49:I[191445,["/_next/static/immutable/chunks/0v6-3q16afmwn.js","/_next/static/immutable/chunks/2ck6yuttil9xz.js","/_next/static/immutable/chunks/3rsnyfmzi6oij.js","/_next/static/immutable/chunks/0t864vwxbayyr.js","/_next/static/immutable/chunks/3vba9hf7-zrge.js","/_next/static/immutable/chunks/16-tr_iilxrhb.js","/_next/static/immutable/chunks/2x03jtn4ys_wx.js","/_next/static/immutable/chunks/0tfe231gghziz.js","/_next/static/immutable/chunks/2ri0u_hhdt48v.js","/_next/static/immutable/chunks/3vpd3gxgxuvxn.js","/_next/static/immutable/chunks/2nv7z5ggl2vxy.js","/_next/static/immutable/chunks/2xoyts_0uq5uj.js","/_next/static/immutable/chunks/2u07s2f6fbivt.js","/_next/static/immutable/chunks/2xqpa5c7ogclt.js","/_next/static/immutable/chunks/1eav89ga2ish_.js","/_next/static/immutable/chunks/234j1a4a10s_s.js","/_next/static/immutable/chunks/2gj-fqwe9ql6k.js","/_next/static/immutable/chunks/3b7s527kqlb86.js","/_next/static/immutable/chunks/3qfv9aanu18_5.js","/_next/static/immutable/chunks/1dm59r-7ja6p-.js","/_next/static/immutable/chunks/1e0jyw4aho8bn.js","/_next/static/immutable/chunks/0q_fqruepll3-.js","/_next/static/immutable/chunks/0-t3xv07arlr0.js","/_next/static/immutable/chunks/1q3vgg603oats.js","/_next/static/immutable/chunks/3_zfwhp9enp9f.js","/_next/static/immutable/chunks/3ifxe0l6v3puc.js","/_next/static/immutable/chunks/1u-ziz4uaewf-.js","/_next/static/immutable/chunks/3hymg46f2cijm.js","/_next/static/immutable/chunks/20u23qwsnyaep.js","/_next/static/immutable/chunks/3fohu7x10eje8.js","/_next/static/immutable/chunks/0hvii51axh-fv.js","/_next/static/immutable/chunks/2azasfm84f4nm.js","/_next/static/immutable/chunks/0yk57mslp5gpo.js","/_next/static/immutable/chunks/0vrqfaof35wkh.js","/_next/static/immutable/chunks/1vwds7vq-f4ct.js","/_next/static/immutable/chunks/11d1k5hd8gyhp.js","/_next/static/immutable/chunks/06f-3e-am-rz0.js","/_next/static/immutable/chunks/2ddrbcod4yybp.js","/_next/static/immutable/chunks/1q7kned6j2qte.js","/_next/static/immutable/chunks/1itl0dp78v8hy.js","/_next/static/immutable/chunks/1nv14oq84mc1d.js","/_next/static/immutable/chunks/3-y1wg0q2kip1.js","/_next/static/immutable/chunks/2ibdfu2l9iggk.js","/_next/static/immutable/chunks/2ity0kkyaf8hb.js","/_next/static/immutable/chunks/3vqctoi0mp5pw.js","/_next/static/immutable/chunks/1-au7zm9m8n_w.js","/_next/static/immutable/chunks/3k21rgnf_61hs.js","/_next/static/immutable/chunks/1ax-wkdfkp0bk.js","/_next/static/immutable/chunks/3qeqp7-3q5oxj.js","/_next/static/immutable/chunks/2wlnf07d6jjbt.js","/_next/static/immutable/chunks/04-0klqh106nh.js"],"WorkTabProvider"] 4a:I[649892,["/_next/static/immutable/chunks/0v6-3q16afmwn.js","/_next/static/immutable/chunks/2ck6yuttil9xz.js","/_next/static/immutable/chunks/3rsnyfmzi6oij.js","/_next/static/immutable/chunks/0t864vwxbayyr.js","/_next/static/immutable/chunks/3vba9hf7-zrge.js","/_next/static/immutable/chunks/16-tr_iilxrhb.js","/_next/static/immutable/chunks/2x03jtn4ys_wx.js","/_next/static/immutable/chunks/0tfe231gghziz.js","/_next/static/immutable/chunks/2ri0u_hhdt48v.js","/_next/static/immutable/chunks/3vpd3gxgxuvxn.js","/_next/static/immutable/chunks/2nv7z5ggl2vxy.js","/_next/static/immutable/chunks/2xoyts_0uq5uj.js","/_next/static/immutable/chunks/2u07s2f6fbivt.js","/_next/static/immutable/chunks/2xqpa5c7ogclt.js","/_next/static/immutable/chunks/1eav89ga2ish_.js","/_next/static/immutable/chunks/234j1a4a10s_s.js","/_next/static/immutable/chunks/2gj-fqwe9ql6k.js","/_next/static/immutable/chunks/3b7s527kqlb86.js","/_next/static/immutable/chunks/3qfv9aanu18_5.js","/_next/static/immutable/chunks/1dm59r-7ja6p-.js","/_next/static/immutable/chunks/1e0jyw4aho8bn.js","/_next/static/immutable/chunks/0q_fqruepll3-.js","/_next/static/immutable/chunks/0-t3xv07arlr0.js","/_next/static/immutable/chunks/1q3vgg603oats.js","/_next/static/immutable/chunks/3_zfwhp9enp9f.js","/_next/static/immutable/chunks/3ifxe0l6v3puc.js","/_next/static/immutable/chunks/1u-ziz4uaewf-.js","/_next/static/immutable/chunks/3hymg46f2cijm.js","/_next/static/immutable/chunks/20u23qwsnyaep.js","/_next/static/immutable/chunks/3fohu7x10eje8.js","/_next/static/immutable/chunks/0hvii51axh-fv.js","/_next/static/immutable/chunks/2azasfm84f4nm.js","/_next/static/immutable/chunks/0yk57mslp5gpo.js","/_next/static/immutable/chunks/0vrqfaof35wkh.js","/_next/static/immutable/chunks/1vwds7vq-f4ct.js","/_next/static/immutable/chunks/11d1k5hd8gyhp.js","/_next/static/immutable/chunks/06f-3e-am-rz0.js","/_next/static/immutable/chunks/2ddrbcod4yybp.js","/_next/static/immutable/chunks/1q7kned6j2qte.js","/_next/static/immutable/chunks/1itl0dp78v8hy.js","/_next/static/immutable/chunks/1nv14oq84mc1d.js","/_next/static/immutable/chunks/3-y1wg0q2kip1.js","/_next/static/immutable/chunks/2ibdfu2l9iggk.js","/_next/static/immutable/chunks/2ity0kkyaf8hb.js","/_next/static/immutable/chunks/3vqctoi0mp5pw.js","/_next/static/immutable/chunks/1-au7zm9m8n_w.js","/_next/static/immutable/chunks/3k21rgnf_61hs.js","/_next/static/immutable/chunks/1ax-wkdfkp0bk.js","/_next/static/immutable/chunks/3qeqp7-3q5oxj.js","/_next/static/immutable/chunks/2wlnf07d6jjbt.js","/_next/static/immutable/chunks/04-0klqh106nh.js"],"WorkHeader"] 4b:T41b,Richard Harris is a Susan Samueli Endowed Chair and Professor in the Department of Anesthesiology and Perioperative Care in the School of Medicine at the University of California at Irvine. His background is in basic science and clinical research in alternative medicine. He received his B.S. degree in Genetics from Purdue University in 1992 and his Ph. D. in Molecular and Cell Biology from UC Berkeley in 1997. Following his graduate work, he completed a postdoctoral fellowship at NIH. He is a graduate of the Maryland Institute of Traditional Chinese Medicine and has received an MS degree in Clinical Research Design and Statistical Analysis at the University of Michigan. Dr. Harris is currently investigating mechanisms of chronic pain and its treatment with acupuncture and shamanism. His recent investigations have focused on the role of brain neurotransmitters and brain network behavior in chronic pain. He was a member of the National Advisory Council for NIH/NCCIH and is a current co-President for the Society for Acupuncture Research.4c:T41b,Richard Harris is a Susan Samueli Endowed Chair and Professor in the Department of Anesthesiology and Perioperative Care in the School of Medicine at the University of California at Irvine. His background is in basic science and clinical research in alternative medicine. He received his B.S. degree in Genetics from Purdue University in 1992 and his Ph. D. in Molecular and Cell Biology from UC Berkeley in 1997. Following his graduate work, he completed a postdoctoral fellowship at NIH. He is a graduate of the Maryland Institute of Traditional Chinese Medicine and has received an MS degree in Clinical Research Design and Statistical Analysis at the University of Michigan. Dr. Harris is currently investigating mechanisms of chronic pain and its treatment with acupuncture and shamanism. His recent investigations have focused on the role of brain neurotransmitters and brain network behavior in chronic pain. He was a member of the National Advisory Council for NIH/NCCIH and is a current co-President for the Society for Acupuncture Research.4d:T67fd,Energy Healing Brain Hyper Scanning in Fibromyalgia 1. Overview Energy medicine or energy healing (EH) is an emerging therapy with significant promise. It is derived from the theory that using the body’s own biological energy a therapeutic effect can be obtained in another individual such as a patient. Preliminary unpublished data from our group in chronic pain patients, suggests that EH, delivered by an experienced practitioner, may be able to reduce self-reported pain symptoms within minutes with effects lasting for weeks to months. In addition to improvements in pain, reductions in other symptoms including fatigue, sleep, and cognitive dysfunction may also be possible with EH. EH practitioners may be trained within a specific tradition such as healing touch, reiki, and qigong, or work via novel unique methods. The energy practitioners that will be used for this study have practiced their unique style of EH for years and one has taken his work through a blinded hospital study demonstrating its feasibility and efficacy.[1] This study took place in inpatient units and the emergency department and found both acceptability and demand for energy medicine. Of 50 reports of pain, 38 (76%) showed marked improvement. Of 29 non-pain-related problems, 23 (79%) showed marked improvement.[1] While this finding is certainly promising, there were no controls used with this study nor were the patients blinded to the treatment, two limitations we seek to address in this investigation. We propose to study EH delivered by a experienced therapists, for the treatment of fibromyalgia (FM), a chronic pain condition that results from aberrant central nervous system function and neurochemistry. This work will be performed at the University of California, Irvine and comply with the university’s Institutional Review Board ethics. Participant recruitment will be for 18 months and funding for this study will be in part through DMT Quest, ResearchHub, and possibly the Subtle Energy Funders Collective. Results and publications from this study will be shared with the public following its conclusion. 2. Introduction Fibromyalgia (FM) is a Common Chronic Pain Syndrome and a Major Public Health Issue. Fibromyalgia (FM) is the second most common rheumatologic disorder, behind osteoarthritis, with 2 - 4% of the populations of industrialized countries affected.[2-4] Overall, it is estimated that FM costs the American taxpayers over $20 billion a year in lost wages and disability.[5] In part this burden on the US healthcare system is our lack of understanding of the specific pathophysiology of the disorder. While research suggests that FM is a central non-nociceptive pain syndrome,[6-8] it is uncertain if the observed neurobiological outcomes are causally related to development of FM. That said, our recent study in children suggests that the development of widespread pain, a hallmark of FM, is preceded by aberrant brain neural function.[9] The study proposed here may provide much needed information into the pathology of this disorder and how it is treated in a clinical setting. For example, if energy healing is able to reduce FM pain specifically, this may identify a non-physical basis for treatment. Our proposed project may also synergize with emerging data indicating a generalized disturbance in central nervous system pain processing in this condition.[10,11] Need for a Neurobiological Model underlying EH for FM. There is a lack of key information about how EH may work for pain. One key missing piece in the field is that there are no objective markers that have been identified that actually track with subjective self-reported pain improvements following treatment with EH. This limitation is a key factor that prevents a more general adoption of this therapy by the medical community. If there is no proposed mechanism of action of EH, then the support for this intervention is weakened. However, an objective marker of chronic pain, that is modulated by EH, that also tracks with self-reported symptom improvement, would be a major advance for the field and also aid the development of a biomedical theory of how this therapy works. Moreover showing that similar brain activity occurs in an energy healer and the patient during treatment would also link the actions of healing at a distance: a key tenet of EH. Finally, our proposed neurobiological outcomes may also detect the effects of EH on brain neuroimaging biomarkers that we have previously found to track with clinical pain in FM, thus supporting the mechanisms of EH in chronic pain. Hypotheses Aim 1: Assess the effects of EH as compared to control, on neuroelectrical activity acquired simultaneously from patients with FM and an energy healer (EEG hyperscan) and relate these brain changes to improvements in clinical pain. Hypothesis 1A: EEG gamma power (co-primary outcome) assessed in FM patients and the healer will be greater during active healing as compared to control. Hypothesis 1B: patient-practitioner brain-to-brain connectivity (co-primary outcome) will be higher during EH as compared to control. Hypothesis 1C: changes in EEG metrics will be correlated with improvements in clinical pain (secondary outcome) during active EH as compared to control. Aim 2 (exploratory): Explore the action of EH on brain explosive synchronization (exploratory outcome), an EEG measure of brain network instability and chronic pain.[19,20] We have previously shown this outcome of network instability to be present in FM participants with increased chronic pain. Hypothesis 2A: Explore the action of EH on heart rate variability, biophoton emission, and skin temperature (exploratory outcomes). Hypothesis 2B: Brain explosive synchronization metrics (network instability) will decrease in conjunction with chronic pain during EH as compared to control (exploratory outcome). Impact. If our hypotheses are proven true, 1) critical information will be provided that may help incorporate EH into mainstream clinical care, 2) EH may be shown to reduce pain symptoms in FM, and 3) we may obtain a better understanding of EH and how it might be utilized in future studies of other chronic pain conditions. 3. Methods Overview. Our overall goal is to understand the role EH plays in modulating EEG neuroimaging markers (primary outcomes) related to altered neural processing of pain in FM as well as the effects it has on clinical pain (secondary outcome), and other exploratory outcomes including: heart rate variability, biophoton emission, and skin temperature. We will study 40 FM patients using brain electroencephalogram (EEG) hyper scanning in an energy healer and the patient simultaneously. We will also collect data on clinical pain changes as well as physiological outcomes in the patient and healer such as heart rate, skin temperature, and biophoton emission, exploratory outcomes that may be associated with EH. Data during energy healing periods will be compared to data acquired during rest as a control for non-specific or placebo treatment effects. Patients will be blinded as to the timing of these periods (see below). At no point will the patient know when the active healing treatment periods will start thus blinding the intervention and controlling for placebo effects. Study Team. This investigation is being led by Richard E. Harris, PhD who is a Susan Samueli Endowed Chair in the Susan Samueli Integrative Health Institute and Professor in the Department of Anesthesiology and Perioperative Care in the School of Medicine at the University of California at Irvine. He received his B.S. degree in Genetics from Purdue University in 1992 and his Ph.D. in Molecular and Cell Biology from UC Berkeley in 1997. Following his graduate work, he completed a postdoctoral fellowship at NIH. He is a graduate of the Maryland Institute of Traditional Chinese Medicine and has received an MS degree in Clinical Research Design and Statistical Analysis at the University of Michigan. Dr. Harris is currently investigating mechanisms of chronic pain and its treatment with acupuncture, energy healing, and shamanism. His investigations over the past 25 years have focused on the role of brain neurotransmitters and brain network behavior in chronic pain patients. and how these outcomes can be modulated by various treatments. He was a board member of the National Advisory Council for NIH/NCCIH and is a previous co-President for the Society for Acupuncture Research. He is joined in this work by Dr. Alessandra Anzolin, a consultant from Spaulding Rehabilitation Hospital. She is a neuroscientist with an in-depth background in biomedical engineering and brain imaging techniques such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). She is a junior faculty at the Spaulding Rehabilitation Hospital, Harvard Medical School, where she is leading several projects with both healthy participants and patients with chronic pain. Since beginning her career, she have been passionate about methodological development to improve biomedical devices and signal processing, as well as the clinical applications that benefit from those advancements. In the realm of pain neuroimaging, her experience has included implementation of novel experimental designs utilizing EEG hyper scanning. This advanced methodology enables one to collect data simultaneously from patients and clinicians and to delve deeper into understanding complex phenomena such as the importance of therapeutic alliance and other non-specific effects during pain treatment. In particular, she has led EEG-hyper scanning projects to study the impact of an augmented compared to a limited clinical context on pain treatment effectiveness and the possibility of boosting therapeutic alliance, empathy, and brain concordance using a Theory of Mind training or psychedelic-assisted therapy in pain management. Results from a completed EEG-hyper scanning pilot [21-23] were published as a brief paper and received several awards at international conferences – e.g. “Outstanding Junior Researcher Award in Basic Science Research” from the Society for Acupuncture and the “Best Translational Research Award” from the US Association for the Study of Pain. She also has recently led the development of non-invasive brain stimulation techniques to modulate specific brain rhythms. This includes the development of a prototype (EEG-gated Auricular Vagal Afferent Nerve Stimulation, EAVANS), a closed-loop peripheral nerve stimulation device. By leveraging EEG data to guide the stimulation process, EAVANS holds the potential to enhance the efficacy of brain stimulation therapies, allowing for a more personalized and non-pharmacological intervention to treat delirium and expedite the recovery of cognitive functions post-anesthesia.[24] The backgrounds of Drs. Harris and Anzolin in chronic pain, brain imaging, and EEG hyper scanning will be valuable in advancing this project. We are purposefully not providing information on the three energy healers that will be used in this study as we do not want to risk participants knowing who will be treating them prior to seeing them in person on the study visit (see below Procedures). That said, the three EHs that will be used practice their own individual style of healing that is not Reiki or Qigong. Each healer has over 15 years of experience in healing pain patients and we have worked with one of the healers on a different mechanistic study that is ongoing. Rationale. Our proposal originates with coupling brain and other physiological outcomes with clinical pain measures incorporated in a treatment trial framework using EH. In addition to evaluating brain response to EH between two individuals simultaneously, we will also investigate the neurocircuitry subserving clinical pain. Neuroimaging markers reflecting FM patients’ clinical pain are crucial to this design, as (a) they conceptually link more closely to important clinical outcome measures, as compared to markers for experimental pain in hyperalgesia and allodynia, and (b) their differential susceptibility to different forms of therapy may underlie the ultimate mechanisms of action of EH. Recent efforts have been increasingly aimed at developing a neurobiological model for chronic nociplastic pain, and our proposal is innovative in that it adds to this burgeoning field of research.[12,13] Procedures. All EH treatments and physiological testing will occur at the Susan Samueli Integrative Health Institute at the University of California at Irvine. 40 participants aged 18-75 years old, with a diagnosis/symptoms of FM for at least 1 year will be consented in person. Ineligible participants will be excluded if they have: epilepsy, bipolar disorder, history of stroke, rhuematoid arthritis, or Lupus. Additional exclusions are any other condition of chronic pain other than fibromyalgia. Following consent participants will undergo a two-week run-in during baseline to washout previous treatment effects and reduce regression to the mean. Following consent and 2 week run-in, participants will attend a single visit with one of three chosen energy healers, during which EEG and control/active EH treatment will occur. Prior to starting this visit, patients will be told verbally, “At some point in this session you will experience energy healing, but you will not know when that is.” After 32-channel EEG cap set up on both the patient and the energy healer, individuals will be seated facing away from each other. There will be no visual interaction between the energy healer and patient during the control and healing sessions. This will help blind the study so that the patients will not know at what time the active EH will take place. An initial 5 minutes of resting eyes closed will be acquired for both individuals, followed by a 10-minute eyes closed resting condition wherein the patient will be queried every 2 minutes about their resting pain level on a scale from 0 to 10 with 0 being “no pain” and 10 being “worst pain imaginable”. This is the no-treatment control condition. Then, in a blinded fashion so the patient does not know, the energy healer will be notified by staff to start the energy healing. At no point will the patient know when the healing will start and at no time will there be active touching of the patient by the healer. During the next 15 minutes of healing, the patient will be queried by staff as to what their pain level currently is in the same fashion as during the prior 10 minute no-treatment control condition. We have piloted this protocol in fibromyalgia patients previously and this duration of treatment and control are adequate to blind the patient and allows enough time for the healer to reduce chronic fibromyalgia pain. We also have show in unpublished pilot data that the EH effects can persist for hours to days following a single treatment, which prevents us from randomizing the order of presentation of the control and active healing periods as active healing would extend into the control period if active healing was done first. (As mentioned above, the patients will not know the fixed order of events.) Following the active EH period, patients and healers will perform an eyes closed 5 minute resting period and be debriefed about the procedure. Our primary outcome is EEG (see below) and secondary outcome is pain, with change in pain intensity and interference, as measured in a 11 point Numerical Rating Scale, anchored at 0 = “no pain” and 10 = “worst pain imaginable”. This will be assessed throughout the control and active EH procedure (see above). We will also include the Brief Pain Inventory [14] and the FM survey criteria [15] as additional secondary pain outcomes acquired prior to and following the EEG visit. We will also use the PROMIS 29 questionnaire to assess fatigue, sleep, and mood. EEG Acquisition (primary outcomes) and Analysis. EEG data will be collected from the energy healer and FM participants simultaneously (hyperscan) to measure synchronized brain activity in each dyad (Energy Healer-FM participant). We use a Brain Products EEG system with 32-channel water-based nets (sensors are distributed accordingly to the International 10-20 system). The EEG caps from the FM participant and the healer will be attached to the same EEG amplifier (BrainAmp) ensuring the millisecond-precision alignment required for the inter-brain connectivity analysis. The EEG equipment has been purchased and tested in pilot acquisitions to ensure rigorous data collection. Gamma Power and Hyperscanning: We use in-house developed MATLAB scripts based on validated pipelines for EEG data processing (EEGLAB). First, we will perform standard preprocessing including bandpass filtering (1-30Hz for inter-brain connectivity assessment and 1-100Hz for gamma analysis), re-referencing, and ocular artifact removal (independent component analysis, ICA). Then Phase Locking Value (PLV) and Partial Directed Coherence (PDC) will be used to measure inter-brain connectivity.