In 26 patients with major depressive disorder (MDD) who had already undergone rTMS, the closer the clinically targeted site was to a subsequently determined personalized target, the better the outcome, Dr. Robin F. H. Cash of The University of Melbourne, in Australia, and colleagues found.
"Our work provides very strong evidence that individual clinical benefit to following brain stimulation is determined by brain connectivity (pathways of communication) between the prefrontal stimulation target and deeper regions of the brain that are involved in emotional regulation," Dr. Cash told Reuters Health in an email. "We developed new methodology which can pinpoint the optimal stimulation target based on an individual's brain scan with unprecedented accuracy."
rTMS involves noninvasively stimulating the brain with electromagnetic pulses to treat depression. It is most effective when delivered to sites in the dorsolateral prefrontal cortex (DLPFC) with negative functional connectivity with the subgenual cingulate cortex (SGC), Dr. Cash and his colleagues explain in JAMA Psychiatry.
Currently, Dr. Cash noted, clinicians have to "blindly guess" the site to be stimulated with rTMS. "Most studies locate the DLPFC stimulation site as 5-6 cm anterior to the motor cortex," he added. "The motor cortex can be easily identified using TMS because when the hand area of the motor cortex is stimulated, it evokes a brief twitch of the hand muscles. However, this 5-6-cm approach is imprecise, and it does not account for individual differences in head dimensions, brain anatomy or brain connectivity."
In the new study, Dr. Cash and his colleagues looked at 26 patients with major depressive disorder (MDD) who had already undergone rTMS for five days a week for three weeks. The authors used pretreatment and post-treatment magnetic resonance imaging (MRI) scans from each patient to compute personalized targets.
Applied targets and the personalized targets were a median of 30 mm apart. The closer the applied and personalized targets were to one another, the more likely a patient was to respond to treatment as assessed on the Montgomery-Aasberg Depression Rating Scale (R, -0.60; P<0.001).
Stronger anticorrelation between the actual target and the SGC was also linked to better outcomes (R, -0.57; P<0.02).
The proximity of the clinically targeted site to a group-average target was not associated with treatment effectiveness.
"Stimulating the wrong site does not appear to be effective - and this is an important consideration as brain stimulation is time intensive with daily treatments for 4-6 weeks," Dr. Cash said.
"In future we want to use brain scans to determine each individual's optimal stimulation target prior to treatment," he said. "It is worth noting that the cost of an MRI is relatively low compared to the cost of TMS treatment. In the future, this may be similar to getting a scan for a broken leg so that we know where to target."
Dr. Cash and his team are now planning a large clinical study of the personalized approach. "We anticipate that the clinical efficacy of TMS will be significantly improved in future by this approach and we will release software to facilitate this process for clinicians," he said.
The study did not have commercial funding. One of Dr. Cash's coauthors holds a patent for a transcranial-direct-current-stimulation device and has multiple industry ties.
SOURCE: https://bit.ly/3o5xTic JAMA Psychiatry, online November 25, 2020.
By Anne Harding
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