Repetitive transcranial magnetic stimulation, or EMTR, was approved by the FDA in 2008 as a safe and effective non-invasive treatment for severe depression resistant to antidepressant drugs. A small coil positioned close to the scalp generates pulsed and repetitive magnetic waves that pass through the skull and stimulate brain cells to relieve symptoms of depression. The procedure has few side effects and is usually prescribed as an alternative or supplementary therapy when several antidepressant drugs and / or psychotherapy do not work.
Despite the increase in the use of rTMS in psychiatry, the rates at which patients respond to therapy and experience remission of frequently disabling symptoms were modest, at best.
Now, for the first time, a team of psychiatrists and biomedical engineers at the University of South Florida have applied an emerging functional neuroimaging technology, known as diffuse optical tomography (DOT), to better understand how EMTr works so they can start improving effectiveness of the technique in treating depression. DOT uses near-infrared light waves and sophisticated algorithms (computer instructions) to produce three-dimensional images of soft tissues, including brain tissue.
Comparing depressed and healthy individuals, the USF researchers demonstrated that this new optical imaging technique can safely and reliably measure changes in brain activity induced during EMR in a target region of the brain involved in mood regulation. Their findings were published on April 1 in the Nature diary Scientific Reports.
This study is a good example of how cross-disciplinary collaboration can advance our general understanding of how a treatment like MTS works. We want to use what we have learned with the application of the diffuse optical tomography device to optimize TMS, so that treatments become more personalized and lead to more remission of depression. “
Shixie Jiang, MD, lead author of the study, third year psychiatry resident, USF Health Morsani College of Medicine
DOT has been used clinically for images of epilepsy, breast cancer and osteoarthritis and to visualize the activation of cortical regions of the brain, but the USF team is the first to introduce the technology to psychiatry to study brain stimulation with STM.
“Diffuse optical tomography is really the only modality that can work with images of the brain at the same time that TMS is administered,” said the study’s principal investigator, Huabei Jiang, PhD, professor in the Department of Medical Engineering and father of Shixie Jiang. The DOT imaging system used for the collaborative study of the USF was built to order in his laboratory at the Faculty of Engineering of the USF.
The researchers point to three main reasons why STM probably did not reach its full potential in the treatment of major depression: non-optimized targeting of brain stimulation; unclear treatment parameters (ie rTMS dose, magnetic pulse patterns and frequencies, rest periods between stimulation intervals) and incomplete knowledge of how nerve cells in the brain respond physiologically to the procedure.
Portable, less expensive and less confining than some other neuroimaging equipment, such as magnetic resonances, the DOT still renders localized 3D images of relatively high resolution. More importantly, Huabei Jiang said, DOT can be used during TMS without interfering with the treatment’s magnetic pulses and without compromising the images and other data generated.
DOT is based on the fact that higher levels of oxygenated blood correlate with more brain activity and increased cerebral blood flow, and lower levels indicate less activity and blood flow. Certain neuroimaging studies have also revealed that depressed people exhibit abnormally low brain activity in the prefrontal cortex, a region of the brain associated with emotional responses and mood regulation.
By measuring changes in near infrared light, DOT detects changes in brain activity and, secondarily, changes in blood volume (flow) that may be triggering activation in the prefrontal cortex. In particular, the device can monitor altered levels of oxygenated, deoxygenated and total hemoglobin, a protein in red blood cells that carries oxygen to tissues.
The USF study analyzed data collected from 13 adults (7 depressed and 6 healthy controls) who underwent DOT imaging tests simultaneously with EMTR at the USF Health psychiatry outpatient clinic. Applying the standard EMRT protocol, treatment was directed to the left dorsolateral prefrontal cortex of the brain – the region most targeted at depression.
The researchers found that depressed patients had significantly less brain activation in response to EMTR than healthy study participants. In addition, the peak brain activation took longer to reach in the depressed group compared to the healthy control group.
This delayed and less robust activation suggests that EMTR, as currently administered according to FDA guidelines, may not be suitable for some patients with severe depression, said Dr. Shixie Jiang. The dose and timing of treatment may need to be adjusted for patients who have weakened responses to brain stimulation at baseline (initial treatment), he added.
Larger clinical trials are needed to validate the results of the preliminary USF study, as well as to develop optimal treatment parameters and to identify other dysfunctional regions in the brain affected by depression that may benefit from targeted stimulation.
“More work is needed,” said Dr. Shixie Jiang, “but advances in neuroimaging with new approaches, such as diffuse optical tomography, hold great promise to help us improve EMR and the results of depression.”