Antidepressant treatments are theorised to act by inducing a positive bias in information processing early on during treatment. Here, we tested for the first time whether this theory generalises to transcranial magnetic stimulation (TMS) treatment, an effective therapy for treatment-resistant depression. 49 patients with major depression received 20 sessions of open-label intermittent theta-burst stimulation applied to left dorsolateral prefrontal cortex. At baseline and after eight stimulation sessions, positive bias was assessed using behavioural and functional magnetic resonance imaging tasks presenting emotional faces. Clinical improvement at the end of treatment was related to an early increase in positive bias (1) in misclassification of emotional faces, (2) in the response of the default mode network (DMN) to emotional faces including rostral anterior cingulate cortex (ACC), and (3) in connectivity between rostral ACC and DMN. These neural changes predicted clinical improvement at the end of treatment beyond early symptom reduction. The results suggest that TMS treatment increases positive bias early on during treatment, and that the neural mechanisms might differ from that of antidepressant drugs.

The authors have declared no competing interest.

NCT04969549

https://osf.io/rhxm2

This research was funded by a Newton International Advanced Fellowship (NAFR12/1010). JOS is a Sir Henry Dale Fellow funded by theRoyal Society and the Wellcome Trust (215451/Z/19/Z). The Wellcome Centre for Integrative Neuroimaging is supported by core funding from the Wellcome Trust (203139/Z/16/Z and 203139/A/16/Z). This project was supported by the NIHR Oxford Health Biomedical Research Centre (NIHR203316). The views expressed arethose of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

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