Sleep, Mindfulness, and Resting (sleep-mindfulness-resting)

1 Thapaliya et al. 2026 β€” Glymphatic Function in ME/CFS (DTI-ALPS)

Full Citation:: Thapaliya K, Marshall-Gradisnik S, Inderyas M, Barnden L. Disrupted glymphatic function and its relationship with sleep and cognitive impairment in ME/CFS assessed via DTI-ALPS. Frontiers in Neuroscience. 2026;20:1875420. (Thapaliya et al. 2026) DOI:: 10.3389/fnins.2026.1875420 PMID:: 42403482 Article Type:: Cross-sectional MRI study (preliminary) Key Findings::

- Global DTI-ALPS index lower in ME/CFS (1.44 Β± 0.086) vs healthy controls (1.51 Β± 0.11, p = 0.014)
- Right-hemisphere DTI-ALPS lower in ME/CFS (1.41 Β± 0.097 vs 1.49 Β± 0.12, p = 0.009); left hemisphere not different
- Global DTI-ALPS correlated with sleep-disturbance severity (r = -0.47, p = 0.013) and impaired concentration (r = -0.43, p = 0.026)

Conclusion:: Impaired glymphatic clearance during sleep may underlie unrefreshing sleep and cognitive dysfunction in ME/CFS. Limitations:: Preliminary, n = 58 (31 ME/CFS, 27 controls); cross-sectional; single site; diagnostic criteria unspecified. ME/CFS Relevance:: First DTI-ALPS glymphatic study in ME/CFS β€” provides a biological substrate for the unrefreshing-sleep symptom, arguing it is disease-driven (F2) rather than primary behavioural insomnia. Certainty Assessment::

- *Quality:* Medium (peer-reviewed, moderate journal)
- *Sample:* n = 58
- *Replication:* Single study, not yet replicated
- *Score:* 0.55 (raw; population 1.00 β†’ discounted 0.55)

2 Mariman et al. 2013 β€” Sleep in Chronic Fatigue Syndrome

Full Citation:: Mariman AN, Vogelaers DP, Tobback E, Delesie LM, Hanoulle IP, Pevernagie DA. Sleep in the chronic fatigue syndrome. Sleep Medicine Reviews. 2013;17(3):193–199. (Mariman et al. 2013) DOI:: 10.1016/j.smrv.2012.06.003 PMID:: 23046847 Article Type:: Narrative review Key Findings::

- Unrefreshing/nonrestorative sleep is a Fukuda minor criterion and very common in CFS
- No demonstrable neurophysiological correlate: PSG findings are not significantly different between CFS and controls
- Discrepancy between subjectively poor and objectively normal sleep suggests psychosocial factors affect sleep-quality perception
- Insufficient evidence that treating primary sleep disorders improves CFS fatigue

Conclusion:: Sleep disturbance in CFS may be comorbid rather than causal; behavioural sleep treatment targets a secondary symptom. Limitations:: Narrative review; heterogeneous diagnostic criteria across source studies. ME/CFS Relevance:: F2 anchor β€” supports the mechanism-skeptic framing that unrefreshing sleep is a downstream epiphenomenon with no objective PSG substrate. Certainty Assessment::

- *Quality:* High (leading sleep-medicine review journal)
- *Sample:* n/a (review)
- *Replication:* Consistent with Watson 2003/2004 twin studies already in corpus
- *Score:* 0.50 (raw; population 1.00 β†’ discounted 0.50)

3 Chao et al. 2021 β€” CBT-I in Gulf War Illness

Full Citation:: Chao LL, Kanady JC, Crocker N, et al. Cognitive behavioral therapy for insomnia in veterans with gulf war illness: Results from a randomized controlled trial. Life Sciences. 2021;279:119147. (Chao et al. 2021) DOI:: 10.1016/j.lfs.2021.119147 PMID:: 33549595 Article Type:: Randomized controlled trial Key Findings::

- n = 85 Gulf War veterans (Kansas GWI + CDC chronic multisymptom illness + insomnia), telephone CBT-I vs waitlist
- CBT-I improved overall GWI symptom severity, fatigue, cognitive dysfunction, depression, anxiety, insomnia severity, and subjective sleep quality
- Benefits on overall GWI severity and most individual measures maintained at 6 months

