Project Summary
Anxiety is characterized by anticipation of potential future threats. However, our basic
understanding of the neurobiology of attentional and perceptual biases to threat in anxiety is
based, not on prestimulus anticipatory response, but on actual neural response to threatening
stimuli. These biases are characterized as being driven in a “bottom-up” manner by threatening
stimuli due to their evolutionary salience or physical characteristics. Hence, our knowledge
regarding top-down anticipatory factors such as expectations, prior knowledge and contexts in
guiding threat perception in anxiety is sparse at best. This stands in stark contrast to substantial
basic cognitive neuroscience research demonstrating that top-down prestimulus factors guide
perception of threatening and non-threatening stimuli, as well as clinical research showing that
anxiety is characterized by inflated expectancies regarding upcoming threats. The overarching
goal of this proposal is to bridge this gap in the literature and 1) examine the neural circuitry that
implements threat-related top-down biases and its contribution to enhanced perception of
threatening stimuli in anxiety and 2) examine whether the neural circuitry implementing top-
down and bottom-up contributions to threat perception and their interaction maps on differently
to different dimensions of anxiety studied transdiagnostically, thereby establishing the clinical
specificity of these measures. Four groups of participants (N=30 each) with a diagnosis of
Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder or no anxiety disorder
with a range of levels of Anxious Apprehension (AP) and Anxious Arousal (AR) will complete a
perceptual decision-making task in which threatening or neutral cues are used to identify
subsequently presented fearful and neutral faces. Signal detection measures as well as cue-
and stimulus-related brain activity will be recorded via functional magnetic resonance imaging in
fusiform face area (FFA), superior temporal sulcus (STS) and amygdala, involved in processing
emotional expressions and ventromedial prefrontal cortex involved in maintaining prestimulus
representations, to test 3 specific aims. The first aim of this proposal is to delineate the
contribution of threat-related cues, as well as prestimulus and stimulus-related neural activity
and connectivity in facilitating subsequent perceptual decision making across all participants.
The second aim is to determine if enhanced perception and increased prestimulus or stimulus-
related neural activity and connectivity due to threat cues is related to AP, even when controlling
for AR and diagnostic group status. The final aim is to determine if enhanced perception of
threat stimulus (irrespective of cue) and related neural activity and connectivity is associated
with AR even when controlling for AP and diagnostic group status. Hence, these aims will
establish the specificity of neural measures of top-down and bottom-up aspects of threat
perception for AP and AR. Overall, this project will represent an important step in clarifying the
neurobiology of anxiety disorders which is predominantly based on prioritized and relatively
automatic processing of threatening stimuli. The proposed research will shed light on how prior
knowledge about threatening information helps to guide perception in normal and anxious
individuals, allowing us to build more comprehensive and ecologically pertinent models in which
prior learning, experiences and expectations factor into explaining threat perception in anxiety.
Importantly, by examining the differential relationship of prestimulus and stimulus-related neural
circuitry with AP and AR transdiagnostically, we hope to uncover potential ways of
understanding the structure of anxiety disorders that are not based on traditional DSM
diagnostic criteria. Finally, identification of these transdiagnostic affective and neural measures
is an important first step towards the development newer treatments for anxiety and
improvement of existing treatments that rely on modification of attentional biases.