Correction, October 24, 2026: An earlier version of this article described a 40-patient, single-site trial as the strongest evidence yet for imaging-guided TMS targeting and as a mature comparison, without stating its size or noting a larger 2024 trial, BRIGhTMIND, that found no difference on its primary outcome. The headline, summary and characterization of the evidence have been revised; the trial’s authors describe it as a step toward a confirmatory trial.
A randomized trial in JAMA Psychiatry found that aiming accelerated transcranial magnetic stimulation with an individual brain scan works better than the standard, cheaper scalp-landmark method. Investigators at Mass General Brigham reported an 80 percent response rate for personalized, connectivity-based targeting, against 60 percent for scalp-based targeting. That answers a question that determines how the fastest-growing form of depression neuromodulation scales: whether the extra cost of imaging is worth it. The result tilts the field toward precision, and toward the cost and infrastructure that precision requires.
Why targeting is the question
TMS, cleared for depression since 2008, stimulates the dorsolateral prefrontal cortex, a brain region tied to mood regulation, with magnetic pulses. Accelerated TMS, which delivers several sessions a day and condenses a multi-week course into about one week, is the field’s frontier, the lineage of the Stanford-developed protocol that won FDA clearance. The unresolved problem has been where to aim. The conventional method uses scalp landmarks, cheap, fast, and requiring no imaging, but it frequently misses the intended cortical site and varies considerably from one patient to the next. The alternative uses an individual’s resting-state functional MRI to locate the prefrontal site most connected to a deeper mood-regulating region, which is personalized but requires a scan and specialized analysis. The whole debate over personalized TMS has turned on whether that extra cost buys better outcomes.
What the trial found
The trial randomized 40 patients with treatment-resistant depression, at a single Mass General Brigham center, to connectivity-based or scalp-based targeting for high-dose accelerated TMS. One month after treatment, the connectivity-based group showed significantly greater improvement on the standard depression rating scale and a higher response rate, 80 percent versus 60 percent, a large but imprecise effect (Cohen’s d analog 0.8, 95% CI 0.26 to 1.54). It is one of few randomized head-to-head comparisons of targeting methods, and a positive one. A larger UK trial, BRIGhTMIND, which randomized 255 patients at five centers to connectivity-guided theta burst stimulation or standard rTMS and so changed the stimulation protocol as well as the target, found no difference on its primary outcome in 2024. Notably, it is a head-to-head of two active targeting methods rather than a comparison against sham, which sidesteps the placebo and blinding problems that have plagued so much of the neuromodulation literature, and that makes the result cleaner than most.
Why it matters beyond the result
TMS is the most widely deployed neuromodulation modality in psychiatry, and accelerated protocols are scaling quickly, which makes the targeting method the fork in how the whole field grows. Scalp-based targeting is cheap, fast, needs no imaging, and can be delivered almost anywhere. Connectivity-based targeting requires an individual functional MRI and expert analysis, which is expensive, specialized, and concentrated at imaging-capable centers. By giving the precision approach its first strong efficacy evidence, this trial pushes the field, and eventually payers and clinical guidelines, toward expecting imaging. That raises per-patient cost, narrows where accelerated TMS can be delivered well, and advantages the commercial players built around precision protocols. The trade is better outcomes for higher cost and less accessibility, and this result moves the field toward paying it.
What the trial doesn’t settle
Several caveats are substantial. The senior authors hold intellectual property on connectivity-based TMS targeting and have commercial ties to companies advancing precision TMS. A trial that favors the method its own authors have a financial stake in warrants scrutiny, even though the authors state the specific intellectual property was not used in the study. Independent replication matters more than usual here. The mechanism is also unresolved. Related work from the same research group found that symptom improvement did not correlate with how much the targeted circuit’s connectivity actually changed. In other words, the personalized approach outperformed in this trial without a clear account of why, a loose end beneath the headline. And this is a single small trial, with durability still to be confirmed in follow-up and replication. The trial demonstrates an efficacy edge, not cost-effectiveness. That is the question payers will ultimately ask: whether the scan is worth it per outcome gained.
The cost of choosing precision
Accelerated TMS is the neuromodulation modality scaling fastest in depression, and this trial bears on the question that governs how it scales. Its answer favors personalization, pending a confirmatory trial. That means the field is heading toward imaging-guided precision, and the cost and concentration that come with it. Unlike the sham-response problem that has dogged vagus nerve and deep brain stimulation, this is a head-to-head comparison of two delivery methods, a sign that TMS sits further along the deployment curve than the rest of the neuromodulation category. The caveats are real: the author conflicts, the unexplained mechanism, and the single-trial status are all worth holding onto. But the direction is clear. The most direct randomized evidence on this question so far favors paying for precision. The result is a version of TMS that needs an MRI and an expert to deliver well, better medicine and less accessible medicine at once. That tradeoff, better outcomes reaching fewer patients, is what to track as accelerated TMS scales.