Conclusion:: A behavioural sleep intervention improves both sleep and non-sleep fatigue/cognitive symptoms in a chronic multisymptom illness. Limitations:: Cross-disease (GWI, not ME/CFS); waitlist control (no active control); single study. ME/CFS Relevance:: F1 cross-disease evidence that CBT-I can improve fatigue/cognitive symptoms alongside sleep β€” the strongest behavioural-sleep-intervention signal available for a ME/CFS-adjacent multisymptom illness. Certainty Assessment::

- *Quality:* Medium-High (RCT, peer-reviewed)
- *Sample:* n = 85
- *Replication:* Single study
- *Score:* 0.70 (raw; population 0.80 β†’ discounted 0.56)

4 Hausswirth et al. 2023 β€” Neuro-Meditation for Long COVID

Full Citation:: Hausswirth C, Schmit C, Rougier Y, Coste A. Positive Impacts of a Four-Week Neuro-Meditation Program on Cognitive Function in Post-Acute Sequelae of COVID-19 Patients: A Randomized Controlled Trial. International Journal of Environmental Research and Public Health. 2023;20(2):1361. (Hausswirth et al. 2023) DOI:: 10.3390/ijerph20021361 PMID:: 36674117 Article Type:: Randomized controlled trial Key Findings::

- n = 34 long COVID (17/17) + 15 healthy normative; ten 30-min Rebalance sessions over 5 weeks
- Choice reaction time shortened only in intervention group (593 Β± 121 β†’ 521 Β± 86 ms, p < 0.001)
- Improved physical/mental fatigue, pain, depression, anxiety, mood, and sleep quality

Conclusion:: Neuro-meditation reduces cognitive impairment and secondary symptoms in long COVID. Limitations:: Small n; single study; commercial program (Rebalance); no PEM/energy-envelope endpoint. ME/CFS Relevance:: F3 β€” mindfulness helps secondary outcomes (sleep, cognition, mood) in a post-viral fatigue population but does not test PEM or energy-envelope outcomes. Certainty Assessment::

- *Quality:* Medium (RCT, moderate journal)
- *Sample:* n = 34
- *Replication:* Single study
- *Score:* 0.50 (raw; population 0.85 β†’ discounted 0.43)

5 Meng et al. 2024 β€” Mindfulness Meditation for Fibromyalgia (Meta-analysis)

Full Citation:: Meng S, Cao C, Zhang M, Dong J, Lu M. Mindfulness Meditation for Fibromyalgia Syndrome: A Systematic Review and Meta-analysis. Pain Physician. 2024;27(8):479–494. (Meng et al. 2024) PMID:: 39621973 Article Type:: Systematic review + meta-analysis Key Findings::

- 10 RCTs (n = 818) from 1,377 citations
- Short-term: FIQ MD -6.20 (95% CI -8.51 to -3.89); PSQI -1.84 (-3.35 to -0.33); BDI -3.26; PSS -4.85 (all P < 0.05)
- Medium-term: BDI and PSS maintained, but FIQ (MD -2.78, P > 0.05) and PSQI (P > 0.05) no longer significant
- Long-term: FIQ still reduced (MD -6.09); GRADE very low to moderate

Conclusion:: Mindfulness improves quality of life, stress, insomnia, and depression short-term, with modest and partly attenuating impact on the core FIQ. Limitations:: Heterogeneous meditation regimens; small/average study quality; GRADE very low to moderate. ME/CFS Relevance:: F3 anchor β€” the most current quantitative estimate of mindfulness effect size in a fibromyalgia (cross-disease) cohort; benefits cluster in secondary outcomes. Certainty Assessment::

- *Quality:* Medium (meta-analysis, moderate journal)
- *Sample:* n = 818 (10 RCTs)
- *Replication:* n/a (synthesis)
- *Score:* 0.65 (raw; population 0.80 β†’ discounted 0.52)

