Spatial Context and Fear Learning

Objective:

To examine the processes involved in distinguishing between threatening and safe conditions, we aim to investigate the neural bases of contextual fear learning using functional magnetic resonance imaging (fMRI). To do this, we will study behavioral, physiological, and brain responses as aversive stimuli are encountered in a virtual environment, and will explore how fear-related responses depend on the surrounding environment. In addition, we will examine how these responses differ in clinical anxiety.

We are interested in studying Pavlovian aversive context conditioning in healthy controls and patients with anxiety disorders. We will examine the extent to which participants learn to discriminate between dangerous and safe virtual contexts, and how this learning maps to the neural networks underlying anxiety and context coding. We expect successful learning of the contextual fear response in healthy controls, as evidenced by differential skin conductance response and neural activation to safe vs. threat context. Accordingly, we anticipate higher neuronal activity in the hippocampus, prefrontal cortex, and amygdala. These findings will be accompanied with increased hippocampus-prefrontal cortex connectivity during approach and exploration of the dangerous context, and increased amygdala activation during anticipation of shock in the dangerous context. Physiologically, SCR will increase in threat context compared to safe context. However, anxious patients are expected to fail to learn to differentiate safe from threat context, exhibiting increased SCR and neural activation in both safe and threat contexts, an index of contextual generalization of fear. Particularly, the lack of contextual fear discrimination in anxious patients will be associated with weaker hippocampal activation to contextual learning. To examine differential context fear conditioning, we will use a virtual reality (VR) paradigm. VR provides an optimal way to probe spatial navigation and simulates context. The VR task presents an outdoor space, which comprises a dangerous (probabilistic electrical shocks) and a safe (no shocks) location. Healthy controls and patients with anxiety disorders will be compared on their physiological and neural reactivity during task performance. Preliminary psychophysiological data suggest that the proposed procedure is an effective way to promote different responses to a safe and dangerous spatial location. Hence, we anticipate that this procedure will allow us to examine brain correlates of differential contextual fear responses in humans and compare them between healthy participants and patients diagnosed with an anxiety disorder.

Study population:

Two study populations, healthy volunteers and patients diagnosed with an anxiety disorder (generalized anxiety disorder (GAD), social anxiety disorder (SAD), panic disorder, and post-traumatic stress disorder) will complete the protocol. Participants will be adult males and females, aged 18 to 50 years.

Design:

This fMRI study will compare performance, physiological and neural measures between healthy adults and patients with anxiety disorders, who perform a threat VR task in the scanner.

The VR task entails navigating in a virtual outdoor environment, which, unbeknownst to the participants is divided into a safe and a dangerous context, which are recognizable by environmental characteristics (e.g., mountain, clouds). The dangerous context is associated with probabilistic shocks, which are never encountered in the safe context. Participants learn about these two contexts as they collect flowers (cues), one at a time, in either context. In the dangerous context, the flowers are associated with 50% chance of a shock

Outcome measures:

The primary outcome measures will be the cerebral fMRI blood-oxygen-level dependent (BOLD) responses to three events: (1) shock anticipation: after collecting the cues (flowers) during anticipation of a potential shock, (2) context exploration: as participants navigate in the threat context or safe context in between trials (which start when a flower appears in the environment), and (3) cue approach: during approach towards the flower, in the threat or safe context. The secondary outcome measures will consist of the changes in psychophysiological responses, such as SCR, heart rate, pupil dilatation, and respiratory rate, which will validate fear responses.