[16] PLV assesses the magnitude of phase synchrony[17] whereas PDC is a spectral estimate of causal connectivity including intensity and directionality.[18] We will compute PLV and PDC on the EEG time series acquired during resting prior to EH and concurrently with EH. Additionally we will compute Power Spectral Density (PSD) in all standard EEG frequency bands, including Delta, Theta, Alpha, Beta, and Gamma. Brain-to-brain connectivity measures and Gamma power (assessed separately for patients and the healer) will be contrasted between resting and active healing time points to assess change associated with the EH treatment as compared to resting control in FM patients and the healer. We expect that if energy transfer occurs between the patient and healer, a signal in EEG coherence between the two individuals may be detected. We will specifically test if this signal in the EG precedes the changes in the patient, which would be indicative of a energy transfer process during healing. Exploratory outcomes: Heart rate variability will be assessed with ECG for both the FM patient as well as the energy healer simultaneously during treatment and resting control conditions. As mentioned above, to control for placebo effects and confounding factors FM patients will not be facing the healer during treatment. This will effectively blind the patient from the timing of the EH and rest periods. ECG will be performed using a Movesense sensor (https://www.movesense.com/) connected to a mobile device (via Bluetooth) which runs the patented electrocardiomatrix (ECM) software invented by the Borjigin lab at the University of Michigan that converts the 2D ECG data into a 3D ECM image that resembles a heatmap. The ECM image captured on the mobile device can be used as a standalone diagnostic tool for intuitive visualization of user’s cardiac conditions in real-time or post-capture. The captured ECG data can be uploaded to the ECM website (developed by Dr. Xu in the Borjigin lab) for quantitative processing (HRV and other outcomes). Finally in addition to ECG and EEG assessment, we will also measure skin temperature, galvanic skin resistance, and single hand biophoton emission during resting control period and active EH for both the healer and the FM patient. All study procedures will be approved by the University of California, Irvine Institutional Review Board, and all data will be securely stored in locked password protected computers at the University of California, Irvine campus. General Analysis. Comparisons between healing and control resting periods will be made for all outcomes using a paired t-Test (see above for EEG analysis). Pearson correlations will be made between change scores in brain neuroimaging outcomes, other physiologic outcomes, and changes in pain. Significant p-values are identified at p<0.05. As this is primarily a pilot mechanistic study with a single primary outcome (EEG), we will make no correction for multiple comparisons. Assessment of exploratory outcomes will be limited to hypothesis generation. Power calculation is pending and will be added later. Ethics and Data Management. All procedures will be approved by the local University of California, Irvine Institutional Review Board. All data will be identified with a unique patient identification number, whose linked personal health information will be kept in a locked cabinet behind a locked door in the Susan Samueli Integrative Health Institute building. Data will be shared with other researchers once the primary analyses are published and all data will be archived for 7 years at the University of California, Irvine after the study is completed 4. Pilot Data (Optional) This study has no pilot data to present. However there has been a study of one of the EH participating in this trial. These data are presented in the first citation in the references.[1] This unblinded and uncontrolled study found that of 50 reports of pain, 38 (76%) showed marked improvement. While this finding is certainly promising, there were no controls used with this study nor were the patients blinded to the treatment, two limitations we seek to address in this investigation. We also seek to find a mechanistic objective outcome that can track with pain improvement with EH. 5. Budget The budget for this work is $250,000 in total over 18 months. This includes personnel salaries (PI 5% effort 30K, study coordinator 100% effort 100K, imaging analyst 50% effort 90K, EEG consultant 10K, and biostatistician 5K), purchasing of equipment and supplies (EEG equipment, supplies and galvanic skin resistance device 5K), travel (4K), and participant recruitment and reimbursement (6K). 6. References 1. Dufresne F, Simmons B, Vlachostergios PJ, Fleischner Z, Joudeh R, Blakeway J, Julliard K. Feasibility of energy medicine in a community teaching hospital: an exploratory case series. J Altern Complement Med. (2015) 21(6),339-49. 2. Wolfe, F., et al., The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. (1995) 38(1): p. 19-28. 3. Jacobsen, S. and S.R. Bredkjaer. The prevalence of fibromyalgia and widespread chronic musculoskeletal pain in the general population. Scand.J.Rheumatol. (1992) 21(5): p. 261-263. 4. Raspe, H., C. Baumgartner, and F. Wolfe. The prevalence of fibromyalgia in a rural German community: How much difference do different criteria make? Arthritis & Rheumatism. (1993) 36(9 (Supplement)): p. S48. 5. Wolfe, F., et al. A prospective, longitudinal, multicenter study of service utilization and costs in fibromyalgia. Arthritis Rheum (1997) 40(9): p. 1560-70. 6. Gracely, R.H., et al. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. (2002) 46(5): p. 1333-1343. 7. Harris, R.E., et al. Decreased central mu-opioid receptor availability in fibromyalgia. J.Neurosci. (2007) 27(37): p. 10000-10006. 8. Mountz, J.M., et al., Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis Rheum. (1995) 38(7): p. 926-938. 9. Kaplan CM, Schrepf A, Mawla I, Ichesco E, Boehnke KF, Beltz A, Foxen-Craft E, Puglia MP, Tsodikov A, Williams DA, Hassett AL, Clauw DJ, Harte SE, Harris RE. Neurobiological antecedents of multisite pain in children. Pain. (2022) Apr 1;163(4):e596-e603. 10. Yunus, M.B., Towards a model of pathophysiology of fibromyalgia: aberrant central pain mechanisms with peripheral modulation. J Rheumatol. (1992) 19(6): p. 846-850. 11. Clauw, D.J. and G.P. Chrousos, Chronic pain and fatigue syndromes: Overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. Neuroimmunomodulation. (1997) 4(3): p. 134-153. 12. Apkarian, A.V., M.N. Baliki, and P. Y. Geha, Towards a theory of chronic pain. Prog Neurobiol. (2009) 87(2): p. 81-97. 13. Tracey, I. and M.C. Bushnell, How neuroimaging studies have challenged us to rethink: is chronic pain a disease? The Journal of Pain. (2009) 10(11): p. 1113-20. 14. Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. (1994) Mar;23(2):129-38. 15. Clauw DJ. Fibromyalgia: a clinical review. JAMA. (2014) 311(15):1547-55. 16. Kang K, Orlandi S, Leung J, et al. Electroencephalographic interbrain synchronization in children with disabilities, their parents, and neurologic music therapists. Eur J Neurosci. Jul 2023;58(1):2367-2383. doi:10.1111/ejn.16036 17. Bastos AM, Schoffelen JM. A Tutorial Review of Functional Connectivity Analysis Methods and Their Interpretational Pitfalls. Front Syst Neurosci. 2015;9:175. doi:10.3389/fnsys.2015.00175 18. Baccala LA, Sameshima K. Partial directed coherence: a new concept in neural structure determination. Biol Cybern. Jun 2001;84(6):463-74. doi:10.1007/PL00007990 19. Joo P, Kim M, Kish B, et al. Brain network hypersensitivity underlies pain crises in sickle cell disease. Sci Rep. Mar 27 2024;14(1):7315. doi:10.1038/s41598-024-57473-5 20. Lee U, Kim M, Lee K, et al. Functional Brain Network Mechanism of Hypersensitivity in Chronic Pain. Sci Rep. Jan 10 2018;8(1):243. doi:10.1038/s41598-017-18657-4 A Anzolin, K. Isenburg, A. Grahl, J. Toppi, M. Yücel, D.M. Ellingsen, J. Gerber, A. Ciaramidaro, L. Astolfi, T.J. Kaptchuk, V. Napadow – “Patient-Clinician Brain Response During Clinical Encounter and Pain Treatment”. In 2020 42nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 306527-1610 Ellingsen DM, Isenburg K, Jung C, Lee J, Gerber J, Mawla I, Sclocco R, Jensen K, Edwards RR, Kelley JM, Kirsch I, Kaptchuk T, Napadow V. Dynamic brain to brain concordance and behavioral mirroring as a mechanism of the patient/clinician interaction. Science advances 6, no. 43 (2020): eabc1304. Ellingsen DM, Isenburg K, Jung C, Lee J, Gerber J, Mawla I, Sclocco R, Grahl A, Anzolin A, Edwards RR, Kelley JM, Kirsch I, Kaptchuk TJ, Napadow V. Brain-to-brain mechanisms underlying pain empathy and social modulation of pain in the patient-clinician interaction. Proc Natl Acad Sci U S A. 2023 Jun 27;120(26):e2212910120. PMID: 37339198, PMCID: PMC10293846, https://doi.org/10.1073/pnas.2212910120. Anzolin A, Das P, Garcia RG, Chen A, Grahl A, Ellis S, Purdon P, Napadow V. Delta power during sleep is modulated by EEG-gated auricular vagal afferent nerve stimulation (EAVANS). Annu Int Conf IEEE Eng Med Biol Soc. 2023 Jul;2023:1-4. 10.1109/EMBC40787.2023.10340971. PMID: 38082663.4e:T68e9,Energy Healing Brain Hyper Scanning in Fibromyalgia 1. Overview Energy medicine or energy healing (EH) is an emerging therapy with significant promise. It is derived from the theory that using the body’s own biological energy a therapeutic effect can be obtained in another individual such as a patient. Preliminary unpublished data from our group in chronic pain patients, suggests that EH, delivered by an experienced practitioner, may be able to reduce self-reported pain symptoms within minutes with effects lasting for weeks to months. In addition to improvements in pain, reductions in other symptoms including fatigue, sleep, and cognitive dysfunction may also be possible with EH. EH practitioners may be trained within a specific tradition such as healing touch, reiki, and qigong, or work via novel unique methods. The energy practitioners that will be used for this study have practiced their unique style of EH for years and one has taken his work through a blinded hospital study demonstrating its feasibility and efficacy.[1] This study took place in inpatient units and the emergency department and found both acceptability and demand for energy medicine. Of 50 reports of pain, 38 (76%) showed marked improvement. Of 29 non-pain-related problems, 23 (79%) showed marked improvement.[1] While this finding is certainly promising, there were no controls used with this study nor were the patients blinded to the treatment, two limitations we seek to address in this investigation. We propose to study EH delivered by a experienced therapists, for the treatment of fibromyalgia (FM), a chronic pain condition that results from aberrant central nervous system function and neurochemistry. This work will be performed at the University of California, Irvine and comply with the university’s Institutional Review Board ethics. Participant recruitment will be for 18 months and funding for this study will be in part through DMT Quest, ResearchHub, and possibly the Subtle Energy Funders Collective. Results and publications from this study will be shared with the public following its conclusion. 2. Introduction Fibromyalgia (FM) is a Common Chronic Pain Syndrome and a Major Public Health Issue. Fibromyalgia (FM) is the second most common rheumatologic disorder, behind osteoarthritis, with 2 - 4% of the populations of industrialized countries affected.[2-4] Overall, it is estimated that FM costs the American taxpayers over $20 billion a year in lost wages and disability.[5] In part this burden on the US healthcare system is our lack of understanding of the specific pathophysiology of the disorder. While research suggests that FM is a central non-nociceptive pain syndrome,[6-8] it is uncertain if the observed neurobiological outcomes are causally related to development of FM. That said, our recent study in children suggests that the development of widespread pain, a hallmark of FM, is preceded by aberrant brain neural function.[9] The study proposed here may provide much needed information into the pathology of this disorder and how it is treated in a clinical setting. For example, if energy healing is able to reduce FM pain specifically, this may identify a non-physical basis for treatment. Our proposed project may also synergize with emerging data indicating a generalized disturbance in central nervous system pain processing in this condition.[10,11] Need for a Neurobiological Model underlying EH for FM. There is a lack of key information about how EH may work for pain. One key missing piece in the field is that there are no objective markers that have been identified that actually track with subjective self-reported pain improvements following treatment with EH. This limitation is a key factor that prevents a more general adoption of this therapy by the medical community. If there is no proposed mechanism of action of EH, then the support for this intervention is weakened. However, an objective marker of chronic pain, that is modulated by EH, that also tracks with self-reported symptom improvement, would be a major advance for the field and also aid the development of a biomedical theory of how this therapy works. Moreover showing that similar brain activity occurs in an energy healer and the patient during treatment would also link the actions of healing at a distance: a key tenet of EH. Finally, our proposed neurobiological outcomes may also detect the effects of EH on brain neuroimaging biomarkers that we have previously found to track with clinical pain in FM, thus supporting the mechanisms of EH in chronic pain. Hypotheses Aim 1: Assess the effects of EH as compared to control, on neuroelectrical activity acquired simultaneously from patients with FM and an energy healer (EEG hyperscan) and relate these brain changes to improvements in clinical pain. Hypothesis 1A: EEG gamma power (co-primary outcome) assessed in FM patients and the healer will be greater during active healing as compared to control. Hypothesis 1B: patient-practitioner brain-to-brain connectivity (co-primary outcome) will be higher during EH as compared to control. Hypothesis 1C: changes in EEG metrics will be correlated with improvements in clinical pain (secondary outcome) during active EH as compared to control. Aim 2 (exploratory): Explore the action of EH on brain explosive synchronization (exploratory outcome), an EEG measure of brain network instability and chronic pain.[19,20] We have previously shown this outcome of network instability to be present in FM participants with increased chronic pain. Hypothesis 2A: Explore the action of EH on heart rate variability, biophoton emission, and skin temperature (exploratory outcomes). Hypothesis 2B: Brain explosive synchronization metrics (network instability) will decrease in conjunction with chronic pain during EH as compared to control (exploratory outcome). Impact. If our hypotheses are proven true, 1) critical information will be provided that may help incorporate EH into mainstream clinical care, 2) EH may be shown to reduce pain symptoms in FM, and 3) we may obtain a better understanding of EH and how it might be utilized in future studies of other chronic pain conditions. 3. Methods Overview. Our overall goal is to understand the role EH plays in modulating EEG neuroimaging markers (primary outcomes) related to altered neural processing of pain in FM as well as the effects it has on clinical pain (secondary outcome), and other exploratory outcomes including: heart rate variability, biophoton emission, and skin temperature. We will study 40 FM patients using brain electroencephalogram (EEG) hyper scanning in an energy healer and the patient simultaneously. We will also collect data on clinical pain changes as well as physiological outcomes in the patient and healer such as heart rate, skin temperature, and biophoton emission, exploratory outcomes that may be associated with EH. Data during energy healing periods will be compared to data acquired during rest as a control for non-specific or placebo treatment effects. Patients will be blinded as to the timing of these periods (see below). At no point will the patient know when the active healing treatment periods will start thus blinding the intervention and controlling for placebo effects. Study Team. This investigation is being led by Richard E. Harris, PhD who is a Susan Samueli Endowed Chair in the Susan Samueli Integrative Health Institute and Professor in the Department of Anesthesiology and Perioperative Care in the School of Medicine at the University of California at Irvine. He received his B.S. degree in Genetics from Purdue University in 1992 and his Ph.D. in Molecular and Cell Biology from UC Berkeley in 1997. Following his graduate work, he completed a postdoctoral fellowship at NIH. He is a graduate of the Maryland Institute of Traditional Chinese Medicine and has received an MS degree in Clinical Research Design and Statistical Analysis at the University of Michigan. Dr. Harris is currently investigating mechanisms of chronic pain and its treatment with acupuncture, energy healing, and shamanism. His investigations over the past 25 years have focused on the role of brain neurotransmitters and brain network behavior in chronic pain patients. and how these outcomes can be modulated by various treatments. He was a board member of the National Advisory Council for NIH/NCCIH and is a previous co-President for the Society for Acupuncture Research. He is joined in this work by Dr. Alessandra Anzolin, a consultant from Spaulding Rehabilitation Hospital. She is a neuroscientist with an in-depth background in biomedical engineering and brain imaging techniques such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). She is a junior faculty at the Spaulding Rehabilitation Hospital, Harvard Medical School, where she is leading several projects with both healthy participants and patients with chronic pain. Since beginning her career, she have been passionate about methodological development to improve biomedical devices and signal processing, as well as the clinical applications that benefit from those advancements. In the realm of pain neuroimaging, her experience has included implementation of novel experimental designs utilizing EEG hyper scanning. This advanced methodology enables one to collect data simultaneously from patients and clinicians and to delve deeper into understanding complex phenomena such as the importance of therapeutic alliance and other non-specific effects during pain treatment. In particular, she has led EEG-hyper scanning projects to study the impact of an augmented compared to a limited clinical context on pain treatment effectiveness and the possibility of boosting therapeutic alliance, empathy, and brain concordance using a Theory of Mind training or psychedelic-assisted therapy in pain management. Results from a completed EEG-hyper scanning pilot [21-23] were published as a brief paper and received several awards at international conferences – e.g. “Outstanding Junior Researcher Award in Basic Science Research” from the Society for Acupuncture and the “Best Translational Research Award” from the US Association for the Study of Pain. She also has recently led the development of non-invasive brain stimulation techniques to modulate specific brain rhythms. This includes the development of a prototype (EEG-gated Auricular Vagal Afferent Nerve Stimulation, EAVANS), a closed-loop peripheral nerve stimulation device. By leveraging EEG data to guide the stimulation process, EAVANS holds the potential to enhance the efficacy of brain stimulation therapies, allowing for a more personalized and non-pharmacological intervention to treat delirium and expedite the recovery of cognitive functions post-anesthesia.[24] The backgrounds of Drs. Harris and Anzolin in chronic pain, brain imaging, and EEG hyper scanning will be valuable in advancing this project. We are purposefully not providing information on the three energy healers that will be used in this study as we do not want to risk participants knowing who will be treating them prior to seeing them in person on the study visit (see below Procedures). That said, the three EHs that will be used practice their own individual style of healing that is not Reiki or Qigong. Each healer has over 15 years of experience in healing pain patients and we have worked with one of the healers on a different mechanistic study that is ongoing. Rationale. Our proposal originates with coupling brain and other physiological outcomes with clinical pain measures incorporated in a treatment trial framework using EH. In addition to evaluating brain response to EH between two individuals simultaneously, we will also investigate the neurocircuitry subserving clinical pain. Neuroimaging markers reflecting FM patients’ clinical pain are crucial to this design, as (a) they conceptually link more closely to important clinical outcome measures, as compared to markers for experimental pain in hyperalgesia and allodynia, and (b) their differential susceptibility to different forms of therapy may underlie the ultimate mechanisms of action of EH. Recent efforts have been increasingly aimed at developing a neurobiological model for chronic nociplastic pain, and our proposal is innovative in that it adds to this burgeoning field of research.