Anterior Cingulate Cortex Causally Supports Meta-Learning.

In dynamic environments with volatile rewards the anterior cingulate cortex (ACC) is believed to determine whether a visual object is relevant and should be chosen. The ACC may achieve this by integrating reward information over time to estimate which objects are worth to explore and which objects should be avoided. Such a higher-order meta-awareness about which objects should be explored predicts that the ACC causally contributes to choices when the reward values of objects are unknown and must be inferred from ongoing exploration. We tested this suggestion in nonhuman primates using a learning task that varied the number of object features that could be relevant, and by controlling the motivational value of choosing objects. During learning the ACC was transiently micro-stimulated when subjects foveated the to-be-chosen stimulus. We found that stimulation selectively impaired learning when feature uncertainty and motivational value of choices were high, which was linked to a deficit in using reward outcomes for feature-specific credit assignment. Application of an adaptive reinforcement learning model confirmed a primary deficit in weighting prediction errors that led to a meta-learning impairment to adaptively increase exploration during learning and to an impaired use of working memory to support learning. These findings provide causal evidence that the reward history traces in ACC are essential for meta-adjusting the exploration-exploitation balance and the strength of working memory of object values during adaptive behavior.

A Multi-task Platform for Profiling Cognitive and Motivational Constructs in Humans and Nonhuman Primates.

Background: Understanding the neurobiological substrates of psychiatric disorders requires comprehensive evaluations of cognitive and motivational functions in preclinical research settings. The translational validity of such evaluations will be supported by (1) tasks with high construct validity that are engaging and easy to teach to human and nonhuman participants, (2) software that enables efficient switching between multiple tasks in single sessions, (3) software that supports tasks across a broad range of physical experimental setups, and (4) by platform architectures that are easily extendable and customizable to encourage future optimization and development. New Method: We describe the Multi-task Universal Suite for Experiments (M-USE), a software platform designed to meet these requirements. It leverages the Unity video game engine and C# programming language to (1) support immersive and engaging tasks for humans and nonhuman primates, (2) allow experimenters or participants to switch between multiple tasks within-session, (3) generate builds that function across computers, tablets, and websites, and (4) is freely available online with documentation and tutorials for users and developers. M-USE includes a task library with seven pre-existing tasks assessing cognitive and motivational constructs of perception, attention, working memory, cognitive flexibility, motivational and affective self-control, relational long-term memory, and visuo-spatial problem solving. Results: M-USE was used to test NHPs on up to six tasks per session, all available as part of the Task Library, and to extract performance metrics for all major cognitive and motivational constructs spanning the Research Domain Criteria (RDoC) of the National Institutes of Mental Health. Comparison with Existing Methods: Other experiment design and control systems exist, but do not provide the full range of features available in M-USE, including a pre-existing task library for cross-species assessments; the ability to switch seamlessly between tasks in individual sessions; cross-platform build capabilities; license-free availability; and its leveraging of video-engine capabilities used to gamify tasks. Conclusions: The new multi-task platform facilitates cross-species translational research for understanding the neurobiological substrates of higher cognitive and motivational functions.

Generating Patient-Specific Acoustic Simulations for Transcranial Focused Ultrasound Procedures Based on Optical Tracking Information.

Optical tracking is a real-time transducer positioning method for transcranial focused ultrasound (tFUS) procedures, but the predicted focus from optical tracking typically does not incorporate subject-specific skull information. Acoustic simulations can estimate the pressure field when propagating through the cranium but rely on accurately replicating the positioning of the transducer and skull in a simulated space. Here, we develop and characterize the accuracy of a workflow that creates simulation grids based on optical tracking information in a neuronavigated phantom with and without transmission through an ex vivo skull cap. The software pipeline could replicate the geometry of the tFUS procedure within the limits of the optical tracking system (transcranial target registration error (TRE): 3.9 ± 0.7 mm). The simulated focus and the free-field focus predicted by optical tracking had low Euclidean distance errors of 0.5±0.1 and 1.2±0.4 mm for phantom and skull cap, respectively, and some skull-specific effects were captured by the simulation. However, the TRE of simulation informed by optical tracking was 4.6±0.2, which is as large or greater than the focal spot size used by many tFUS systems. By updating the position of the transducer using the original TRE offset, we reduced the simulated TRE to 1.1 ± 0.4 mm. Our study describes a software pipeline for treatment planning, evaluates its accuracy, and demonstrates an approach using MR-acoustic radiation force imaging as a method to improve dosimetry. Overall, our software pipeline helps estimate acoustic exposure, and our study highlights the need for image feedback to increase the accuracy of tFUS dosimetry.

Gains and Losses Affect Learning Differentially at Low and High Attentional Load.

Prospective gains and losses influence cognitive processing, but it is unresolved how they modulate flexible learning in changing environments. The prospect of gains might enhance flexible learning through prioritized processing of reward-predicting stimuli, but it is unclear how far this learning benefit extends when task demands increase. Similarly, experiencing losses might facilitate learning when they trigger attentional reorienting away from loss-inducing stimuli, but losses may also impair learning by increasing motivational costs or when negative outcomes are overgeneralized. To clarify these divergent views, we tested how varying magnitudes of gains and losses affect the flexible learning of feature values in environments that varied attentional load by increasing the number of interfering object features. With this task design, we found that larger prospective gains improved learning efficacy and learning speed, but only when attentional load was low. In contrast, expecting losses impaired learning efficacy, and this impairment was larger at higher attentional load. These findings functionally dissociate the contributions of gains and losses on flexible learning, suggesting they operate via separate control mechanisms. One mechanism is triggered by experiencing loss and reduces the ability to reduce distractor interference, impairs assigning credit to specific loss-inducing features, and decreases efficient exploration during learning. The second mechanism is triggered by experiencing gains, which enhances prioritizing reward-predicting stimulus features as long as the interference of distracting features is limited. Taken together, these results support a rational theory of cognitive control during learning, suggesting that experiencing losses and experiencing distractor interference impose costs for learning.