Fast Depressive Symptom Improvement in Bipolar Disorder Type 1 after Stanford Accelerated Intelligent Neuromodulation Therapy: A Two-Site Feasibility and Safety Open Label Trial

Background: Brain oscillations, which reflect the organized activity of neuronal assemblies, play a crucial role in brain function and are altered in conditions such as depression, schizophrenia, and stroke.While transcranial electric currents have shown therapeutic potential in modulating these oscillations, the direct effects on brain dynamics during stimulation remain elusive due to the inability to record oscillatory changes concurrently.Moreover, inability to assess brain oscillations during stimulation renders closed-loop paradigms unfeasible.Here, we introduce a promising approach to overcome this limitation and highlight the possibility of influencing brain activity and behavior beyond the motor system.Objectives/Hypothesis: In a series of experiments involving healthy volunteers, we used closed-loop amplitude-modulated transcranial alternating current stimulation (CLAM-tACS) to modulate brain oscillations in motor regions and beyond.Specifically, we investigated whether phaselocked, state-dependent stimulation can enhance or suppress oscillatory activity and related brain functions across different paradigms.Methods: In a series of studies, we employed CLAM-tACS that combines artifact attenuation with real-time phase-tracking and stimulation of brain rhythms.Oscillations across different frequency bands, such as theta, frontoparietal alpha or central mu, were targeted.Results: Across multiple experiments, phase-dependent enhancement and suppression of oscillations were observed.We found consistent effects on behavioral outcome measures that correlated with specific stimulation phase angles.Conclusions: Our findings suggest that CLAM-tACS can be effectively applied beyond the motor system to modulate brain function and behavior.However, limitations of the approach have to be further explored and application in clinical populations tested.