216.

[vi] Bakker, Nathan, et al. "TMS of the Dorsomedial Prefrontal Cortex for Major Depression: Safety, Tolerability, Effectiveness, and Outcome Predictors for 10 Hz Versus Intermittent Theta-burst Stimulation." Brain stimulation (2014).

[vii] Bakker, Nathan, et al. "TMS of the Dorsomedial Prefrontal Cortex for Major Depression: Safety, Tolerability, Effectiveness, and Outcome Predictors for 10 Hz Versus Intermittent Theta-burst Stimulation." Brain stimulation (2014).

[viii] O’Reardon, John P., et al. "Efficacy and safety of..,” (footnote1)

[ix] Pallanti, S., et al. "Unilateral low frequency versus sequential bilateral repetitive transcranial magnetic stimulation: is simpler better for treatment of resistant depression?." Neuroscience 167.2 (2010): 323-328.

[x] Fitzgerald, Paul B., Sarah Fountain, and Zafiris J. Daskalakis. "A comprehensive review of the effects of TMS on motor cortical excitability and inhibition." Clinical Neurophysiology 117.12 (2006): 2584-2596.

[xi] Chen, Jianjun, et al. "Left versus right repetitive transcranial magnetic stimulation in treating major depression: a meta-analysis of randomised controlled trials." Psychiatry research 210.3 (2013): 1260-1264.

[xii] Berlim, Marcelo T., Frederique Van den Eynde, and Z. Jeff Daskalakis "Clinically meaningful efficacy and acceptability of low-frequency repetitive transcranial magnetic stimulation (TMS) for treating primary major depression: a meta-analysis of randomized, double-blind and sham-controlled trials." Neuropsychopharmacology 38.4 (2013): 543-551.

37 Washington Square West Suite 1D

(C) Copyright 2020 by Shelly Menolascino MD.  All Rights Reserved.

Diplomate of the American Board of Psychiatry and Neurology

Diplomate in Advanced Psychopharmacology

P (212) 647-9187

F (212) 243-1451

New York, NY 10011