# Neuroeconomic mechanisms of counterfactual thinking > **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $827,454 ## Abstract PROJECT SUMMARY / ABSTRACT There is a fundamental gap in understanding how neurons integrate hypothetical information when making decisions. This includes not only predicting future outcomes before making choices but also evaluating consequences of unselected alternatives. These computations serve as the basis of counterfactual thinking and regret processing. This phenomenon is central to a wide range of cognitive capabilities but whose dysfunction, despite contributing to numerous psychiatric disorders, is poorly understood. My long-term goal is to uncover the mechanisms governing counterfactual thinking, how the brain binds hypothetical value to unselected actions, and how this translates into changes in motivated behavior. This proposal will determine how single neurons in the nucleus accumbens (NAc) – a critical node of value integration and action selection – support counterfactual thinking constrained by its known inputs. We will leverage innovative approaches in rodent neuroeconomics that we developed to capture complex, evolutionarily conserved decision-making processes across species. We will combine this with cutting-edge brain-wide imaging tools and novel circuit-dissection technologies we developed to measure circuit physiology at an unprecedented level. Our central hypothesis is that populations of functionally distinct neurons in the NAc defined by upstream inputs are differentially involved in assigning credit to missed reward-related opportunities due to different unselected actions. This hypothesis is based on our preliminary data implicating multiple circuits that converge in the NAc and may play distinct roles in action-specific forms of counterfactual thinking. This hypothesis will be tested by pursuing two specific aims: 1) Characterize hypothetical value encoding of NAc neurons defined by their upstream inputs; and 2) Establish a link between afferent activity in the NAc and action-specific forms of counterfactual thinking. First, single-cell NAc activity categorized by the structures projecting to them will be recorded during decision-making behavior in mice. We will characterize firing properties following economic situations known to invoke representations of missed opportunities and will manipulate their excitability using chemogenetics to alter the impact of decision history on future behavior. Second, we will record activity of axonal afferent fibers from major excitatory inputs into the NAc simultaneously with single NAc cells and use optogenetics to manipulate input terminals during distinct action-selection processes. This approach is innovative because it captures input-output circuit physiology in ways never before measured in freely behaving animals using our newly engineered open two-color Miniscope. This is significant because it answers a fundamental biological question: how do single neurons integrate hypothetical value and assign credit to unselected actions? Furthermore, this work will test competing theori... ## Key facts - **NIH application ID:** 10872413 - **Project number:** 1R01MH136230-01 - **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI - **Principal Investigator:** Brian Musa Sweis - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $827,454 - **Award type:** 1 - **Project period:** 2024-07-01 → 2029-01-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10872413 ## Citation > US National Institutes of Health, RePORTER application 10872413, Neuroeconomic mechanisms of counterfactual thinking (1R01MH136230-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10872413. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*