Expedition for new symptom-specific TMS targets: Protocol for the first randomized causal circuit mapping trial

Area of Science:

• Neuroscience
• Psychiatry
• Brain Stimulation

Background:

• Functional neuroimaging identifies brain function correlates, not causes.
• Transcranial magnetic stimulation (TMS) enables causal brain mapping by randomizing targets.
• This approach controls for confounders and compares clinical outcomes across targeted circuits.

Purpose of the Study:

• To build a multidimensional atlas of causally involved brain circuits.
• To identify TMS targets for transdiagnostic constructs and specific psychopathology symptoms.
• To define optimal TMS target circuits across various psychiatric diagnoses.

Main Methods:

• 90 participants with depression, OCD, GAD, or schizophrenia received accelerated intermittent theta burst stimulation (aiTBS).
• aiTBS was applied to random left prefrontal cortex targets in two phases, with deep circuit-based phenotyping.
• Schizophrenia patients received an open-label extension targeting the rostromedial prefrontal cortex (rmPFC).

Main Results:

• (Study is ongoing, results not yet available)

Conclusions:

• To map circuitry connected to TMS sites that causally modify behaviors.
• To complement lesion and stimulation studies for defining optimal TMS targets.
• To advance understanding of brain circuit engagement in transdiagnostic and diagnosis-specific behaviors.