Real-time fMRI Biofeedback Targeting the Orbitofrontal Cortex for Contamination Anxiety

Summary

Here we present a method for training people to control a brain area involved in contamination anxiety and for probing the relationship between contamination anxiety and brain connectivity patterns.

Abstract

We present a method for training subjects to control activity in a region of their orbitofrontal cortex associated with contamination anxiety using biofeedback of real-time functional magnetic resonance imaging (rt-fMRI) data. Increased activity of this region is seen in relationship with contamination anxiety both in control subjects¹ and in individuals with obsessive-compulsive disorder (OCD),² a relatively common and often debilitating psychiatric disorder involving contamination anxiety. Although many brain regions have been implicated in OCD, abnormality in the orbitofrontal cortex (OFC) is one of the most consistent findings.^{3, 4} Furthermore, hyperactivity in the OFC has been found to correlate with OCD symptom severity⁵ and decreases in hyperactivity in this region have been reported to correlate with decreased symptom severity.⁶ Therefore, the ability to control this brain area may translate into clinical improvements in obsessive-compulsive symptoms including contamination anxiety. Biofeedback of rt-fMRI data is a new technique in which the temporal pattern of activity in a specific region (or associated with a specific distributed pattern of brain activity) in a subject's brain is provided as a feedback signal to the subject. Recent reports indicate that people are able to develop control over the activity of specific brain areas when provided with rt-fMRI biofeedback.^7-12 In particular, several studies using this technique to target brain areas involved in emotion processing have reported success in training subjects to control these regions.^13-18 In several cases, rt-fMRI biofeedback training has been reported to induce cognitive, emotional, or clinical changes in subjects.^{8, 9, 13, 19} Here we illustrate this technique as applied to the treatment of contamination anxiety in healthy subjects. This biofeedback intervention will be a valuable basic research tool: it allows researchers to perturb brain function, measure the resulting changes in brain dynamics and relate those to changes in contamination anxiety or other behavioral measures. In addition, the establishment of this method serves as a first step towards the investigation of fMRI-based biofeedback as a therapeutic intervention for OCD. Given that approximately a quarter of patients with OCD receive little benefit from the currently available forms of treatment,^20-22 and that those who do benefit rarely recover completely, new approaches for treating this population are urgently needed.

Protocol

1. Stimulus Development

Extensive stimulus development is needed. Contamination-related and neutral images must be collected and piloted to ensure the anxiety induced by these stimuli is balanced across provocation conditions and significantly greater in the provocation conditions than in the neutral conditions. More specifically, the following four stimulus sets are needed:

1. Localizer stimuli: 300 contamination-related images and 300 neutral images are used to localize the region of the orbitofrontal cortex (OFC) involved in contamination anxiety. These must be piloted to assure that the contamination-related im....

Discussion

Biofeedback of real-time fMRI data is a new technique and more work is needed to optimize this method so as to maximize learning in subjects. Recent studies have explored how learning changes with different numbers of runs or scanning sessions,^{14, 18, 27} how the feedback paradigm affects learning²⁸, and whether the learning induced by a given biofeedback protocol results in changes in brain function that persist beyond the end of the biofeedback training period.^{15, 18, 27, 29} However, a .......