[12,13] Procedures. All EH treatments and physiological testing will occur at the Susan Samueli Integrative Health Institute at the University of California at Irvine. 40 participants aged 18-75 years old, with a diagnosis/symptoms of FM for at least 1 year will be consented in person. Ineligible participants will be excluded if they have: epilepsy, bipolar disorder, history of stroke, rhuematoid arthritis, or Lupus. Additional exclusions are any other condition of chronic pain other than fibromyalgia. Following consent participants will undergo a two-week run-in during baseline to washout previous treatment effects and reduce regression to the mean. Following consent and 2 week run-in, participants will attend a single visit with one of three chosen energy healers, during which EEG and control/active EH treatment will occur. Prior to starting this visit, patients will be told verbally, “At some point in this session you will experience energy healing, but you will not know when that is.” After 32-channel EEG cap set up on both the patient and the energy healer, individuals will be seated facing away from each other. There will be no visual interaction between the energy healer and patient during the control and healing sessions. This will help blind the study so that the patients will not know at what time the active EH will take place. An initial 5 minutes of resting eyes closed will be acquired for both individuals, followed by a 10-minute eyes closed resting condition wherein the patient will be queried every 2 minutes about their resting pain level on a scale from 0 to 10 with 0 being “no pain” and 10 being “worst pain imaginable”. This is the no-treatment control condition. Then, in a blinded fashion so the patient does not know, the energy healer will be notified by staff to start the energy healing. At no point will the patient know when the healing will start and at no time will there be active touching of the patient by the healer. During the next 15 minutes of healing, the patient will be queried by staff as to what their pain level currently is in the same fashion as during the prior 10 minute no-treatment control condition. We have piloted this protocol in fibromyalgia patients previously and this duration of treatment and control are adequate to blind the patient and allows enough time for the healer to reduce chronic fibromyalgia pain. We also have show in unpublished pilot data that the EH effects can persist for hours to days following a single treatment, which prevents us from randomizing the order of presentation of the control and active healing periods as active healing would extend into the control period if active healing was done first. (As mentioned above, the patients will not know the fixed order of events.) Following the active EH period, patients and healers will perform an eyes closed 5 minute resting period and be debriefed about the procedure. Our primary outcome is EEG (see below) and secondary outcome is pain, with change in pain intensity and interference, as measured in a 11 point Numerical Rating Scale, anchored at 0 = “no pain” and 10 = “worst pain imaginable”. This will be assessed throughout the control and active EH procedure (see above). We will also include the Brief Pain Inventory [14] and the FM survey criteria [15] as additional secondary pain outcomes acquired prior to and following the EEG visit. We will also use the PROMIS 29 questionnaire to assess fatigue, sleep, and mood. EEG Acquisition (primary outcomes) and Analysis. EEG data will be collected from the energy healer and FM participants simultaneously (hyperscan) to measure synchronized brain activity in each dyad (Energy Healer-FM participant). We use a Brain Products EEG system with 32-channel water-based nets (sensors are distributed accordingly to the International 10-20 system). The EEG caps from the FM participant and the healer will be attached to the same EEG amplifier (BrainAmp) ensuring the millisecond-precision alignment required for the inter-brain connectivity analysis. The EEG equipment has been purchased and tested in pilot acquisitions to ensure rigorous data collection. Gamma Power and Hyperscanning: We use in-house developed MATLAB scripts based on validated pipelines for EEG data processing (EEGLAB). First, we will perform standard preprocessing including bandpass filtering (1-30Hz for inter-brain connectivity assessment and 1-100Hz for gamma analysis), re-referencing, and ocular artifact removal (independent component analysis, ICA). Then Phase Locking Value (PLV) and Partial Directed Coherence (PDC) will be used to measure inter-brain connectivity.[16] PLV assesses the magnitude of phase synchrony[17] whereas PDC is a spectral estimate of causal connectivity including intensity and directionality.[18] We will compute PLV and PDC on the EEG time series acquired during resting prior to EH and concurrently with EH. Additionally we will compute Power Spectral Density (PSD) in all standard EEG frequency bands, including Delta, Theta, Alpha, Beta, and Gamma. Brain-to-brain connectivity measures and Gamma power (assessed separately for patients and the healer) will be contrasted between resting and active healing time points to assess change associated with the EH treatment as compared to resting control in FM patients and the healer. We expect that if energy transfer occurs between the patient and healer, a signal in EEG coherence between the two individuals may be detected. We will specifically test if this signal in the EG precedes the changes in the patient, which would be indicative of a energy transfer process during healing. Exploratory outcomes: Heart rate variability will be assessed with ECG for both the FM patient as well as the energy healer simultaneously during treatment and resting control conditions. As mentioned above, to control for placebo effects and confounding factors FM patients will not be facing the healer during treatment. This will effectively blind the patient from the timing of the EH and rest periods. ECG will be performed using a Movesense sensor (https://www.movesense.com/) connected to a mobile device (via Bluetooth) which runs the patented electrocardiomatrix (ECM) software invented by the Borjigin lab at the University of Michigan that converts the 2D ECG data into a 3D ECM image that resembles a heatmap. The ECM image captured on the mobile device can be used as a standalone diagnostic tool for intuitive visualization of user’s cardiac conditions in real-time or post-capture. The captured ECG data can be uploaded to the ECM website (developed by Dr. Xu in the Borjigin lab) for quantitative processing (HRV and other outcomes). Finally in addition to ECG and EEG assessment, we will also measure skin temperature, galvanic skin resistance, and single hand biophoton emission during resting control period and active EH for both the healer and the FM patient. All study procedures will be approved by the University of California, Irvine Institutional Review Board, and all data will be securely stored in locked password protected computers at the University of California, Irvine campus. General Analysis. Comparisons between healing and control resting periods will be made for all outcomes using a paired t-Test (see above for EEG analysis). Pearson correlations will be made between change scores in brain neuroimaging outcomes, other physiologic outcomes, and changes in pain. Significant p-values are identified at p<0.05. As this is primarily a pilot mechanistic study with a single primary outcome (EEG), we will make no correction for multiple comparisons. Assessment of exploratory outcomes will be limited to hypothesis generation. Power calculation is pending and will be added later. Ethics and Data Management. All procedures will be approved by the local University of California, Irvine Institutional Review Board. All data will be identified with a unique patient identification number, whose linked personal health information will be kept in a locked cabinet behind a locked door in the Susan Samueli Integrative Health Institute building. Data will be shared with other researchers once the primary analyses are published and all data will be archived for 7 years at the University of California, Irvine after the study is completed 4. Pilot Data (Optional) This study has no pilot data to present. However there has been a study of one of the EH participating in this trial. These data are presented in the first citation in the references.[1] This unblinded and uncontrolled study found that of 50 reports of pain, 38 (76%) showed marked improvement. While this finding is certainly promising, there were no controls used with this study nor were the patients blinded to the treatment, two limitations we seek to address in this investigation. We also seek to find a mechanistic objective outcome that can track with pain improvement with EH. 5. Budget The budget for this work is $250,000 in total over 18 months. This includes personnel salaries (PI 5% effort 30K, study coordinator 100% effort 100K, imaging analyst 50% effort 90K, EEG consultant 10K, and biostatistician 5K), purchasing of equipment and supplies (EEG equipment, supplies and galvanic skin resistance device 5K), travel (4K), and participant recruitment and reimbursement (6K). 6. References 1. Dufresne F, Simmons B, Vlachostergios PJ, Fleischner Z, Joudeh R, Blakeway J, Julliard K. Feasibility of energy medicine in a community teaching hospital: an exploratory case series. J Altern Complement Med. (2015) 21(6),339-49. 2. Wolfe, F., et al., The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. (1995) 38(1): p. 19-28. 3. Jacobsen, S. and S.R. Bredkjaer. The prevalence of fibromyalgia and widespread chronic musculoskeletal pain in the general population. Scand.J.Rheumatol. (1992) 21(5): p. 261-263. 4. Raspe, H., C. Baumgartner, and F. Wolfe. The prevalence of fibromyalgia in a rural German community: How much difference do different criteria make? Arthritis & Rheumatism. (1993) 36(9 (Supplement)): p. S48. 5. Wolfe, F., et al. A prospective, longitudinal, multicenter study of service utilization and costs in fibromyalgia. Arthritis Rheum (1997) 40(9): p. 1560-70. 6. Gracely, R.H., et al. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. (2002) 46(5): p. 1333-1343. 7. Harris, R.E., et al. Decreased central mu-opioid receptor availability in fibromyalgia. J.Neurosci. (2007) 27(37): p. 10000-10006. 8. Mountz, J.M., et al., Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis Rheum. (1995) 38(7): p. 926-938. 9. Kaplan CM, Schrepf A, Mawla I, Ichesco E, Boehnke KF, Beltz A, Foxen-Craft E, Puglia MP, Tsodikov A, Williams DA, Hassett AL, Clauw DJ, Harte SE, Harris RE. Neurobiological antecedents of multisite pain in children. Pain. (2022) Apr 1;163(4):e596-e603. 10. Yunus, M.B., Towards a model of pathophysiology of fibromyalgia: aberrant central pain mechanisms with peripheral modulation. J Rheumatol. (1992) 19(6): p. 846-850. 11. Clauw, D.J. and G.P. Chrousos, Chronic pain and fatigue syndromes: Overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. Neuroimmunomodulation. (1997) 4(3): p. 134-153. 12. Apkarian, A.V., M.N. Baliki, and P. Y. Geha, Towards a theory of chronic pain. Prog Neurobiol. (2009) 87(2): p. 81-97. 13. Tracey, I. and M.C. Bushnell, How neuroimaging studies have challenged us to rethink: is chronic pain a disease? The Journal of Pain. (2009) 10(11): p. 1113-20. 14. Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. (1994) Mar;23(2):129-38. 15. Clauw DJ. Fibromyalgia: a clinical review. JAMA. (2014) 311(15):1547-55. 16. Kang K, Orlandi S, Leung J, et al. Electroencephalographic interbrain synchronization in children with disabilities, their parents, and neurologic music therapists. Eur J Neurosci. Jul 2023;58(1):2367-2383. doi:10.1111/ejn.16036 17. Bastos AM, Schoffelen JM. A Tutorial Review of Functional Connectivity Analysis Methods and Their Interpretational Pitfalls. Front Syst Neurosci. 2015;9:175. doi:10.3389/fnsys.2015.00175 18. Baccala LA, Sameshima K. Partial directed coherence: a new concept in neural structure determination. Biol Cybern. Jun 2001;84(6):463-74. doi:10.1007/PL00007990 19. Joo P, Kim M, Kish B, et al. Brain network hypersensitivity underlies pain crises in sickle cell disease. Sci Rep. Mar 27 2024;14(1):7315. doi:10.1038/s41598-024-57473-5 20. Lee U, Kim M, Lee K, et al. Functional Brain Network Mechanism of Hypersensitivity in Chronic Pain. Sci Rep. Jan 10 2018;8(1):243. doi:10.1038/s41598-017-18657-4 A Anzolin, K. Isenburg, A. Grahl, J. Toppi, M. Yücel, D.M. Ellingsen, J. Gerber, A. Ciaramidaro, L. Astolfi, T.J. Kaptchuk, V. Napadow – “Patient-Clinician Brain Response During Clinical Encounter and Pain Treatment”. In 2020 42nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 306527-1610 Ellingsen DM, Isenburg K, Jung C, Lee J, Gerber J, Mawla I, Sclocco R, Jensen K, Edwards RR, Kelley JM, Kirsch I, Kaptchuk T, Napadow V. Dynamic brain to brain concordance and behavioral mirroring as a mechanism of the patient/clinician interaction. Science advances 6, no. 43 (2020): eabc1304. Ellingsen DM, Isenburg K, Jung C, Lee J, Gerber J, Mawla I, Sclocco R, Grahl A, Anzolin A, Edwards RR, Kelley JM, Kirsch I, Kaptchuk TJ, Napadow V. Brain-to-brain mechanisms underlying pain empathy and social modulation of pain in the patient-clinician interaction. Proc Natl Acad Sci U S A. 2023 Jun 27;120(26):e2212910120. PMID: 37339198, PMCID: PMC10293846, https://doi.org/10.1073/pnas.2212910120. Anzolin A, Das P, Garcia RG, Chen A, Grahl A, Ellis S, Purdon P, Napadow V. Delta power during sleep is modulated by EEG-gated auricular vagal afferent nerve stimulation (EAVANS). Annu Int Conf IEEE Eng Med Biol Soc. 2023 Jul;2023:1-4. 10.1109/EMBC40787.2023.10340971. PMID: 38082663. 4f:T93fc,{"type":"doc","content":[{"type":"heading","attrs":{"id":"bd5a778c-b288-40aa-81a9-a8f0b8437d16","data-toc-id":"bd5a778c-b288-40aa-81a9-a8f0b8437d16","textAlign":"left","level":1},"content":[{"type":"text","text":"Energy Healing Brain Hyper Scanning in Fibromyalgia"}]},{"type":"heading","attrs":{"id":"9fb6d144-2972-436b-8299-8421f1066135","data-toc-id":"9fb6d144-2972-436b-8299-8421f1066135","textAlign":"left","level":2},"content":[{"type":"text","text":"1. Overview"}]},{"type":"paragraph","attrs":{"id":"f1da5db1-27a9-474a-ab3b-5b3e8c3dd8f1","class":null,"textAlign":"left"},"content":[{"type":"text","text":"Energy medicine or energy healing (EH) is an emerging therapy with significant promise. It is derived from the theory that using the body’s own biological energy a therapeutic effect can be obtained in another individual such as a patient. Preliminary unpublished data from our group in chronic pain patients, suggests that EH, delivered by an experienced practitioner, may be able to reduce self-reported pain symptoms within minutes with effects lasting for weeks to months. In addition to improvements in pain, reductions in other symptoms including fatigue, sleep, and cognitive dysfunction may also be possible with EH."}]},{"type":"paragraph","attrs":{"id":"726ea82d-c1c5-416b-9a42-4da6faa0f0a2","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"EH practitioners may be trained within a specific tradition such as healing touch, reiki, and qigong, or work via novel unique methods. The energy practitioners that will be used for this study have practiced their unique style of EH for years and one has taken his work through a blinded hospital study demonstrating its feasibility and efficacy.[1] This study took place in inpatient units and the emergency department and found both acceptability and demand for energy medicine. Of 50 reports of pain, 38 (76%) showed marked improvement. Of 29 non-pain-related problems, 23 (79%) showed marked improvement.[1] While this finding is certainly promising, there were no controls used with this study nor were the patients blinded to the treatment, two limitations we seek to address in this investigation."}]},{"type":"paragraph","attrs":{"id":"a20bb3b6-9f5f-489d-9773-90f9f306e36b","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"We propose to study EH delivered by a experienced therapists, for the treatment of fibromyalgia (FM), a chronic pain condition that results from aberrant central nervous system function and neurochemistry. This work will be performed at the University of California, Irvine and comply with the university’s Institutional Review Board ethics. Participant recruitment will be for 18 months and funding for this study will be in part through DMT Quest, ResearchHub, and possibly the Subtle Energy Funders Collective. Results and publications from this study will be shared with the public following its conclusion."}]},{"type":"heading","attrs":{"id":"0b1af640-6d70-4b04-8701-3c43c7372056","data-toc-id":"0b1af640-6d70-4b04-8701-3c43c7372056","textAlign":"left","level":2},"content":[{"type":"text","text":"2. Introduction"}]},{"type":"paragraph","attrs":{"id":"ffc1b9a6-1ffc-4c4c-b571-4b9e6ddfc20a","class":null,"textAlign":"left"},"content":[{"type":"text","marks":[{"type":"bold"},{"type":"italic"}],"text":"Fibromyalgia (FM) is a Common Chronic Pain Syndrome and a Major Public Health Issue. "},{"type":"text","text":"Fibromyalgia (FM) is the second most common rheumatologic disorder, behind osteoarthritis, with 2 - 4% of the populations of industrialized countries affected.[2-4] Overall, it is estimated that FM costs the American taxpayers over $20 billion a year in lost wages and disability.[5] In part this burden on the US healthcare system is our lack of understanding of the specific pathophysiology of the disorder. While research suggests that FM is a central non-nociceptive pain syndrome,[6-8] it is uncertain if the observed neurobiological outcomes are causally related to development of FM. That said, our recent study in children suggests that the development of widespread pain, a hallmark of FM, is preceded by aberrant brain neural function.[9] The study proposed here may provide much needed information into the pathology of this disorder and how it is treated in a clinical setting. For example, if energy healing is able to reduce FM pain specifically, this may identify a non-physical basis for treatment. Our proposed project may also synergize with emerging data indicating a generalized disturbance in central nervous system pain processing in this condition.[10,11]"}]},{"type":"paragraph","attrs":{"id":"5ae1cdac-bbcf-4946-bef5-cfdf50cb2ff5","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"},{"type":"italic"}],"text":"Need for a Neurobiological Model underlying EH for FM."},{"type":"text","text":" There is a lack of key information about how EH may work for pain. One key missing piece in the field is that there are no objective markers that have been identified that actually track with subjective self-reported pain improvements following treatment with EH. This limitation is a key factor that prevents a more general adoption of this therapy by the medical community. If there is no proposed mechanism of action of EH, then the support for this intervention is weakened. However, an objective marker of chronic pain, that is modulated by EH, that also tracks with self-reported symptom improvement, would be a major advance for the field and also aid the development of a biomedical theory of how this therapy works. Moreover showing that similar brain activity occurs in an energy healer and the patient during treatment would also link the actions of healing at a distance: a key tenet of EH. Finally, our proposed neurobiological outcomes may also detect the effects of EH on brain neuroimaging biomarkers that we have previously found to track with clinical pain in FM, thus supporting the mechanisms of EH in chronic pain."}]},{"type":"paragraph","attrs":{"id":"cd821375-1e86-403c-8b3e-c5616a270241","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"}],"text":"Hypotheses "}]},{"type":"paragraph","attrs":{"id":"4a744dcd-f293-4876-8c15-3f5396272490","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"}],"text":"Aim 1:"},{"type":"text","text":" Assess the effects of EH as compared to control, on neuroelectrical activity acquired simultaneously from patients with FM and an energy healer (EEG hyperscan) and relate these brain changes to improvements in clinical pain. "},{"type":"text","marks":[{"type":"italic"}],"text":" Hypothesis 1A:"},{"type":"text","text":" EEG gamma power (co-primary outcome) assessed in FM patients and the healer will be greater during active healing as compared to control. "},{"type":"text","marks":[{"type":"italic"}],"text":"Hypothesis 1B:"},{"type":"text","text":" patient-practitioner brain-to-brain connectivity (co-primary outcome) will be higher during EH as compared to control. "},{"type":"text","marks":[{"type":"italic"}],"text":"Hypothesis 1C:"},{"type":"text","text":" changes in EEG metrics will be correlated with improvements in clinical pain (secondary outcome) during active EH as compared to control."}]},{"type":"paragraph","attrs":{"id":"192a0b6d-68cf-4798-b0b7-af34f64298f9","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"}],"text":"Aim 2 (exploratory):"},{"type":"text","text":" Explore the action of EH on brain explosive synchronization (exploratory outcome), an EEG measure of brain network instability and chronic pain.[19,20] We have previously shown this outcome of network instability to be present in FM participants with increased chronic pain. "},{"type":"text","marks":[{"type":"italic"}],"text":"Hypothesis 2A:"},{"type":"text","text":" Explore the action of EH on heart rate variability, biophoton emission, and skin temperature (exploratory outcomes). "},{"type":"text","marks":[{"type":"italic"}],"text":"Hypothesis 2B: "},{"type":"text","text":"Brain explosive synchronization metrics (network instability) will decrease in conjunction with chronic pain during EH as compared to control (exploratory outcome). "}]},{"type":"paragraph","attrs":{"id":"e69eafa8-abfe-4d22-a1d8-8812818dd6e3","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"}],"text":"Impact. "},{"type":"text","text":" If our hypotheses are proven true, 1) critical information will be provided that may help incorporate EH into mainstream clinical care, 2) EH may be shown to reduce pain symptoms in FM, and 3) we may obtain a better understanding of EH and how it might be utilized in future studies of other chronic pain conditions."