Targeted Brain Stimulation to Quiet Mania: A Reward-Circuit Approach to Treating Bipolar Disorder
This invention is a noninvasive brain stimulation method that applies continuous theta burst stimulation (cTBS) to specific reward-network brain regions — the ventrolateral prefrontal cortex (vlPFC) and/or dorsal anterior cingulate cortex (dACC) — to reduce manic/hypomanic symptoms in individuals with bipolar disorder. Because it targets the underlying neural circuitry driving mania rather than broadly acting on brain chemistry, it offers a potential pathway to symptom relief with fewer side effects than current pharmacological treatments.
Description
The method works by first locating a predetermined neural target in the individual's brain — the vlPFC or dACC — regions in the brain's reward network that show abnormally elevated activity during "reward expectancy" (the anticipation of a future reward) in people with bipolar disorder and in those at elevated risk of mania. This target can be identified by measuring brain activity associated with elevated reward expectation, allowing the stimulation site to be individualized to each patient rather than applied at a fixed, generic location. Once the target is located, continuous theta burst stimulation — a noninvasive form of transcranial magnetic stimulation delivered in patterned bursts — is applied to dampen (inhibit) activity in that region. In disclosed embodiments, stimulation is delivered in blocks of pulses, optionally starting at a lower intensity and ramping to a higher intensity over a determined period. More broadly, the invention also encompasses applying noninvasive inhibitory stimulation generally (not limited to cTBS) to these same reward-network targets. By reducing overactivity in the specific circuitry linked to reward hypersensitivity, impulsivity, and goal-driven arousal, the approach is designed to directly counteract core neural drivers of mania/hypomania rather than treating symptoms indirectly.Applications
- Adjunct or alternative treatment for mania/hypomania in patients with Bipolar I Disorder- Neuromodulation-based therapy for individuals at elevated risk of developing bipolar disorder, prior to full onset
- Integration into existing TMS/TBS clinical treatment platforms and neuromodulation device offerings
- Companion diagnostic/targeting tool using reward-expectancy brain activity to individualize neurostimulation therapy
- Treatment option for patients who cannot tolerate or do not respond well to pharmacological mania treatments
Advantages
- Noninvasive method for treating mania, avoiding the risks associated with invasive procedures- Individualized targeting based on each patient's own reward-expectancy brain activity, rather than a one-size-fits-all stimulation site
- Uses inhibitory stimulation to directly reduce overactive reward-circuit signaling implicated in mania, rather than broadly acting pharmacology
- Flexible stimulation protocol, including a ramp-up (lower-intensity) block followed by a full-intensity block, which may improve tolerability
- Potential for fewer side effects than current mania medications, based on the noninvasive nature of the stimulation