A computational network dynamical modeling for abnormal oscillation and deep brain stimulation control of obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is associated with multi-nodal abnormalities in brain networks, characterized by recurrent intrusive thoughts (obsessions) and repetitive behaviours or mental acts (compulsions), which might manifest as pathological low-frequency oscillations in the frontal EEG and low-frequency bursting firing patterns in the subthalamus nucleus (STN). Abnormalities in the cortical-striatal-thalamic-cortical (CSTC) loop, including dysregulation of serotonin, dopamine, and glutamate systems, are considered to contribute to certain types of OCD. Here, we extend a biophysical computational model to investigate the effect of orbitofronto-subcortical loop abnormalities on network oscillations. Particularly, the OCD lesion process is simulated by the loss of connectivity from striatal parvalbumin interneurons (PV) to medium spiny neurons (MSNs), excessive activation to the hyperdirect pathway, and high dopamine concentrations. By calculating low-frequency oscillation power in the STN, STN burst index, and average firing rates levels of the cortex and thalamus, we demonstrate that the model can explain the pathology of glutamatergic and dopamine system dysregulation, the effects of pathway imbalance, and neuropsychiatric treatment in OCD. In addition, results indicate the abnormal brain rhythms caused by the dysregulation of orbitofronto-subcortical loop may serve as a biomarker of OCD. Our studies can help to understand the cause of OCD, thereby facilitating the diagnosis of OCD and the development of new therapeutics.