Neural Mechanisms of Acceptance and Commitment Therapy for Chronic Pain: A Network-Based fMRI Approach
Open accessAbstract
Over 100 million Americans suffer from chronic pain (CP), which causes more disability than any other medical condition in the U.S. at a cost of $560-$635 billion per year (IOM, 2011). Opioid analgesics are frequently used to treat CP. However, long term use of opioids can cause brain changes such as opioid-induced hyperalgesia that, over time, increase pain sensation. Also, opioids fail to treat complex psychological factors that worsen pain-related disability, including beliefs about and emotional responses to pain. Cognitive behavioral therapy (CBT) can be efficacious for CP. However, CBT generally does not focus on important factors needed for long-term functional improvement, including attainment of personal goals and the psychological flexibility to choose responses to pain. Acceptance and Commitment Therapy (ACT) has been recognized as an effective, non-pharmacologic treatment for a variety of CP conditions. However, little is known about the neurologic mechanisms underlying ACT. We conducted an ACT intervention in women (n=9) with chronic musculoskeletal pain. Functional magnetic resonance imaging (fMRI) data were collected pre- and post-ACT, and changes in functional connectivity (FC) were measured using Network-Based Statistics (NBS). Behavioral outcomes were measured using validated assessments such as the Acceptance & Action Questionnaire (AAQ-II), the Chronic Pain Acceptance Questionnaire (CPAQ), the Center for Epidemiologic Studies Depression Scale (CES-D), and the NIH Toolbox Neuro-QoL™ (Quality of Life in Neurological Disorders) scales. Results suggest that, following the four-week ACT intervention, participants exhibited reductions in brain activation within and between key networks including self-reflection (default mode, DMN), emotion (salience, SN), and cognitive control (frontal parietal, FPN). These changes in connectivity strength were correlated with changes in behavioral outcomes including decreased depression and pain interference, and increased participation in social roles. This study is one of the first to demonstrate that improved function across the DMN, SN, and FPN may drive the positive outcomes associated with ACT. This study contributes to the emerging evidence supporting the use of neurophysiological indices to characterize treatment effects of alternative and complementary mind-body therapies. Perspective: This article identifies neural mechanisms that may mediate behavioral changes associated with Acceptance and Commitment Therapy (ACT) in persons with chronic musculoskeletal pain. This information could potentially help clinicians to determine which mind-body therapies may benefit specific patients as part of an integrative pain management approach.
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In the initial report, effects were observed in 10 nodes out of 101 triple-network nodes, and those same 10 nodes were used in the following analysis with the seven pain nodes.
“In our initial report [21] we tested for changes in brain networks underlying ACT-related outcomes in those with CMP using only triple network nodes without the inclusion of pain nodes (t > 2.1 for the 101 nodes of the DMN, FPN, and SN). We observed effects in 10 nodes out of 101 triple network nodes and used those same 10 for the following analysis in conjunction with Waller and colleagues’ [35]”
From Graph theory analysis of induced neural plasticity post-Acceptance and Commitment Therapy for chronic pain (2020) · cites this paper as [21]
The Methods (Network Based Statistic; page unavailable) say the initial analysis tested all 101 DMN, FPN, and SN nodes, and the Results identify a network of 10 nodes with ACT-related connectivity changes. The cited paper reports a threshold of t > 2.5, not t > 2.1. It does not document the subsequent analysis combining those 10 nodes with seven pain nodes. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe functional connectivity changes involving regions of the DMN, FPN, SN, and pain network, alongside previously reported positive behavioral outcomes, are convincing underlying reasons for how ACT effectively alleviates chronic pain symptomology.
“These functional connectivity changes involving regions of the DMN, FPN, SN, and pain network (alongside previously reported positive behavioral outcomes, [21]) are convincing underlying reasons for the way ACT effectively alleviates chronic pain symptomology.”
From Graph theory analysis of induced neural plasticity post-Acceptance and Commitment Therapy for chronic pain (2020) · cites this paper as [21]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredDecreased functional connectivity in the left putamen/right insula and left insula/right thalamus may contribute to enhanced quality of life reported post-ACT.
“So, decreased functional connectivity in these regions may contribute to enhanced quality of life that is reported post-ACT [21,40].”
