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

The overall goal of this procedure is to train people to control a region of their brain involved in contamination anxiety, and to see if this training alters brain function and improves control over contamination anxiety. This is accomplished by first identifying a region of the subject's orbital frontal cortex involved in contamination anxiety. That will be a target area for a biofeedback intervention.

The next step is to assess prior to the biofeedback intervention, the level of anxiety, the subject experiences in response to contamination related images, as well as their brain connectivity patterns. The subject is then trained via biofeedback to control the target brain region. The final step is to assess whether subjects have developed greater control over their target brain area and over their contamination anxiety as a result of the biofeedback and whether such changes are associated with changes in connectivity to the target brain area.

Ultimately, this approach will reveal whether biofeedback of real-time FMRI has potential clinical value for patients with obsessive compulsive disorder and will probe the neural basis of contamination anxiety. Real time. FMRI biofeedback has potential therapeutic value for many different forms of mental illness because it may enable individuals to control aspects of their brain function that give rise to symptoms.

Here we investigate whether it can help people control their contamination anxiety. If so, it may be clinically useful for patients with obsessive compulsive disorder. The approach presented here combining biofeedback with before and after assessments of clinical variables and brain connectivity can also address basic questions in neuroscience and psychiatry.

The biofeedback allows us to alter brain dynamics, and we can then measure how changes in brain connectivity give rise to differences in clinical or cognitive variables. Prior to initiating this experiment, extensive stimulus development is needed. Contamination related and neutral images must first be collected and then piloted to ensure the anxiety induced by these stimuli is balanced across provocation conditions and that anxiety is significantly greater in the provocation conditions than in the neutral conditions.

When pilot studies are complete, potential subjects should be recruited and screened to identify healthy individuals who can safely participate in MRI experiments and who report high levels of contamination anxiety, and a desire to learn to control that anxiety. For this experiment, subjects come in on four separate days scheduled at approximately half week intervals so that the entire study takes two weeks to complete. The flow chart seen here outlines the protocol in addition for each subject that will receive true biofeedback sessions.

Another subject should be recruited who is matched in age and gender to receive sham biofeedback before every MR session. The subjects are screened for metal on day one, a high resolution structural image. Then two runs of resting state functional data are collected, followed by three localizer runs of functional data in which the subject alternates between viewing intense contamination related images and neutral images at 42nd intervals.

These localizer runs are used to localize the region of the OFC activated by contamination anxiety. Following the day one imaging session subjects meet with the clinical psychologist who has expertise in anxiety disorders for a reappraisal strategy development session. The aim of this session is to develop an individualized cognitive strategy for the subject that provides them with some initial control over activity in their orbital frontal cortex.

These strategies for raising or lowering OFC activity are intended only to provide some initial limited ability to control the OFC. During the biofeedback sessions, subjects will have the chance to experiment with their cognitive strategies and receive direct feedback, thereby allowing them to develop increasing control over the OFC. Next, the data collected in the day one localizer is analyzed prior to the day two session.

The resulting team map indicates which regions of the brain were more active when the subject viewed contamination related images than when they viewed neutral images. The top 30 pixels in this TM map located within the OFC or adjacent frontal polar region are selected to represent that particular subject's target region of the OFC for their upcoming biofeedback scans. This region is then translated from functional space into the anatomical space via a rigid registration with the nearest neighbor interpolation.

A control region is also defined to include all the white matter in the brain and is translated into the same space from the MNI brain. These two regions will be used by the real-time analysis program during the day two biofeedback session. On day two of the experiment, subjects first participate in an out of magnet assessment session.

Before each assessment session, subjects are verbally instructed to attempt to minimize their anxiety while viewing the upcoming contamination related images. Next, they are directed with detailed onscreen instructions to report the level of contamination related anxiety they feel in response to the images. Galvanic skin response is simultaneously monitored.

Subjects then participate in a 1.5 hour realtime FMRI biofeedback session. The session begins with the collection of axial anatomical images in the same slice locations as the functional data. Then a functional reference scan is collected next.

The two regions of interest are translated into the functional space of the current session via a concatenation of two rigid registrations. The first registration maps the regions from the anatomical space of day one to the anatomical space of day two. The second registration maps the regions from the anatomical space of day two to the space of the functional reference scan of day two.

While the regions are being registered, there are two functional runs collected that are referred to as control task runs. These runs do not involve biofeedback, but are used to assess the ability of subjects to control activity within their OFC region of interest when exposed to contamination related images. While in the scanner, subjects view images with an arrow that points up or down for contamination related images or forward for neutral images.

Subjects are told to try to increase activity in their OFC when the arrow points up to try to decrease activity in their OFC when it points down and simply relax when the arrow points to the right. The arrow and picture change every 26 seconds alternating through the three conditions after the control task runs, and when the target region and control region have been registered to the current functional space. Six biofeedback runs or sham biofeedback runs depending on the subject are conducted.

The biofeedback runs are used to train subjects to control activity in their O-F-C-R-O-I. They are similar to the control task runs except that subjects receive feedback at the bottom of the screen regarding their success in controlling the brain area. The biofeedback display shown here has been sped up, but otherwise reflects exactly what a subject viewed during biofeedback.

Sham biofeedback runs will be identical to the biofeedback runs, except that subjects will view the time course of activity in the OFC from a previous age and gender matched subjects biofeedback run to the degree that the biofeedback subject was able to control activity in the OFC. The sham subject will appear to be equally successful during the sham runs, resulting in similar impressions of success. Finally, two more control task runs are collected for each subject.

Then the subjects should return on day three for a scanning session identical to day two, but using separate matched sets of stimuli on day four subjects should participate in a final assessment session. Then a final one hour MR imaging session in which resting state functional connectivity data is collected after data is collected for all subjects. Subjects who received real biofeedback can be contrasted with subjects who received sham biofeedback to determine whether they developed greater control over their target region and whether that enabled them to exert greater control over their contamination anxiety.

Changes in contamination anxiety in biofeedback subjects are related to changes in control over their target region and to changes in functional connectivity patterns. Here we see a screenshot of the visual display from one of the final biofeedback runs of a subject who successfully gained control over their OFC. The run ends with the neutral condition and hence the arrow is white and pointing forward.

This subject also showed greater control over their contamination anxiety as indicated by lower anxiety ratings in the post intervention assessment session, and had greater control over their orbital frontal cortex during the control task runs. This method has great potential in psychiatry, both as a clinical treatment and a research tool for investigating the neural substrates that underlie clinical symptoms.