6 Schmidt et al. 2011 β€” MBSR for Fibromyalgia (3-arm RCT)

Full Citation:: Schmidt S, Grossman P, Schwarzer B, Jena S, Naumann J, Walach H. Treating fibromyalgia with mindfulness-based stress reduction: results from a 3-armed randomized controlled trial. Pain. 2011;152(2):361–369. (Schmidt et al. 2011) DOI:: 10.1016/j.pain.2010.10.043 PMID:: 21146930 Article Type:: Randomized controlled trial (3-arm) Key Findings::

- n = 177 female fibromyalgia; MBSR vs active control vs waitlist; 82% completed
- No significant between-group difference on primary outcome (HRQoL at 2 months)
- Only MBSR showed significant pre-to-post HRQoL improvement (P = 0.02); MBSR improved 6/8 secondary outcomes vs active control 3 and waitlist 2

Conclusion:: Primary-outcome analysis did not support MBSR efficacy; MBSR patients benefited most on secondary measures with small effect sizes. Limitations:: Null on primary; effect sizes small; patient burden/motivation confounds. ME/CFS Relevance:: F3 null-on-primary anchor β€” mindfulness helps secondary/wellbeing outcomes but does not robustly beat active control on the core QoL endpoint. Certainty Assessment::

- *Quality:* High (top-tier journal, large RCT)
- *Sample:* n = 177
- *Replication:* Null primary consistent with EUDAIMON 2019 (screened, not added)
- *Score:* 0.75 (raw; population 0.80 β†’ discounted 0.60)

7 Porter and Jason 2022 β€” Mindfulness for Long COVID / ME/CFS

Full Citation:: Porter N, Jason LA. Mindfulness Meditation Interventions for Long COVID: Biobehavioral Gene Expression and Neuroimmune Functioning. Neuropsychiatric Disease and Treatment. 2022;18:2599–2626. (Porter and Jason 2022) DOI:: 10.2147/NDT.S379653 PMID:: 36387947 Article Type:: Narrative review Key Findings::

- Meditation has been found to reduce fatigue and unrefreshing sleep
- In post-viral infection, meditation is reported to enhance immunity and reduce inflammatory-driven pathogenesis
- Argues for mindfulness as a treatment strategy for Long COVID and ME/CFS symptom and underlying pathology

Conclusion:: Mindfulness is a plausible adjunct for post-viral fatigue (Long COVID / ME/CFS), but direct trial evidence remains limited. Limitations:: Narrative review; proponent framing; no new primary data. ME/CFS Relevance:: F1 consensus-adjacent source β€” establishes the mindfulness-for-ME/CFS research program and its claimed mechanism (neuroimmune/gene-expression). Certainty Assessment::

- *Quality:* Medium (narrative review)
- *Sample:* n/a
- *Replication:* n/a
- *Score:* 0.45 (raw; population 0.85 β†’ discounted 0.38)

8 Cossu et al. 2025 β€” HRV-BF in Long COVID CFS/ME (Phase II)

Full Citation:: Cossu G, Kalcev G, Primavera D, et al. The Use of Heart Rate Variability-Biofeedback (HRV-BF) as an Adjunctive Intervention in Chronic Fatigue Syndrome (CSF/ME) in Long COVID: Results of a Phase II Controlled Feasibility Trial. Journal of Clinical Medicine. 2025;14(15):5363. (Cossu et al. 2025) DOI:: 10.3390/jcm14155363 PMID:: 40806985 Article Type:: Phase II controlled feasibility trial (quasirandom) Key Findings::

- 10 HRV-BF sessions twice weekly over 5 weeks vs treatment-as-usual; drop-out 5.56%
- Significantly greater improvement in severe fatigue in intervention group (H = 4.083, p = 0.043)
- Across all outcomes, tendency toward improvement (binomial test, p < 0.0001)

Conclusion:: HRV-BF is feasible and well-tolerated; supports Phase III trials for fatigue in Long COVID CFS/ME. Limitations:: Quasirandom (not true randomization); small; feasibility design. ME/CFS Relevance:: F1 β€” direct CFS/ME-criteria autonomic intervention; engages the vagal/parasympathetic-tone mechanism relevant to ME/CFS dysautonomia. Certainty Assessment::

- *Quality:* Medium (controlled feasibility)
- *Sample:* small (drop-out 5.56%)
- *Replication:* Single study
- *Score:* 0.55 (raw; population 0.85 β†’ discounted 0.47)

