Sarina Iwabuchi

Sarina Iwabuchi photo

Project Title: 

Investigating the physiology of targeted neuromodulation in major depressive disorder

Host Organisation: 

University of Nottingham, Centre for Translational Neuroimaging in Mental Health

Short biography

I carried out my CASCADE-FELLOWS fellowship at the Centre for Neuroimaging in Mental Health, University of Nottingham, under the supervision of Dr Lena Palaniyappan, investigating the physiological effects of Transcranial Magnetic Stimulation (TMS) on the human brain using a range of neuroimaging techniques. I was also involved in a clinical trial with the hope of developing more effective treatments using TMS for patients with affective disorders.

Prior to becoming a CASCADE-FELLOWS fellow, I completed my undergraduate training at the University of Canterbury in 2006, followed by a BSc (Hons) and MSc from the University of Auckland in 2007 and 2008 respectively. I then completed my doctoral studies in the School of Psychology in 2013, supervised by Professor Ian Kirk and Associate Professors Karen Waldie and Lynette Tippett, focusing on investigating the complex relationship between the structure and function of the human brain using a variety of neuroimaging methods.

I completed my CASCADE-FELLOWS fellowship in July 2016 and am now working on further imaging research work in a clinical setting at the University of Nottingham.

Brief description of research project

The disruption of brain networks in patients with depression is now well-documented, however the vast majority of current standard treatments are generally non-specific and ineffective, highlighting a great need for interventions focussing on directly modulating these brain networks. A new drug-free, innovative treatment is now available called transcranial magnetic stimulation (TMS) which works by sending magnetic pulses into the brain to correct the imbalance of chemicals in the brain, and reorganise the communication between specific brain regions, though the underlying mechanisms are not well understood.

Using functional MRI and MRI-guided neuronavigation techniques to pinpoint specific individualised networks, we investigated the direct effects of TMS on brain circuitry and chemistry in healthy individuals. This approach has revealed changes in communication between important brain regions including the interaction between the frontal and limbic systems, as well as alterations in brain chemistry such as GABA. For the first time, we have an understanding of the direct effects TMS has on the brain. Knowing these changes means treatment can be smarter as it can be better tailored to each patient’s brain.

Our second phase of the study extended the first, by running a patient trial to understand the effects of TMS treatment and how this might relate to clinical efficacy. Preliminary results of the trial indicate promise for treating treatment-resistant depression with rTMS. There was a significant reduction in depression scores at both 1 month and 3 month follow up, with over two thirds of patients showing clinical response by the end of 3 months. We also found that depression severity is associated with the strength to which the frontal and limbic systems are connected, with similar pattern also emerging for levels of GABA in the frontal cortex. We have also found that the strength of connectivity of the fronto-limbic circuitry (used for identifying each patient’s TMS target) before treatment, is predictive of the treatment efficacy, 3 months following treatment. Our results thus far offer great promise for the potential applications of TMS in the treatment of difficult to treat depression and demonstrate that with further optimisation of treatment parameters will improve response rates. Furthermore, there is preliminary evidence that individual patterns of brain connectivity may predict the degree to which patients respond to treatment. This will be vital for the identification of individuals who are most likely to respond to rTMS and ultimately reduce the burden associated with ineffective treatments.

We have demonstrated that it is possible to modulate deep brain structures using TMS by identifying specific circuitry. With further optimisation, TMS may be a useful and effective alternative for not only patients with depression, but also benefit other diseases that may respond to neuromodulation approaches (e.g. tinnitus, Parkinson’s disease and stroke rehabilitation.)