Systems Neuroscience and Pain Lab

Learned Volitional Control Over Brain fMRI Activation and Pain

Control over brain activation and pain learned by using real-time functional MRI

Proc Natl Acad Sci USA (2005)

deCharms, R. C., Maeda, F., Glover, G. H., Ludlow, D., Pauly, J. M., Soneji, D., Gabrieli, J. D., and Mackey, S. C.

We all consciously and unconsciously control our brain for every activity we initiate, every thought we have, and every emotion or sensation we experience. Until recently, it has been unclear as to what extent we can learn to control brain activity—more specifically, the activity of specific brain regions--and what impact that control would have on us. Well-defined regions of the brain are responsible for the perception of pain, and, in our pilot study, we sought to answer two questions:

Functional magnetic resonance imaging (fMRI) is a tool that allows researchers to open windows into the brain and “see” brain activity. Until recently, fMRI data needed to be analyzed off-line with the results being unavailable until many hours after the subject was scanned. Through software developed by Dr. Christopher deCharms in collaboration with Stanford University, we are now able to analyze the imaging data in near real time and show a subject being scanned their own brain activity on a moment by moment basis.

PNAS, December 2005

Due to the magnitude and complexity of this study, we put together an interdisciplinary team of researchers to tackle the two questions above. This team included: Dr. Christopher deCharms (principle investigator for Omneuron, a San Francisco bay area startup), Dr. Fumiko Maeda (research associate), Dr. John Gabrieli (formerly professor of the Stanford Department of Psychology ; he is now at MIT), Dr. John Pauly (associate professor of electrical engineering), Dr. Gary Glover (professor of radiology and director, radiological sciences laboratory), Deepak Soneji and David Ludlow (research assistants in Dr. Mackey’s lab), and Dr. Sean Mackey (principle investigator who led the Stanford team).

We initially took 8 healthy subjects and used the real time fMRI information to help them learn to control their brain activations.

Visual images subjects and patients visualized while changing their brain activity. PNAS, December 2005

The initial part of the study involved exposing healthy subjects to a heat stimulus. First, outside of the scanner, we heated a small area of their skin using a computer-controlled Peltier device. We determined which temperature resulted in their experiencing a pain score of 7 out of 10 – where 0=no pain and 10=the worst pain imaginable. We then scanned their brain, while their skin was heated, to locate the regions of the brain responsible for their perception of pain. We found that an area of the brain – the rostral anterior cingulate cortex (rACC) – was reliably and strongly activated in these subjects. Resultantly, we focused on this area. We then placed subjects in the scanner and, while intermittently heating their skin, asked them to change their brain activity while watching a visual representation of this activity. The visuals used were both a moving line graph as well as a virtual flame that got brighter or dimmer as their brain activity increased or decreased, respectively.

Greatest Training Effect in Rostral Anterior Cingulate Cortex, PNAS, December 2005

To help jumpstart the process, we gave them suggestions as to how they could change their brain activity in the rACC. This included changing the focus of their attention on the pain, changing emotional value of the pain, as well as other similar strategies. Over several sessions, we monitored how well they learned to control the rACC and also had them rank their pain perception. We found a significant increase in the subject’s ability to control brain activation throughout training.

Control Over rACC Activation Increases With Training, PNAS, December 2005

These results provided a positive answer to our first question as to whether subjects could learn to voluntarily control brain activity in a specific brain region.

As an answer to our second question, we found a significant increase in the ability of healthy subjects to control their pain with repeated training.

Control Pain Perception Increases With Training, PNAS, December 2005

This was not a placebo response. Multiple control groups were run to insure that the rACC was truly modulating pain and that the immediate visual information of the rtfMRI information did indeed assist the subject in modulating their pain. We found that none of the control groups had an effect from training and no significant difference in pain. Overall, the healthy subjects using the real time information demonstrated an average of 23% enhancement in control over pain intensity and 38% enhancement in control over pain unpleasantness as compared with subjects in the control groups who did not receive the real time fMRI training.

Finally, we enrolled 8 patients with chronic intractable pain to test our original two questions. The study was conducted much like the healthy controls, except the patients used their own spontaneous/endogenous pain rather than an externally applied stimulus. In the small group of pain patients, they too demonstrated an ability to control their brain activity and subsequently their pain level. Overall, the pain patients noticed a 64% decrease in pain ratings on the McGill Pain Questionnaire (a survey form that measures both the sensory and emotional aspect of pain) and an average of 44% decrease on a visual analogue scale.

Taken together, these results suggest that, using real time fMRI, people can learn to strengthen the function of a specific region of the brain and, through that change, the regions associated with the perception of pain. It is similar to exercising muscles, but, in this case, the “muscle” is an area in the brain. We are currently conducting experiments to determine if other regions of the brain involved in pain processing can also be controlled.

A Message for Patients Suffering From Chronic Pain

We recognize that chronic pain hugely impacts not only patients but their families and friends as well. Often people seek out the newest research and treatments in the hopes of reducing their pain and suffering. While we are excited about the results of this study, we believe some cautions are in order in interpreting our results.

First, this was a small pilot study. Furthermore, while we studied 8 patients with chronic pain, they only made up a small part of our overall study design. The majority of the study involved healthy subjects experiencing an experimentally induced noxious stimulus (i.e., a non-injuring heat/pain stimulus). Consequently, although the results were statistically significant and the magnitude of the effects were clinically significant, these results must be replicated on a much larger scale.

Secondly, we did not actively monitor the duration of effect for the patients with chronic pain. Therefore, we have not shown that the results have any long-term effectiveness. We are currently studying that question.

Consequently, this study should not be interpreted to suggest that real time fMRI is in any way to be thought of as a current treatment for chronic pain. There is much science and work to be done to demonstrate real clinical benefit. Although optimistic about the future, the authors advise that patients not get their hopes up that this method would cure their chronic pain. Our results do not give any indication to support that.


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