9 Windthorst et al. 2017 β€” HRV-BF vs GET in CFS

Full Citation:: Windthorst P, Mazurak N, Kuske M, et al. Heart rate variability biofeedback therapy and graded exercise training in management of chronic fatigue syndrome: An exploratory pilot study. Journal of Psychosomatic Research. 2017;93:6–13. (Windthorst et al. 2017) DOI:: 10.1016/j.jpsychores.2016.11.014 PMID:: 28107894 Article Type:: Exploratory pilot RCT Key Findings::

- n = 28 women with CFS (50.3 Β± 9.3 y); HRV-BF vs GET, 5-month follow-up
- General fatigue improved significantly after both HRV-BF and GET
- HRV-BF improved cognitive fatigue, mental QoL, and depression; GET improved physical QoL

Conclusion:: Both interventions reduce fatigue; HRV-BF has additional mental-health benefit, GET additional physical benefit. Limitations:: Small pilot; single study; GET used as comparator (not a BPS-promotion study). ME/CFS Relevance:: F1 β€” direct ME/CFS HRV-BF pilot; suggests autonomic retraining is viable and complements (rather than replaces) physical approaches. Certainty Assessment::

- *Quality:* Medium (pilot RCT)
- *Sample:* n = 28
- *Replication:* Single study
- *Score:* 0.45 (raw; population 1.00 β†’ discounted 0.45)

10 Carta et al. 2024 β€” HRV-BF in Fibromyalgia (NULL)

Full Citation:: Carta MG, Testa G, Stocchino S, et al. The efficacy of heart rate variability biofeedback training on sleep disorders and impact of fibromyalgia: Results of a phase II randomized controlled trial. Journal of Psychosomatic Research. 2024;181:111664. (Carta et al. 2024) DOI:: 10.1016/j.jpsychores.2024.111664 PMID:: 38652978 Article Type:: Phase II randomized controlled trial Key Findings::

- n = 64 fibromyalgia; HRV-BF + standard therapy vs standard therapy
- No statistical differences between groups over time in any primary or secondary outcome
- Feasible: 71.9% completion, no side effects

Conclusion:: HRV-BF did not demonstrate efficacy in fibromyalgia; further larger studies needed. Limitations:: Small phase II; null result. ME/CFS Relevance:: F2/F3 null result β€” direct negative evidence that the parasympathetic-tone rationale does not translate to measurable benefit in fibromyalgia, tempering enthusiasm for HRV-BF as a general fatigue intervention. Certainty Assessment::

- *Quality:* Medium-High (RCT, peer-reviewed)
- *Sample:* n = 64
- *Replication:* Null (consistent with fibromyalgia null literature)
- *Score:* 0.60 (raw; population 0.80 β†’ discounted 0.48)

11 Kos et al. 2015 β€” Activity Pacing Self-Management in CFS

Full Citation:: Kos D, van Eupen I, Meirte J, et al. Activity Pacing Self-Management in Chronic Fatigue Syndrome: A Randomized Controlled Trial. The American Journal of Occupational Therapy. 2015;69(5):6905290020. (Kos et al. 2015) DOI:: 10.5014/ajot.2015.016287 PMID:: 26356665 Article Type:: Randomized controlled trial Key Findings::

- n = 33 women with CFS (41.1 Β± 11.2 y); activity pacing self-management vs relaxation
- COPM scores improved in both groups (p = .03); only Satisfaction significantly favored pacing (effect size 0.74 [0.11, 1.4])
- CIS decreased only in the pacing group (p < .01)

Conclusion:: Pacing is feasible and modestly effective for participation, but shows no advantage on the primary performance endpoint. Limitations:: Small n; single study; control (relaxation) also improved. ME/CFS Relevance:: F4 pacing-debate β€” direct ME/CFS pacing RCT with modest/partial benefit, consistent with contested pacing efficacy. Certainty Assessment::

- *Quality:* Medium (RCT)
- *Sample:* n = 33
- *Replication:* Single study
- *Score:* 0.45 (raw; population 1.00 β†’ discounted 0.45)

