Role of the Orbitofrontal Cortex and Midbrain Dopamine Neurons in Associative Learning from reward Prediction Errors

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of Maryland
Investigators Name
Ogawa, Masaaki. MD, PhD

Tourette Syndrome (TS) is frequently associated with Obsessive-Compulsive Disorder (OCD). A common feature of OCD and TS is an inability to inhibit unwanted actions that follow premonitory experiences such as sensations (TS) and thoughts (OCD). This similarity indicates a common underlying inability to inhibit inappropriate and unwanted responses, an ability which has long been linked to the prefrontal sub-region of the brain known as the orbitofrontal cortex (OFC). Consistent with this proposal, human brain imaging studies have demonstrated changes in OFC function in TS and OCD. For example, patients with OCD show reduced activation of the OFC during reversal learning which is a type of associative learning that is exquisitely sensitive to manipulations that disrupt OFC function. However, the precise role that the OFC plays in supporting adaptive behavior in reversal-like settings remains controversial. As a result, it is difficult to speculate on the neural changes affecting OFC-dependent reversal learning in OCD. Here, we propose to test a novel hypothesis—namely that the OFC contributes to behavioral control in part via support of associative learning and reward prediction error signaling by downstream dopaminergic systems, which are also implicated in pathophysiology of TS and OCD. The breakdown of normal control of the OFC in patients with disorders such as TS and OCD may lead to abnormal dopamine release in other brain regions, thereby leading to abnormal, stimulus-driven behaviors such as tics and obsessive-compulsive behaviors. From this work, we expect to better understand how the orbitofrontal cortex of the brain supports adaptive behavior in settings such as reversal learning. This improved understanding may provide novel insights into the circuit abnormality causing TS and OCD and ultimately suggest new therapeutic approaches for these disorders. Masaaki Ogawa, M.D., Ph.D. University of Maryland School of Medicine Baltimore, MD Award: $40,000 (Fellowship) Commentary: In addition to often being co-associated, Tourette Syndrome (TS) and Obsessive-Compulsive Disorder (OCD) are similar in that a premonitory urge is followed by an inappropriate and unwanted action. This observation has led scientists to propose that a similar glitch in normal brain function may be responsible for both disorders. In his study Dr. Ogawa will focus on a part of the brain involved in decision-making and which is thought to be implicated in both TS and OCD. More specifically, Dr. Ogawa will attempt to determine whether dysfunction in this part of the brain results in an abnormal release of a brain chemical called dopamine in other parts of the brain. An abnormal amount of dopamine in the brain has long been implicated in the generation of tics. Results from this study may help us better understand the neurological basis of TS and OCD. Tourette Association of America Inc. – Research Grant Award 2009-2010