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Updated: May 25, 2026

Optogenetic Manipulation of Neuronal Activity to Modulate Behavior in Freely Moving Mice
Published on: October 27, 2020
Interactions between transient and sustained neural signals support the generation and regulation of anxious emotion
Leah H Somerville1, Dylan D Wagner, Gagan S Wig
1Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College, New York, NY 10044, USA. lhs@wjh.harvard.edu
Abstract:
Anxious emotion can manifest on brief (threat response) and/or persistent (chronic apprehension and arousal) timescales, and prior work has suggested that these signals are supported by separable neural circuitries. This fMRI study utilized a mixed block-event-related emotional provocation paradigm in 55 healthy participants to simultaneously measure brief and persistent anxious emotional responses, testing the specificity of, and interactions between, these potentially distinct systems. Results indicated that components of emotional processing networks were uniquely sensitive to transient and sustained anxious emotion. Whereas the amygdala and midbrain showed only transient responses, the ventral basal forebrain and anterior insula showed sustained activity during extended emotional contexts that tracked positively with task-evoked anxiety. States of lesser anxiety were associated with greater sustained activity in the ventromedial prefrontal cortex. Furthermore, ventromedial prefrontal recruitment was lower in individuals with higher scores on intolerance of uncertainty measures, and this hyporecruitment predicted greater transient amygdala responding to potential threat cues. This work demonstrates how brain circuitries interact across temporal scales to support brief and persistent anxious emotion and suggests potentially divergent mechanisms of dysregulation in clinical syndromes marked by brief versus persistent symptoms of anxiety.
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