12 Meeus et al. 2010 β€” Pain Physiology Education vs Pacing

Full Citation:: Meeus M, Nijs J, Van Oosterwijck J, Van Alsenoy V, Truijen S. Pain physiology education improves pain beliefs in patients with chronic fatigue syndrome compared with pacing and self-management education: a double-blind randomized controlled trial. Archives of Physical Medicine and Rehabilitation. 2010;91(8):1153–1159. (Meeus et al. 2010) DOI:: 10.1016/j.apmr.2010.04.020 PMID:: 20684894 Article Type:: Double-blind randomized controlled trial Key Findings::

- N = 48 CFS patients with chronic pain; single session pain physiology education vs pacing/self-management education
- Education group had better pain neurophysiology understanding (P < .001) and reduced pain-catastrophizing rumination (P = .009)
- Cohen d effect sizes 0.79–2.53

Conclusion:: Pain physiology education outperforms pacing education for pain beliefs in the short term. Limitations:: Single session; short-term outcome only; pacing was the control arm. ME/CFS Relevance:: F4 pacing-debate β€” a single pacing/self-management session changed pain cognitions less than pain-physiology education, questioning the standalone efficacy of brief pacing education. Certainty Assessment::

- *Quality:* Medium (double-blind RCT)
- *Sample:* N = 48
- *Replication:* Single study
- *Score:* 0.50 (raw; population 1.00 β†’ discounted 0.50)

13 Xie et al. 2024 β€” PLWNT Qigong for CFS (Protocol)

Full Citation:: Xie F, You Y, Gu Y, Xu J, Yao F. Effects of the Prolong Life With Nine Turn-Method Qigong on Fatigue, Insomnia, Anxiety, and Gastrointestinal Disorders in Patients With Chronic Fatigue Syndrome: Protocol for a Randomized Controlled Trial. JMIR Research Protocols. 2024;13:e53347. (Xie et al. 2024) DOI:: 10.2196/53347 PMID:: 38407950 Article Type:: Registered RCT protocol Key Findings::

- n = 208 planned (age 20–60); 12-week PLWNT Qigong vs CBT (1:1); 8-week follow-up
- Primary = Multidimensional Fatigue Inventory 20; secondary = PSQI, GSRS, HADS, fMRI, gut microbiota

Conclusion:: Will test whether mind-body Qigong relieves fatigue, insomnia, anxiety, and GI symptoms in CFS. Limitations:: Protocol only β€” no efficacy data yet. ME/CFS Relevance:: F1 pipeline marker β€” documents an active mind-body RCT in CFS with sleep (PSQI) as a named secondary outcome. Certainty Assessment::

- *Quality:* Low (protocol, no results)
- *Sample:* planned n = 208
- *Replication:* n/a
- *Score:* 0.35 (raw; population 1.00 β†’ discounted 0.35)

