Background & Aims

Cognitive behavioral therapy (CBT) is an effective approach for managing chronic pain. Magnetic resonance imaging (MRI) has been especially used to study neural response to CBT in patients with chronic pain, revealing changes in areas such as the orbitofrontal cortex (OFC), the dorsolateral prefrontal cortex (DLPFC), and the inferior frontal gyrus (IFG) 2, 4, 7. However, neurophysiological studies have been scarce. Electroencephalography (EEG) studies have shown changes in brain activity of the left frontal area after psychotherapy, including CBT 1, 3. However, these results are not specific to CBT, and large regions of interest (ROIs) provided limited structural details. Therefore, we used magnetoencephalography (MEG) source images co-registered with MRI data to explore the neural mechanisms underpinning CBT’s efficacy. We designated the OFC, IFG, and DLPFC as ROIs, and hypothesized that these regions would exhibit changes in power associated with symptom improvement following CBT.

Methods

We administered resting-state MEG scans and MRI structural imaging to 30 patients with chronic pain and 31 age-matched healthy controls. In patients, MEG was measured before and after CBT that they engaged in a 12-session group program 5, 6. MEG data were examined by using power spectral density (PSD) and multiscale entropy (MSE) analysis within the OFC, IFG, and DLPFC set as ROIs. Initially, we identified regions displaying significant differences between patients before CBT and healthy controls. Then, we examined changes in PSD and MSE within these regions after conducting CBT. Furthermore, we applied support vector machine (SVM) analysis to these obtained PSD and MSE data to assess the potential for classifying treatment effects.

Results

In patients with chronic pain, CBT resulted in significant changes in brain activity, specifically in the gamma2 frequency range (60 – 90 Hz) in the right IFG and in the MSE within the right DLPFC. The change in pain intensity between pretreatment and post-treatment periods of CBT showed a positive correlation with these neurophysiological changes. Furthermore, a SVM classifier was able to predict which patients would respond to the treatment, and those predicted as responders exhibited higher rates of improvement compared to the non-responders.

Conclusions

This study highlights the critical involvement of the right IFG and DLPFC in reducing pain intensity through CBT. Accumulating further evidence is imperative for future developments.

References

1.Day MA, Matthews N, Mattingley JB, Ehde DM, Turner AP, Williams RM, Jensen MP. Change in brain oscillations as a mechanism of mindfulness-meditation, cognitive therapy, and mindfulness-based cognitive therapy for chronic low back pain. Pain Med. 22:1804-1813, 2021
2.Jensen KB, Kosek E, Wicksell R, Kemani M, Olsson G, Merle JV, Kadetoff D, Ingvar M. Cognitive behavioral therapy increases pain-evoked activation of the prefrontal cortex in patients with fibromyalgeia. Pain. 153:1495-1503, 2012
3.Jensen MP, Hakimian S, Ehde DM, Day MA, Pettet MW, Yoshino A, Ciol MA. Pain-related beliefs, cognitive processes, and electroencephalography band power as predictors and mediators of the effects of psychological chronic pain interventions. Pain. 162:2036-2050, 2021
4.Seminowicz DA, Shpaner M, Keaser ML, Krauthamer GM, Mantegna J, Dumas JA, Newhouse PA, Filippi CG, Keefe FJ, Naylor MR. Cognitive-behavioral therapy increases prefrontal cortex gray matter in patients with chronic pain. J Pain. 14:1573-1584, 2013
5.Yoshino A, Okamoto Y, Horikoshi M, Oshita K, Nakamura R, Otsuru N, Yoshimura S, Tanaka K, Takagaki K, Jinnin R. Effectiveness of group cognitive behavioral therapy (GCBT) for somatoform pain disorder patients in Japan: A preliminary non?case?control study. Psychiatry Clin Neurosci. 69:763-772, 2015
6.Yoshino A, Okamoto Y, Jinnin R, Takagaki K, Mori A, Yamawaki S. The role of coping with negative emotions in cognitive behavioral therapy for persistent somatoform pain disorder: is it more important than pain catastrophizing? Psychiatry Clin Neurosci. 73:560-565, 2019
7.Yoshino A, Okamoto Y, Okada G, Takamura M, Ichikawa N, Shibasaki C, Yokoyama S, Doi M, Jinnin R, Yamashita H. Changes in resting-state brain networks after cognitive–behavioral therapy for chronic pain. Psychol Med. 48:1148–1156, 2018

Presenting Author

Atsuo Yoshino

Poster Authors

Atsuo Yoshino

MD, PhD

Hiroshima University

Lead Author

E-mail

Toru Maekawa

Ph.D.

Lead Author

E-mail

Ryuji Nakamura

Ph.D.

Lead Author

E-mail

Kai Ushio

Ph.D.

Lead Author

E-mail

Tomoaki Katagiri

M.D.

Lead Author

E-mail

Shigehito Shiota

Ph.D.

Lead Author

E-mail

Katsuyuki Moriwaki

Ph.D.

Lead Author

E-mail

Yasuo Tsutsumi

Ph.D.

Lead Author

E-mail

Topics

  • Pain Imaging