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Chronic pain has been shown to be successfully treated with cognitive behavioral therapy (CBT).^1,2 Magnetic resonance imaging (MRI) has been used in past research and has shown increases in brain gray matter, including in the right inferior frontal gyrus (IFG) and the right dorsolateral prefrontal cortex (DLPFC) following CBT, correlated with improvement in the intensity of pain.³ However, the underlying neural mechanisms of CBT still are not well understood. 

To examine resting-state brain activity, various neuroimaging techniques have been employed, including functional MRI and electroencephalography, both of which have some drawbacks.⁴ Magnetoencephalography (MEG), on the other hand, has the advantage of being able to localize and quantify cortical activity, but there are limited data from MEG studies to help explore the neurophysiological effects of CBT.^4,5

Clinical assessments and neuroimaging: putting them together

To add to the body of evidence, Atsuo Yoshino, MD, PhD, of the Health Service Center and the Center for Brain, Mind and KANSEI Sciences Research, Hiroshima University in Hiroshima, Japan, and colleagues, studied the neurophysiological effects of CBT on chronic pain by using MEG.⁴

The investigation compared resting-state MEGs from patients with chronic pain to those of healthy controls (between June 2020 and August 2022). The MEGs were done prior to the group CBT sessions (12 sessions) and after, along with clinical assessments. Machine analysis using support vector machine (SVM) analysis was done on the MEG data, looking at the classification of treatment effects.⁴ The regions of interest (ROI) in the frontal region that were studied were the orbitofrontal cortex, the right IFG, and the right DLPFC.⁴

Study participants answered clinical questionnaires and underwent neuroimaging (MEGs and MRIs) within 2 weeks prior to starting CBT. For this study, chronic pain was defined as a mean pain intensity rating of 鈮� 3 on the 0-10 Numerical Rating Scale. To assess the pain, the short form of the McGill Pain Questionnaire was used (including the Present Pain Intensity and a visual analog scale [VAS]), and the Pain Catastrophizing Scale was used to look at the level of catastrophic pain-related thinking a patient has. Depressive symptoms were assessed using the Beck Depression Inventory-Second Edition, and anxiety levels were measured using the State-Trait Anxiety Inventory. 

Each of the CBT sessions had a particular goal: sessions 1-3 included psychological education on pain and self-monitoring; sessions 4 and 5 were on relaxation/breathing techniques; session 6 concentrated on initiating behavioral activation; and sessions 7-12 used cognitive restructuring.⁴

Transformative effects of CBT

After CBT, significant improvements were present in almost all of the clinical indicators (P<.05 for all). Additionally, the investigators found that the irregular power spectral density (PSD) in the right IFG鈥檚 gamma2 band and the right DLPFC鈥檚 multiscale sample entropy (MSE) in these patients normalized after the CBT program. They also found positive correlations between the VAS score changes before and after the treatment and the MSE changes.⁴

Employing SVM model

Using the PSD and MSE data, the authors developed an SVM machine-learning model.¹ Using the SVM, they found that the improvement rate was significantly higher in the SVM-predicted healthy control group than in the SVM-predicted patient group (P=.04), which supported this classification method. This SVM found the differences between the patients with chronic pain before their treatment and the healthy controls. It also was successful in looking at the efficacy of treatment, supporting the theory that resting-state MEG signatures could detect patients with chronic pain and assess treatment effects with a high level of accuracy.⁴

What changes in brain activity tell us

The researchers also found that there were changes in the right IFG and right DLPFC, which were associated with CBT treatment. This supports the role that the IFG has in the cognitive processing of perceptions of pain, including pain-related fear. The investigators also discovered that the gamma2 power of the right IFG was higher in the patients with chronic pain compared with the healthy controls; this power decreased with CBT. The MSE was increased in the right DLPFC of patients with chronic pain compared with healthy controls, which indicated increased irregularity. This irregularity decreased after CBT and was positively correlated with decreased subjective pain.⁴

Limitations

The authors mentioned some limitations to their study. One is that they did not account for the possibility that a treatment (such as an antidepressant) might have an effect on pain perception. Additionally, as there was not a therapy control group, there may have been placebo effects of psychotherapy, as have been shown in past studies on the treatment of chronic pain.⁴

In summary

The authors found that by using MEG to investigate the impact of CBT on neural system processes in patients with chronic pain, they showed that CBT improved various irregular neural patterns, particularly those associated with the right IFG and DLPFC. They also demonstrated that a correlation exists between improved pain intensity scores and neural changes following CBT. Additionally, the potential use of SVM in assessing treatment efficacy was studied. Overall, the investigators postulate that 鈥溾��the right IFG and the right DLPFC play pivotal roles in modulating the cognitive processing of pain perceptions and possibly contribute significantly to therapeutic mechanisms.鈥�⁴

Published: May 01, 2024