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Impairment in orbitofrontal cortex linked to cognitive inflexibility

Suppressing neural activity of the orbitofrontal cortex (OFC) made rats less likely to modify their behaviour in response to negative reinforcement or changes in the probability of receiving rewards, finds new research published this week in The Journal of Neuroscience. The findings, which demonstrate the distinct ways that parts of the brain’s prefrontal cortex (PFC) contribute to different aspects of reward-seeking behaviour, could have implications for our understanding of the cognitive inflexibility that accompanies some psychiatric disorders.

The researchers, led by Dr. Stan Floresco and Dr. Gemma Dalton from the UBC Department of Psychology and Djavad Mowafaghian Centre for Brain Health, investigated five distinct regions of the OFC, a sub-region of the PFC in the brain’s frontal lobe, to determine the relationships between each part of the brain and how they affect decision-making.

“We routinely have to adjust our behaviour to changes in our environments to obtain certain goals, but performing a ‘correct’ action doesn’t always yield us our desired rewards,” says Dr. Floresco. “In these situations, our brains keep records of which actions are more likely to be more profitable in the long term.”

“We found that when we shut down activity in different regions of the orbitofrontal cortex, our animals had great difficulty learning from the consequences of their actions, and were slower to update their behaviour when reward contingencies changed,” Dr. Floresco explains. “Moreover, it seems like different functions are contracted out to different portions of the cortex – the part along the middle of the brain seems to help distinguish responses that yield high probability rewards from lower ones, while the more lateral parts help an organism learn from its mistakes.”

Dysfunction in the OFC has been observed in numerous psychiatric disorders, including schizophrenia and depression. Reversal learning, or the ability to moderate behaviour in anticipation of risk or reward probability, is made possible by interactions between different regions of the OFC and medial PFC; by impairing any of these, the rats were less able to gauge the probability of receiving rewards for specific behaviours, and were less deterred by negative or less assured outcomes.

“Our hope is that these findings will help refine our understanding of how different regions of the frontal lobes contribute to normal functions (such as cognitive flexibility) and in turn help us identify mechanisms of abnormal function,” says Dr. Floresco. “One of our next steps is to investigate how the neurotransmitter dopamine (which has also been implicated in psychiatric disorders) may work in these regions to facilitate these functions.”

CItation:

GL Dalton, NY Wang, AG Phillips, SB Floresco. Multifaceted Contributions by Different Regions of the Orbitofrontal and Medial Prefrontal Cortex to Probabilistic Reversal Learning.  The Journal of Neuroscience. February 2016, 36(6):1996-2006; doi:10.1523/JNEUROSCI.3366-15.2016