# Mechanistic dissection of cognitive thalamocortical engagement in attention and hierarchical reasoning.

> **NIH NIH P50** · PRINCETON UNIVERSITY · 2024 · $466,862

## Abstract

Abstract
Higher order thalamic regions play critical roles in cognitive processing by regulating their cortical targets.
Data from both such regions, the pulvinar and mediodorsal thalamus, indicate that their engagement in
decision making increases in challenging conditions, including perceptual uncertainty. Schizophrenia is a
disorder characterized by heightened susceptibitly to uncertainty on one end and perturbed connectivity
between higher order thalamus and associative cortical targets, on another. Therefore, identifying the
mechanistic links between higher order thalamic engagement and cognitive processing is translationally-
relevant; higher order thalamic regions may be viable targets for neurostimulation in treatment-resistant
schizophrenia. This project will utilize Tupaia Bellangeri (Tree shrews) as a model organism to contribute to
the overall Aims of this Center. Tupaia is a basal primate with a brain size amenable for optical perturbations
that can be readily observed at the level of behavior, tightening the casual inferences that can be made about
brain-behavior relationships. In Aim I of this project, we will build upon our extensive preliminary data on MD
thalamic function. This will be in close collaboration with P3, which will perform analogous experiments in
macaque collectively identifying the mechanisms by which the MD regulates interactions between frontal
cortical areas in the context of hierarchical reasoning. In Aim II, we will use the visual system of Tupaia to ask
analogous questions on pulvinar regulation of dorsal versus ventral visual stream engagement in a motion
vs. color switching task; this will be coordinated closely with P1, which will target the pulvinar in the macaque.
Lastly, Aim III will leverage a pharmacological model relevant to the pathophysiology of schizophrenia (chronic
methamphetamine) to examine brain-behavior relationships in the context of task performance. This will be
done in close coordination with P5, which will interrogate higher order thalamic structure in humans with
schizophrenia and healthy controls. In all Aims, there will be close collaboration with P4, Cores B and C, to
ensure that the data contributes general insights for building a biologically-plausible model of the human
thalamus. Altogether, successful completion of our Aims promises to contribute to the overall vision of this
Center in propelling the basic understanding of thalamocortical processing and cognition forward, as well as
deriving translational insights for treatment of schizophrenia.

## Key facts

- **NIH application ID:** 10819528
- **Project number:** 5P50MH132642-02
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Michael M Halassa
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $466,862
- **Award type:** 5
- **Project period:** 2023-04-03 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10819528

## Citation

> US National Institutes of Health, RePORTER application 10819528, Mechanistic dissection of cognitive thalamocortical engagement in attention and hierarchical reasoning. (5P50MH132642-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10819528. Licensed CC0.

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