From Graph theory analysis of induced neural plasticity post-Acceptance and Commitment Therapy for chronic pain (2020) · cites this paper as [21]
The Results (Network Based Statistic and Correlation Analysis; page not available) report decreased functional connectivity after ACT and associations between some connectivity changes and quality-of-life measures. They identify different connections, however, and do not link left putamen–right insula or left insula–right thalamus connectivity to improved quality of life. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAytur and colleagues' results suggest that heightened connectivity between the triple network returned to a lower, healthier level of connectivity post-ACT.
“Those results suggest that levels of heightened connectivity between the triple network returned to a lower, healthier level of connectivity post-ACT.”
From Graph theory analysis of induced neural plasticity post-Acceptance and Commitment Therapy for chronic pain (2020) · cites this paper as [21]
The Results (Network Based Statistic; page unavailable) report decreased functional connectivity in 10 connections of the triple network after ACT, and the Correlation Analysis links several connectivity changes to behavioral improvements. The paper does not establish that connectivity returned to a previously healthy or normal level; it reports a decrease, not a measured return to such a benchmark. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAvailable evidence points to neurophysiological brain correlates of clinical improvement after acceptance and commitment therapy in chronic pain, supporting the usefulness of acceptance and commitment therapy in chronic pain populations such as central pain sensitization syndromes.
“Additionally, available evidence points to the neurophysiological brain correlates of clinical improvement after ACT in chronic pain [88,89], supporting the usefulness of ACT in chronic pain populations such as CPSS.”
From Effectiveness of acceptance and commitment therapy in central pain sensitization syndromes: A systematic review (2021) · cites this paper as [88]
A study exploring the mechanisms of ACT for persistent pain revealed statistically significant improvements in depression, satisfaction with social role and pain acceptance pre-to-post ACT.
“A study exploring the mechanisms of ACT for persistent pain revealed statistically significant improvements in depression, satisfaction with social role and pain acceptance pre-to-post ACT [22].”
Individual sensitivity to sound varies considerably: some individuals are highly sensitive to even minor sounds, others benefit from gentle background noise that masks disturbances.
“Individual sensitivity to sound varies considerably: while some individuals are highly sensitive to even minor sounds, others benefit from gentle background noise that masks disturbances [54,55].”
From Pre-Sleep Anxiety: Mechanisms and Therapeutic Approaches in Clinical Practice. (2026) · cites this paper as [55]
The Discussion’s ‘Limitations and Future Directions’ section addresses sensitivity to pain, not sound. Searches for sound sensitivity, background noise, and auditory masking found no passage in our copy addressing the claim. The indexed passages provide no page numbers. (LLM, conf=0.76)
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Functional Causal Mediation Analysis With an Application to Brain Connectivity
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Anatomical Global Spatial Normalization
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Acceptance and commitment therapy for chronic pain
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Causal Mediation in the Development of Painful Temporomandibular Disorder
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Central sensitization as a component of post-deployment syndrome
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Mindfulness-Based Therapy Regulates Brain Connectivity in Major Depression
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Acceptance and Commitment Therapy and the Cognitive Behavioral Tradition
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Factors predicting the long-term illness course in a cohort of depressed inpatients
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Self-citationNetwork Alterations in Comorbid Chronic Pain and Opioid Addiction: An Exploratory Approach
Smallwood, R. F., Price, L. R., Campbell, J. L., Garrett, A. S., Atalla, S., Monroe, T. B., Aytur, S., Potter, J. S., & Robin, D. A. (2019) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2019.00174 · Cited by 13 · see citing works
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New generation psychological treatments in chronic pain
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“Additionally, available evidence points to the neurophysiological brain correlates of clinical improvement after ACT in chronic pain [88,89], supporting the usefulness of ACT in chronic pain populations such as CPSS.”
BackgroundAdvances in targeting central sensitization and brain plasticity in chronic pain
Bazzari, A. H., & Bazzari, F. H. (2022) · The Egyptian Journal of Neurology Psychiatry and Neurosurgery · doi:10.1186/s41983-022-00472-y · Cited by 40 · see citing works
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“These functional connectivity changes involving regions of the DMN, FPN, SN, and pain network (alongside previously reported positive behavioral outcomes, Aytur et al., 2020), are convincing underlying reasons for the way ACT effectively alleviates chronic pain symptomology.”
