Saturday, September 7, 2024
9/7/2024
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. We expect that findings from this research will provide insights into the brain mechanisms underlying anxiety disorders and facilitate translational efforts across species and into clinical settings.
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