Search

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.

Behavioral and economic theory dictates that we decide between options based on their values. However, humans and animals eagerly seek information about uncertain future rewards, even when this information does not provide any objective value. This implies that decisions can be made by endowing information with subjective value and integrating it with the value of extrinsic rewards, but the mechanism is unknown. Using a novel multi-attribute decision making task we found that human and monkey value judgements are regulated by strikingly conserved computational principles, including how they compute the value of information and scale it with information’s timing and ability to resolve a specific form of uncertainty. We then identified a neural substrate in a highly conserved and ancient structure, the lateral habenula (LHb). LHb neurons signal the subjective value of choice options integrating the value of information with extrinsic rewards, and LHb activity both predicts and causally influences online decisions. Key input regions to LHb provide the necessary ingredients for these computations, but do not themselves signal an integrated value signal to guide multi attribute decisions. Our data thus identifies neural mechanisms of the conserved computations underlying multi-attribute, value-based decisions to seek information about the future.

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.

Humans and other primates interact with the world by observing and exploring visual objects. In particular, they often seek out the opportunities to view novel objects that they have never seen before, even when they have no extrinsic primary reward value. However, despite the importance of novel visual objects in our daily life, we currently lack an understanding of how primate brain circuits control the motivation to seek out novelty. We found that novelty-seeking is regulated by a small understudied subcortical region, the zona incerta (ZI). In a task in which monkeys made eye movements to familiar objects to obtain the opportunity to view novel objects, many ZI neurons were preferentially activated by predictions of future novel objects and displayed burst excitations before gaze shifts to gain access to novel objects. Low intensity electrical stimulation of ZI facilitated gaze shifts, while inactivations of ZI reduced novelty-seeking. Surprisingly, additional experiments showed that this ZI-dependent novelty seeking behavior is not regulated by canonical neural circuitry for reward seeking. The habenula-dopamine pathway, known to reflect reward predictions that control reward seeking, was relatively inactive during novelty-seeking behavior in which novelty had no extrinsic reward value. Instead, high channel-count electrophysiological experiments and anatomical tracing identified a prominent source of control signals for novelty seeking in the anterior ventral medial temporal cortex (AVMTC), a brain region known to be crucially involved in visual processing and object memory. In addition to their well-known function in signaling the novelty or familiarity of objects in the current environment, AVMTC neurons reflected the predictions of future novel objects, akin to the way neurons in reward-circuitry predict future rewards in order to control reward-seeking. Our data uncover a network of primate brain areas that regulate novelty-seeking. The behavioral and neural distinctions between novelty-seeking and reward-processing highlight how the brain can accomplish behavioral flexibility, providing a mechanism to explore novel objects.

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.