# Superior Colliculus Pathways for Defensive Behavior and Emotional Arousal

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $678,941

## Abstract

ABSTRACT
 Alterations in brain circuits underlying defensive behavior are thought to substantially contribute to the
dysfunction present in anxiety disorders, which frequently emerge in adolescence, affect roughly one in three
individuals in their lifetime, and are a leading cause of health burden globally. Research in nonhuman animal
models shows that defensive responses to threats are mediated by multiple subcortical pathways involving the
superior colliculus, and human neuroimaging studies show that functional alterations in the colliculus-pulvinar-
amygdala pathway are present in individuals with post-traumatic stress disorder and anxiety. However, it is
presently unclear how the human superior colliculus contributes to fear and anxiety, whether by participating in
subcortical circuits that coordinate defensive behavior, or via pathways to cortical systems involved in spatial
attention, emotional arousal, and emotional experience more broadly. The long-term goal of the proposed
research is to develop a mechanistic understanding of human superior colliculus pathways across domains of
function relevant to mental health. Here we aim to characterize its contribution to defensive behavior and
emotional experience across multiple tasks in a community-based functional magnetic resonance imaging
study and using data from the Adolescent Brain Cognitive Development Study. Aim 1 evaluates the
functional specificity of superior colliculus pathways, using machine learning techniques to model
pathway connectivity as individuals perform tasks involving probabilistic avoidance learning, spatial attention,
and naturalistic aversive experience concurrent with fMRI. The functional relevance of each pathway will be
established by examining correlations between pathway activation and task-relevant behavior. Aim 2
identifies how looming threat is encoded in the human superior colliculus, its connectivity with cortical
systems, and its relationship with subjective experience. We will use computational neuroimaging approaches
to evaluate whether fMRI signal in the superior colliculus is better explained by encoding models that capture
dynamic or static representations of threat and characterize how representations of threat encoded in the
superior colliculus covary with activity in cortical systems and self-reported experience. Aim 3 will determine
the relationship between individual differences in frontal-superior colliculus pathway activity and
anxiety symptoms during adolescence. We will test the hypothesis that cortical pathways to the superior
colliculus attenuate responses to threat cues and are negatively associated with individual differences in
anxiety using data from the Adolescent Brain Cognitive Development Study. Completing these aims will
provide foundational knowledge of how the superior colliculus is involved in defensive behavior, subjective
fear, and emotional arousal, and the degree to which alterations in specific pathways are related to anxiety....

## Key facts

- **NIH application ID:** 10979860
- **Project number:** 1R01MH134972-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Philip Augustus Kragel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $678,941
- **Award type:** 1
- **Project period:** 2024-07-18 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10979860

## Citation

> US National Institutes of Health, RePORTER application 10979860, Superior Colliculus Pathways for Defensive Behavior and Emotional Arousal (1R01MH134972-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10979860. Licensed CC0.

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