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PreprintCited by 21Functional Brain Connectivity StudiesPain Mechanisms and TreatmentsMindfulness and Compassion Interventions

Graph theory analysis of induced neural plasticity post-Acceptance and Commitment Therapy for chronic pain

Open access
Meier, Sarah K., Ray, Kimberly L., Waller, Noah C., Gendron, Barry C., Aytur, Semra A., Robin, Donald A.·2020·Brain Sciences
DOI 10.1101/2020.10.19.20212605PMC PMC7823706

Preprint — published as 10.3390/brainsci11010010 · Paper page

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Abstract

Chronic musculoskeletal pain affects the lives of over 50 million individuals in the United States, at a cost of more than $550 billion each year. Chronic pain leads to functional brain changes within those suffering from the condition. Not only does the primary pain network transform as the condition changes from acute to persistent pain, a state of hyper-connectivity also exists between the default mode, frontoparietal, and salience networks. Graph theory analysis has recently been used to investigate treatment-driven brain network changes. For example, current research suggests that Acceptance and Commitment Therapy (ACT) may reduce the chronic pain associated hyper-connectivity between the default mode, frontoparietal, and salience networks, as well as within the salience network. This study extended previous work by examining the associations between the three networks above and a meta-analytically derived pain network. Results indicate decreased connectivity within the pain network (including left putamen, right insula, left insula, and right thalamus) in addition to triple network connectivity changes after the four-week Acceptance and Commitment therapy intervention.

AI snapshot

Written from the paper’s full text.

TL;DR

This study used graph-theory Network-Based Statistic analysis of resting-state fMRI to test whether a four-week Acceptance and Commitment Therapy (ACT) intervention changed connectivity in the default mode, frontoparietal, salience, and meta-analytically derived pain networks in chronic musculoskeletal pain. It reports decreased connectivity within and across these networks post-ACT, including pain-network nodes such as left putamen, bilateral insula, and right thalamus.

Key findings

  • Among the 101 DMN/FPN/SN nodes, ACT was associated with reduced connectivity in a subset of 10 nodes connected by 10 edges (t > 2.5, p = 0.05).
  • When the 10 previously identified triple-network nodes were combined with 7 pain-network nodes (17 total), NBS showed lowered connectivity across 7 nodes and 6 edges (t > 2.5, p = 0.004).
  • In the full analysis of 108 nodes (101 triple-network plus 7 pain nodes), ACT was associated with decreased connectivity across 31 nodes and 34 edges (t > 3.4, p = 0.036).
  • Pain-network nodes involved in decreased functional connections included the left putamen, right insula, left insula, and right thalamus; no increases in connectivity were observed in any NBS test.

Methods

  • Nine female participants (age 47.59 ± 16.54 years; eight right-handed) with chronic musculoskeletal pain for at least three months and Brief Pain Inventory pain interference ≥4 completed eight 90-minute twice-weekly group ACT sessions over four weeks.
  • Resting-state fMRI was collected pre-treatment and within two weeks post-treatment on a Siemens 3T Magnetom Prisma scanner; data were preprocessed in SPM12, parcellated into DMN, FPN, and SN regions from the Power atlas, and combined with a seven-node pain network derived from a meta-analysis using activation likelihood estimation and meta-analytic connectivity modeling.
  • Functional connectivity changes were assessed with the Network-Based Statistic using 10,000 permutations and one-tailed t-tests across multiple thresholds, testing both increases and decreases pre- to post-ACT.

Limitations

  • The paper states limitations including small sample size, variability in individual pain experiences and age, a sample limited to white female participants, possible selection bias, lack of a control group, and limited documentation of long-term ACT effects without follow-up retention data.
  • Evident from the text: the study analyzed only nine completers, all female, with no healthy control comparison and no post-treatment follow-up beyond the second scan, so findings are preliminary and not generalizable across genders or to controlled treatment comparisons.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1101/2020.10.19.20212605

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

12 of 19 cited sources checked · 0 supported · 2 flagged · accuracy not yet measured

  • Premisecitation

    Chronic pain is associated with elevated functional connectivity among the DMN, FPN, and SN.

