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Anterior default mode brain state dynamics predict depressive symptom severity before and during TMS treatment

Forster, C.; Gohil, C.; Burgher, B.; Kuzovkin, I.; van Es, M. W. J.; Woolrich, M. W.; Vidaurre, D.; van den Heuvel, M.; Higgins, C.; Cocchi, L.

2026-06-01 neuroscience
10.64898/2026.05.27.728312 bioRxiv
Show abstract

Transcranial magnetic stimulation (TMS) targeting the left dorsolateral prefrontal cortex is known to progressively reduce symptoms of depression. However, the neural mechanisms supporting this effect are poorly understood. To address this gap, we analysed longitudinal EEG recordings from 70 people undergoing TMS therapy and fitted an established dynamic network model of resting-state activity. Greater baseline symptom severity was associated with reduced occupancy of and fewer transitions into an anterior default mode brain state, alongside increased activity in a posterior default mode state. During treatment, decreases in anterior default mode state engagement following TMS predicted symptom improvement in the latter half of the intervention. Brain state activity exhibited structured, cyclical dynamics, with slower cycles linked to greater baseline severity. These findings suggest that symptoms of depression are characterised by gradual alterations in brain state dynamics, highlighting a central and dissociable role of default mode brain states in the persistence and remission of symptoms.

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