In a milestone for psychiatric research, a team at the University of Minnesota Medical School has secured a $4.4 million grant to conduct the first-in-the-world study of brain stimulation designed specifically to understand and treat severe forms of Bipolar disorder. The investigation is led by Ziad Nahas, M.D., a renowned expert in neuromodulation and mood disorders.
Why This Study Matters
Bipolar disorder affects millions of people worldwide and encompasses a spectrum of mood states—mania, hypomania, depression, and mixed episodes. Despite numerous pharmacological and psychotherapy options, a significant subset of individuals with severe or treatment-resistant bipolar disorder continue to struggle with debilitating symptoms, high relapse rates, and diminished quality of life. Traditional treatments often fall short because the underlying brain circuitry and individual variability are complex.
This new study shifts the paradigm by targeting the brain’s networks directly through electrical stimulation. The hope: to move beyond symptom management and toward modifying the underlying brain circuits involved in mood regulation, thereby offering new treatment avenues for severe and refractory cases. Research in brain stimulation for bipolar disorder has suggested promising potential. For example, one recent review noted that brain-stimulation treatments represent an important opportunity to address not just acute mood episodes but also cognitive dysfunction in euthymic (non-mood-episode) phases.
About the Research Team & Their Track Record
Dr. Nahas brings deep expertise in functional neuroimaging and neuromodulation across multiple modalities—including TMS (Transcranial Magnetic Stimulation), VNS (Vagus Nerve Stimulation), EpCS (Epidural Prefrontal Cortical Stimulation), DBS (Deep Brain Stimulation), and ECT/FEAST. The research will specifically test a novel type of brain stimulation — known as Personalized and Adaptive Cortico Electrostimulation (PACE) — shown to treat depressive symptoms. Other MnDRIVE Brain Conditions neuromodulation researchers and UMN team members involved in this study are Drs. David Darrow, Damien Fair, Tay Netoff, Ziad Nahas, and Alexander Opitz.
Under his leadership, previous studies at UMN have already explored targeted brain stimulation for treatment-resistant depression. In one such study, they implanted electrodes on the cortical surface in a procedure called Prefrontal Cortical Stimulation (PCS) and achieved remission in ~60% of participants at 7 months and again at 5 years.
The Grant and the Study Plan
With the new $4.4 M funding over the next three years, the team is poised to extend their neuromodulation work into the domain of severe bipolar disorder—marking the first study of its kind globally. While full protocol details are still emerging, we know the plan includes:
Using individualized brain‐imaging and functional mapping to identify key mood-regulation circuits in each participant.
Implanting electrodes or stimulation leads in targeted brain areas (likely cortical surface or near-surface targets) tailored to an individual’s brain map.
Adjusting stimulation settings on a personalized basis (so-called “brain-fingerprinting”) to optimize effect while monitoring safety.
Longitudinal follow-up to assess changes in mood states (mania, depression, mixed), cognitive functioning, quality of life, and possibly brain network connectivity and biomarkers.
Safety and ethical oversight, including comprehensive screening and monitoring of participants.
What Sets This Study Apart
Personalization – Rather than one-size-fits-all brain stimulation, this study will use each participant’s functional brain networks to guide electrode placement and stimulation parameters.
Severe Bipolar Focus – Many neuromodulation studies have focused on unipolar depression. This is one of the first to target severe bipolar disorder, which poses unique treatment challenges (e.g., mixed states, rapid cycling, comorbidities).
Circuit-Based Intervention – The goal is to intervene at the network level (brain circuits for mood regulation) rather than only targeting single neurotransmitter systems.
Longitudinal and Translational – The study aims to produce not only clinical outcomes but mechanistic insights (how brain networks change under stimulation) that may inform future therapies.
Potential Clinical and Societal Impact
If successful, the implications are profound:
For patients: A new avenue of treatment for those with severe and refractory bipolar disorder who have few options left.
For clinicians: Enhanced understanding of brain-circuit dysfunction in bipolar disorder and how to modulate it with precision.
For research: A blueprint for personalized neuromodulation in mood disorders; potential application to other illnesses (e.g., schizophrenia, PTSD, cognitive dysfunction).
For society: Reduction in disability, fewer hospitalizations, improved productivity and quality of life for individuals living with bipolar disorder.
What’s Next
The research team will begin recruiting eligible participants (likely adults with severe bipolar disorder who have not responded to multiple treatments) and proceed through screening, brain imaging, surgical electrode implantation, and personalized stimulation tuning. Concurrently, they will collect neuroimaging and EEG data to model network changes over time. Updates will follow as the study progresses and — in time — results may open doors to new neuromodulation protocols.
