Neural dynamics in co-morbid schizophrenia and OCD: A computational approach

Area of Science:

• Neuroscience
• Computational Psychiatry
• Systems Biology

Background:

• Obsessive-compulsive disorder (OCD) and schizophrenia exhibit higher than chance co-morbidity, suggesting shared neuropathophysiology.
• Repetitive behaviors in both disorders may stem from perseverative thoughts and motor sequences within cortico-striatal networks.
• Existing computational models offer a framework for investigating these complex network dynamics.

Purpose of the Study:

• To extend a computational model of cortico-striatal dynamics to explore the co-morbidity of OCD and schizophrenia.
• To investigate how variations in functional connectivity within overlapping neural networks influence network oscillatory activity.
• To examine the emergence of disorder-specific network dynamics and parameter sensitivity.

Main Methods:

• Extended a previously published computational model of cortico-striatal network dynamics.
• Focused on the emergence of network oscillatory activity and parameter sensitivity analysis.
• Simulated functional connectivity variations in overlapping networks relevant to OCD and schizophrenia.

Main Results:

• Opposing activity levels in orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) are characteristic of schizophrenia and OCD.
• Over-compensation of the primary pathology in the model can lead to the emergence of the other disorder.
• Network oscillatory behavior is sensitive to modulations in cortico-striatal and cortico-cortical connections, including those involving the dorsolateral prefrontal cortex (DLPFC).

Conclusions:

• The study provides a mechanistic model predicting that dynamic over-compensation of neuropathophysiology can result in secondary co-morbid disease.
• Optimal modulation windows exist for treatments targeting cortical self-inhibition (e.g., SSRIs) and striatal dopaminergic input (e.g., antipsychotics).
• Disruption and compensatory processes within the cortico-striato-thalamic network contribute to the neuropathophysiology and heterogeneity of schizo-obsessive spectrum disorders.