The Section on Neurophysiology studies the frontal cortex and related parts of the brain. The present project was premised on the idea that making decisions about what to do and when to do it requires three distinct neural processes: comparison of the relative value of alternative actions (known as valuation or evaluation), selection of the alternative with the highest current value, and inhibition of rejected alternatives. Because the ability to evaluate, select, and inhibit a vast array of potential thoughts and actions is so fundamental to everyday life, dysfunction in any of these decision-making processes has potentially wide-ranging and deeply debilitating effects. Thus, it is not surprising that dysfunction of these three neural processes has been implicated in the thought disorders characteristic of schizophrenia, the deficits at the root of attention deficit hyperactivity disorder (ADHD), and the inability to willfully control thoughts and behavior in obsessive-compulsive disorder (OCD). Human brain imaging and clinical neuropsychological studies have provided evidence for a frontal-lobe contribution to all three decision-making processes, with much emphasis on the role of the prefrontal cortex. Currently, however, we lack a systems-level understanding of how these areas and specific receptor pathways work together to achieve these three fundamental processes of decision making: valuation, behavioral inhibition and behavioral selection. Accordingly, we hypothesized that the orbital prefrontal cortex (PFo) and both the core and shell of the nucleus accumbens, two parts of the basal ganglia, suppress a prepotent tendency to choose the largest of two values, but that they do so in different ways, some related to valuation, others to general or specific inhibition, and others to affirmative selection of a goal or response. If this is the case, they we predict that neurons in these areas should differ when subjects decide what to do based on a prepotent response rule (select the largest value), as opposed to the antithesis of that rule (select the smallest of two values). The foundation for this project is the reversed contingency task. We previously showed that rhesus monkeys can learn this task, in contradiction of previously published results (Murray et al., 2005). In the present neurophysiological part of the project, a red cue signaled that the payoff contingency will be the receipt of four identical food items for choosing four items (the prepotent task) and a blue cue signaled the contingency will be the receipt of only one food item for choosing four, along with the receipt of four food items for choosing one (the reversed contingency task). We used a moveable, multi-electrode drive, fitted to a newly designed drive base to record up to 16 areas simultaneously, typically targeting 5-10 areas per recording session. Extracellular recordings of single neurons, eye movements, and EMGs were analyzed. In a preliminary analysis, we found that 235 of 458 neurons, 51% of the sample throughout the frontal cortex and striatum, showed a statistically significant difference between the reversed contingency and prepotent tasks. In control tasks, 198 of 432 (45%) neurons showed a significant relationship with the amount of a self-imposed delay, and 167 of 362 cells (46%) reflected the amount of effort needed to produce a reward. There was thus a high percentage of both reverse-contingency and prepotent neurons, and both types were widely distributed, as were the many delay and effort neurons. We conclude that inhibitory control derives from many sources in the telencephalon, with subcortical structures such as the striatum and the amygdala being especially enriched in reverse contingency neurons, and cortical structures such as the orbital prefrontal cortex being enriched in prepotent neurons.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002876-01
Application #
7594603
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2007
Total Cost
$610,672
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code