References

Carta, Mauro Giovanni, Giorgia Testa, Serena Stocchino, Gabriele Finco, Federica Sancassiani, Maria Teresa Littera, Maria Cristina Deidda, Antonio Ventriglio, Dinesh Bhugra, and Giulia Cossu. 2024. β€œThe Efficacy of Heart Rate Variability Biofeedback Training on Sleep Disorders and Impact of Fibromyalgia: Results of a Phase II Randomized Controlled Trial.” Journal of Psychosomatic Research 181: 111664. https://doi.org/10.1016/j.jpsychores.2024.111664.
Chao, Linda L., Jennifer C. Kanady, Nicole Crocker, Laura D. Straus, Jennifer Hlavin, Thomas J. Metzler, Shira Maguen, and Thomas C. Neylan. 2021. β€œCognitive Behavioral Therapy for Insomnia in Veterans with Gulf War Illness: Results from a Randomized Controlled Trial.” Life Sciences 279: 119147. https://doi.org/10.1016/j.lfs.2021.119147.
Cossu, Giulia, Goce Kalcev, Diego Primavera, Stefano Lorrai, Alessandra Perra, Alessia Galetti, et al. 2025. β€œThe Use of Heart Rate Variability-Biofeedback (HRV-BF) as an Adjunctive Intervention in Chronic Fatigue Syndrome (CSF/ME) in Long COVID: Results of a Phase II Controlled Feasibility Trial.” Journal of Clinical Medicine 14 (15): 5363. https://doi.org/10.3390/jcm14155363.
Hausswirth, Christophe, Cyril Schmit, Yann Rougier, and Alexandre Coste. 2023. β€œPositive Impacts of a Four-Week Neuro-Meditation Program on Cognitive Function in Post-Acute Sequelae of COVID-19 Patients: A Randomized Controlled Trial.” International Journal of Environmental Research and Public Health 20 (2): 1361. https://doi.org/10.3390/ijerph20021361.
Kos, Daphne, Inge van Eupen, Jill Meirte, Deborah Van Cauwenbergh, Greta Moorkens, Mira Meeus, and Jo Nijs. 2015. β€œActivity Pacing Self-Management in Chronic Fatigue Syndrome: A Randomized Controlled Trial.” The American Journal of Occupational Therapy 69 (5): 6905290020. https://doi.org/10.5014/ajot.2015.016287.
Mariman, An N., Dirk P. Vogelaers, Els Tobback, Liesbeth M. Delesie, Ignace P. Hanoulle, and Dirk A. Pevernagie. 2013. β€œSleep in the Chronic Fatigue Syndrome.” Sleep Medicine Reviews 17 (3): 193–99. https://doi.org/10.1016/j.smrv.2012.06.003.
Meeus, Mira, Jo Nijs, Jessica Van Oosterwijck, Veerle Van Alsenoy, and Steven Truijen. 2010. β€œPain Physiology Education Improves Pain Beliefs in Patients with Chronic Fatigue Syndrome Compared with Pacing and Self-Management Education: A Double-Blind Randomized Controlled Trial.” Archives of Physical Medicine and Rehabilitation 91 (8): 1153–59. https://doi.org/10.1016/j.apmr.2010.04.020.
Meng, Shuo, Chunfeng Cao, Minghua Zhang, Jing Dong, and Minpeng Lu. 2024. β€œMindfulness Meditation for Fibromyalgia Syndrome: A Systematic Review and Meta-Analysis.” Pain Physician 27 (8): 479–94. https://pubmed.ncbi.nlm.nih.gov/39621973/.
Porter, Nicole, and Leonard A. Jason. 2022. β€œMindfulness Meditation Interventions for Long COVID: Biobehavioral Gene Expression and Neuroimmune Functioning.” Neuropsychiatric Disease and Treatment 18: 2599–2626. https://doi.org/10.2147/NDT.S379653.
Schmidt, Stefan, Paul Grossman, Barbara Schwarzer, Susanne Jena, Johannes Naumann, and Harald Walach. 2011. β€œTreating Fibromyalgia with Mindfulness-Based Stress Reduction: Results from a 3-Armed Randomized Controlled Trial.” Pain 152 (2): 361–69. https://doi.org/10.1016/j.pain.2010.10.043.
Thapaliya, Kiran, Sonya Marshall-Gradisnik, Maira Inderyas, and Leighton Barnden. 2026. β€œDisrupted Glymphatic Function and Its Relationship with Sleep and Cognitive Impairment in ME/CFS Assessed via DTI-ALPS.” Frontiers in Neuroscience 20: 1875420. https://doi.org/10.3389/fnins.2026.1875420.
Windthorst, Petra, Nazar Mazurak, Marvin Kuske, Arno Hipp, Katrin E. Giel, Paul Enck, Andreas Nieß, Stephan Zipfel, and Martin Teufel. 2017. β€œHeart Rate Variability Biofeedback Therapy and Graded Exercise Training in Management of Chronic Fatigue Syndrome: An Exploratory Pilot Study.” Journal of Psychosomatic Research 93: 6–13. https://doi.org/10.1016/j.jpsychores.2016.11.014.
Xie, Fangfang, Yanli You, Yuanjia Gu, Jiatuo Xu, and Fei Yao. 2024. β€œEffects of the Prolong Life with Nine Turn-Method Qigong on Fatigue, Insomnia, Anxiety, and Gastrointestinal Disorders in Patients with Chronic Fatigue Syndrome: Protocol for a Randomized Controlled Trial.” JMIR Research Protocols 13: e53347. https://doi.org/10.2196/53347.