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Causal Lesion Network Guided Treatment of Bipolar Mania With Transcranial Electrical Stimulation

Mania is a core symptom of bipolar disorder involving periods of euphoria, delusions, and overactivity. Mania occurs in multiple medical and psychiatric illnesses and can be refractory to existing treatments. Two recent studies using brain lesion mapping of psychiatrically healthy individuals presenting with mania identified causal locations in the brain, including the orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), and inferior temporal gyrus (ITG), that were associated with new onset mania symptoms. Moreover, these identified brain regions have also been implicated in bipolar mania with specific disruption in network communication between the amygdala and ventro-lateral prefrontal cortex. The OFC is of particular interest because it is a brain structure that is associated with inhibitory control, risk-taking behavior and reward, which are major behavioral components of mania. Thus, the association between OFC with mania symptoms, inhibitory control, risk-taking behavior and reward suggests that this region could be targeted using noninvasive brain stimulation. While several studies have non-invasively targeted the DLPFC for mania, no study to date has non-invasively stimulated the OFC with either transcranial direct current stimulation (tDCS) or alternating current (tACS) in bipolar disorder and examined its effects on mania, inhibitory control, or risk-taking behavior. However, a study in healthy volunteers showed that cathodal stimulation to the OFC enhanced inhibitory control and decreased risk-taking behavior. Recently, researches have showed that targeting the OFC with tACS, personalized to the individual's intrinsic beta-gamma frequency of the reward network, that individuals showed rapid, reversible, frequency-specific modulation of reward-guided choice behavior and learning. Here we aim to answer the question of whether noninvasive brain stimulation when optimally targeted and personalized to an individual's beta-gamma frequency to the OFC can improve emotional cognitive processing and mania symptoms compared to tDCS or sham targeting. The knowledge gained from this study will provide a marker for clinical response and allow personalized treatment for patients with bipolar disorder.