}]},{"type":"heading","attrs":{"id":"0db6d9d2-5160-4031-8053-b51e8be72364","data-toc-id":"0db6d9d2-5160-4031-8053-b51e8be72364","textAlign":"left","level":2},"content":[{"type":"text","text":"3. Methods"}]},{"type":"paragraph","attrs":{"id":"e6d7a7e5-d8cd-4c0c-ab46-65f56e038c93","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"},{"type":"italic"}],"text":"Overview."},{"type":"text","text":" "},{"type":"text","marks":[{"type":"textStyle","attrs":{"fontSize":"12pt","fontFamily":"Aptos, sans-serif","color":"rgb(0, 0, 0)"}}],"text":"Our overall goal is to understand the role EH plays in modulating EEG neuroimaging markers (primary outcomes) related to altered neural processing of pain in FM as well as the effects it has on clinical pain (secondary outcome), and other exploratory outcomes including: heart rate variability, biophoton emission, and skin temperature. We will study 40 FM patients using brain electroencephalogram (EEG) hyper scanning in an energy healer and the patient simultaneously. We will also collect data on clinical pain changes as well as physiological outcomes in the patient and healer such as heart rate, skin temperature, and biophoton emission, exploratory outcomes that may be associated with EH. Data during energy healing periods will be compared to data acquired during rest as a control for non-specific or placebo treatment effects. Patients will be blinded as to the timing of these periods (see below). At no point will the patient know when the active healing treatment periods will start thus blinding the intervention and controlling for placebo effects."},{"type":"text","text":" "}]},{"type":"paragraph","attrs":{"id":"39ca9aa8-fe5f-47a0-9a2c-7d663b563413","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"},{"type":"italic"}],"text":"Study Team. "},{"type":"text","text":" This investigation is being led by Richard E. Harris, PhD who is a Susan Samueli Endowed Chair in the Susan Samueli Integrative Health Institute and Professor in the Department of Anesthesiology and Perioperative Care in the School of Medicine at the University of California at Irvine. He received his B.S. degree in Genetics from Purdue University in 1992 and his Ph.D. in Molecular and Cell Biology from UC Berkeley in 1997. Following his graduate work, he completed a postdoctoral fellowship at NIH. He is a graduate of the Maryland Institute of Traditional Chinese Medicine and has received an MS degree in Clinical Research Design and Statistical Analysis at the University of Michigan. Dr. Harris is currently investigating mechanisms of chronic pain and its treatment with acupuncture, energy healing, and shamanism. His investigations over the past 25 years have focused on the role of brain neurotransmitters and brain network behavior in chronic pain patients. and how these outcomes can be modulated by various treatments. He was a board member of the National Advisory Council for NIH/NCCIH and is a previous co-President for the Society for Acupuncture Research. "}]},{"type":"paragraph","attrs":{"id":"bc5039c2-7e6d-4b87-ae54-9d99197d9827","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"He is joined in this work by Dr. Alessandra Anzolin, a consultant from Spaulding Rehabilitation Hospital. She is a neuroscientist with an in-depth background in biomedical engineering and brain imaging techniques such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). She is a junior faculty at the Spaulding Rehabilitation Hospital, Harvard Medical School, where she is leading several projects with both healthy participants and patients with chronic pain. Since beginning her career, she have been passionate about methodological development to improve biomedical devices and signal processing, as well as the clinical applications that benefit from those advancements. In the realm of pain neuroimaging, her experience has included implementation of novel experimental designs utilizing EEG hyper scanning. This advanced methodology enables one to collect data simultaneously from patients and clinicians and to delve deeper into understanding complex phenomena such as the importance of therapeutic alliance and other non-specific effects during pain treatment. In particular, she has led EEG-hyper scanning projects to study the impact of an augmented compared to a limited clinical context on pain treatment effectiveness and the possibility of boosting therapeutic alliance, empathy, and brain concordance using a Theory of Mind training or psychedelic-assisted therapy in pain management. Results from a completed EEG-hyper scanning pilot [21-23] were published as a brief paper and received several awards at international conferences – e.g. “Outstanding Junior Researcher Award in Basic Science Research” from the Society for Acupuncture and the “Best Translational Research Award” from the US Association for the Study of Pain. She also has recently led the development of non-invasive brain stimulation techniques to modulate specific brain rhythms. This includes the development of a prototype (EEG-gated Auricular Vagal Afferent Nerve Stimulation, EAVANS), a closed-loop peripheral nerve stimulation device. By leveraging EEG data to guide the stimulation process, EAVANS holds the potential to enhance the efficacy of brain stimulation therapies, allowing for a more personalized and non-pharmacological intervention to treat delirium and expedite the recovery of cognitive functions post-anesthesia.[24]"}]},{"type":"paragraph","attrs":{"id":"a5114e1d-08f9-44d8-8187-8cff001333a9","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"The backgrounds of Drs. Harris and Anzolin in chronic pain, brain imaging, and EEG hyper scanning will be valuable in advancing this project."}]},{"type":"paragraph","attrs":{"id":"c8596fe2-de12-47ec-bc0a-4c1c306dfae6","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"We are purposefully not providing information on the three energy healers that will be used in this study as we do not want to risk participants knowing who will be treating them prior to seeing them in person on the study visit (see below Procedures). That said, the three EHs that will be used practice their own individual style of healing that is not Reiki or Qigong. Each healer has over 15 years of experience in healing pain patients and we have worked with one of the healers on a different mechanistic study that is ongoing."}]},{"type":"paragraph","attrs":{"id":"84cd16ce-7bf6-4762-a292-b5f37263ea69","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"},{"type":"italic"}],"text":"Rationale."},{"type":"text","marks":[{"type":"italic"}],"text":" "},{"type":"text","text":" Our proposal originates with coupling brain and other physiological outcomes with clinical pain measures incorporated in a treatment trial framework using EH. In addition to evaluating brain response to EH between two individuals simultaneously, we will also investigate the neurocircuitry subserving clinical pain. Neuroimaging markers reflecting FM patients’ clinical pain are crucial to this design, as (a) they conceptually link more closely to important clinical outcome measures, as compared to markers for experimental pain in hyperalgesia and allodynia, and (b) their differential susceptibility to different forms of therapy may underlie the ultimate mechanisms of action of EH. Recent efforts have been increasingly aimed at developing a neurobiological model for chronic nociplastic pain, and our proposal is innovative in that it adds to this burgeoning field of research.[12,13]"}]},{"type":"paragraph","attrs":{"id":"d66210d7-1407-4b04-942f-15fe770aee18","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"},{"type":"italic"}],"text":"Procedures."},{"type":"text","text":" All EH treatments and physiological testing will occur at the Susan Samueli Integrative Health Institute at the University of California at Irvine. 40 participants aged 18-75 years old, with a diagnosis/symptoms of FM for at least 1 year will be consented in person. Ineligible participants will be excluded if they have: epilepsy, bipolar disorder, history of stroke, rhuematoid arthritis, or Lupus. Additional exclusions are any other condition of chronic pain other than fibromyalgia. "}]},{"type":"paragraph","attrs":{"id":"a72c676a-ebbe-4282-bb96-6a378085cb18","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"Following consent participants will undergo a two-week run-in during baseline to washout previous treatment effects and reduce regression to the mean. Following consent and 2 week run-in, participants will attend a single visit with one of three chosen energy healers, during which EEG and control/active EH treatment will occur. Prior to starting this visit, patients will be told verbally, “At some point in this session you will experience energy healing, but you will not know when that is.” After 32-channel EEG cap set up on both the patient and the energy healer, individuals will be seated facing away from each other. There will be no visual interaction between the energy healer and patient during the control and healing sessions. This will help blind the study so that the patients will not know at what time the active EH will take place. An initial 5 minutes of resting eyes closed will be acquired for both individuals, followed by a 10-minute eyes closed resting condition wherein the patient will be queried every 2 minutes about their resting pain level on a scale from 0 to 10 with 0 being “no pain” and 10 being “worst pain imaginable”. This is the no-treatment control condition. Then, in a blinded fashion so the patient does not know, the energy healer will be notified by staff to start the energy healing. At no point will the patient know when the healing will start and at no time will there be active touching of the patient by the healer. During the next 15 minutes of healing, the patient will be queried by staff as to what their pain level currently is in the same fashion as during the prior 10 minute no-treatment control condition. We have piloted this protocol in fibromyalgia patients previously and this duration of treatment and control are adequate to blind the patient and allows enough time for the healer to reduce chronic fibromyalgia pain. We also have show in unpublished pilot data that the EH effects can persist for hours to days following a single treatment, which prevents us from randomizing the order of presentation of the control and active healing periods as active healing would extend into the control period if active healing was done first. (As mentioned above, the patients will not know the fixed order of events.) Following the active EH period, patients and healers will perform an eyes closed 5 minute resting period and be debriefed about the procedure."}]},{"type":"paragraph","attrs":{"id":"0870f311-88b9-4008-a49f-0ac4a5c6c94c","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"Our primary outcome is EEG (see below) and secondary outcome is pain, with change in pain intensity and interference, as measured in a 11 point Numerical Rating Scale, anchored at 0 = “no pain” and 10 = “worst pain imaginable”. This will be assessed throughout the control and active EH procedure (see above). We will also include the Brief Pain Inventory [14] and the FM survey criteria [15] as additional secondary pain outcomes acquired prior to and following the EEG visit. We will also use the PROMIS 29 questionnaire to assess fatigue, sleep, and mood."}]},{"type":"paragraph","attrs":{"id":"c6765c66-a46e-4558-8340-e80000654e07","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"italic"}],"text":"EEG Acquisition (primary outcomes) and Analysis."},{"type":"text","text":" EEG data will be collected from the energy healer and FM participants simultaneously (hyperscan) to measure synchronized brain activity in each dyad (Energy Healer-FM participant). We use a Brain Products EEG system with 32-channel water-based nets (sensors are distributed accordingly to the International 10-20 system). The EEG caps from the FM participant and the healer will be attached to the same EEG amplifier (BrainAmp) ensuring the millisecond-precision alignment required for the inter-brain connectivity analysis. The EEG equipment has been purchased and tested in pilot acquisitions to ensure rigorous data collection. "},{"type":"text","marks":[{"type":"italic"}],"text":"Gamma Power and Hyperscanning:"},{"type":"text","text":" We use in-house developed MATLAB scripts based on validated pipelines for EEG data processing (EEGLAB). First, we will perform standard preprocessing including bandpass filtering (1-30Hz for inter-brain connectivity assessment and 1-100Hz for gamma analysis), re-referencing, and ocular artifact removal (independent component analysis, ICA). Then Phase Locking Value (PLV) and Partial Directed Coherence (PDC) will be used to measure inter-brain connectivity.[16] PLV assesses the magnitude of phase synchrony[17] whereas PDC is a spectral estimate of causal connectivity including intensity and directionality.[18] We will compute PLV and PDC on the EEG time series acquired during resting prior to EH and concurrently with EH. Additionally we will compute Power Spectral Density (PSD) in all standard EEG frequency bands, including Delta, Theta, Alpha, Beta, and Gamma. Brain-to-brain connectivity measures and Gamma power (assessed separately for patients and the healer) will be contrasted between resting and active healing time points to assess change associated with the EH treatment as compared to resting control in FM patients and the healer. We expect that if energy transfer occurs between the patient and healer, a signal in EEG coherence between the two individuals may be detected. We will specifically test if this signal in the EG precedes the changes in the patient, which would be indicative of a energy transfer process during healing."}]},{"type":"paragraph","attrs":{"id":"a6a34420-3828-46c6-b031-c7a597d8d5cf","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"italic"}],"text":"Exploratory outcomes:"},{"type":"text","text":" Heart rate variability will be assessed with ECG for both the FM patient as well as the energy healer simultaneously during treatment and resting control conditions. As mentioned above, to control for placebo effects and confounding factors FM patients will not be facing the healer during treatment. This will effectively blind the patient from the timing of the EH and rest periods. ECG will be performed using a Movesense sensor ("},{"type":"text","marks":[{"type":"link","attrs":{"href":"https://www.movesense.com/","target":"_blank","rel":"noopener noreferrer nofollow","class":"link inline-flex items-center hover:underline transition-colors duration-200"}}],"text":"https://www.movesense.com/"},{"type":"text","text":") connected to a mobile device (via Bluetooth) which runs the patented electrocardiomatrix (ECM) software invented by the Borjigin lab at the University of Michigan that converts the 2D ECG data into a 3D ECM image that resembles a heatmap. The ECM image captured on the mobile device can be used as a standalone diagnostic tool for intuitive visualization of user’s cardiac conditions in real-time or post-capture. The captured ECG data can be uploaded to the ECM website (developed by Dr. Xu in the Borjigin lab) for quantitative processing (HRV and other outcomes). Finally in addition to ECG and EEG assessment, we will also measure skin temperature, galvanic skin resistance, and single hand biophoton emission during resting control period and active EH for both the healer and the FM patient. "}]},{"type":"paragraph","attrs":{"id":"2b684ac5-67cc-441d-bfd0-4538793b4659","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"All study procedures will be approved by the University of California, Irvine Institutional Review Board, and all data will be securely stored in locked password protected computers at the University of California, Irvine campus."}]},{"type":"paragraph","attrs":{"id":"0a98df58-9e3c-4c07-a3bd-e31e8402c53c","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"},{"type":"italic"}],"text":"General Analysis."},{"type":"text","text":" Comparisons between healing and control resting periods will be made for all outcomes using a paired t-Test (see above for EEG analysis). Pearson correlations will be made between change scores in brain neuroimaging outcomes, other physiologic outcomes, and changes in pain. Significant p-values are identified at p<0.05. As this is primarily a pilot mechanistic study with a single primary outcome (EEG), we will make no correction for multiple comparisons. Assessment of exploratory outcomes will be limited to hypothesis generation. "},{"type":"text","marks":[{"type":"italic"}],"text":"Power calculation is pending and will be added later."}]},{"type":"paragraph","attrs":{"id":"50d79b70-0a93-49c1-82f1-15ab63c4b18c","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"},{"type":"italic"}],"text":"Ethics and Data Management."},{"type":"text","text":" All procedures will be approved by the local University of California, Irvine Institutional Review Board. All data will be identified with a unique patient identification number, whose linked personal health information will be kept in a locked cabinet behind a locked door in the Susan Samueli Integrative Health Institute building. Data will be shared with other researchers once the primary analyses are published and all data will be archived for 7 years at the University of California, Irvine after the study is completed"}]},{"type":"heading","attrs":{"id":"655a235c-48c1-40dd-a413-aa416a373f33","data-toc-id":"655a235c-48c1-40dd-a413-aa416a373f33","textAlign":"left","level":2},"content":[{"type":"text","text":"4. Pilot Data (Optional)"}]},{"type":"paragraph","attrs":{"id":"ec4b39a6-3f1b-406d-921b-a90486fb9f13","class":null,"textAlign":"left"},"content":[{"type":"text","text":"This study has no pilot data to present. However there has been a study of one of the EH participating in this trial. These data are presented in the first citation in the references.[1] This unblinded and uncontrolled study found that of 50 reports of pain, 38 (76%) showed marked improvement. While this finding is certainly promising, there were no controls used with this study nor were the patients blinded to the treatment, two limitations we seek to address in this investigation. We also seek to find a mechanistic objective outcome that can track with pain improvement with EH."}]},{"type":"heading","attrs":{"id":"74214f1c-3ae8-4149-a3bd-cc3f234aa044","data-toc-id":"74214f1c-3ae8-4149-a3bd-cc3f234aa044","textAlign":"left","level":2},"content":[{"type":"text","text":"5. Budget"}]},{"type":"paragraph","attrs":{"id":"c272e9cc-5ad2-4898-ac07-acb0dbde755a","class":null,"textAlign":"left"},"content":[{"type":"text","text":"The budget for this work is $250,000 in total over 18 months. This includes personnel salaries (PI 5% effort 30K, study coordinator 100% effort 100K, imaging analyst 50% effort 90K, EEG consultant 10K, and biostatistician 5K), purchasing of equipment and supplies (EEG equipment, supplies and galvanic skin resistance device 5K), travel (4K), and participant recruitment and reimbursement (6K)."}]},{"type":"heading","attrs":{"id":"a7a153a1-cb2e-492e-9d5b-686b559eed1e","data-toc-id":"a7a153a1-cb2e-492e-9d5b-686b559eed1e","textAlign":"left","level":2},"content":[{"type":"text","text":"6. References"}]},{"type":"paragraph","attrs":{"id":"e656ef6f-45ee-446b-92c7-c1b0fea520ac","class":null,"textAlign":"left"},"content":[{"type":"text","text":"1. Dufresne F, Simmons B, Vlachostergios PJ, Fleischner Z, Joudeh R, Blakeway J, Julliard K. Feasibility of energy medicine in a community teaching hospital: an exploratory case series. J Altern Complement Med. (2015) 21(6),339-49."}]},{"type":"paragraph","attrs":{"id":"c64823ef-afed-45fe-877b-65c66734313a","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"2. Wolfe, F., et al., The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. (1995) 38(1): p. 19-28."}]},{"type":"paragraph","attrs":{"id":"1e64f21b-0eea-4538-b224-d7d45b0f6059","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"3. Jacobsen, S. and S.R. Bredkjaer. The prevalence of fibromyalgia and widespread chronic musculoskeletal pain in the general population. Scand.J.Rheumatol. (1992) 21(5): p. 261-263."}]},{"type":"paragraph","attrs":{"id":"7157edd7-5c56-4f31-a07d-0a819f059d39","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"4. Raspe, H., C. Baumgartner, and F. Wolfe. The prevalence of fibromyalgia in a rural German community: How much difference do different criteria make? Arthritis & Rheumatism. (1993) 36(9 (Supplement)): p. S48."}]},{"type":"paragraph","attrs":{"id":"cdfff18d-736c-46d1-970d-988fb17ddcfe","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"5. Wolfe, F., et al. A prospective, longitudinal, multicenter study of service utilization and costs in fibromyalgia. Arthritis Rheum (1997) 40(9): p. 1560-70."}]},{"type":"paragraph","attrs":{"id":"4ffb6452-d31a-49b1-98b4-0030d15bc833","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"6. Gracely, R.H., et al. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. (2002) 46(5): p. 1333-1343."}]},{"type":"paragraph","attrs":{"id":"49c695f0-bdbe-4586-8732-7b6780f86986","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"7. Harris, R.E., et al. Decreased central mu-opioid receptor availability in fibromyalgia. J.Neurosci. (2007) 27(37): p. 10000-10006."}]},{"type":"paragraph","attrs":{"id":"0c75f9c9-cc32-46bb-97ef-2dd2b34e1fe5","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"8. Mountz, J.M., et al., Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis Rheum. (1995) 38(7): p. 926-938. "}]},{"type":"paragraph","attrs":{"id":"b054858b-a970-49ea-9c31-262c091862d4","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"9. Kaplan CM, Schrepf A, Mawla I, Ichesco E, Boehnke KF, Beltz A, Foxen-Craft E, Puglia MP, Tsodikov A, Williams DA, Hassett AL, Clauw DJ, Harte SE, Harris RE. Neurobiological antecedents of multisite pain in children. Pain. (2022) Apr 1;163(4):e596-e603."}]},{"type":"paragraph","attrs":{"id":"119bcdaa-7660-4e75-a44f-bde9c54fcd7b","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"10. Yunus, M.B., Towards a model of pathophysiology of fibromyalgia: aberrant central pain mechanisms with peripheral modulation. J Rheumatol. (1992) 19(6): p. 846-850."