Depression is the most well-established indication for non-invasive brain stimulation as therapy. Yet the mechanisms of stimulation treatment action remain to be understood. During therapy, cognition is not measured, controlled or manipulated. We believe this is a missed opportunity. Cognitive tasks measure brain function - information processing. Dysfunctional information processing causally underpins symptoms. Therefore, to understand how stimulation treats symptoms, we need to understand how stimulation changes information processing and how this impacts symptoms.

Affective biases are ubiquitous in depression: when depressed, people prioritize negative over positive information, a bias believed to maintain symptoms. Using cognitive tasks to measure affective biases, we have conducted proof-of-concept experimental medicine studies to test whether TMS and TES work by reducing these biases.

We present data from a theta burst TMS treatment trial testing this mechanistic hypothesis. We present data from an ongoing study testing if a novel form of monophasic theta burst TMS has a stronger functional impact on affective bias, working memory and fronto-vagal pathway entrainment in low mood than conventional biphasic theta burst TMS. Finally, we present a series of TES experiments which show that TES has a significantly greater functional impact on cognitive dysfunction in low mood when applied during a reward learning task than when applied during rest, indicating a potential future strategy to enhance therapeutic efficacy.

Overall, our research aims to understand how stimulation works, who it works for, and how to make it work better.