Optimizing and Individualizing Neuromodulatory Treatments: Mapping and Targeting Suicide Circuits in the Brain

Their goal is to refine our understanding of the neural circuitry associated with treatment response, ultimately leading to more targeted and effective neuromodulatory techniques. Neurostimulation, using techniques such as transcranial magnetic stimulation (TMS), serves a dual purpose: as a treatment and as a tool for understanding brain function. When applied to specific brain regions, these techniques activate neural circuits. By combining neurostimulation with imaging tools like MRI or PET, researchers can visualize the activated pathways and correlate them with treatment outcomes.

While ECT is effective, it affects multiple brain regions simultaneously. In contrast, TMS offers more precise targeting, potentially optimizing treatment efficacy while reducing side effects.

Identifying Pathways Associated with Suicidality

In a recent exploratory study, Camprodon and colleagues investigated biomarkers of antisuicidal response. The study involved 16 patients with moderate to severe suicide risk, who underwent resting-state functional MRI (rsfMRI) before and after treatment. Depression severity and suicide risk were assessed using the QUIDS-SR and Concise Health Risk Tracking Self-Report (CHRT-SR) questionnaires, respectively.

Participants received MRI-guided accelerated intermittent theta-burst stimulation (iTBS), an FDA-approved noninvasive TMS variant for treatment-resistant depression. The protocol consisted of 10 daily iTBS sessions delivered to the right inferior parietal lobule (IPL) cluster of the Executive Control Network (ECN).

Circuits Associated with iTBS Response

To examine the relationship between brain functional connectivity and clinical outcomes, the team conducted whole-brain regressions using changes in suicidal risk (measured using the CHRT) and depressive symptom severity (QUIDS).

Key findings include:

• • Three patients showed a 27% reduction in suicide risk after a single day of MRI-guided accelerated iTBS
  • Connectivity between the anterior cingulate cortex (ACC) and two right IPL clusters predicted and explained iTBS’s antisuicidal effects
  • The predictor biomarker cluster was located within the dorsal attention network, while the response biomarker cluster was within the ECN
  • iTBS increased functional connectivity between the ECN-IPL target and the ACC, the response biomarker

This exploratory study has identified circuit predictor and response biomarkers of antisuicide response. Predictor biomarkers help identify patients likely to respond to treatment, while response biomarkers indicate treatment effectiveness.

Next Steps

Dr. Camprodon’s team plans to continue this research, mapping suicide circuits in patients with various psychiatric disorders, including major depressive disorder and borderline personality disorder. This approach acknowledges that suicidal ideation can occur with or without depressive symptoms, depending on the underlying condition.

By visualizing neural circuits associated with suicidal ideation across different disorders, researchers aim to develop more individualized and optimized treatments. This ongoing research represents a significant step toward understanding the complex neurobiology of suicide risk and improving targeted interventions for those at risk.

For more information on this research study and how to participate, visit the Mass General Brigham Rally website HERE.