Biology subjects

Roseboom, P. H.

Publications and source records attributed to Roseboom, P. H..

4 recordsLinked to original sources

bioRxiv2026

Extended amygdala function is governed by threat probability, not uncertainty

Anxiety is a universal experience that arises as we anticipate negative events that may or may not happen. When extreme, anxiety is a major cause of distress, suffering, and disability-adjusted life years, with nearly one in four individuals experiencing clinically relevant anxiety in their lifetime1-3. Elucidating the biological basis of anxiety has the potential to help people understand, cope with, and ultimately receive improved treatments for their anxiety. The canonical neuroscientific model of anxiety posits that distinct regions of the extended amygdala (EA) elicit distress that is conditional on threat uncertainty4. Here, we refute this model using a precise computational framework to disambiguate specific dimensional facets of threat uncertainty in a racially diverse sample of 104 individuals. We show that self-report, psychophysiological, and neural correlates of threat anticipation are much more strongly associated with threat probability than uncertainty per se. Importantly, EA regions, including the central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis (BST), were most reliably associated with threat probability--contrary to the canonical model. Re-examination of the pioneering experiments that motivated the canonical model reveal a previously unappreciated confound between probability and uncertainty, suggesting the novel hypothesis that EA regions differ in their sensitivity to low-probability threats. Our fMRI data support this, showing that BST is more sensitive to low-probability threats than Ce. Moreover, lesion experiments in rhesus monkeys (Macaca mulatta) demonstrate that BST causally contributes to defensive behavior in low-probability threat contexts. Together, these data reconcile previous empirical inconsistencies, provide a fresh theoretical perspective on the neurobiology of anxiety, and underscore the theoretical importance of a formal lingua franca for coordinated cross-species emotion research.

neuroscience↗

bioRxiv2025

The development of trait anxiety in nonhuman primates during the first year of life

Anxious Temperament (AT) is a nonhuman primate phenotype that models childhood behavioral inhibition, a prominent risk factor for anxiety disorders and stress-related psychopathology. To understand its earliest antecedents, we characterized ATs developmental trajectory over the first year of life. Infant monkeys (n=35, 24 female) were longitudinally phenotyped for AT by assessing threat-related increases in freezing behavior, reductions in coo-calling, and increases in circulating cortisol at 1.5, 6, 12, 24, and 52 weeks. AT levels increased linearly, reaching mature levels by 52 weeks. Individual differences in AT, and its components, were stable across development. These findings support further studies during early primate life aimed to uncover neurobiological factors mediating development of this phenotype, which in humans is linked to stress-related psychopathology.

animal behavior and cognition↗

bioRxiv2023

DREADD-mediated amygdala activation is sufficient to induce anxiety-like responses in young nonhuman primates

Anxiety disorders are among the most prevalent psychiatric disorders, with symptoms often beginning early in life. To model the pathophysiology of human pathological anxiety, we utilized Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in a nonhuman primate model of anxious temperament to selectively increase neuronal activity of the amygdala. Subjects included 10 young rhesus macaques; 5 received bilateral infusions of AAV5-hSyn-HA-hM3Dq into the dorsal amygdala, and 5 served as controls. Subjects underwent behavioral testing in the human intruder paradigm following clozapine or vehicle administration, prior to and following surgery. Behavioral results indicated that clozapine treatment post-surgery increased freezing across different threat-related contexts in hM3Dq subjects. This effect was again observed approximately 1.9 years following surgery, indicating the long-term functional capacity of DREADD-induced neuronal activation. [11C]deschloroclozapine PET imaging demonstrated amygdala hM3Dq-HA specific binding, and immunohistochemistry revealed that hM3Dq-HA expression was most prominent in basolateral nuclei. Electron microscopy confirmed expression was predominantly on neuronal membranes. Together, these data demonstrate that activation of primate amygdala neurons is sufficient to induce increased anxiety-related behaviors, which could serve as a model to investigate pathological anxiety in humans.

neuroscience↗

bioRxiv2019

Transcriptional Profiling of Primate Central Nucleus of the Amygdala Neurons to Understand the Molecular Underpinnings of Early Life Anxious Temperament

Children exhibiting extreme anxious temperament (AT) are at an increased risk to develop anxiety and depression. Work in young rhesus monkeys mechanistically links the central nucleus of the amygdala (Ce) to AT. Here, we used laser capture microscopy and RNA sequencing in 47 young rhesus monkeys to investigate AT s molecular underpinnings by focusing on lateral Ce (CeL) neurons. We found 528 AT-related transcripts, including protein kinase C type-delta (PKC{delta}), a CeL microcircuit cell marker implicated in rodent threat processing. We characterized PKC{delta} neurons in the rhesus CeL, compared their distribution to the mouse, and demonstrated that a subset of these neurons project to the laterodorsal bed nucleus of the stria terminalis (BSTLd). These findings present evidence in the primate of a CeL to BSTLd circuit that maybe relevant to understanding human anxiety and points to specific molecules within this circuit that could serve as potential treatment targets for anxiety disorders.

neuroscience↗