Brain Activity May Predict Treatment Response in Chronic Pain

Nancy A. Melville

March 07, 2018

ANAHEIM, California — Unique patterns of brain activity, assessed with electroencephalography (EEG), may predict response to specific nonpharmacologic chronic pain treatments.

Results from a randomized controlled trial show that patients with higher levels of the alpha EEG bandwidth, known to indicate a calm or relaxed brain state, had a greater response to hypnotic cognitive therapy and a lower response to standard cognitive therapy.

The study also showed that patients who were "hypnotizable," were also less likely to respond to cognitive therapy for pain.

"This is the first time, as far as we know, that EEG or hypnotizability have been used to predict outcomes in cognitive therapy or education," said senior author, Mark Jensen, PhD, professor and vice chair for research of the Department of Rehabilitation Medicine at the University of Washington, Seattle.

"The findings need to be replicated, but the most intriguing part of it is that different patterns of brain activity may help us identify people with chronic pain who are more likely to respond to cognitive therapy," he added.

The study was presented here at the American Pain Society (APS) 2018 meeting.

Treatment Choice Guidance 

For the study, the investigators randomly assigned patients with chronic pain to receive 4 weeks of treatment with one of four interventions:

  • Pain education that involved teaching patients about how pain works (n = 42);

  • Cognitive therapy that focused on helping patents to identify and reduce negative thoughts (n = 44);

  • Hypnosis that focused on pain reduction (n = 43); or

  • Hypnotic cognitive therapy, which involved making hypnotic suggestions for changing thoughts about the meaning of pain (n = 44).

The trial was recently completed and post-data assessment is still underway, but Jensen reported that treatment responses were generally as expected, with medium to large effect sizes in all four treatment groups in terms of pain intensity and interference. Effect sizes on depression were smaller.

However, after examining potential moderators of treatment response investigators found some surprises. For instance, they speculated that catastrophizing, or viewing the pain as being worse than it actually is, would significantly influence response rates, because the therapies, particularly cognitive therapy, are often effective for catastrophizing in other contexts.  However, this was not the case.

EEG assessments were conducted as part of an exploratory analysis showing that higher levels of alpha brain activity were linked to an increased response to hypnotic cognitive therapy and decreased response to cognitive therapy.

"The big surprise in the analysis was the alpha difference — people showing more alpha were more likely to respond to hypnotic cognitive therapy and less to cognitive therapy," Jensen said.

Other documented brain activity patterns include delta, the predominant oscillation during deep sleep; theta, indicating feeling sleepy or focused attention; and beta/gamma, indicating more intense brain processing/thinking.

The exploratory analysis also included the evaluation of hypnotizability, assessed by using the Stanford Clinical Hypnotizability Scale, which showed that those with higher hypnotizability scores were also less likely to respond to cognitive therapy. However, greater hypnotizability was associated with a superior response to pain education.

"This suggests that if patients are found to be hypnotizable, clinicians may perhaps want to steer them away from cognitive behavioral therapy avenues. These patients may respond more to education."

In terms of other EEG measures, the authors hypothesized that higher levels of theta, a slow-wave measure associated with memory, would be linked to a better response to hypnosis. However, improvements associated with higher theta were limited to depression, with no effects on pain intensity or interference.

"Theta may be useful for improving depression with hypnosis but might not facilitate the benefits of hypnotic suggestions for changes in pain beliefs," Jensen said.

Overall, the findings offer novel insights that, if replicated, could help guide clinicians to prescribing the most beneficial therapies.

The study represents the Limit, Activate & Enhance (LAE) model, which is designed to "match patients to treatments a priori to optimize outcomes," Jensen said.

Toward Precision Medicine

Another study presented at the meeting, that also used the LAE model and an exploratory analysis of EEG measures, looked at mindfulness meditation and cognitive therapy compared to mindfulness-based cognitive therapy for the treatment of chronic pain.

The study included an intent-to-treat sample of 69 patients with chronic low back pain, who were randomly assigned to receive eight weekly, 2-hour sessions of one of the three interventions: mindfulness meditation, cognitive therapy, or mindfulness-based cognitive therapy.

Results from this study showed that those with high catastrophizing had an improved response to treatment with mindfulness meditation. However, catastrophizing was not associated with improvements in pain when such patients were treated with cognitive therapy.

In terms of EEG measures, patients with low levels of alpha brain waves showed the best responses to cognitive therapy, consistent with the findings in Jensen and colleagues' study, which showed that high levels of alpha brain waves were associated with a decreased response to cognitive therapy.

Furthermore, increases in alpha levels were associated with a greater improvement in pain intensity resulting from mindful meditation. However, these findings were strongest at 4 weeks, with a smaller effect size at 8 weeks.

As suggested in the Jensen et al study, the findings are consistent with the hypothesis that calmness linked to higher alpha levels is more conducive to hypnotherapy.

"It's possible that cognitive therapy may be more useful for a brain that's 'buzzing,'" said the study's senior author, Melissa Day, PhD, from the University of Queensland, Australia.

Regarding mindfulness meditation, it's possible that "baseline alpha differentially predicts outcomes," she said.

The study "adds further evidence that 'different brains' may be more or less suited to different treatments," Day said.  "The LAE model has utility for a priori hypothesis generation, but likely needs refinement."

Commenting on the findings for Medscape Medical News, Lonnie K. Zeltzer, MD, director of the Pediatric Pain and Palliative Care Program and distinguished professor of pediatrics, anesthesiology, psychiatry and biobehavioral sciences at the David Geffen School of Medicine at the University of California Los Angeles, said that, ultimately, these studies may represent an important advancement toward individualized or precision medicine.

"I think the point is that 'one size doesn't fit all.' In other words, we are heading towards precision medicine, which means that from among well-studied pain interventions, we need to find which is best for whom, and when, and how much and how long," she said.

The study received funding from the National Institutes of Health, National Center for Medical Rehabilitation Research, and National Center for Complementary and Integrative Health. Day and colleagues' study was supported by the Australian Government National Health and Medical Research Council. Zeltzer has disclosed no relevant financial relationships.

American Pain Society (APS) 2018. Presented March 5, 2018.

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