Repetitive transcranial magnetic stimulation (rTMS) has become a successful and widely accepted treatment for depression. Traditionally, choosing the most suitable site to place the magnetic coil on the patient’s head has relied on some relative guesswork between two main areas involved in treatment. This may soon change.
As part of neurocare academy’s interview series, Dr Trevor Brown connects with leading researchers worldwide to learn more about the current state of research and the future of digital therapeutics. In this episode, Trevor speaks with leading rTMS scientist Dr. Martijn Arns. Research by Arns and his team has successfully established a strong connection between heart and brain to allow clinicians to apply rTMS more effectively.
Their results were presented during the 4th International Brain Stimulation Conference late last year, bringing rTMS practitioners one step closer to precision psychiatry
Clinicians have been using rTMS successfully for some time in patients suffering from treatment resistant depression. The treatment has been found to be highly effective, especially when combined with psychotherapy. Patients who have not responded well to antidepressant medications, or are struggling with their side effects, have reported long-lasting relief from depressive symptoms following rTMS.
Clinicians who offer rTMS sessions have had one challenge in particular: finding the best possible stimulation site. This is the location on the patient’s head where the magnetic coils are placed for the treatment. Currently, doctors choose one of two sites. Both have shown similar results in terms of effectiveness on a group level.
Dr Brown and Dr Arns discuss how there are marked differences between individual treatment responses. Knowing exactly where to target right from the start would be like being able to turn the light on in a dark room for doctors and their patients.
Finding an optimal treatment for depression
Being able to offer the most efficient treatment without guesswork not only makes the clinician’s work easier, it can also be life-changing for patients who find relief from their symptoms sooner than they would otherwise.
The optimal treatment location may differ between individuals. It may depend on differences in neural networks and the patient’s brain anatomy. Being able to choose the most promising location directly is the key to improved treatment and outcomes.
Arns and his colleagues were looking for the specific prefrontal area that would be most effective in generating a response to antidepressant treatment. Whilst this would be possible with the help of MRI technology, this is prohibitively expensive for individual treatment. As a result, the team started looking for other biomarkers that could be measured more cost-effectively.
Choosing the right biomarker
Having tried different approaches, including electroencephalograms (EEGs), it was a study from 1964 that put the scientists on the right track. What they found was a connection between the patient’s heart rate and the area of stimulation. The team could see clearly whether they were aiming the magnetic coils at the right network of a person’s brain if it related to heart rate deceleration. They had found their biomarker.
Arns and his team summarized and published the initial results of their neuro-cardiac-guided TMS (NCG-TMS) research in a paper establishing their NCG-TMS 1.0 methodology. The scientists had discovered that a patient’s heart rate decelerates when the clinician chooses the correct target, which connects to deeper brain regions, which then impacts the heart rate.
Put simply, they monitored the heart rate with the help of an electrocardiogram (ECG) and monitored the changes relative to the site used for TMS.
Having discovered the connection they were looking for, Arns and his team then replicated their results to ensure what they had found was not a coincidence. They extended their research to add two more biomarkers. The team showed that blood pressure dropped significantly when the right area was stimulated whilst heart rate variability increased.
Arns concluded this technique can help distinguish between two groups patients. Having identified where to apply rTMS, this could help doctors and patients improve their outcomes to treatment.
This technique helps personalise where we are targeting and can establish a frontal excitability threshold. We’ll be testing this in a prospective study including neurocare clinics, if this NCG TMS 2.0 stratified rTMS approach improves clinical outcomes of rTMS treatment
Dr. Martijn Arns, Research Director, Brainclinics Foundation
Taking the research further
Having established the connection between heart and brain, the team took their research further. They were able to prove the causation between brain stimulation and responses of the parasympathetic nervous system. Their data proves how much rTMS applied in the right place influences a subject’s heart rate. This is how causal heart-brain coupling was established and how the NCG-TMS 2.0 methodology was born.
Because the scientists now had several biomarkers to measure, they were able to correlate their responses. This helped distinguish between specific and non-specific side effects and proved that their methodology worked.
Dr. Martijn Arns’ research has opened up the question of whether it is possible to measure how rTMS pulses access depression networks within the brain of a patient via a simple cardiac device. This would make it easier for clinicians to use in a variety of circumstances.
Linking the cardiac device used to measure biomarkers to an app makes the process easy for clinicians. The app – HeartBrainConnect – is now available to clinicians and patients. Patients can follow their treatment and receive personalized biofeedback. The goal is to allow them to prevent recurring problems and relapse.
About the series
neurocare brings the world of neuroscience into clinical practice. We educate professionals worldwide in the correct use of TMS, tDCS, Neurofeedback and other emerging techniques, and share the latest knowledge and updates as well as the history of these digital therapeutics. Neuroscientist Dr Trevor Brown, who features on neurocare’s Learning Management System, an online training platform, connects with leading researchers each month as part of a new interview series to discuss present and future clinical applications of neurostimulation techniques (e.g. TMS, tDCS) as well as exploring the use of EEG and Neurofeedback in clinical and research settings.