}]},{"type":"paragraph","attrs":{"id":"00d9c122-6360-46b9-b46b-29e8e30dcd21","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"11. Clauw, D.J. and G.P. Chrousos, Chronic pain and fatigue syndromes: Overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. Neuroimmunomodulation. (1997) 4(3): p. 134-153."}]},{"type":"paragraph","attrs":{"id":"509ad8cd-3d53-462c-81a1-d1cce5ede846","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"12. Apkarian, A.V., M.N. Baliki, and P. Y. Geha, Towards a theory of chronic pain. Prog Neurobiol. (2009) 87(2): p. 81-97."}]},{"type":"paragraph","attrs":{"id":"677fffb3-30ca-4544-a558-99c9b71a533c","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"13. Tracey, I. and M.C. Bushnell, How neuroimaging studies have challenged us to rethink: is chronic pain a disease? The Journal of Pain. (2009) 10(11): p. 1113-20."}]},{"type":"paragraph","attrs":{"id":"e87ab5e7-18b8-4664-b916-95644b04b76a","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"14. Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. (1994) Mar;23(2):129-38."}]},{"type":"paragraph","attrs":{"id":"2d819f45-0907-4cac-bb70-09ac5a5ea940","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"15. Clauw DJ. Fibromyalgia: a clinical review. JAMA. (2014) 311(15):1547-55."}]},{"type":"paragraph","attrs":{"id":"01052576-72dc-4ea1-a62a-d0283ad0c758","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"16. Kang K, Orlandi S, Leung J, et al. Electroencephalographic interbrain synchronization in children with disabilities, their parents, and neurologic music therapists. Eur J Neurosci. Jul 2023;58(1):2367-2383. doi:10.1111/ejn.16036"}]},{"type":"paragraph","attrs":{"id":"b730d6fa-587c-462c-b41a-71dbd19660a2","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"17. Bastos AM, Schoffelen JM. A Tutorial Review of Functional Connectivity Analysis Methods and Their Interpretational Pitfalls. Front Syst Neurosci. 2015;9:175. doi:10.3389/fnsys.2015.00175 "}]},{"type":"paragraph","attrs":{"id":"b22e8bfd-10fd-4e75-bb26-c7c827587f42","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"18. Baccala LA, Sameshima K. Partial directed coherence: a new concept in neural structure determination. Biol Cybern. Jun 2001;84(6):463-74. doi:10.1007/PL00007990"}]},{"type":"paragraph","attrs":{"id":"93d10dc8-6cde-4c9b-a416-4093ace75c4b","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"19. Joo P, Kim M, Kish B, et al. Brain network hypersensitivity underlies pain crises in sickle cell disease. Sci Rep. Mar 27 2024;14(1):7315. doi:10.1038/s41598-024-57473-5"}]},{"type":"paragraph","attrs":{"id":"fe65f0ff-b7b0-4ae2-ba19-6b8c9fc76806","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"20. Lee U, Kim M, Lee K, et al. Functional Brain Network Mechanism of Hypersensitivity in Chronic Pain. Sci Rep. Jan 10 2018;8(1):243. doi:10.1038/s41598-017-18657-4"}]},{"type":"orderedList","attrs":{"start":21},"content":[{"type":"listItem","content":[{"type":"paragraph","attrs":{"id":"b363ece4-9e6d-4f09-bbcc-46e9ca7ecf0e","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"A Anzolin, K. Isenburg, A. Grahl, J. Toppi, M. Yücel, D.M. Ellingsen, J. Gerber, A. Ciaramidaro, L. Astolfi, T.J. Kaptchuk, V. Napadow – “Patient-Clinician Brain Response During Clinical Encounter and Pain Treatment”. In 2020 42nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 306527-1610"}]}]},{"type":"listItem","content":[{"type":"paragraph","attrs":{"id":"5b65c7c8-240a-420f-b1e3-1cfe44173383","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"Ellingsen DM, Isenburg K, Jung C, Lee J, Gerber J, Mawla I, Sclocco R, Jensen K, "},{"type":"text","marks":[{"type":"italic"}],"text":"Edwards RR, "},{"type":"text","text":"Kelley JM, Kirsch I, Kaptchuk T, Napadow V. Dynamic brain to brain concordance and behavioral mirroring as a mechanism of the patient/clinician interaction. Science advances 6, no. 43 (2020): eabc1304."}]}]},{"type":"listItem","content":[{"type":"paragraph","attrs":{"id":"3654d012-c64e-48ba-a04f-d918ffea92fd","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"Ellingsen DM, Isenburg K, Jung C, Lee J, Gerber J, Mawla I, Sclocco R, Grahl A, Anzolin A, Edwards RR, Kelley JM, Kirsch I, Kaptchuk TJ, Napadow V. Brain-to-brain mechanisms underlying pain empathy and social modulation of pain in the patient-clinician interaction. Proc Natl Acad Sci U S A. 2023 Jun 27;120(26):e2212910120. PMID: 37339198, PMCID: PMC10293846, "},{"type":"text","marks":[{"type":"link","attrs":{"href":"https://doi.org/10.1073/pnas.2212910120","target":"_blank","rel":"noopener noreferrer nofollow","class":"link"}}],"text":"https://doi.org/10.1073/pnas.2212910120"},{"type":"text","text":"."}]}]},{"type":"listItem","content":[{"type":"paragraph","attrs":{"id":"f26f4e00-eaca-4105-b541-37dcd60a22d2","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"Anzolin A, Das P, Garcia RG, Chen A, Grahl A, Ellis S, Purdon P, Napadow V. Delta power during sleep is modulated by EEG-gated auricular vagal afferent nerve stimulation (EAVANS). Annu Int Conf IEEE Eng Med Biol Soc. 2023 Jul;2023:1-4. 10.1109/EMBC40787.2023.10340971. PMID: 38082663."}]}]}]},{"type":"paragraph","attrs":{"id":"ab703307-1885-40b7-a20f-46207fc3e5c7","class":null,"textAlign":null}}]}50:T68e9,Energy Healing Brain Hyper Scanning in Fibromyalgia 1. Overview Energy medicine or energy healing (EH) is an emerging therapy with significant promise. It is derived from the theory that using the body’s own biological energy a therapeutic effect can be obtained in another individual such as a patient. Preliminary unpublished data from our group in chronic pain patients, suggests that EH, delivered by an experienced practitioner, may be able to reduce self-reported pain symptoms within minutes with effects lasting for weeks to months. In addition to improvements in pain, reductions in other symptoms including fatigue, sleep, and cognitive dysfunction may also be possible with EH. EH practitioners may be trained within a specific tradition such as healing touch, reiki, and qigong, or work via novel unique methods. The energy practitioners that will be used for this study have practiced their unique style of EH for years and one has taken his work through a blinded hospital study demonstrating its feasibility and efficacy.[1] This study took place in inpatient units and the emergency department and found both acceptability and demand for energy medicine. Of 50 reports of pain, 38 (76%) showed marked improvement. Of 29 non-pain-related problems, 23 (79%) showed marked improvement.[1] While this finding is certainly promising, there were no controls used with this study nor were the patients blinded to the treatment, two limitations we seek to address in this investigation. We propose to study EH delivered by a experienced therapists, for the treatment of fibromyalgia (FM), a chronic pain condition that results from aberrant central nervous system function and neurochemistry. This work will be performed at the University of California, Irvine and comply with the university’s Institutional Review Board ethics. Participant recruitment will be for 18 months and funding for this study will be in part through DMT Quest, ResearchHub, and possibly the Subtle Energy Funders Collective. Results and publications from this study will be shared with the public following its conclusion. 2. Introduction Fibromyalgia (FM) is a Common Chronic Pain Syndrome and a Major Public Health Issue. Fibromyalgia (FM) is the second most common rheumatologic disorder, behind osteoarthritis, with 2 - 4% of the populations of industrialized countries affected.[2-4] Overall, it is estimated that FM costs the American taxpayers over $20 billion a year in lost wages and disability.[5] In part this burden on the US healthcare system is our lack of understanding of the specific pathophysiology of the disorder. While research suggests that FM is a central non-nociceptive pain syndrome,[6-8] it is uncertain if the observed neurobiological outcomes are causally related to development of FM. That said, our recent study in children suggests that the development of widespread pain, a hallmark of FM, is preceded by aberrant brain neural function.[9] The study proposed here may provide much needed information into the pathology of this disorder and how it is treated in a clinical setting. For example, if energy healing is able to reduce FM pain specifically, this may identify a non-physical basis for treatment. Our proposed project may also synergize with emerging data indicating a generalized disturbance in central nervous system pain processing in this condition.[10,11] Need for a Neurobiological Model underlying EH for FM. There is a lack of key information about how EH may work for pain. One key missing piece in the field is that there are no objective markers that have been identified that actually track with subjective self-reported pain improvements following treatment with EH. This limitation is a key factor that prevents a more general adoption of this therapy by the medical community. If there is no proposed mechanism of action of EH, then the support for this intervention is weakened. However, an objective marker of chronic pain, that is modulated by EH, that also tracks with self-reported symptom improvement, would be a major advance for the field and also aid the development of a biomedical theory of how this therapy works. Moreover showing that similar brain activity occurs in an energy healer and the patient during treatment would also link the actions of healing at a distance: a key tenet of EH. Finally, our proposed neurobiological outcomes may also detect the effects of EH on brain neuroimaging biomarkers that we have previously found to track with clinical pain in FM, thus supporting the mechanisms of EH in chronic pain. Hypotheses Aim 1: Assess the effects of EH as compared to control, on neuroelectrical activity acquired simultaneously from patients with FM and an energy healer (EEG hyperscan) and relate these brain changes to improvements in clinical pain. Hypothesis 1A: EEG gamma power (co-primary outcome) assessed in FM patients and the healer will be greater during active healing as compared to control. Hypothesis 1B: patient-practitioner brain-to-brain connectivity (co-primary outcome) will be higher during EH as compared to control. Hypothesis 1C: changes in EEG metrics will be correlated with improvements in clinical pain (secondary outcome) during active EH as compared to control. Aim 2 (exploratory): Explore the action of EH on brain explosive synchronization (exploratory outcome), an EEG measure of brain network instability and chronic pain.[19,20] We have previously shown this outcome of network instability to be present in FM participants with increased chronic pain. Hypothesis 2A: Explore the action of EH on heart rate variability, biophoton emission, and skin temperature (exploratory outcomes). Hypothesis 2B: Brain explosive synchronization metrics (network instability) will decrease in conjunction with chronic pain during EH as compared to control (exploratory outcome). Impact. If our hypotheses are proven true, 1) critical information will be provided that may help incorporate EH into mainstream clinical care, 2) EH may be shown to reduce pain symptoms in FM, and 3) we may obtain a better understanding of EH and how it might be utilized in future studies of other chronic pain conditions. 3. Methods Overview. Our overall goal is to understand the role EH plays in modulating EEG neuroimaging markers (primary outcomes) related to altered neural processing of pain in FM as well as the effects it has on clinical pain (secondary outcome), and other exploratory outcomes including: heart rate variability, biophoton emission, and skin temperature. We will study 40 FM patients using brain electroencephalogram (EEG) hyper scanning in an energy healer and the patient simultaneously. We will also collect data on clinical pain changes as well as physiological outcomes in the patient and healer such as heart rate, skin temperature, and biophoton emission, exploratory outcomes that may be associated with EH. Data during energy healing periods will be compared to data acquired during rest as a control for non-specific or placebo treatment effects. Patients will be blinded as to the timing of these periods (see below). At no point will the patient know when the active healing treatment periods will start thus blinding the intervention and controlling for placebo effects. Study Team. This investigation is being led by Richard E. Harris, PhD who is a Susan Samueli Endowed Chair in the Susan Samueli Integrative Health Institute and Professor in the Department of Anesthesiology and Perioperative Care in the School of Medicine at the University of California at Irvine. He received his B.S. degree in Genetics from Purdue University in 1992 and his Ph.D. in Molecular and Cell Biology from UC Berkeley in 1997. Following his graduate work, he completed a postdoctoral fellowship at NIH. He is a graduate of the Maryland Institute of Traditional Chinese Medicine and has received an MS degree in Clinical Research Design and Statistical Analysis at the University of Michigan. Dr. Harris is currently investigating mechanisms of chronic pain and its treatment with acupuncture, energy healing, and shamanism. His investigations over the past 25 years have focused on the role of brain neurotransmitters and brain network behavior in chronic pain patients. and how these outcomes can be modulated by various treatments. He was a board member of the National Advisory Council for NIH/NCCIH and is a previous co-President for the Society for Acupuncture Research. He is joined in this work by Dr. Alessandra Anzolin, a consultant from Spaulding Rehabilitation Hospital. She is a neuroscientist with an in-depth background in biomedical engineering and brain imaging techniques such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). She is a junior faculty at the Spaulding Rehabilitation Hospital, Harvard Medical School, where she is leading several projects with both healthy participants and patients with chronic pain. Since beginning her career, she have been passionate about methodological development to improve biomedical devices and signal processing, as well as the clinical applications that benefit from those advancements. In the realm of pain neuroimaging, her experience has included implementation of novel experimental designs utilizing EEG hyper scanning. This advanced methodology enables one to collect data simultaneously from patients and clinicians and to delve deeper into understanding complex phenomena such as the importance of therapeutic alliance and other non-specific effects during pain treatment. In particular, she has led EEG-hyper scanning projects to study the impact of an augmented compared to a limited clinical context on pain treatment effectiveness and the possibility of boosting therapeutic alliance, empathy, and brain concordance using a Theory of Mind training or psychedelic-assisted therapy in pain management. Results from a completed EEG-hyper scanning pilot [21-23] were published as a brief paper and received several awards at international conferences – e.g. “Outstanding Junior Researcher Award in Basic Science Research” from the Society for Acupuncture and the “Best Translational Research Award” from the US Association for the Study of Pain. She also has recently led the development of non-invasive brain stimulation techniques to modulate specific brain rhythms. This includes the development of a prototype (EEG-gated Auricular Vagal Afferent Nerve Stimulation, EAVANS), a closed-loop peripheral nerve stimulation device. By leveraging EEG data to guide the stimulation process, EAVANS holds the potential to enhance the efficacy of brain stimulation therapies, allowing for a more personalized and non-pharmacological intervention to treat delirium and expedite the recovery of cognitive functions post-anesthesia.[24] The backgrounds of Drs. Harris and Anzolin in chronic pain, brain imaging, and EEG hyper scanning will be valuable in advancing this project. We are purposefully not providing information on the three energy healers that will be used in this study as we do not want to risk participants knowing who will be treating them prior to seeing them in person on the study visit (see below Procedures). That said, the three EHs that will be used practice their own individual style of healing that is not Reiki or Qigong. Each healer has over 15 years of experience in healing pain patients and we have worked with one of the healers on a different mechanistic study that is ongoing. Rationale. Our proposal originates with coupling brain and other physiological outcomes with clinical pain measures incorporated in a treatment trial framework using EH. In addition to evaluating brain response to EH between two individuals simultaneously, we will also investigate the neurocircuitry subserving clinical pain. Neuroimaging markers reflecting FM patients’ clinical pain are crucial to this design, as (a) they conceptually link more closely to important clinical outcome measures, as compared to markers for experimental pain in hyperalgesia and allodynia, and (b) their differential susceptibility to different forms of therapy may underlie the ultimate mechanisms of action of EH. Recent efforts have been increasingly aimed at developing a neurobiological model for chronic nociplastic pain, and our proposal is innovative in that it adds to this burgeoning field of research.[12,13] Procedures. All EH treatments and physiological testing will occur at the Susan Samueli Integrative Health Institute at the University of California at Irvine. 40 participants aged 18-75 years old, with a diagnosis/symptoms of FM for at least 1 year will be consented in person. Ineligible participants will be excluded if they have: epilepsy, bipolar disorder, history of stroke, rhuematoid arthritis, or Lupus. Additional exclusions are any other condition of chronic pain other than fibromyalgia. Following consent participants will undergo a two-week run-in during baseline to washout previous treatment effects and reduce regression to the mean. Following consent and 2 week run-in, participants will attend a single visit with one of three chosen energy healers, during which EEG and control/active EH treatment will occur. Prior to starting this visit, patients will be told verbally, “At some point in this session you will experience energy healing, but you will not know when that is.” After 32-channel EEG cap set up on both the patient and the energy healer, individuals will be seated facing away from each other. There will be no visual interaction between the energy healer and patient during the control and healing sessions. This will help blind the study so that the patients will not know at what time the active EH will take place. An initial 5 minutes of resting eyes closed will be acquired for both individuals, followed by a 10-minute eyes closed resting condition wherein the patient will be queried every 2 minutes about their resting pain level on a scale from 0 to 10 with 0 being “no pain” and 10 being “worst pain imaginable”. This is the no-treatment control condition. Then, in a blinded fashion so the patient does not know, the energy healer will be notified by staff to start the energy healing. At no point will the patient know when the healing will start and at no time will there be active touching of the patient by the healer. During the next 15 minutes of healing, the patient will be queried by staff as to what their pain level currently is in the same fashion as during the prior 10 minute no-treatment control condition. We have piloted this protocol in fibromyalgia patients previously and this duration of treatment and control are adequate to blind the patient and allows enough time for the healer to reduce chronic fibromyalgia pain. We also have show in unpublished pilot data that the EH effects can persist for hours to days following a single treatment, which prevents us from randomizing the order of presentation of the control and active healing periods as active healing would extend into the control period if active healing was done first. (As mentioned above, the patients will not know the fixed order of events.) Following the active EH period, patients and healers will perform an eyes closed 5 minute resting period and be debriefed about the procedure. Our primary outcome is EEG (see below) and secondary outcome is pain, with change in pain intensity and interference, as measured in a 11 point Numerical Rating Scale, anchored at 0 = “no pain” and 10 = “worst pain imaginable”. This will be assessed throughout the control and active EH procedure (see above). We will also include the Brief Pain Inventory [14] and the FM survey criteria [15] as additional secondary pain outcomes acquired prior to and following the EEG visit. We will also use the PROMIS 29 questionnaire to assess fatigue, sleep, and mood. EEG Acquisition (primary outcomes) and Analysis. EEG data will be collected from the energy healer and FM participants simultaneously (hyperscan) to measure synchronized brain activity in each dyad (Energy Healer-FM participant). We use a Brain Products EEG system with 32-channel water-based nets (sensors are distributed accordingly to the International 10-20 system). The EEG caps from the FM participant and the healer will be attached to the same EEG amplifier (BrainAmp) ensuring the millisecond-precision alignment required for the inter-brain connectivity analysis. The EEG equipment has been purchased and tested in pilot acquisitions to ensure rigorous data collection. Gamma Power and Hyperscanning: We use in-house developed MATLAB scripts based on validated pipelines for EEG data processing (EEGLAB). First, we will perform standard preprocessing including bandpass filtering (1-30Hz for inter-brain connectivity assessment and 1-100Hz for gamma analysis), re-referencing, and ocular artifact removal (independent component analysis, ICA). Then Phase Locking Value (PLV) and Partial Directed Coherence (PDC) will be used to measure inter-brain connectivity.[16] PLV assesses the magnitude of phase synchrony[17] whereas PDC is a spectral estimate of causal connectivity including intensity and directionality.