How altered orbitofrontal signaling contributes to deficits in outcome-guided behavior in drug addiction

• Applicant: Dr. Jana Tegelbeckers
• Subject Area: Human Cognitive and Systems Neuroscience ; Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 403227351

The numbers of patients with substance use disorder (SUD) and deaths from drug overdose are world-wide on the rise, resulting in growing costs for health systems and societies. Thus, there is an urgent need for a better understanding of the processes leading to drug intake and addiction. Addiction is characterized by an inability to control drug-seeking behavior despite better knowledge of the negative outcomes of consumption. This failure to adequately engage in outcome-guided behavior might be related to deficient orbitofrontal signaling. The orbitofrontal cortex (OFC) is involved in hosting a “cognitive map” which serves as an associative structure enabling mental simulations of yet unexperienced outcomes. The proposed project aims to investigate the functioning of orbitofrontal cognitive maps in SUD patients. First, a sensory preconditioning task adapted from animal research will be performed by SUD patients during fMRI scanning to provide insight into their potential behavioral and neural deficits during outcome inference. Subsequently, OFC activity will be modulated with transcranial magnetic stimulation (TMS) to influence the behavioral impairments of patients with SUD in the same task. In summary, this project will shed light on the involvement of orbitofrontal functioning in drug addiction. In addition, this represents an important first step towards the potential use of modern stimulation techniques to alter deficient decision making in SUD patients.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Thorsten Kahnt, Ph.D.