    “Not only does each network independently demonstrate changes in functional connectivity in response to different types of chronic pain stimuli, it has been demonstrated that there is elevated functional connectivity among the DMN, FPN, and SN in individuals suffering from CMP [12,13,14,15,16,17,18].”
    Quote in the paperSubstantial claim6 of 7 sources checked
    • cites [12] source
    • cites [13] source

      The Results (Network decomposition) report alterations in the DMN, salience, and attentional networks across chronic pain conditions, but these are gray-matter findings, not evidence of elevated functional connectivity among the DMN, FPN, and SN. The Results (Resting-state connectivity maps) describe connectivity between insular regions and the DMN or salience network in healthy volunteers, including anticorrelations; they do not establish the claimed elevation in people with chronic pain. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [14] 2016, Abnormal cross-network functional connectivity in chronic pain and its association with clinical symptoms, Brain Structure and Function source

      The Results (§3.2; page unavailable) report stronger anticorrelation—not elevated positive connectivity—between the salience-network seed and default-mode regions in patients with chronic knee osteoarthritis. They also report reduced central-executive-network connectivity in a cluster that the Discussion (§4; page unavailable) places largely within the salience network. The paper therefore does not demonstrate elevated connectivity among the three networks. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [15] Higham, D.J. , & Higham, N.J. (2016). MATLAB guide (Vol. 150). Siam. source

      The Conclusion and the Discussion section on inter-network connectivity report associations between mindfulness and connectivity among the DMN, salience network, and central executive network. A search for chronic pain, CMP, and elevated connectivity found no passage in our copy addressing connectivity among these networks in people with chronic pain. The cited paper therefore does not verify the chronic-pain claim. (LLM, conf=0.77)

      Experimental — accuracy not yet measured
    • cites [16] 2019, Chronic pain in adults with sickle cell disease is associated with alterations in functional connectivity of the brain, PLOS ONE source

      The Results (page unavailable) report elevated connectivity within the DMN and right executive attention network—a frontoparietal network—in fibromyalgia, as well as increased connectivity between each of those networks and the insula with greater spontaneous pain. The paper does not evaluate the salience network as a network or demonstrate elevated connectivity among all three networks. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [17] source

      The Discussion reports increased DMN–SN connectivity in chronic widespread pain patients with higher pain sensitivity, and the Conclusion says this increase is modulated by pain sensitivity. The Methods define and analyze DMN and SN nodes, but not the FPN; this paper therefore does not support elevated connectivity among all three networks. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [18] 2013, Default mode network functional connectivity altered in failed Back surgery syndrome, The Journal of Pain source

      The Results (‘Altered FNCs in PSPD patients’) report reduced connectivity between the right FPN and SN, not elevated connectivity. The study concerns persistent somatoform pain disorder, and its reported increases involve the sensorimotor network rather than connectivity among the DMN, FPN, and SN. (LLM, conf=0.87)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    Activation of the left putamen, right insula, left insula, and right thalamus has been linked to thoughts of helplessness, pessimism, and rumination in chronic musculoskeletal pain.

    “Activation of these regions has been linked to thoughts of helplessness, pessimism, and rumination in the instance of CMP [40].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [40] 2019, Chronic widespread pain patients show disrupted cortical connectivity in default mode and salience networks, modulated by pain sensitivity, Journal of Pain Research source

      The Results (pages unavailable) describe insular activation during noxious heat stimulation, while the Discussion describes thalamic deactivation associated with reduced pain unpleasantness during meditation. Our copy does not link the named regions to helplessness, pessimism, or rumination in chronic musculoskeletal pain; searches for those terms and for putamen and chronic pain found no such passage. (LLM, conf=0.77)

      Experimental — accuracy not yet measured
  • Premisecitation

    Aytur 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.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [21] Mano, H. , Kotecha, G. , Leibnitz, K. , Matsubara, T. , Sprenger, C. , Nakae, A. , …Seymour, B. (2018). Classification and characterisation of brain network changes in chronic back pain: A multicenter study. Wellcome Open Research, 3. https://doi.org/10.12688/wellcomeopenres.14069.2 source

