A neural mechanism for conserved value computations integrating information and rewards.

Behavioral and economic theory dictate that we decide between options based on their values. However, humans and animals eagerly seek information about uncertain future rewards, even when this does not provide any objective value. This implies that decisions are made by endowing information with subjective value and integrating it with the value of extrinsic rewards, but the mechanism is unknown. Here, we show that human and monkey value judgements obey strikingly conserved computational principles during multi-attribute decisions trading off information and extrinsic reward. We then identify a neural substrate in a highly conserved ancient structure, the lateral habenula (LHb). LHb neurons signal subjective value, integrating information's value with extrinsic rewards, and the LHb predicts and causally influences ongoing decisions. Neurons in key input areas to the LHb largely signal components of these computations, not integrated value signals. Thus, our data uncover neural mechanisms of conserved computations underlying decisions to seek information about the future.

The zona incerta in control of novelty seeking and investigation across species.

Many organisms rely on a capacity to rapidly replicate, disperse, and evolve when faced with uncertainty and novelty. But mammals do not evolve and replicate quickly. They rely on a sophisticated nervous system to generate predictions and select responses when confronted with these challenges. An important component of their behavioral repertoire is the adaptive context-dependent seeking or avoiding of perceptually novel objects, even when their values have not yet been learned. Here, we outline recent cross-species breakthroughs that shed light on how the zona incerta (ZI), a relatively evolutionarily conserved brain area, supports novelty-seeking and novelty-related investigations. We then conjecture how the architecture of the ZI's anatomical connectivity - the wide-ranging top-down cortical inputs to the ZI, and its specifically strong outputs to both the brainstem action controllers and to brain areas involved in action value learning - place the ZI in a unique role at the intersection of cognitive control and learning.

Laser stimulation of the skin for quantitative study of decision-making and motivation.

Neuroeconomics studies how decision-making is guided by the value of rewards and punishments. But to date, little is known about how noxious experiences impact decisions. A challenge is the lack of an aversive stimulus that is dynamically adjustable in intensity and location, readily usable over many trials in a single experimental session, and compatible with multiple ways to measure neuronal activity. We show that skin laser stimulation used in human studies of aversion can be used for this purpose in several key animal models. We then use laser stimulation to study how neurons in the orbitofrontal cortex (OFC), an area whose many roles include guiding decisions among different rewards, encode the value of rewards and punishments. We show that some OFC neurons integrated the positive value of rewards with the negative value of aversive laser stimulation, suggesting that the OFC can play a role in more complex choices than previously appreciated.

A primate temporal cortex-zona incerta pathway for novelty seeking.

Primates interact with the world by exploring visual objects; they seek opportunities to view novel objects even when these have no extrinsic reward value. How the brain controls this novelty seeking is unknown. Here we show that novelty seeking in monkeys is regulated by the zona incerta (ZI). As monkeys made eye movements to familiar objects to trigger an opportunity to view novel objects, many ZI neurons were preferentially activated by predictions of novel objects before the gaze shift. Low-intensity ZI stimulation facilitated gaze shifts, whereas ZI inactivation reduced novelty seeking. ZI-dependent novelty seeking was not regulated by neurons in the lateral habenula or by many dopamine neurons in the substantia nigra, traditionally associated with reward seeking. But the anterior ventral medial temporal cortex, an area important for object vision and memory, was a prominent source of novelty predictions. These data uncover a functional pathway in the primate brain that regulates novelty seeking.

Primate Nigrostriatal Dopamine System Regulates Saccadic Response Inhibition.

Animals need to inhibit inappropriate actions that would lead to unwanted outcomes. Although this ability, called response inhibition, is impaired in neurological/psychiatric disorders with dopaminergic dysfunctions, how dopamine regulates response inhibition remains unclear. Here we investigated neuronal signals of the nigrostriatal dopamine system in monkeys performing a saccadic countermanding task. Subsets of dopamine neurons in the substantia nigra and striatal neurons receiving the dopaminergic input were activated when the monkey was required to cancel a planned saccadic eye movement. These activations were stronger when canceling the eye movements was successful compared with failed and were enhanced in demanding trials. The activated dopamine neurons were distributed mainly in the dorsolateral, but not in the ventromedial, part of the nigra. Furthermore, pharmacological blockade of dopaminergic neurotransmission in the striatum dampened the performance of canceling saccadic eye movements. The present findings indicate that disruption of nigrostriatal dopamine signaling causes impairments in response inhibition.