Scientists discover a neural signature that predicts how depressed patients will respond to brain stimulation

A team of scientists have discovered a biomarker that could help predict whether brain stimulation will increase the effectiveness of therapy for those suffering from depression. Their findings have been published in the journal Neuropsychopharmacology.

“Cognitive behavioural therapy (CBT) is the most effective psychological therapy for depression, but it still only works in 50-60% of cases. We wanted to see if a non-invasive way of increasing activity in the prefrontal cortex, transcranial direct current stimulation (tDCS), improves the effectiveness of an eight-week course of CBT for depression,” explained Camilla Nord, an investigator scientist in the MRC Cognition and Brain Sciences Unit at the University of Cambridge.

“A number of previous studies had shown that tDCS improves performance on difficult cognitive tasks, such as attention and cognitive control – both of which are key components of CBT. So, we ran a double-blind randomised controlled trial, a powerful way to test if a treatment is more effective than placebo, which in our case was a ‘sham’ stimulation that was indistinguishable from tDCS for both the patients and the scientists running the sessions.”

“Crucially, we also measured brain activity using functional magnetic resonance imaging (fMRI) before and after the trial, to see if we could predict, based on brain activity, which patients would respond to the combined treatment,” said Nord, who is the corresponding author of the study.

The study of 39 unmedicated patients with major depressive disorder failed to provide clear evidence that tDCS enhanced the therapeutic effect of CBT on average. Instead, the researchers found that tDCS was associated with a wide range of responses.

“We found mixed effects of the combined treatment on depression, indicating it is not appropriate for all patients. This is important as this type of brain stimulation has become very popular, both in research and in commercial applications,” Nord explained to PsyPost.

However, the researchers also found that greater activation in a particular brain region prior to treatment was associated with positive responses to tDCS. They were able to predict clinical response with 86% accuracy using this measure.

“We discovered a ‘biomarker’ — a brain signature that predicted which patients’ mood would improve from the treatment. Specifically, we could strongly predict which patients would respond to tDCS based on the activation in the brain region targeted by tDCS (the dorsolateral prefrontal cortex), which we measured in the fMRI scan conducted before patients began the trial. In future, this measure could be used to select patients for larger trials and, potentially, in clinics using tDCS to treat depression,” Nord said.

The study — like all research — includes some caveats.

“Our study was the first to combine brain stimulation with CBT, and therefore needs to be replicated by another, larger study (or more) before we can be certain of any of its results. A future question to test is whether certain aspects of the brain stimulation (such as frequency or dose) could be adjusted on an individual basis, which could potentially increase the number of people who find it effective,” Nord said.

“More and more, research is showing that there is no one-size-fits-all treatment for mental health disorders. We show that this particular brain stimulation treatment may not be right for everyone, and we uncover one possible reason why – differences in activity in the brain region being stimulated. Particularly when it comes to popular experimental treatments like tDCS, it is essential to understand why some patients respond, and some do not, before using the treatment on a large scale.”

The study, “Neural predictors of treatment response to brain stimulation and psychological therapy in depression: a double-blind randomized controlled trial“, was authored by Camilla L. Nord, D. Chamith Halahakoon, Tarun Limbachya, Caroline Charpentier, Níall Lally, Vincent Walsh, Judy Leibowitz, Stephen Pilling, and Jonathan P. Roiser.