# P5: Mechanistic Multi-Region Brain Models

> **NIH NIH U19** · PRINCETON UNIVERSITY · 2024 · $665,296

## Abstract

Project Summary/Abstract: Project 5, Mechanistic Multi-Region Brain Models
 Elucidating the specific computational roles of different brain areas and how they work together to solve
complex evidence-accumulation and decision-making problems is a key goal of our U19 program and of the
BRAIN initiative. This project will take advantage of the unique multi-region experimental datasets from
Projects 1-4 to construct a set of mechanistic models of how multiple brain regions work together to perform
our accumulation-of-evidence based decision-making task.
 Aim 1 focuses on the role of the basal ganglia, often associated with the gating or selection of actions,
within our cognitive decision-making task. Building on the experimental data in Project 4, Multi-Region
Interactions, we will construct models hypothesizing how the two core pathways traversing the basal ganglia,
the direct and indirect pathways, may serve to gate evidence or position information to accumulator circuits in
the neocortex. In turn, we will build models of how accumulated evidence from the neocortex is used to drive
the transition from evidence-seeking to choice-selective actions in the basal ganglia.
 Aim 2 focuses on the role of the entorhinal cortex and hippocampus, and their interactions with sensory
and frontal regions of neocortex, in generating the joint cognitive map of animal position and accumulated
evidence observed in our neural recordings of Project 2, Geometry of Neural Dynamics and Representations.
The model will provide a powerful theory, grounded in biologically plausible mechanisms, for how cognitive
maps are formed and will form predictions for neuronal manifold structures and effects of causal manipulations
in our entorhinal, hippocampal, and neocortical recording experiments.
 Aim 3 focuses on the role of the cerebellum, and its interactions with neocortical
accumulation-of-evidence circuits, in decision-making. Drawing inspiration from classic motor cerebellar
experiments suggesting how the cerebellum may mediate the production of smooth, well-coordinated motor
actions, we propose a new theory of the cognitive cerebellum as stabilizing noisy neural trajectories to produce
smooth cognitive actions. This Aim will be informed by, and in turn form predictions for, the Cerebellar aim of
Project 4, Multi-Region Interactions.
 Aim 4 will combine the regional models of Aims 1 to 3 with a further model of multiple interacting
neocortical regions to produce a single, large scale model of accumulation-of-evidenced based
decision-making. The model will be informed by data from all projects and will enable us to dissect the roles of
individual regions and their interactions in the performance of the many variants of our decision-making task.
 Taken together, we expect that these modeling efforts, deeply integrated with experiments in the other
four Projects, will substantially advance three priority areas of the BRAIN Initiative: the brain in action,
demonstrating causality...

## Key facts

- **NIH application ID:** 10900690
- **Project number:** 5U19NS132720-02
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** MARK S GOLDMAN
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $665,296
- **Award type:** 5
- **Project period:** 2023-08-08 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900690

## Citation

> US National Institutes of Health, RePORTER application 10900690, P5: Mechanistic Multi-Region Brain Models (5U19NS132720-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10900690. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