      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 measured
  • Interpretationreasoning

    Decreased 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].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [21] Mano, H. , Kotecha, G. , Leibnitz, K. , Matsubara, T. , Sprenger, C. , Nakae, A. , …Seymour, B. (2018). Classification and characterisation of brain network changes in chronic back pain: A multicenter study. Wellcome Open Research, 3. https://doi.org/10.12688/wellcomeopenres.14069.2 source

      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 measured
    • cites [40] 2019, Chronic widespread pain patients show disrupted cortical connectivity in default mode and salience networks, modulated by pain sensitivity, Journal of Pain Research source

      The Results (Post-Meditation Training: MRI Session 2 Analyses; page unavailable) report regional activation and deactivation associated with pain ratings after mindfulness meditation. Searches for the specified functional-connectivity pairs, ACT, and quality of life found no passage connecting those pairs to post-ACT quality of life. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
  • Findingown data

    In the 17-node analysis combining the 10 triple-network nodes and the seven pain nodes, the NBS revealed lowered connectivity after ACT across seven nodes and six edges corresponding to DMN, FPN, SN, or the pain network (t > 2.5, p = 0.004).

    “We subsequently tested for effects of ACT on the 10 nodes identified in the previous analysis (Figure 2A) combined with the seven pain nodes (17 nodes total). In doing so, the NBS revealed lowered levels of connectivity as a result of ACT across seven nodes and six edges corresponding to DMN, FPN, SN, or the pain network when aggregated together (Figure 2B; t > 2.5 p = 0.004).”
    Quote in the paperSubstantial claim
  • May combine two claims. 7
  • Classified as probably not a substantial claim. 6

  • May combine two claims.

    Interpretationreasoning

    The 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.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [21] Mano, H. , Kotecha, G. , Leibnitz, K. , Matsubara, T. , Sprenger, C. , Nakae, A. , …Seymour, B. (2018). Classification and characterisation of brain network changes in chronic back pain: A multicenter study. Wellcome Open Research, 3. https://doi.org/10.12688/wellcomeopenres.14069.2 source

      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 measured

  • May combine two claims.

    Premiseown data

    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]”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [21] Mano, H. , Kotecha, G. , Leibnitz, K. , Matsubara, T. , Sprenger, C. , Nakae, A. , …Seymour, B. (2018). Classification and characterisation of brain network changes in chronic back pain: A multicenter study. Wellcome Open Research, 3. https://doi.org/10.12688/wellcomeopenres.14069.2 source

      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 measured
    • cites [35] SAS. (2002). SAS 9.1.3 Help and Documentation. Cary, NC: SAS Institute Inc.

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Permutation testing is used to ascribe a p-value controlled for the family wise error to each connected component based on its size.

    “Explicitly, permutation testing is used to ascribe a p-value controlled for the family wise error to each connected component based on its size [24].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] 2018, The Triple Network Model, Insight, and Large-Scale Brain Organization in Autism, Biological Psychiatry source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Selection bias may play a role such that participants who self-selected to participate may have been different from the general population.

    “Selection bias may play a role such that participants who self-selected to participate may have been different from the general population.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Ten participants began initial testing, but one individual ended the baseline scan early due to a medical condition and was eliminated from the study.

    “Ten participants began initial testing. However, one individual ended the baseline scan early due to a medical condition, was eliminated from the study at that time, and was prorated for their time in the study.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The acceptance technique of ACT produces lower self-rated pain intensity, depression, pain-related anxiety, and pain avoidance while increasing physical, social, and occupational ability.

    “The acceptance technique of ACT has been shown to produce lower self-rated pain intensity, depression, pain-related anxiety, and pain avoidance while increasing physical, social, and occupational ability [23].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] source

  • May combine two claims.

    Interpretationown data

    The current analyses expose changes to the pain network as a result of ACT, contrary to prior research suggesting ACT can reduce pain symptomatology without altering the pain network.

