Transcranial Magnetic Stimulation TMS rTMS Depression

Transcranial Magnetic Stimulation has been used at a high frequency to stimulate the left dorsolateral prefrontal cortex. By using a high frequency, the brain area being targeted becomes more active than it normally would be. A recent meta-analysis indicates that stimulating this area has mood elevating properties in depressed patients.

Thirty double-blind sham-controlled parallel studies with 1164 patients comparing the percentage change in depression scores from baseline to endpoint of active versus sham treatment were included.

"These findings show that high-frequency rTMS over the left DLPFC is superior to sham in the treatment of depression. The effect size is robust and comparable to at least a subset of commercially available antidepressant drug agents."

Researchers have had considerable difficulty in distinguishing rTMS from sham for many trials, though. Depression is a multifaceted disorder with many different symptoms that are associated with different brain areas. Stimulating the left dorsolateral prefrontal cortex with rTMS is relatively selective and might only be expected to improve a subset of depression symptoms. Left dorsolateral prefrontal dysfunction (LDPFC) is associated with pseudodepressive symptoms. These type of symptoms include apathy, indifference, anergia, poor concentration and psychomotor retardation. Stimulation of this area would be less likely to improve extreme sadness, pleasure and sleep difficulty which may be associated with other brain areas.
Researchers have also found that low frequency stimulation of the right dorsolateral prefrontal cortex which is on the right side of the brain also has a mood elevating effect. Low frequency stimulation does the opposite of high frequency stimulation. It decreases brain activity in the area being targeted. More recently researchers have found a way to squeeze even more of a response out of low frequency rTMS by "priming".

"Recent research has suggested that preceding low-frequency rTMS with a period of low-intensity, 6-Hz stimulation ("priming") enhances the physiological effects of low-frequency stimulation."
"Low-intensity, high-frequency priming stimulation appears to enhance the response to low-frequency, right-sided rTMS treatment in patients with treatment-resistant depression."

So basically this is using a higher frequency to stimulate the target area which is then followed by stimulation with a lower frequency that inhibits brain function. This may allow researchers to decrease brain activity to an even greater degree than with just using regular low frequency rTMS. Exciting the brain with high frequency rTMS has the potential to cause a siezure, so scientists are limited in how high a frequency they can go. Low frequency rTMS on the other hand, inhibits brain functioning and does not have the same risk of causing seizures. It is much easier to decrease brain activity in certain areas than increase brain activity.

I think in the future what is need are better rating scales which correlate depression symptoms with specific brain dysfunctional areas. That way scientists will be better able to measure the response when selectively activating or deactivating a brain area. This would decrease the signal to noise ratio and enable researchers to better distinguish the sham (placebo) TMS from the real TMS.