The future of brain circuit-targeted therapeutics

Area of Science:

• Neuroscience
• Neuromodulation
• Brain Circuit Therapeutics

Background:

• Brain stimulation techniques like transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and focused ultrasound (FUS) are increasingly used for neuropsychiatric disorders.
• Effective treatment relies on precise targeting of specific brain circuits.
• Current methods for target identification and modulation require a structured framework.

Purpose of the Study:

• To propose a comprehensive three-phase framework for identifying and modulating brain circuit targets for neuromodulation therapies.
• To guide the selection of appropriate stimulation targets and modalities for treating neuropsychiatric conditions.

Main Methods:

• Phase 1: Target identification using correlative neuroimaging, retrospective optimization, and lesion localization.
• Phase 2: Target optimization via personalized neuroimaging, physiological monitoring, and state engagement (pharmacological/psychological).
• Phase 3: Modality selection considering the advantages and tradeoffs of different brain stimulation techniques.

Main Results:

• The proposed framework integrates multiple approaches for target identification and optimization.
• It provides a systematic method for choosing the most suitable stimulation modality or combination.
• Preliminary literature supports various components of the framework, indicating its potential clinical utility.

Conclusions:

• The framework offers a structured approach to advancing brain circuit therapeutics.
• Further research is needed to address unanswered questions and refine the framework.
• This work presents opportunities for future growth in research and clinical applications of neuromodulation.