[18] We will compute PLV and PDC on the EEG time series acquired during resting prior to EH and concurrently with EH. Additionally we will compute Power Spectral Density (PSD) in all standard EEG frequency bands, including Delta, Theta, Alpha, Beta, and Gamma. Brain-to-brain connectivity measures and Gamma power (assessed separately for patients and the healer) will be contrasted between resting and active healing time points to assess change associated with the EH treatment as compared to resting control in FM patients and the healer. We expect that if energy transfer occurs between the patient and healer, a signal in EEG coherence between the two individuals may be detected. We will specifically test if this signal in the EG precedes the changes in the patient, which would be indicative of a energy transfer process during healing. Exploratory outcomes: Heart rate variability will be assessed with ECG for both the FM patient as well as the energy healer simultaneously during treatment and resting control conditions. As mentioned above, to control for placebo effects and confounding factors FM patients will not be facing the healer during treatment. This will effectively blind the patient from the timing of the EH and rest periods. ECG will be performed using a Movesense sensor (https://www.movesense.com/) connected to a mobile device (via Bluetooth) which runs the patented electrocardiomatrix (ECM) software invented by the Borjigin lab at the University of Michigan that converts the 2D ECG data into a 3D ECM image that resembles a heatmap. The ECM image captured on the mobile device can be used as a standalone diagnostic tool for intuitive visualization of user’s cardiac conditions in real-time or post-capture. The captured ECG data can be uploaded to the ECM website (developed by Dr. Xu in the Borjigin lab) for quantitative processing (HRV and other outcomes). Finally in addition to ECG and EEG assessment, we will also measure skin temperature, galvanic skin resistance, and single hand biophoton emission during resting control period and active EH for both the healer and the FM patient. All study procedures will be approved by the University of California, Irvine Institutional Review Board, and all data will be securely stored in locked password protected computers at the University of California, Irvine campus. General Analysis. Comparisons between healing and control resting periods will be made for all outcomes using a paired t-Test (see above for EEG analysis). Pearson correlations will be made between change scores in brain neuroimaging outcomes, other physiologic outcomes, and changes in pain. Significant p-values are identified at p<0.05. As this is primarily a pilot mechanistic study with a single primary outcome (EEG), we will make no correction for multiple comparisons. Assessment of exploratory outcomes will be limited to hypothesis generation. Power calculation is pending and will be added later. Ethics and Data Management. All procedures will be approved by the local University of California, Irvine Institutional Review Board. All data will be identified with a unique patient identification number, whose linked personal health information will be kept in a locked cabinet behind a locked door in the Susan Samueli Integrative Health Institute building. Data will be shared with other researchers once the primary analyses are published and all data will be archived for 7 years at the University of California, Irvine after the study is completed 4. Pilot Data (Optional) This study has no pilot data to present. However there has been a study of one of the EH participating in this trial. These data are presented in the first citation in the references.[1] This unblinded and uncontrolled study found that of 50 reports of pain, 38 (76%) showed marked improvement. While this finding is certainly promising, there were no controls used with this study nor were the patients blinded to the treatment, two limitations we seek to address in this investigation. We also seek to find a mechanistic objective outcome that can track with pain improvement with EH. 5. Budget The budget for this work is $250,000 in total over 18 months. This includes personnel salaries (PI 5% effort 30K, study coordinator 100% effort 100K, imaging analyst 50% effort 90K, EEG consultant 10K, and biostatistician 5K), purchasing of equipment and supplies (EEG equipment, supplies and galvanic skin resistance device 5K), travel (4K), and participant recruitment and reimbursement (6K). 6. References 1. Dufresne F, Simmons B, Vlachostergios PJ, Fleischner Z, Joudeh R, Blakeway J, Julliard K. Feasibility of energy medicine in a community teaching hospital: an exploratory case series. J Altern Complement Med. (2015) 21(6),339-49. 2. Wolfe, F., et al., The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. (1995) 38(1): p. 19-28. 3. Jacobsen, S. and S.R. Bredkjaer. The prevalence of fibromyalgia and widespread chronic musculoskeletal pain in the general population. Scand.J.Rheumatol. (1992) 21(5): p. 261-263. 4. Raspe, H., C. Baumgartner, and F. Wolfe. The prevalence of fibromyalgia in a rural German community: How much difference do different criteria make? Arthritis & Rheumatism. (1993) 36(9 (Supplement)): p. S48. 5. Wolfe, F., et al. A prospective, longitudinal, multicenter study of service utilization and costs in fibromyalgia. Arthritis Rheum (1997) 40(9): p. 1560-70. 6. Gracely, R.H., et al. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. (2002) 46(5): p. 1333-1343. 7. Harris, R.E., et al. Decreased central mu-opioid receptor availability in fibromyalgia. J.Neurosci. (2007) 27(37): p. 10000-10006. 8. Mountz, J.M., et al., Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis Rheum. (1995) 38(7): p. 926-938. 9. Kaplan CM, Schrepf A, Mawla I, Ichesco E, Boehnke KF, Beltz A, Foxen-Craft E, Puglia MP, Tsodikov A, Williams DA, Hassett AL, Clauw DJ, Harte SE, Harris RE. Neurobiological antecedents of multisite pain in children. Pain. (2022) Apr 1;163(4):e596-e603. 10. Yunus, M.B., Towards a model of pathophysiology of fibromyalgia: aberrant central pain mechanisms with peripheral modulation. J Rheumatol. (1992) 19(6): p. 846-850. 11. Clauw, D.J. and G.P. Chrousos, Chronic pain and fatigue syndromes: Overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. Neuroimmunomodulation. (1997) 4(3): p. 134-153. 12. Apkarian, A.V., M.N. Baliki, and P. Y. Geha, Towards a theory of chronic pain. Prog Neurobiol. (2009) 87(2): p. 81-97. 13. Tracey, I. and M.C. Bushnell, How neuroimaging studies have challenged us to rethink: is chronic pain a disease? The Journal of Pain. (2009) 10(11): p. 1113-20. 14. Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. (1994) Mar;23(2):129-38. 15. Clauw DJ. Fibromyalgia: a clinical review. JAMA. (2014) 311(15):1547-55. 16. Kang K, Orlandi S, Leung J, et al. Electroencephalographic interbrain synchronization in children with disabilities, their parents, and neurologic music therapists. Eur J Neurosci. Jul 2023;58(1):2367-2383. doi:10.1111/ejn.16036 17. Bastos AM, Schoffelen JM. A Tutorial Review of Functional Connectivity Analysis Methods and Their Interpretational Pitfalls. Front Syst Neurosci. 2015;9:175. doi:10.3389/fnsys.2015.00175 18. Baccala LA, Sameshima K. Partial directed coherence: a new concept in neural structure determination. Biol Cybern. Jun 2001;84(6):463-74. doi:10.1007/PL00007990 19. Joo P, Kim M, Kish B, et al. Brain network hypersensitivity underlies pain crises in sickle cell disease. Sci Rep. Mar 27 2024;14(1):7315. doi:10.1038/s41598-024-57473-5 20. Lee U, Kim M, Lee K, et al. Functional Brain Network Mechanism of Hypersensitivity in Chronic Pain. Sci Rep. Jan 10 2018;8(1):243. doi:10.1038/s41598-017-18657-4 A Anzolin, K. Isenburg, A. Grahl, J. Toppi, M. Yücel, D.M. Ellingsen, J. Gerber, A. Ciaramidaro, L. Astolfi, T.J. Kaptchuk, V. Napadow – “Patient-Clinician Brain Response During Clinical Encounter and Pain Treatment”. In 2020 42nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 306527-1610 Ellingsen DM, Isenburg K, Jung C, Lee J, Gerber J, Mawla I, Sclocco R, Jensen K, Edwards RR, Kelley JM, Kirsch I, Kaptchuk T, Napadow V. Dynamic brain to brain concordance and behavioral mirroring as a mechanism of the patient/clinician interaction. Science advances 6, no. 43 (2020): eabc1304. Ellingsen DM, Isenburg K, Jung C, Lee J, Gerber J, Mawla I, Sclocco R, Grahl A, Anzolin A, Edwards RR, Kelley JM, Kirsch I, Kaptchuk TJ, Napadow V. Brain-to-brain mechanisms underlying pain empathy and social modulation of pain in the patient-clinician interaction. Proc Natl Acad Sci U S A. 2023 Jun 27;120(26):e2212910120. PMID: 37339198, PMCID: PMC10293846, https://doi.org/10.1073/pnas.2212910120. Anzolin A, Das P, Garcia RG, Chen A, Grahl A, Ellis S, Purdon P, Napadow V. Delta power during sleep is modulated by EEG-gated auricular vagal afferent nerve stimulation (EAVANS). Annu Int Conf IEEE Eng Med Biol Soc. 2023 Jul;2023:1-4. 10.1109/EMBC40787.2023.10340971. PMID: 38082663. 51:T93fc,{"type":"doc","content":[{"type":"heading","attrs":{"id":"bd5a778c-b288-40aa-81a9-a8f0b8437d16","data-toc-id":"bd5a778c-b288-40aa-81a9-a8f0b8437d16","textAlign":"left","level":1},"content":[{"type":"text","text":"Energy Healing Brain Hyper Scanning in Fibromyalgia"}]},{"type":"heading","attrs":{"id":"9fb6d144-2972-436b-8299-8421f1066135","data-toc-id":"9fb6d144-2972-436b-8299-8421f1066135","textAlign":"left","level":2},"content":[{"type":"text","text":"1. Overview"}]},{"type":"paragraph","attrs":{"id":"f1da5db1-27a9-474a-ab3b-5b3e8c3dd8f1","class":null,"textAlign":"left"},"content":[{"type":"text","text":"Energy medicine or energy healing (EH) is an emerging therapy with significant promise. It is derived from the theory that using the body’s own biological energy a therapeutic effect can be obtained in another individual such as a patient. Preliminary unpublished data from our group in chronic pain patients, suggests that EH, delivered by an experienced practitioner, may be able to reduce self-reported pain symptoms within minutes with effects lasting for weeks to months. In addition to improvements in pain, reductions in other symptoms including fatigue, sleep, and cognitive dysfunction may also be possible with EH."}]},{"type":"paragraph","attrs":{"id":"726ea82d-c1c5-416b-9a42-4da6faa0f0a2","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"EH practitioners may be trained within a specific tradition such as healing touch, reiki, and qigong, or work via novel unique methods. The energy practitioners that will be used for this study have practiced their unique style of EH for years and one has taken his work through a blinded hospital study demonstrating its feasibility and efficacy.[1] This study took place in inpatient units and the emergency department and found both acceptability and demand for energy medicine. Of 50 reports of pain, 38 (76%) showed marked improvement. Of 29 non-pain-related problems, 23 (79%) showed marked improvement.[1] While this finding is certainly promising, there were no controls used with this study nor were the patients blinded to the treatment, two limitations we seek to address in this investigation."}]},{"type":"paragraph","attrs":{"id":"a20bb3b6-9f5f-489d-9773-90f9f306e36b","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"We propose to study EH delivered by a experienced therapists, for the treatment of fibromyalgia (FM), a chronic pain condition that results from aberrant central nervous system function and neurochemistry. This work will be performed at the University of California, Irvine and comply with the university’s Institutional Review Board ethics. Participant recruitment will be for 18 months and funding for this study will be in part through DMT Quest, ResearchHub, and possibly the Subtle Energy Funders Collective. Results and publications from this study will be shared with the public following its conclusion."}]},{"type":"heading","attrs":{"id":"0b1af640-6d70-4b04-8701-3c43c7372056","data-toc-id":"0b1af640-6d70-4b04-8701-3c43c7372056","textAlign":"left","level":2},"content":[{"type":"text","text":"2. Introduction"}]},{"type":"paragraph","attrs":{"id":"ffc1b9a6-1ffc-4c4c-b571-4b9e6ddfc20a","class":null,"textAlign":"left"},"content":[{"type":"text","marks":[{"type":"bold"},{"type":"italic"}],"text":"Fibromyalgia (FM) is a Common Chronic Pain Syndrome and a Major Public Health Issue. "},{"type":"text","text":"Fibromyalgia (FM) is the second most common rheumatologic disorder, behind osteoarthritis, with 2 - 4% of the populations of industrialized countries affected.[2-4] Overall, it is estimated that FM costs the American taxpayers over $20 billion a year in lost wages and disability.[5] In part this burden on the US healthcare system is our lack of understanding of the specific pathophysiology of the disorder. While research suggests that FM is a central non-nociceptive pain syndrome,[6-8] it is uncertain if the observed neurobiological outcomes are causally related to development of FM. That said, our recent study in children suggests that the development of widespread pain, a hallmark of FM, is preceded by aberrant brain neural function.[9] The study proposed here may provide much needed information into the pathology of this disorder and how it is treated in a clinical setting. For example, if energy healing is able to reduce FM pain specifically, this may identify a non-physical basis for treatment. Our proposed project may also synergize with emerging data indicating a generalized disturbance in central nervous system pain processing in this condition.[10,11]"}]},{"type":"paragraph","attrs":{"id":"5ae1cdac-bbcf-4946-bef5-cfdf50cb2ff5","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"},{"type":"italic"}],"text":"Need for a Neurobiological Model underlying EH for FM."},{"type":"text","text":" There is a lack of key information about how EH may work for pain. One key missing piece in the field is that there are no objective markers that have been identified that actually track with subjective self-reported pain improvements following treatment with EH. This limitation is a key factor that prevents a more general adoption of this therapy by the medical community. If there is no proposed mechanism of action of EH, then the support for this intervention is weakened. However, an objective marker of chronic pain, that is modulated by EH, that also tracks with self-reported symptom improvement, would be a major advance for the field and also aid the development of a biomedical theory of how this therapy works. Moreover showing that similar brain activity occurs in an energy healer and the patient during treatment would also link the actions of healing at a distance: a key tenet of EH. Finally, our proposed neurobiological outcomes may also detect the effects of EH on brain neuroimaging biomarkers that we have previously found to track with clinical pain in FM, thus supporting the mechanisms of EH in chronic pain."}]},{"type":"paragraph","attrs":{"id":"cd821375-1e86-403c-8b3e-c5616a270241","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"}],"text":"Hypotheses "}]},{"type":"paragraph","attrs":{"id":"4a744dcd-f293-4876-8c15-3f5396272490","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"}],"text":"Aim 1:"},{"type":"text","text":" Assess the effects of EH as compared to control, on neuroelectrical activity acquired simultaneously from patients with FM and an energy healer (EEG hyperscan) and relate these brain changes to improvements in clinical pain. "},{"type":"text","marks":[{"type":"italic"}],"text":" Hypothesis 1A:"},{"type":"text","text":" EEG gamma power (co-primary outcome) assessed in FM patients and the healer will be greater during active healing as compared to control. "},{"type":"text","marks":[{"type":"italic"}],"text":"Hypothesis 1B:"},{"type":"text","text":" patient-practitioner brain-to-brain connectivity (co-primary outcome) will be higher during EH as compared to control. "},{"type":"text","marks":[{"type":"italic"}],"text":"Hypothesis 1C:"},{"type":"text","text":" changes in EEG metrics will be correlated with improvements in clinical pain (secondary outcome) during active EH as compared to control."}]},{"type":"paragraph","attrs":{"id":"192a0b6d-68cf-4798-b0b7-af34f64298f9","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"}],"text":"Aim 2 (exploratory):"},{"type":"text","text":" Explore the action of EH on brain explosive synchronization (exploratory outcome), an EEG measure of brain network instability and chronic pain.[19,20] We have previously shown this outcome of network instability to be present in FM participants with increased chronic pain. "},{"type":"text","marks":[{"type":"italic"}],"text":"Hypothesis 2A:"},{"type":"text","text":" Explore the action of EH on heart rate variability, biophoton emission, and skin temperature (exploratory outcomes). "},{"type":"text","marks":[{"type":"italic"}],"text":"Hypothesis 2B: "},{"type":"text","text":"Brain explosive synchronization metrics (network instability) will decrease in conjunction with chronic pain during EH as compared to control (exploratory outcome). "}]},{"type":"paragraph","attrs":{"id":"e69eafa8-abfe-4d22-a1d8-8812818dd6e3","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"}],"text":"Impact. "},{"type":"text","text":" If our hypotheses are proven true, 1) critical information will be provided that may help incorporate EH into mainstream clinical care, 2) EH may be shown to reduce pain symptoms in FM, and 3) we may obtain a better understanding of EH and how it might be utilized in future studies of other chronic pain conditions."}]},{"type":"heading","attrs":{"id":"0db6d9d2-5160-4031-8053-b51e8be72364","data-toc-id":"0db6d9d2-5160-4031-8053-b51e8be72364","textAlign":"left","level":2},"content":[{"type":"text","text":"3. Methods"}]},{"type":"paragraph","attrs":{"id":"e6d7a7e5-d8cd-4c0c-ab46-65f56e038c93","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"},{"type":"italic"}],"text":"Overview."},{"type":"text","text":" "},{"type":"text","marks":[{"type":"textStyle","attrs":{"fontSize":"12pt","fontFamily":"Aptos, sans-serif","color":"rgb(0, 0, 0)"}}],"text":"Our overall goal is to understand the role EH plays in modulating EEG neuroimaging markers (primary outcomes) related to altered neural processing of pain in FM as well as the effects it has on clinical pain (secondary outcome), and other exploratory outcomes including: heart rate variability, biophoton emission, and skin temperature. We will study 40 FM patients using brain electroencephalogram (EEG) hyper scanning in an energy healer and the patient simultaneously. We will also collect data on clinical pain changes as well as physiological outcomes in the patient and healer such as heart rate, skin temperature, and biophoton emission, exploratory outcomes that may be associated with EH. Data during energy healing periods will be compared to data acquired during rest as a control for non-specific or placebo treatment effects. Patients will be blinded as to the timing of these periods (see below). At no point will the patient know when the active healing treatment periods will start thus blinding the intervention and controlling for placebo effects."},{"type":"text","text":" "}]},{"type":"paragraph","attrs":{"id":"39ca9aa8-fe5f-47a0-9a2c-7d663b563413","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"},{"type":"italic"}],"text":"Study Team. "},{"type":"text","text":" This investigation is being led by Richard E. Harris, PhD who is a Susan Samueli Endowed Chair in the Susan Samueli Integrative Health Institute and Professor in the Department of Anesthesiology and Perioperative Care in the School of Medicine at the University of California at Irvine. He received his B.S. degree in Genetics from Purdue University in 1992 and his Ph.D. in Molecular and Cell Biology from UC Berkeley in 1997. Following his graduate work, he completed a postdoctoral fellowship at NIH. He is a graduate of the Maryland Institute of Traditional Chinese Medicine and has received an MS degree in Clinical Research Design and Statistical Analysis at the University of Michigan. Dr. Harris is currently investigating mechanisms of chronic pain and its treatment with acupuncture, energy healing, and shamanism. His investigations over the past 25 years have focused on the role of brain neurotransmitters and brain network behavior in chronic pain patients. and how these outcomes can be modulated by various treatments. He was a board member of the National Advisory Council for NIH/NCCIH and is a previous co-President for the Society for Acupuncture Research. "}]},{"type":"paragraph","attrs":{"id":"bc5039c2-7e6d-4b87-ae54-9d99197d9827","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"He is joined in this work by Dr. Alessandra Anzolin, a consultant from Spaulding Rehabilitation Hospital. She is a neuroscientist with an in-depth background in biomedical engineering and brain imaging techniques such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). She is a junior faculty at the Spaulding Rehabilitation Hospital, Harvard Medical School, where she is leading several projects with both healthy participants and patients with chronic pain. Since beginning her career, she have been passionate about methodological development to improve biomedical devices and signal processing, as well as the clinical applications that benefit from those advancements. In the realm of pain neuroimaging, her experience has included implementation of novel experimental designs utilizing EEG hyper scanning. This advanced methodology enables one to collect data simultaneously from patients and clinicians and to delve deeper into understanding complex phenomena such as the importance of therapeutic alliance and other non-specific effects during pain treatment. In particular, she has led EEG-hyper scanning projects to study the impact of an augmented compared to a limited clinical context on pain treatment effectiveness and the possibility of boosting therapeutic alliance, empathy, and brain concordance using a Theory of Mind training or psychedelic-assisted therapy in pain management. Results from a completed EEG-hyper scanning pilot [21-23] were published as a brief paper and received several awards at international conferences – e.g. “Outstanding Junior Researcher Award in Basic Science Research” from the Society for Acupuncture and the “Best Translational Research Award” from the US Association for the Study of Pain. She also has recently led the development of non-invasive brain stimulation techniques to modulate specific brain rhythms. This includes the development of a prototype (EEG-gated Auricular Vagal Afferent Nerve Stimulation, EAVANS), a closed-loop peripheral nerve stimulation device. By leveraging EEG data to guide the stimulation process, EAVANS holds the potential to enhance the efficacy of brain stimulation therapies, allowing for a more personalized and non-pharmacological intervention to treat delirium and expedite the recovery of cognitive functions post-anesthesia.