Prefrontal cortical pathways mediating cognitive control enhancement from internal capsule stimulation.

Area of Science:

• Neuroscience
• Neurosurgery
• Psychiatry

Background:

• Deep brain stimulation (DBS) of the ventral internal capsule/ventral striatum (VCVS) treats psychiatric disorders.
• Patient response to VCVS DBS varies due to incomplete understanding of underlying brain mechanisms.
• VCVS DBS can enhance cognitive control, a key deficit in many psychiatric conditions.

Purpose of the Study:

• To identify specific prefrontal cortical pathways within the internal capsule associated with improved cognitive control during VCVS DBS.
• To elucidate the neural circuitry mediating cognitive control enhancement via VCVS DBS.

Main Methods:

• Four participants with VCVS DBS underwent the Multi-Source Interference Task (MSIT) across 27 stimulation settings.
• Task performance was measured by response time (RT).
• Personalized pathway activation models analyzed axonal recruitment in prefrontal cortical fiber bundles to correlate with RT.

Main Results:

• Right-sided VCVS stimulation yielded greater cognitive control improvements (faster MSIT RTs) compared to left-sided stimulation.
• Activation of right dorsal prefrontal pathways, linked to the dorsolateral prefrontal cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC), strongly predicted faster RTs.
• No left-sided pathways were found to be associated with performance improvements.

Conclusions:

• VCVS DBS effects on cognitive control are primarily mediated by right dorsal prefrontal cortical axons projecting from the dlPFC and dmPFC.
• Targeting these specific pathways could optimize VCVS DBS strategies for psychiatric disorders with impaired cognitive control.