Rewiring Hope: A Custom-Fit Approach to Depression
By Luis F. Rivera-Chavez
When you break a bone, it’s easy to point to the problem and where to fix it. With a brain tumor, you need an image of the brain to locate it. Some tumors are harder to remove than others, but it is possible to see exactly where the trouble is. Depression, however, is different. It isn’t caused by something you can see on a scan. Instead, it comes from faulty connections that are spread diffusely throughout the brain. According to a recent study, custom-fit brain stimulation, through a technique known as transcranial direct current stimulation (tDCS) might give doctors a new tool to fine-tune the brain’s wiring.
Depression is a serious illness that affects around 332 million people in the world. There are effective treatments available, such as psychotherapy and different anti-depressant medications. Unfortunately, at least 30% of people suffering from depression might not respond to standard interventions. Besides, drugs are not specific to the brain networks that have been found to be involved in this condition and therefore can produce some side effects. That is why research on novel treatments for depression is very much needed.
Years of brain imaging studies have shown that depression isn’t tied to a single spot in the brain, but to disrupted patterns in how different brain areas communicate with each other, what neuroscientists call networks. In particular, researchers have linked depressive symptoms to problems in the “frontoparietal” and “salience” networks, which normally help regulate emotions and filter important information. In recent years, tDCS has emerged as a safe & non-invasive way to influence these networks with potential applications for treating depression, among other conditions. This technique delivers a weak electrical current through electrodes placed on the scalp. Rather than making neurons fire directly, the current changes how easily brain cells become active and consequently can modulate those networks that are dysfunctional. In depression, the usual target is a region called the dorsolateral prefrontal cortex (DLPFC), a key hub in the frontoparietal network. However, targeting this region has had mixed results so far. An issue that potentially impacts efficacy is that the applied current has been shown to affect other brain areas beyond the intended target. The reasonable solution is to try to be more specific, hence the recently developed high definition (HD) tDCS. This exciting new technique uses the patient’s own brain scan to adjust the stimulation settings, allowing the current to be delivered more precisely to a specific region, like the DLPFC. In other words, it’s a more personalized, custom-fit version of tDCS.
Example of tDCS setup. Adapted from: Yokoi, Y., Sumiyoshi, T. Application of transcranial direct current stimulation to psychiatric disorders: trends and perspectives. Neuropsychiatr Electrophysiol 1, 10 (2015).
A clinical trial led by Jog and colleagues, recently published in Jama Network Open, tested whether HD tDCS could improve symptoms of depression. They recruited people with moderate to severe depression and randomly assigned them to two groups: one received active HD-tDCS therapy, while the other underwent a “sham” session. The sham procedure was designed to mimic the sensation of real tDCS without actually delivering the standard current. As with other clinical trials, comparing an active treatment to a sham or placebo group helps reveal the true effect of the therapy. The procedure was ‘double-blind’, meaning neither participants nor the researchers who assessed them knew which treatment was being given. Both groups received sessions of tDCS therapy (active or sham) for 12 consecutive workdays.
What made this trial different was the personalized setup. Each participant had an MRI scan during their initial visit, which researchers used to pinpoint the exact location of the DLPFC. Using a neuronavigation system, they then mapped this spot onto the scalp and marked it on custom-fitted caps. These caps allowed the electrodes to be placed in exactly the right position for all subsequent HD-tDCS sessions, ensuring that the stimulation targeted the intended brain region as precisely as possible.
Results were encouraging. Among the 49 people who received the active treatment compared to the 31 in the sham group, those in the active group showed fewer depressive symptoms both midway and at the end of the study. They were also more likely to achieve remission. In fact, 16 of the 17 depression-related symptoms that were measured showed significant improvement — including sadness, guilt, insomnia, loss of interest in activities, difficulty concentrating, and even suicidality. As an exploratory analysis, researchers also found that HD t-DCS improved anxiety symptoms, such as excessive worry and physical complaints like cramps, indigestion, palpitations and headaches.
The plot shows how depressive symptoms changed throughout the time of the study, with additional measurements at 2 and 4 weeks after treatment was complete. Depressive symptoms were measured by a scale called Hamilton Depression Rating Scale. Adapted from: Jog MA, Norris V, Pfeiffer P, et al. Personalized High-Definition Transcranial Direct Current Stimulation for the Treatment of Depression: A Randomized Clinical Trial. JAMA Netw Open. 2025;8(9):e2531189.
It is important to note that most participants were also taking antidepressant medication, and the trial was not designed to compare tDCS directly with drug therapy. Even so, these findings are promising and suggest that tDCS could become a valuable addition to the range of available treatments, one that can be adjusted to each person’s brain. Since depression affects people differently, having options matters.
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