    “Despite prior research suggesting that ACT can reduce pain symptomatology without altering the pain network, the current analyses do expose changes to the pain network as a result of ACT.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The analysis tested for both increases and decreases in connectivity across a range of t-statistic thresholds to ensure that reported significant findings are robust.

    “While we predicted that we would observe decreases in connectivity as a result of ACT, NBS t-tests are one-tailed; therefore, we tested for both increases and decreases in connectivity between pre- and post-ACT across a range of t-statistic thresholds to ensure that reported significant findings are robust.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Study design and conductnone given

    The long-term effects of ACT on pain management are not well documented.

    “Lastly, the long-term effects of ACT on pain management are not well documented.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    There was no control group; no comparisons were made between individuals with chronic pain and a healthy control population.

    “Another limitation lies within the lack of a control group. No comparisons were made between the individuals with chronic pain and a healthy control population who were not experiencing chronic pain.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    A main limitation of the current study is the sample and its size.

    “A main limitation in the current study is the sample and its size.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Traditional pain medications do little to affect both the hyper-connectivity and the perceived quality of life existing in those with chronic pain.

    “Analyses of alternative treatments for CMP are important as traditional pain medications do little to affect both the hyper-connectivity and dully perceived quality of life existing in those with chronic pain.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] source
12 of 12

  • The paper relies on this without support.

    Prior to this study, little was known about how the brain can change in response to specific interventions in chronic musculoskeletal pain.

    “Prior to this study, as well as Aytur and colleagues’ study [21], little was known about how the brain can change in response to specific interventions in certain disease states, such as CMP.”

  • The paper relies on this without support.

    The extent to which ACT interacts with the hypothesized neural systems underlying chronic pain was unknown.

    “The extent to which ACT interacts with the hypothesized neural systems underlying chronic pain was also unknown.”

  • The paper relies on this without support.

    Pain itself affects cognitive and emotional brain networks.

    “However, connectivity between the triple network and the pain network may change post-ACT since pain itself affects cognitive and emotional brain networks.”

  • The paper relies on this without support.

    ACT is considered a well-established treatment for chronic musculoskeletal pain by the American Psychological Association.

    “It is considered a “well-established” treatment for CMP by the American Psychological Association.”

  • The paper relies on this without support.

    Subjective reports suggest decreased levels of perceived pain due to ACT.

    “This work is important as subjective reports suggest decreased levels of perceived pain due to ACT, a treatment focusing on cognition and emotion rather than pain itself.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Available 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 [89]

Cites

Flagged first, then by citations

2 of the 53 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Higham, D.J. , & Higham, N.J. (2016). MATLAB guide (Vol. 150). Siam.
  2. Neuroscience Bulletin, 34, 208–215. https://doi.org/10.1007/s12264-017-0150-1 · DOI

Cited by

Sorted by citations

Related

Authors
Meier, S. K., Ray, K. L., Waller, N. C., Gendron, B. C., Aytur, S. A., & Robin, D. A.
Affiliations
  • University of New Hampshire (US)
  • The University of Texas at Austin (US)
  • Wentworth Douglass Hospital (US)
Corresponding author
Meier, Sarah K.
ORCID
Venue
Brain Sciences
Publisher
openRxiv
Published
2020-10-21
Volume
11
Issue
1
Pages
10-10
ISSN
2076-3425 (ISSN-L)
DOI
10.1101/2020.10.19.20212605
PMC
PMC7823706
OpenAlex
W3018185936
Cited by
21
References
53
Citations by year
2025: 5 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 3
FWCI
1.49
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Brain Sciences (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • University of New Hampshire Scholars Repository (University of New Hampshire at Manchester) (submittedVersion)
  • Europe PMC (PubMed Central) (submittedVersion, other-oa)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
University of New Hampshire
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Social Sciences › Psychology › Clinical Psychology › Mindfulness and Compassion Interventions
Keywords
acceptance and commitment therapy, chronic musculoskeletal pain, neuroplasticity, brain network connectivity, default mode network, frontoparietal network, salience network, pain network, insula, putamen, thalamus, hyperconnectivity

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