What's the science?

Some mood disorders are characterized by irrational, pessimistic, persistent thoughts. These thoughts are related to more cautious/pessimistic and inflexible decision making or evaluation. We don’t know the neural mechanisms involved in these pessimistic evaluations. However, the caudate nucleus is known to be involved in mood disorders, and is known to be involved in behavioral flexibility. This week in Neuron, Amemori and colleagues stimulated the caudate nucleus in primates to understand the role of the nucleus in persistent negative states and value evaluation.

How did they do it?

Two monkeys performed a behavioral task while one of 15-18 electrodes distributed throughout the caudate nucleus was stimulated using a microstimulation technique. Local field potentials were recorded from the other electrodes simultaneously. In the behavioral task, the monkey was shown a red bar, with the size of the bar indicating the amount of food the monkey was about to receive, and a yellow bar indicating the size of an air puff to the face (which it disliked) the monkey was about to receive. It used a joystick to indicate one of two choices: it either chose to a) accept the airpuff and food (taking into account the size of each) (‘approach’ choice) or b) to avoid the airpuff and receive a very small amount of food (‘avoidant’ choice). Decision and reaction time was recorded. 112 stimulation experiments (across both monkeys) and 74 recording-only experiments (across both monkeys) were performed (each experiment consisted of 150-250 trials). In the stimulation experiment, a threshold of 5% was set indicating a change in decision frequency in stimulation-on versus stimulation off-blocks. If the threshold was passed during stimulation (decisions tended to be either more ‘approach’ or more ‘avoidant’) the stimulation was considered effective. The effect of microstimulation on decision behavior during the task was analyzed.

What did they find?

Microstimulation at most sites did not change decision behavior. However, stimulation at about a quarter of the sites increased avoidant choices, and stimulation at a few sites increased approach choices. These effective sites were distributed throughout the caudate nucleus. Sites where stimulation invoked avoidant decisions were considered to be part of a ‘generative circuit’. Neuronal spiking activity was more likely to encode avoidant decisions near these negative effective sites. To see whether stimulation had persistent effects, the authors assessed follow-up blocks without stimulation after stimulation blocks, and found that increased avoidant decisions persisted 78% of the time after effective stimulation at negative sites, while positive effect were maintained only 10% of the time following stimulation at positive sites. This suggests that stimulation at negative sites could induce persistent negative mood. A tendency for stimulation at negative effective sites to induce a repetitive pattern of avoidant decision was also found, suggesting negative stimulation resulted in repetitive avoidant behavior. Oscillatory brain activity in the beta frequency band is known to be associated with maintenance of cognitive states. Therefore, the authors tested whether changes in beta band oscillations were related to decision making. They identified electrodes where task-related beta band activity could be observed, and found that there was greater beta band power prior to avoidant decisions when stimulation was off. During follow-up following stimulation, beta band power tracked choices even more closely, suggesting stimulation enhanced this relationship.