Research Projects

Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder that affects patients with impulsivity and impaired decision-making. Traditional treatments like cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) are recommended for OCD, but many patients show only partial recovery or are found refractory. Deep brain stimulation (DBS) is a new treatment intervention for refractory patients with severe therapy-resistant OCD. DBS targets include the medial forebrain bundle, orbitofrontal cortex, anterior cingulate cortex, nucleus accumbens, ventral capsule/ventral striatum (VC/VS), subthalamic nucleus (STN), internal globus pallidus (GPi), and bed nucleus of the stria terminalis. Several brain regions, including the ventral capsule/ventral striatum (VC/VS), subthalamic nucleus (STN), internal globus pallidus (GPi), and bed nucleus of the stria terminalis, have been proposed for DBS treatment due to their surplus advantage on cognitive domain. However, the underlying mechanisms of these two DBS targets remain speculative, and no comparative study has been conducted for these two DBS targets. This proposal aims to explore the underlying mechanisms of STN-DBS vs. ALIC-DBS involved in cognitive improvement. The main objective of this proposal is to compare the two different brain targets ALIC and STN of DBS for the improvement of cognitive dysfunctions seen after severe OCD. The research also aims to identify the development of neuronal connectivity from the seed region ALIC or STN to the cognitive regulating brain centers after DBS and find chronic effects of DBS in the rodent OCD model, both behaviorally and biochemically. The proposed research consists of three main objectives: comparing the impact of STN-DBS vs. ALIC-DBS on cognitive dysfunctions using a preclinical OCD model, investigating the neuronal mechanisms involved in neurocognitive improvement, and examining the underlying molecular mechanisms involved in neurocognitive improvement. The data from this project may aid in clinical DBS application in patients with OCD.