[24]"}]},{"type":"paragraph","attrs":{"id":"a5114e1d-08f9-44d8-8187-8cff001333a9","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"The backgrounds of Drs. Harris and Anzolin in chronic pain, brain imaging, and EEG hyper scanning will be valuable in advancing this project."}]},{"type":"paragraph","attrs":{"id":"c8596fe2-de12-47ec-bc0a-4c1c306dfae6","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"We are purposefully not providing information on the three energy healers that will be used in this study as we do not want to risk participants knowing who will be treating them prior to seeing them in person on the study visit (see below Procedures). That said, the three EHs that will be used practice their own individual style of healing that is not Reiki or Qigong. Each healer has over 15 years of experience in healing pain patients and we have worked with one of the healers on a different mechanistic study that is ongoing."}]},{"type":"paragraph","attrs":{"id":"84cd16ce-7bf6-4762-a292-b5f37263ea69","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"},{"type":"italic"}],"text":"Rationale."},{"type":"text","marks":[{"type":"italic"}],"text":" "},{"type":"text","text":" Our proposal originates with coupling brain and other physiological outcomes with clinical pain measures incorporated in a treatment trial framework using EH. In addition to evaluating brain response to EH between two individuals simultaneously, we will also investigate the neurocircuitry subserving clinical pain. Neuroimaging markers reflecting FM patients’ clinical pain are crucial to this design, as (a) they conceptually link more closely to important clinical outcome measures, as compared to markers for experimental pain in hyperalgesia and allodynia, and (b) their differential susceptibility to different forms of therapy may underlie the ultimate mechanisms of action of EH. Recent efforts have been increasingly aimed at developing a neurobiological model for chronic nociplastic pain, and our proposal is innovative in that it adds to this burgeoning field of research.[12,13]"}]},{"type":"paragraph","attrs":{"id":"d66210d7-1407-4b04-942f-15fe770aee18","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"},{"type":"italic"}],"text":"Procedures."},{"type":"text","text":" All EH treatments and physiological testing will occur at the Susan Samueli Integrative Health Institute at the University of California at Irvine. 40 participants aged 18-75 years old, with a diagnosis/symptoms of FM for at least 1 year will be consented in person. Ineligible participants will be excluded if they have: epilepsy, bipolar disorder, history of stroke, rhuematoid arthritis, or Lupus. Additional exclusions are any other condition of chronic pain other than fibromyalgia. "}]},{"type":"paragraph","attrs":{"id":"a72c676a-ebbe-4282-bb96-6a378085cb18","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"Following consent participants will undergo a two-week run-in during baseline to washout previous treatment effects and reduce regression to the mean. Following consent and 2 week run-in, participants will attend a single visit with one of three chosen energy healers, during which EEG and control/active EH treatment will occur. Prior to starting this visit, patients will be told verbally, “At some point in this session you will experience energy healing, but you will not know when that is.” After 32-channel EEG cap set up on both the patient and the energy healer, individuals will be seated facing away from each other. There will be no visual interaction between the energy healer and patient during the control and healing sessions. This will help blind the study so that the patients will not know at what time the active EH will take place. An initial 5 minutes of resting eyes closed will be acquired for both individuals, followed by a 10-minute eyes closed resting condition wherein the patient will be queried every 2 minutes about their resting pain level on a scale from 0 to 10 with 0 being “no pain” and 10 being “worst pain imaginable”. This is the no-treatment control condition. Then, in a blinded fashion so the patient does not know, the energy healer will be notified by staff to start the energy healing. At no point will the patient know when the healing will start and at no time will there be active touching of the patient by the healer. During the next 15 minutes of healing, the patient will be queried by staff as to what their pain level currently is in the same fashion as during the prior 10 minute no-treatment control condition. We have piloted this protocol in fibromyalgia patients previously and this duration of treatment and control are adequate to blind the patient and allows enough time for the healer to reduce chronic fibromyalgia pain. We also have show in unpublished pilot data that the EH effects can persist for hours to days following a single treatment, which prevents us from randomizing the order of presentation of the control and active healing periods as active healing would extend into the control period if active healing was done first. (As mentioned above, the patients will not know the fixed order of events.) Following the active EH period, patients and healers will perform an eyes closed 5 minute resting period and be debriefed about the procedure."}]},{"type":"paragraph","attrs":{"id":"0870f311-88b9-4008-a49f-0ac4a5c6c94c","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"Our primary outcome is EEG (see below) and secondary outcome is pain, with change in pain intensity and interference, as measured in a 11 point Numerical Rating Scale, anchored at 0 = “no pain” and 10 = “worst pain imaginable”. This will be assessed throughout the control and active EH procedure (see above). We will also include the Brief Pain Inventory [14] and the FM survey criteria [15] as additional secondary pain outcomes acquired prior to and following the EEG visit. We will also use the PROMIS 29 questionnaire to assess fatigue, sleep, and mood."}]},{"type":"paragraph","attrs":{"id":"c6765c66-a46e-4558-8340-e80000654e07","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"italic"}],"text":"EEG Acquisition (primary outcomes) and Analysis."},{"type":"text","text":" EEG data will be collected from the energy healer and FM participants simultaneously (hyperscan) to measure synchronized brain activity in each dyad (Energy Healer-FM participant). We use a Brain Products EEG system with 32-channel water-based nets (sensors are distributed accordingly to the International 10-20 system). The EEG caps from the FM participant and the healer will be attached to the same EEG amplifier (BrainAmp) ensuring the millisecond-precision alignment required for the inter-brain connectivity analysis. The EEG equipment has been purchased and tested in pilot acquisitions to ensure rigorous data collection. "},{"type":"text","marks":[{"type":"italic"}],"text":"Gamma Power and Hyperscanning:"},{"type":"text","text":" We use in-house developed MATLAB scripts based on validated pipelines for EEG data processing (EEGLAB). First, we will perform standard preprocessing including bandpass filtering (1-30Hz for inter-brain connectivity assessment and 1-100Hz for gamma analysis), re-referencing, and ocular artifact removal (independent component analysis, ICA). Then Phase Locking Value (PLV) and Partial Directed Coherence (PDC) will be used to measure inter-brain connectivity.[16] PLV assesses the magnitude of phase synchrony[17] whereas PDC is a spectral estimate of causal connectivity including intensity and directionality.[18] We will compute PLV and PDC on the EEG time series acquired during resting prior to EH and concurrently with EH. Additionally we will compute Power Spectral Density (PSD) in all standard EEG frequency bands, including Delta, Theta, Alpha, Beta, and Gamma. Brain-to-brain connectivity measures and Gamma power (assessed separately for patients and the healer) will be contrasted between resting and active healing time points to assess change associated with the EH treatment as compared to resting control in FM patients and the healer. We expect that if energy transfer occurs between the patient and healer, a signal in EEG coherence between the two individuals may be detected. We will specifically test if this signal in the EG precedes the changes in the patient, which would be indicative of a energy transfer process during healing."}]},{"type":"paragraph","attrs":{"id":"a6a34420-3828-46c6-b031-c7a597d8d5cf","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"italic"}],"text":"Exploratory outcomes:"},{"type":"text","text":" Heart rate variability will be assessed with ECG for both the FM patient as well as the energy healer simultaneously during treatment and resting control conditions. As mentioned above, to control for placebo effects and confounding factors FM patients will not be facing the healer during treatment. This will effectively blind the patient from the timing of the EH and rest periods. ECG will be performed using a Movesense sensor ("},{"type":"text","marks":[{"type":"link","attrs":{"href":"https://www.movesense.com/","target":"_blank","rel":"noopener noreferrer nofollow","class":"link inline-flex items-center hover:underline transition-colors duration-200"}}],"text":"https://www.movesense.com/"},{"type":"text","text":") connected to a mobile device (via Bluetooth) which runs the patented electrocardiomatrix (ECM) software invented by the Borjigin lab at the University of Michigan that converts the 2D ECG data into a 3D ECM image that resembles a heatmap. The ECM image captured on the mobile device can be used as a standalone diagnostic tool for intuitive visualization of user’s cardiac conditions in real-time or post-capture. The captured ECG data can be uploaded to the ECM website (developed by Dr. Xu in the Borjigin lab) for quantitative processing (HRV and other outcomes). Finally in addition to ECG and EEG assessment, we will also measure skin temperature, galvanic skin resistance, and single hand biophoton emission during resting control period and active EH for both the healer and the FM patient. "}]},{"type":"paragraph","attrs":{"id":"2b684ac5-67cc-441d-bfd0-4538793b4659","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"All study procedures will be approved by the University of California, Irvine Institutional Review Board, and all data will be securely stored in locked password protected computers at the University of California, Irvine campus."}]},{"type":"paragraph","attrs":{"id":"0a98df58-9e3c-4c07-a3bd-e31e8402c53c","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"},{"type":"italic"}],"text":"General Analysis."},{"type":"text","text":" Comparisons between healing and control resting periods will be made for all outcomes using a paired t-Test (see above for EEG analysis). Pearson correlations will be made between change scores in brain neuroimaging outcomes, other physiologic outcomes, and changes in pain. Significant p-values are identified at p<0.05. As this is primarily a pilot mechanistic study with a single primary outcome (EEG), we will make no correction for multiple comparisons. Assessment of exploratory outcomes will be limited to hypothesis generation. "},{"type":"text","marks":[{"type":"italic"}],"text":"Power calculation is pending and will be added later."}]},{"type":"paragraph","attrs":{"id":"50d79b70-0a93-49c1-82f1-15ab63c4b18c","class":"MsoNormal","textAlign":null},"content":[{"type":"text","marks":[{"type":"bold"},{"type":"italic"}],"text":"Ethics and Data Management."},{"type":"text","text":" All procedures will be approved by the local University of California, Irvine Institutional Review Board. All data will be identified with a unique patient identification number, whose linked personal health information will be kept in a locked cabinet behind a locked door in the Susan Samueli Integrative Health Institute building. Data will be shared with other researchers once the primary analyses are published and all data will be archived for 7 years at the University of California, Irvine after the study is completed"}]},{"type":"heading","attrs":{"id":"655a235c-48c1-40dd-a413-aa416a373f33","data-toc-id":"655a235c-48c1-40dd-a413-aa416a373f33","textAlign":"left","level":2},"content":[{"type":"text","text":"4. Pilot Data (Optional)"}]},{"type":"paragraph","attrs":{"id":"ec4b39a6-3f1b-406d-921b-a90486fb9f13","class":null,"textAlign":"left"},"content":[{"type":"text","text":"This study has no pilot data to present. However there has been a study of one of the EH participating in this trial. These data are presented in the first citation in the references.[1] This unblinded and uncontrolled study found that of 50 reports of pain, 38 (76%) showed marked improvement. While this finding is certainly promising, there were no controls used with this study nor were the patients blinded to the treatment, two limitations we seek to address in this investigation. We also seek to find a mechanistic objective outcome that can track with pain improvement with EH."}]},{"type":"heading","attrs":{"id":"74214f1c-3ae8-4149-a3bd-cc3f234aa044","data-toc-id":"74214f1c-3ae8-4149-a3bd-cc3f234aa044","textAlign":"left","level":2},"content":[{"type":"text","text":"5. Budget"}]},{"type":"paragraph","attrs":{"id":"c272e9cc-5ad2-4898-ac07-acb0dbde755a","class":null,"textAlign":"left"},"content":[{"type":"text","text":"The budget for this work is $250,000 in total over 18 months. This includes personnel salaries (PI 5% effort 30K, study coordinator 100% effort 100K, imaging analyst 50% effort 90K, EEG consultant 10K, and biostatistician 5K), purchasing of equipment and supplies (EEG equipment, supplies and galvanic skin resistance device 5K), travel (4K), and participant recruitment and reimbursement (6K)."}]},{"type":"heading","attrs":{"id":"a7a153a1-cb2e-492e-9d5b-686b559eed1e","data-toc-id":"a7a153a1-cb2e-492e-9d5b-686b559eed1e","textAlign":"left","level":2},"content":[{"type":"text","text":"6. References"}]},{"type":"paragraph","attrs":{"id":"e656ef6f-45ee-446b-92c7-c1b0fea520ac","class":null,"textAlign":"left"},"content":[{"type":"text","text":"1. Dufresne F, Simmons B, Vlachostergios PJ, Fleischner Z, Joudeh R, Blakeway J, Julliard K. Feasibility of energy medicine in a community teaching hospital: an exploratory case series. J Altern Complement Med. (2015) 21(6),339-49."}]},{"type":"paragraph","attrs":{"id":"c64823ef-afed-45fe-877b-65c66734313a","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"2. Wolfe, F., et al., The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. (1995) 38(1): p. 19-28."}]},{"type":"paragraph","attrs":{"id":"1e64f21b-0eea-4538-b224-d7d45b0f6059","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"3. Jacobsen, S. and S.R. Bredkjaer. The prevalence of fibromyalgia and widespread chronic musculoskeletal pain in the general population. Scand.J.Rheumatol. (1992) 21(5): p. 261-263."}]},{"type":"paragraph","attrs":{"id":"7157edd7-5c56-4f31-a07d-0a819f059d39","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"4. Raspe, H., C. Baumgartner, and F. Wolfe. The prevalence of fibromyalgia in a rural German community: How much difference do different criteria make? Arthritis & Rheumatism. (1993) 36(9 (Supplement)): p. S48."}]},{"type":"paragraph","attrs":{"id":"cdfff18d-736c-46d1-970d-988fb17ddcfe","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"5. Wolfe, F., et al. A prospective, longitudinal, multicenter study of service utilization and costs in fibromyalgia. Arthritis Rheum (1997) 40(9): p. 1560-70."}]},{"type":"paragraph","attrs":{"id":"4ffb6452-d31a-49b1-98b4-0030d15bc833","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"6. Gracely, R.H., et al. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. (2002) 46(5): p. 1333-1343."}]},{"type":"paragraph","attrs":{"id":"49c695f0-bdbe-4586-8732-7b6780f86986","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"7. Harris, R.E., et al. Decreased central mu-opioid receptor availability in fibromyalgia. J.Neurosci. (2007) 27(37): p. 10000-10006."}]},{"type":"paragraph","attrs":{"id":"0c75f9c9-cc32-46bb-97ef-2dd2b34e1fe5","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"8. Mountz, J.M., et al., Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis Rheum. (1995) 38(7): p. 926-938. "}]},{"type":"paragraph","attrs":{"id":"b054858b-a970-49ea-9c31-262c091862d4","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"9. Kaplan CM, Schrepf A, Mawla I, Ichesco E, Boehnke KF, Beltz A, Foxen-Craft E, Puglia MP, Tsodikov A, Williams DA, Hassett AL, Clauw DJ, Harte SE, Harris RE. Neurobiological antecedents of multisite pain in children. Pain. (2022) Apr 1;163(4):e596-e603."}]},{"type":"paragraph","attrs":{"id":"119bcdaa-7660-4e75-a44f-bde9c54fcd7b","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"10. Yunus, M.B., Towards a model of pathophysiology of fibromyalgia: aberrant central pain mechanisms with peripheral modulation. J Rheumatol. (1992) 19(6): p. 846-850."}]},{"type":"paragraph","attrs":{"id":"00d9c122-6360-46b9-b46b-29e8e30dcd21","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"11. Clauw, D.J. and G.P. Chrousos, Chronic pain and fatigue syndromes: Overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. Neuroimmunomodulation. (1997) 4(3): p. 134-153."}]},{"type":"paragraph","attrs":{"id":"509ad8cd-3d53-462c-81a1-d1cce5ede846","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"12. Apkarian, A.V., M.N. Baliki, and P. Y. Geha, Towards a theory of chronic pain. Prog Neurobiol. (2009) 87(2): p. 81-97."}]},{"type":"paragraph","attrs":{"id":"677fffb3-30ca-4544-a558-99c9b71a533c","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"13. Tracey, I. and M.C. Bushnell, How neuroimaging studies have challenged us to rethink: is chronic pain a disease? The Journal of Pain. (2009) 10(11): p. 1113-20."}]},{"type":"paragraph","attrs":{"id":"e87ab5e7-18b8-4664-b916-95644b04b76a","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"14. Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. (1994) Mar;23(2):129-38."}]},{"type":"paragraph","attrs":{"id":"2d819f45-0907-4cac-bb70-09ac5a5ea940","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"15. Clauw DJ. Fibromyalgia: a clinical review. JAMA. (2014) 311(15):1547-55."}]},{"type":"paragraph","attrs":{"id":"01052576-72dc-4ea1-a62a-d0283ad0c758","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"16. Kang K, Orlandi S, Leung J, et al. Electroencephalographic interbrain synchronization in children with disabilities, their parents, and neurologic music therapists. Eur J Neurosci. Jul 2023;58(1):2367-2383. doi:10.1111/ejn.16036"}]},{"type":"paragraph","attrs":{"id":"b730d6fa-587c-462c-b41a-71dbd19660a2","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"17. Bastos AM, Schoffelen JM. A Tutorial Review of Functional Connectivity Analysis Methods and Their Interpretational Pitfalls. Front Syst Neurosci. 2015;9:175. doi:10.3389/fnsys.2015.00175 "}]},{"type":"paragraph","attrs":{"id":"b22e8bfd-10fd-4e75-bb26-c7c827587f42","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"18. Baccala LA, Sameshima K. Partial directed coherence: a new concept in neural structure determination. Biol Cybern. Jun 2001;84(6):463-74. doi:10.1007/PL00007990"}]},{"type":"paragraph","attrs":{"id":"93d10dc8-6cde-4c9b-a416-4093ace75c4b","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"19. Joo P, Kim M, Kish B, et al. Brain network hypersensitivity underlies pain crises in sickle cell disease. Sci Rep. Mar 27 2024;14(1):7315. doi:10.1038/s41598-024-57473-5"}]},{"type":"paragraph","attrs":{"id":"fe65f0ff-b7b0-4ae2-ba19-6b8c9fc76806","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"20. Lee U, Kim M, Lee K, et al. Functional Brain Network Mechanism of Hypersensitivity in Chronic Pain. Sci Rep. Jan 10 2018;8(1):243. doi:10.1038/s41598-017-18657-4"}]},{"type":"orderedList","attrs":{"start":21},"content":[{"type":"listItem","content":[{"type":"paragraph","attrs":{"id":"b363ece4-9e6d-4f09-bbcc-46e9ca7ecf0e","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"A Anzolin, K. Isenburg, A. Grahl, J. Toppi, M. Yücel, D.M. Ellingsen, J. Gerber, A. Ciaramidaro, L. Astolfi, T.J. Kaptchuk, V. Napadow – “Patient-Clinician Brain Response During Clinical Encounter and Pain Treatment”. In 2020 42nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 306527-1610"}]}]},{"type":"listItem","content":[{"type":"paragraph","attrs":{"id":"5b65c7c8-240a-420f-b1e3-1cfe44173383","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"Ellingsen DM, Isenburg K, Jung C, Lee J, Gerber J, Mawla I, Sclocco R, Jensen K, "},{"type":"text","marks":[{"type":"italic"}],"text":"Edwards RR, "},{"type":"text","text":"Kelley JM, Kirsch I, Kaptchuk T, Napadow V. Dynamic brain to brain concordance and behavioral mirroring as a mechanism of the patient/clinician interaction. Science advances 6, no. 43 (2020): eabc1304."}]}]},{"type":"listItem","content":[{"type":"paragraph","attrs":{"id":"3654d012-c64e-48ba-a04f-d918ffea92fd","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"Ellingsen DM, Isenburg K, Jung C, Lee J, Gerber J, Mawla I, Sclocco R, Grahl A, Anzolin A, Edwards RR, Kelley JM, Kirsch I, Kaptchuk TJ, Napadow V. Brain-to-brain mechanisms underlying pain empathy and social modulation of pain in the patient-clinician interaction. Proc Natl Acad Sci U S A. 2023 Jun 27;120(26):e2212910120. PMID: 37339198, PMCID: PMC10293846, "},{"type":"text","marks":[{"type":"link","attrs":{"href":"https://doi.org/10.1073/pnas.2212910120","target":"_blank","rel":"noopener noreferrer nofollow","class":"link"}}],"text":"https://doi.org/10.1073/pnas.2212910120"},{"type":"text","text":"."}]}]},{"type":"listItem","content":[{"type":"paragraph","attrs":{"id":"f26f4e00-eaca-4105-b541-37dcd60a22d2","class":"MsoNormal","textAlign":null},"content":[{"type":"text","text":"Anzolin A, Das P, Garcia RG, Chen A, Grahl A, Ellis S, Purdon P, Napadow V. Delta power during sleep is modulated by EEG-gated auricular vagal afferent nerve stimulation (EAVANS). Annu Int Conf IEEE Eng Med Biol Soc. 2023 Jul;2023:1-4. 10.1109/EMBC40787.2023.10340971. PMID: 38082663."}]}]}]},{"type":"paragraph","attrs":{"id":"ab703307-1885-40b7-a20f-46207fc3e5c7","class":null,"textAlign":null}}]}52:T7fd1,

