New insights into brain stimulation therapy effectiveness

The treatment involves placing an electromagnetic coil against a patient’s head to deliver magnetic pulses which stimulate mood-regulating brain cells and has been used as an effective treatment option for depression in Australia and globally for two decades.

Unlike other treatments for depression, TMS has minimal side effects.

The treatment has been particularly helpful as an alternative therapy for depression in patients who experience adverse side effects from medication.

University of Melbourne researchers have previously showed that TMS for depression can be personalised by identifying synchrony in brain activity between the stimulation site at the front of the brain and a deeper region involved in mood regulation, because TMS can’t directly reach this deep region, the signal has to travel through connected brain areas.

New research, published in Nature Neuroscience, used computational models to delineate how TMS travels within a patient’s brain, revealing the nerve pathways that connect the front of the brain to the deeper mood region.

The work showed that TMS treatment works better when these connecting pathways are shorter and more direct, meaning the TMS signal has fewer steps to travel before reaching the depression-related region in the brain.

Dr Caio Seguin from the Department of Psychiatry said the research team replicated the findings across medical data from two groups of people with treatment-resistant depression.

“All patients received repetitive TMS treatment to the front of the brain, but the exact stimulation site varied between individuals,” he said.

“We then calculated how many steps along the pathways the TMS signal had to travel through for each patient to reach the deeper region linked to depression, known as the subgenual cingulate.

“We compared how much each patient's symptoms improved after treatment and the results showed patients who had a fewer number of steps for the signal to travel through to reach the depression-related brain region, experienced better treatment outcomes.”

Dr Seguin said the TMS signal is like a message passed along a chain, each relay introduces noise and attenuation, so the signal becomes weaker and less precise the further it travels.

Professor Andrew Zalesky said the study investigates the physical connections for the first time.

“Patients with a more direct pathway from the stimulated site to the deep target region are likely to respond better to the treatment. This gives hope of personalising the stimulation site to a target with the fewest possible steps to the target,” he said.

“We hope that, in the near future, we will be able to map a patient’s precise network of nerve fibres and find out exactly where to stimulate to maximise the activation of their anti-depressant circuit”.

Associate Professor Robin Cash from the Departments of Biomedical Engineering and Psychiatry said that this work forms part of their ongoing research efforts to improve therapeutic TMS outcomes in depression. “Continued research will enable these findings to be translated to patient care”.

The research team are currently running a multisite clinical trial (Melbourne, Sydney, Brisbane) of TMS for depression investigating the benefits of personalising the stimulation target to best align with circuits involved in depression, based on their recent research.

Interested individuals are encouraged to get in touch here.

The research team gratefully acknowledges funding from the NHMRC and ARC.