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From Low-Grade Inflammation in Osteoarthritis to Neuropsychiatric Sequelae: A Narrative Review
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Acupuncture Enhances Dorsal Raphe Functional Connectivity in Knee Osteoarthritis With Chronic Pain
Gao, N., Shi, H., Hu, S., Zha, B., Yuan, A., Shu, J., Fan, Y., Bai, J., Xie, H., Cui, J., et al. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2021.813723 · Cited by 17 · see citing works
The neurobiology of functional neurological disorders characterised by impaired awareness
Milano, B. A., Moutoussis, M., & Convertino, L. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1122865 · Cited by 19 · see citing works
Addressing physical pain with religion and spirituality during and after the COVID-19 pandemic
Oberholzer, A. E. (2022) · HTS Teologiese Studies / Theological Studies · doi:10.4102/hts.v78i4.7393 · Cited by 14 · see citing works
Implications on hypnotherapy: Neuroplasticity, epigenetics and pain
Császár, N., Scholkmann, F., & Bókkon, I. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.10.001 · Cited by 13 · see citing works
Zhang, Y.-N., Xing, X., Chen, L., Dong, X., Pan, H., Hua, X., & Wang, K. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.843815 · Cited by 12 · see citing works
Voyer, H., Aytur, S., & Tanda, N. (2023) · Preventing Chronic Disease · doi:10.5888/pcd20.230182 · Cited by 12 · see citing works
Self-citationPain Management Treatments and Opioid Use Disorder Risk in Medicaid Patients
Rudolph, K. E., Williams, N., Diaz, I. M., Forrest, S. E., Hoffman, K. L., Samples, H., Olfson, M., Doan, L., Cerdá, M., & Ross, R. K. (2024) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2024.07.006 · Cited by 12 · see citing works
Çalışkan, E., & Gökkaya, F. (2025) · Current Pain and Headache Reports · doi:10.1007/s11916-025-01373-4 · Cited by 10 · see citing works
Gerdle, B. U. C., Dragioti, E., Fischer, M. R., Dong, H., & Ringqvist, Å. (2023) · Frontiers in Pain Research · doi:10.3389/fpain.2023.1244606 · Cited by 10 · see citing works
Nie, Q., He, F., Dong, L., Lin, X., Lin, J., Wang, Y., & Xie, Y. (2025) · Journal of NeuroEngineering and Rehabilitation · doi:10.1186/s12984-025-01692-y · Cited by 9 · see citing works
Smith, P. J., Whitson, H. E., Merwin, R. M., O’Hayer, C. V., & Strauman, T. J. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1256430 · Cited by 8 · see citing works
Vasiliou, V., Konstantinou, N., Christou, Y., Papacostas, S., Constantinidou, F., Heracleous, E., Seimenis, I., & Karekla, M. (2024) · European Journal of Pain · doi:10.1002/ejp.4734 · Cited by 8 · see citing works
Reddan, M. C. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.700833 · Cited by 6 · see citing works
Jäger, M., Terry, J., & Rance, J. (2021) · International Journal of Osteopathic Medicine · doi:10.1016/j.ijosm.2021.12.004 · Cited by 6 · see citing works
Shao, S., Zhang, Y., Yang, M., Li, C., Zhao, R., Liu, Z., Wu, M., Liu, Y., Zhu, Z., & Cui, L. (2024) · Journal of School Psychology · doi:10.1016/j.jsp.2024.101357 · Cited by 5 · see citing works
Wang, D., Lin, B., Du, J., Liu, W., Sun, T., Li, Q., & Xiao, L. (2025) · International Journal of Clinical and Health Psychology · doi:10.1016/j.ijchp.2025.100543 · Cited by 6 · see citing works
Lord, B., Allen, J. J. B., Young, S., & Sanguinetti, J. L. (2024) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2024.12.005 · Cited by 6 · see citing works
fMRI-based explanations for how meditation could modulate pain processing
Golshan, F., & Mickleborough, M. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1561580 · Cited by 5 · see citing works
Preliminary study: quantification of chronic pain from physiological data
Cheng, Z., Ly, F. S., Santander, T., Turki, E., Zhao, Y., Yoo, J., Lonergan, K., Gray, J., Li, C., Yang, H. T., et al. (2022) · PAIN Reports · doi:10.1097/pr9.0000000000001039 · Cited by 3 · see citing works
