A cognitive neural circuit biotype of depression showing functional and behavioral improvement after TMS in the B-SMART-trial

A cognitive biotype of depression characterized by treatment resistance, impaired cognitive control behavioral performance and dysfunction in the cognitive control circuit, comprising the dorsolateral prefrontal cortex (dLPFC) and dorsal anterior cingulate cortex (dACC), has previously been identified.

Therapeutic transcranial magnetic stimulation (TMS) to the left dLPFC is a promising option for individuals whose depression does not respond to pharmacotherapy.

Here, 43 veterans with treatment-resistant depression were assessed before TMS, after early TMS and post-TMS using functional magnetic resonance imaging during a Go–NoGo paradigm, behavioral cognitive control tests and symptom questionnaires.

Veterans were stratified at baseline based on task-evoked dLPFC–dACC connectivity, and it was demonstrated that TMS-related improvement in cognitive control circuit connectivity and behavioral performance is specific to individuals with reduced connectivity at baseline (cognitive biotype +), whereas individuals with intact connectivity at baseline (cognitive biotype ?) did not demonstrate significant changes.

These findings show that dLPFC–dACC connectivity during cognitive control is both a promising diagnostic biomarker for a cognitive biotype of depression and a response biomarker for cognitive improvement after TMS applied to the dLPFC.

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Read the full publication here.

Tozzi, L., Bertrand, C., Hack, L.M. et al. A cognitive neural circuit biotype of depression showing functional and behavioral improvement after transcranial magnetic stimulation in the B-SMART-fMRI trial. Nat. Mental Health 2, 987–998 (2024).

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