Project Summary. The brain systems that control our motivation, emotions, and decisions rely at their most fundamental level on predicting the future: learning what outcomes to expect, when they will arrive, and how valuable they will be. It is only natural that we are strongly motivated to seek information that will reduce our uncertainty. But despite its importance in everyday decision making and clinical settings, little is known about how information seeking behavior is controlled – how the brain anticipates information, endows it with value, and sends it to motivational circuits to drive behavior. We identified set of anatomically connected areas, including the anterior cingulate cortex and subregions of the basal ganglia, that encode the quantitative level of reward uncertainty to control information seeking to resolve that uncertainty. We also showed that the value of information is computed through a conserved algorithm in the brains of macaques and humans, and that this algorithm governs value-based decisions through the lateral habenula (LHb). Leveraging this insight, the Aims will answer several key questions. We will study a crucial but understudied pathway in primates: concentrating on whether and how the thalamus causally mediates prefrontal cortical computations that regulate information seeking. And we will assess how the anatomically defined cortical-basal ganglia-thalamus loop performs the computational steps of estimating and representing reward probability distributions, computing their uncertainties, and how it causally uses these representations to set the value of information and regulate information seeking decisions. Our key overarching hypothesis is that the thalamus transmits information about uncertainty to the cortex and causally regulates cortical uncertainty processing to control information seeking. Aim 1 will uncover whether and how the primate thalamus regulates the motivation to seek information to reduce uncertainty through online modulation of the neocortex. Based on preliminary data, we hypothesize that anterior medial thalamus is a key source of uncertainty signals, and that it causally regulates cortical computation to guide information seeking. Aim 2 will assess whether and how different subregions within the cortical basal ganglia thalamic loop represent probability distributions and their uncertainties and use them to motivate information seeking decisions. Our hypothesis is that the decision variables in the cortex are computed from distributional representations of value and uncertainty to guide deliberative information seeking decisions through LHb and moment-to-moment information seeking behavior through the basal ganglia, and that these processes are dependent on thalamic inputs. The Aims offer an unprecedented opportunity to understand the mechanisms of information seeking, and to study clinically relevant primate brain areas that have remained understudied. In the long term, research on informatio...