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Campbell, R., Podugu, S. D. V. P. R., & Morris, M. (2025) · Clinical Gerontologist · doi:10.1080/07317115.2025.2487008 · Cited by 3 · see citing works
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Emotional freedom techniques in mental health care: evidence review, gaps, and future directions
Salicru, S. (2025) · Academia Mental Health and Well-Being · doi:10.20935/mhealthwellb7723 · Cited by 2 · see citing works
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Brain Functional Connectome Gradients Analysis Study of Chronic Back Pain
Junchao, Y. A. N. G., Xiaolong, Y. I. N., Huang, L. T., JIANG, F., Li, Z., & Liang, S. (2024) · Rehabilitation Medicine · doi:10.3724/sp.j.1329.2024.05006 · Cited by 1 · see citing works
Bariani, B., Pinto, B. S., Santos, L. A., Benatti, R. G., Lessa, M. P. M., Loureiro, J. C., Silva, J. F., Silva, V. A., Cardeal, H. B., Pereira, J. L., et al. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.120182 · Cited by 1 · see citing works
Mindfulness-Based Acceptance and Commitment Therapy
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Acceptance and commitment therapy for chronic pain: a quasiexperimental study
Miyazaki, E. S., Banaco, R. A., Domingos, N. A. M., Martins, G. B., & Miyazaki, M. C. D. O. S. (2023) · Estudos de Psicologia (Campinas) · doi:10.1590/1982-0275202340e210067
“Several studies provide data supporting the use of ACT for patients with chronic pain (Aytur et al., 2021; Hann & McCracken, 2014; McCracken & Vowles, 2014; Rickardsson et al., 2021; Yang & McCracken, 2014).”
Pre-Sleep Anxiety: Mechanisms and Therapeutic Approaches in Clinical Practice.
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Linking fMRI, Pain, and Addictions
Aytur, S., Roy, G., Doyle, M., Ray, K. L., Meier, S. K., & Robin, D. A. (2022) · Springer eBooks · doi:10.1007/978-3-030-67928-6_33-1
Self-citationLinking fMRI, Pain, and Addictions
Aytur, S., Roy, G., Doyle, M., Ray, K. L., Meier, S. K., & Robin, D. A. (2022) · Springer eBooks · doi:10.1007/978-3-030-92392-1_33
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Introduction to Neuromodulation-Based Therapies for Chronic Pain
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Affect before diagnosis: applying affective neuroscience to psychiatry
White, J. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1858824
NEUROPSYCHOLOGICAL MODEL OF PERSONALIZED PSYCHOTHERAPY FOR CHRONIC PAIN
Осіпов, В. М. (2026) · Ukrains kyi Visnyk Psykhonevrolohii · doi:10.36927/2079-0325-v34-is2-2026-3
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- Authors
- Aytur, S. A., Ray, K. L., Meier, S. K., Campbell, J., Gendron, B., Waller, N., & Robin, D. A.
- Affiliations
- University of New Hampshire (US)
- The University of Texas at Austin (US)
- Wentworth Douglass Hospital (US)
- Corresponding author
- Aytur, Semra A.
- Venue
- Frontiers in Human Neuroscience
- Publisher
- openRxiv
- Published
- 2020-08-13
- Volume
- 15
- Pages
- 587018-587018
- ISSN
- 1662-5161 (ISSN-L)
- PMC
- PMC7892587
- OpenAlex
- W3129133049
- Cited by
- 49
- References
- 117
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 7 · 2023: 12 · 2022: 10 · 2021: 5 · 2020: 1
- FWCI
- 5.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Human Neuroscience (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Mindfulness and Compassion Interventions
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- acceptance and commitment therapy, chronic pain, chronic musculoskeletal pain, functional connectivity, default mode network, salience network, frontoparietal network, psychological flexibility, pain interference, depression, quality of life, mind-body interventions, network-based statistics
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