Developing Brain Imaging Analysis Expertise for Predicting Treatment Response to Brain Stimulation in Geriatric Depression

Depressive disorders are among the leading causes of incapacity and disability worldwide.

The burden of geriatric depression is expected to increase due to population ageing and its negative impact on clinical conditions and physical and cognitive abilities.

Given the limited efficacy of antidepressant drugs, novel treatments such as theta-burst brain stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), are being developed.

However, to further advance the field towards treatment personalisation, increasing understanding of TBS antidepressant mechanisms and identifying treatment responders are important issues.

Although neuroimaging assessments have been used to address these questions in TMS trials in adult depression, no studies have used neuroimaging in TBS trials in geriatric depression yet. Our group in Brazil is a leading brain stimulation centre, although neuroimaging expertise is lacking.

Recently, we have successfully applied for a NARSAD grant to perform a randomized sham-controlled, clinical trial evaluating the safety and efficacy of TBS in 108 patients with geriatric depression.

Therefore, the aim of this project is to leverage this ongoing trial to build capacity in neuroimaging analyses by performing magnetic resonance imaging (MRI) assessments at baseline and after 7-10 days of treatment onset in 80 patients.

The scientific goal is to test a hypothesis about treatment action: that TBS will reduce negative bias (which causally maintains negative mood) after 1 week of treatment, and patients who show this neurocognitive change will be the ones who go on to respond clinically after 6 weeks.

In terms of capacity building, the award of the Newton Fellowship would firmly establish and strengthen our new collaborative partnership with the UK co-applicant and the Wellcome Centre for Integrative Neuroimaging (WIN) at the University of Oxford.

The UK co-applicant, Oxford Psychiatry, and the WIN Centre, respectively, are internationally renowned for their work using multimodal neuroimaging to understand mechanisms of action of brain stimulation, of antidepressants, and to predict individual response to these interventions.

The budget of this fellowship would allow not only brain imaging data to be acquired, but would also enable two 3-month visits of a Brazilian researcher to WIN, where he/she would be trained in state-of-the-art neuroimaging analyses that can then be applied in present and future brain stimulation trials by our group in Brazil.

Scientifically, this proposal and its outcomes will help advance towards next-generation precision brain stimulation, by incorporating cognitive/neuroimaging readouts that inform about mechanism and individual response.