# Causal brainwide interactions underlying internal states and decisions

> **NIH NIH U19** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2021 · $514,723

## Abstract

Summary/Abstract, Project 2
Even in the same environment, an animal may make different decisions on different occasions, because its
internal state, such as engagement in a task, interacts powerfully with external inputs to determine behavior.
This proposal’s overarching goal is to understand how internal states influence decisions and to identify the
underlying neural mechanisms. The team is part of the International Brain Laboratory (IBL), an established
consortium that has developed a standardized mouse decision-making task and standardized methods for
training, neural measurement, and data analysis, along with a working, scalable infrastructure for sharing data.
The goal of Project 2 is to establish the causal influence of brain regions and cell types on inter-regional
communication and state-dependent decision-making by integrating optogenetic perturbations at specific times
during the task with simultaneous recordings of neural populations and functional ultrasound. We will consider
two types of internal states: engaged/disengaged task performance and left/right biases due to the statistical
structure of the environment, which varies across blocks of trials. In Aim 1, we will examine the role of subcortical
structures in state-dependent decision-making with systematic optogenetic manipulations while well-trained mice
perform the IBL decision task. In Aim 2, we will examine the causal effects of inhibiting target regions and/or cell
types of interest on communication between other regions, using Neuropixels probes and functional ultrasound.
In Aim 3, to integrate our results, we will develop dynamical computational models of multi-region population
activity during our causal manipulations. These models will account for the effects of manipulation in one brain
region on behavior and activity in other regions, and their dependence on internal states. The results will help
interpret our experiments and refine them by suggesting other combinations of regions to record and manipulate.
Together, these experiments will integrate cutting-edge experimental and computational methods to characterize
the causal interactions of brainwide regions and their dependence on internal state.

## Key facts

- **NIH application ID:** 10294674
- **Project number:** 1U19NS123716-01
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** Ilana Witten
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $514,723
- **Award type:** 1
- **Project period:** 2021-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10294674

## Citation

> US National Institutes of Health, RePORTER application 10294674, Causal brainwide interactions underlying internal states and decisions (1U19NS123716-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10294674. Licensed CC0.

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