Energy Healing Brain Hyper Scanning in Fibromyalgia

1. Overview

Energy medicine or energy healing (EH) is an emerging therapy with significant promise. It is derived from the theory that using the body’s own biological energy a therapeutic effect can be obtained in another individual such as a patient. Preliminary unpublished data from our group in chronic pain patients, suggests that EH, delivered by an experienced practitioner, may be able to reduce self-reported pain symptoms within minutes with effects lasting for weeks to months. In addition to improvements in pain, reductions in other symptoms including fatigue, sleep, and cognitive dysfunction may also be possible with EH.

EH practitioners may be trained within a specific tradition such as healing touch, reiki, and qigong, or work via novel unique methods. The energy practitioners that will be used for this study have practiced their unique style of EH for years and one has taken his work through a blinded hospital study demonstrating its feasibility and efficacy.[1] This study took place in inpatient units and the emergency department and found both acceptability and demand for energy medicine. Of 50 reports of pain, 38 (76%) showed marked improvement. Of 29 non-pain-related problems, 23 (79%) showed marked improvement.[1] While this finding is certainly promising, there were no controls used with this study nor were the patients blinded to the treatment, two limitations we seek to address in this investigation.

We propose to study EH delivered by a experienced therapists, for the treatment of fibromyalgia (FM), a chronic pain condition that results from aberrant central nervous system function and neurochemistry. This work will be performed at the University of California, Irvine and comply with the university’s Institutional Review Board ethics. Participant recruitment will be for 18 months and funding for this study will be in part through DMT Quest, ResearchHub, and possibly the Subtle Energy Funders Collective. Results and publications from this study will be shared with the public following its conclusion.

2. Introduction

Fibromyalgia (FM) is a Common Chronic Pain Syndrome and a Major Public Health Issue. Fibromyalgia (FM) is the second most common rheumatologic disorder, behind osteoarthritis, with 2 - 4% of the populations of industrialized countries affected.[2-4] Overall, it is estimated that FM costs the American taxpayers over $20 billion a year in lost wages and disability.[5] In part this burden on the US healthcare system is our lack of understanding of the specific pathophysiology of the disorder. While research suggests that FM is a central non-nociceptive pain syndrome,[6-8] it is uncertain if the observed neurobiological outcomes are causally related to development of FM. That said, our recent study in children suggests that the development of widespread pain, a hallmark of FM, is preceded by aberrant brain neural function.[9] The study proposed here may provide much needed information into the pathology of this disorder and how it is treated in a clinical setting. For example, if energy healing is able to reduce FM pain specifically, this may identify a non-physical basis for treatment. Our proposed project may also synergize with emerging data indicating a generalized disturbance in central nervous system pain processing in this condition.[10,11]

Need for a Neurobiological Model underlying EH for FM. There is a lack of key information about how EH may work for pain. One key missing piece in the field is that there are no objective markers that have been identified that actually track with subjective self-reported pain improvements following treatment with EH. This limitation is a key factor that prevents a more general adoption of this therapy by the medical community. If there is no proposed mechanism of action of EH, then the support for this intervention is weakened. However, an objective marker of chronic pain, that is modulated by EH, that also tracks with self-reported symptom improvement, would be a major advance for the field and also aid the development of a biomedical theory of how this therapy works. Moreover showing that similar brain activity occurs in an energy healer and the patient during treatment would also link the actions of healing at a distance: a key tenet of EH. Finally, our proposed neurobiological outcomes may also detect the effects of EH on brain neuroimaging biomarkers that we have previously found to track with clinical pain in FM, thus supporting the mechanisms of EH in chronic pain.

Hypotheses

Aim 1: Assess the effects of EH as compared to control, on neuroelectrical activity acquired simultaneously from patients with FM and an energy healer (EEG hyperscan) and relate these brain changes to improvements in clinical pain. Hypothesis 1A: EEG gamma power (co-primary outcome) assessed in FM patients and the healer will be greater during active healing as compared to control. Hypothesis 1B: patient-practitioner brain-to-brain connectivity (co-primary outcome) will be higher during EH as compared to control. Hypothesis 1C: changes in EEG metrics will be correlated with improvements in clinical pain (secondary outcome) during active EH as compared to control.

Aim 2 (exploratory): Explore the action of EH on brain explosive synchronization (exploratory outcome), an EEG measure of brain network instability and chronic pain.[19,20] We have previously shown this outcome of network instability to be present in FM participants with increased chronic pain. Hypothesis 2A: Explore the action of EH on heart rate variability, biophoton emission, and skin temperature (exploratory outcomes). Hypothesis 2B: Brain explosive synchronization metrics (network instability) will decrease in conjunction with chronic pain during EH as compared to control (exploratory outcome).

Impact. If our hypotheses are proven true, 1) critical information will be provided that may help incorporate EH into mainstream clinical care, 2) EH may be shown to reduce pain symptoms in FM, and 3) we may obtain a better understanding of EH and how it might be utilized in future studies of other chronic pain conditions.

3. Methods

Overview. Our overall goal is to understand the role EH plays in modulating EEG neuroimaging markers (primary outcomes) related to altered neural processing of pain in FM as well as the effects it has on clinical pain (secondary outcome), and other exploratory outcomes including: heart rate variability, biophoton emission, and skin temperature. We will study 40 FM patients using brain electroencephalogram (EEG) hyper scanning in an energy healer and the patient simultaneously. We will also collect data on clinical pain changes as well as physiological outcomes in the patient and healer such as heart rate, skin temperature, and biophoton emission, exploratory outcomes that may be associated with EH. Data during energy healing periods will be compared to data acquired during rest as a control for non-specific or placebo treatment effects. Patients will be blinded as to the timing of these periods (see below). At no point will the patient know when the active healing treatment periods will start thus blinding the intervention and controlling for placebo effects.

Study Team. This investigation is being led by Richard E. Harris, PhD who is a Susan Samueli Endowed Chair in the Susan Samueli Integrative Health Institute and Professor in the Department of Anesthesiology and Perioperative Care in the School of Medicine at the University of California at Irvine. He received his B.S. degree in Genetics from Purdue University in 1992 and his Ph.D. in Molecular and Cell Biology from UC Berkeley in 1997. Following his graduate work, he completed a postdoctoral fellowship at NIH. He is a graduate of the Maryland Institute of Traditional Chinese Medicine and has received an MS degree in Clinical Research Design and Statistical Analysis at the University of Michigan. Dr. Harris is currently investigating mechanisms of chronic pain and its treatment with acupuncture, energy healing, and shamanism. His investigations over the past 25 years have focused on the role of brain neurotransmitters and brain network behavior in chronic pain patients. and how these outcomes can be modulated by various treatments. He was a board member of the National Advisory Council for NIH/NCCIH and is a previous co-President for the Society for Acupuncture Research.

He is joined in this work by Dr. Alessandra Anzolin, a consultant from Spaulding Rehabilitation Hospital. She is a neuroscientist with an in-depth background in biomedical engineering and brain imaging techniques such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). She is a junior faculty at the Spaulding Rehabilitation Hospital, Harvard Medical School, where she is leading several projects with both healthy participants and patients with chronic pain. Since beginning her career, she have been passionate about methodological development to improve biomedical devices and signal processing, as well as the clinical applications that benefit from those advancements. In the realm of pain neuroimaging, her experience has included implementation of novel experimental designs utilizing EEG hyper scanning. This advanced methodology enables one to collect data simultaneously from patients and clinicians and to delve deeper into understanding complex phenomena such as the importance of therapeutic alliance and other non-specific effects during pain treatment. In particular, she has led EEG-hyper scanning projects to study the impact of an augmented compared to a limited clinical context on pain treatment effectiveness and the possibility of boosting therapeutic alliance, empathy, and brain concordance using a Theory of Mind training or psychedelic-assisted therapy in pain management. Results from a completed EEG-hyper scanning pilot [21-23] were published as a brief paper and received several awards at international conferences – e.g. “Outstanding Junior Researcher Award in Basic Science Research” from the Society for Acupuncture and the “Best Translational Research Award” from the US Association for the Study of Pain. She also has recently led the development of non-invasive brain stimulation techniques to modulate specific brain rhythms. This includes the development of a prototype (EEG-gated Auricular Vagal Afferent Nerve Stimulation, EAVANS), a closed-loop peripheral nerve stimulation device. By leveraging EEG data to guide the stimulation process, EAVANS holds the potential to enhance the efficacy of brain stimulation therapies, allowing for a more personalized and non-pharmacological intervention to treat delirium and expedite the recovery of cognitive functions post-anesthesia.[24]

The backgrounds of Drs. Harris and Anzolin in chronic pain, brain imaging, and EEG hyper scanning will be valuable in advancing this project.

We are purposefully not providing information on the three energy healers that will be used in this study as we do not want to risk participants knowing who will be treating them prior to seeing them in person on the study visit (see below Procedures). That said, the three EHs that will be used practice their own individual style of healing that is not Reiki or Qigong. Each healer has over 15 years of experience in healing pain patients and we have worked with one of the healers on a different mechanistic study that is ongoing.

Rationale. Our proposal originates with coupling brain and other physiological outcomes with clinical pain measures incorporated in a treatment trial framework using EH. In addition to evaluating brain response to EH between two individuals simultaneously, we will also investigate the neurocircuitry subserving clinical pain. Neuroimaging markers reflecting FM patients’ clinical pain are crucial to this design, as (a) they conceptually link more closely to important clinical outcome measures, as compared to markers for experimental pain in hyperalgesia and allodynia, and (b) their differential susceptibility to different forms of therapy may underlie the ultimate mechanisms of action of EH. Recent efforts have been increasingly aimed at developing a neurobiological model for chronic nociplastic pain, and our proposal is innovative in that it adds to this burgeoning field of research.[12,13]

Procedures. All EH treatments and physiological testing will occur at the Susan Samueli Integrative Health Institute at the University of California at Irvine. 40 participants aged 18-75 years old, with a diagnosis/symptoms of FM for at least 1 year will be consented in person. Ineligible participants will be excluded if they have: epilepsy, bipolar disorder, history of stroke, rhuematoid arthritis, or Lupus. Additional exclusions are any other condition of chronic pain other than fibromyalgia.

Following consent participants will undergo a two-week run-in during baseline to washout previous treatment effects and reduce regression to the mean. Following consent and 2 week run-in, participants will attend a single visit with one of three chosen energy healers, during which EEG and control/active EH treatment will occur. Prior to starting this visit, patients will be told verbally, “At some point in this session you will experience energy healing, but you will not know when that is.” After 32-channel EEG cap set up on both the patient and the energy healer, individuals will be seated facing away from each other. There will be no visual interaction between the energy healer and patient during the control and healing sessions. This will help blind the study so that the patients will not know at what time the active EH will take place. An initial 5 minutes of resting eyes closed will be acquired for both individuals, followed by a 10-minute eyes closed resting condition wherein the patient will be queried every 2 minutes about their resting pain level on a scale from 0 to 10 with 0 being “no pain” and 10 being “worst pain imaginable”. This is the no-treatment control condition. Then, in a blinded fashion so the patient does not know, the energy healer will be notified by staff to start the energy healing. At no point will the patient know when the healing will start and at no time will there be active touching of the patient by the healer. During the next 15 minutes of healing, the patient will be queried by staff as to what their pain level currently is in the same fashion as during the prior 10 minute no-treatment control condition. We have piloted this protocol in fibromyalgia patients previously and this duration of treatment and control are adequate to blind the patient and allows enough time for the healer to reduce chronic fibromyalgia pain. We also have show in unpublished pilot data that the EH effects can persist for hours to days following a single treatment, which prevents us from randomizing the order of presentation of the control and active healing periods as active healing would extend into the control period if active healing was done first. (As mentioned above, the patients will not know the fixed order of events.) Following the active EH period, patients and healers will perform an eyes closed 5 minute resting period and be debriefed about the procedure.

Our primary outcome is EEG (see below) and secondary outcome is pain, with change in pain intensity and interference, as measured in a 11 point Numerical Rating Scale, anchored at 0 = “no pain” and 10 = “worst pain imaginable”. This will be assessed throughout the control and active EH procedure (see above). We will also include the Brief Pain Inventory [14] and the FM survey criteria [15] as additional secondary pain outcomes acquired prior to and following the EEG visit. We will also use the PROMIS 29 questionnaire to assess fatigue, sleep, and mood.

EEG Acquisition (primary outcomes) and Analysis. EEG data will be collected from the energy healer and FM participants simultaneously (hyperscan) to measure synchronized brain activity in each dyad (Energy Healer-FM participant). We use a Brain Products EEG system with 32-channel water-based nets (sensors are distributed accordingly to the International 10-20 system). The EEG caps from the FM participant and the healer will be attached to the same EEG amplifier (BrainAmp) ensuring the millisecond-precision alignment required for the inter-brain connectivity analysis. The EEG equipment has been purchased and tested in pilot acquisitions to ensure rigorous data collection. Gamma Power and Hyperscanning: We use in-house developed MATLAB scripts based on validated pipelines for EEG data processing (EEGLAB). First, we will perform standard preprocessing including bandpass filtering (1-30Hz for inter-brain connectivity assessment and 1-100Hz for gamma analysis), re-referencing, and ocular artifact removal (independent component analysis, ICA). Then Phase Locking Value (PLV) and Partial Directed Coherence (PDC) will be used to measure inter-brain connectivity.[16] PLV assesses the magnitude of phase synchrony[17] whereas PDC is a spectral estimate of causal connectivity including intensity and directionality.[18] We will compute PLV and PDC on the EEG time series acquired during resting prior to EH and concurrently with EH. Additionally we will compute Power Spectral Density (PSD) in all standard EEG frequency bands, including Delta, Theta, Alpha, Beta, and Gamma. Brain-to-brain connectivity measures and Gamma power (assessed separately for patients and the healer) will be contrasted between resting and active healing time points to assess change associated with the EH treatment as compared to resting control in FM patients and the healer. We expect that if energy transfer occurs between the patient and healer, a signal in EEG coherence between the two individuals may be detected. We will specifically test if this signal in the EG precedes the changes in the patient, which would be indicative of a energy transfer process during healing.

Exploratory outcomes: Heart rate variability will be assessed with ECG for both the FM patient as well as the energy healer simultaneously during treatment and resting control conditions. As mentioned above, to control for placebo effects and confounding factors FM patients will not be facing the healer during treatment. This will effectively blind the patient from the timing of the EH and rest periods. ECG will be performed using a Movesense sensor (https://www.movesense.com/) connected to a mobile device (via Bluetooth) which runs the patented electrocardiomatrix (ECM) software invented by the Borjigin lab at the University of Michigan that converts the 2D ECG data into a 3D ECM image that resembles a heatmap. The ECM image captured on the mobile device can be used as a standalone diagnostic tool for intuitive visualization of user’s cardiac conditions in real-time or post-capture. The captured ECG data can be uploaded to the ECM website (developed by Dr. Xu in the Borjigin lab) for quantitative processing (HRV and other outcomes). Finally in addition to ECG and EEG assessment, we will also measure skin temperature, galvanic skin resistance, and single hand biophoton emission during resting control period and active EH for both the healer and the FM patient.

All study procedures will be approved by the University of California, Irvine Institutional Review Board, and all data will be securely stored in locked password protected computers at the University of California, Irvine campus.

General Analysis. Comparisons between healing and control resting periods will be made for all outcomes using a paired t-Test (see above for EEG analysis). Pearson correlations will be made between change scores in brain neuroimaging outcomes, other physiologic outcomes, and changes in pain. Significant p-values are identified at p<0.05. As this is primarily a pilot mechanistic study with a single primary outcome (EEG), we will make no correction for multiple comparisons. Assessment of exploratory outcomes will be limited to hypothesis generation. Power calculation is pending and will be added later.

Ethics and Data Management. All procedures will be approved by the local University of California, Irvine Institutional Review Board. All data will be identified with a unique patient identification number, whose linked personal health information will be kept in a locked cabinet behind a locked door in the Susan Samueli Integrative Health Institute building. Data will be shared with other researchers once the primary analyses are published and all data will be archived for 7 years at the University of California, Irvine after the study is completed

4. Pilot Data (Optional)

This study has no pilot data to present. However there has been a study of one of the EH participating in this trial. These data are presented in the first citation in the references.[1] This unblinded and uncontrolled study found that of 50 reports of pain, 38 (76%) showed marked improvement. While this finding is certainly promising, there were no controls used with this study nor were the patients blinded to the treatment, two limitations we seek to address in this investigation. We also seek to find a mechanistic objective outcome that can track with pain improvement with EH.

5. Budget

The budget for this work is $250,000 in total over 18 months. This includes personnel salaries (PI 5% effort 30K, study coordinator 100% effort 100K, imaging analyst 50% effort 90K, EEG consultant 10K, and biostatistician 5K), purchasing of equipment and supplies (EEG equipment, supplies and galvanic skin resistance device 5K), travel (4K), and participant recruitment and reimbursement (6K).

6. References

1. Dufresne F, Simmons B, Vlachostergios PJ, Fleischner Z, Joudeh R, Blakeway J, Julliard K. Feasibility of energy medicine in a community teaching hospital: an exploratory case series. J Altern Complement Med. (2015) 21(6),339-49.

2. Wolfe, F., et al., The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. (1995) 38(1): p. 19-28.

3. Jacobsen, S. and S.R. Bredkjaer. The prevalence of fibromyalgia and widespread chronic musculoskeletal pain in the general population. Scand.J.Rheumatol. (1992) 21(5): p. 261-263.

4. Raspe, H., C. Baumgartner, and F. Wolfe. The prevalence of fibromyalgia in a rural German community: How much difference do different criteria make? Arthritis & Rheumatism. (1993) 36(9 (Supplement)): p. S48.

5. Wolfe, F., et al. A prospective, longitudinal, multicenter study of service utilization and costs in fibromyalgia. Arthritis Rheum (1997) 40(9): p. 1560-70.

6. Gracely, R.H., et al. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. (2002) 46(5): p. 1333-1343.

7. Harris, R.E., et al. Decreased central mu-opioid receptor availability in fibromyalgia. J.Neurosci. (2007) 27(37): p. 10000-10006.

8. Mountz, J.M., et al., Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis Rheum. (1995) 38(7): p. 926-938.

9. Kaplan CM, Schrepf A, Mawla I, Ichesco E, Boehnke KF, Beltz A, Foxen-Craft E, Puglia MP, Tsodikov A, Williams DA, Hassett AL, Clauw DJ, Harte SE, Harris RE. Neurobiological antecedents of multisite pain in children. Pain. (2022) Apr 1;163(4):e596-e603.

10. Yunus, M.B., Towards a model of pathophysiology of fibromyalgia: aberrant central pain mechanisms with peripheral modulation. J Rheumatol. (1992) 19(6): p. 846-850.

11. Clauw, D.J. and G.P. Chrousos, Chronic pain and fatigue syndromes: Overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. Neuroimmunomodulation. (1997) 4(3): p. 134-153.

12. Apkarian, A.V., M.N. Baliki, and P. Y. Geha, Towards a theory of chronic pain. Prog Neurobiol. (2009) 87(2): p. 81-97.

13. Tracey, I. and M.C. Bushnell, How neuroimaging studies have challenged us to rethink: is chronic pain a disease? The Journal of Pain. (2009) 10(11): p. 1113-20.

14. Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. (1994) Mar;23(2):129-38.

15. Clauw DJ. Fibromyalgia: a clinical review. JAMA. (2014) 311(15):1547-55.

16. Kang K, Orlandi S, Leung J, et al. Electroencephalographic interbrain synchronization in children with disabilities, their parents, and neurologic music therapists. Eur J Neurosci. Jul 2023;58(1):2367-2383. doi:10.1111/ejn.16036

17. Bastos AM, Schoffelen JM. A Tutorial Review of Functional Connectivity Analysis Methods and Their Interpretational Pitfalls. Front Syst Neurosci. 2015;9:175. doi:10.3389/fnsys.2015.00175

18. Baccala LA, Sameshima K. Partial directed coherence: a new concept in neural structure determination. Biol Cybern. Jun 2001;84(6):463-74. doi:10.1007/PL00007990

19. Joo P, Kim M, Kish B, et al. Brain network hypersensitivity underlies pain crises in sickle cell disease. Sci Rep. Mar 27 2024;14(1):7315. doi:10.1038/s41598-024-57473-5

20. Lee U, Kim M, Lee K, et al. Functional Brain Network Mechanism of Hypersensitivity in Chronic Pain. Sci Rep. Jan 10 2018;8(1):243. doi:10.1038/s41598-017-18657-4

A Anzolin, K. Isenburg, A. Grahl, J. Toppi, M. Yücel, D.M. Ellingsen, J. Gerber, A. Ciaramidaro, L. Astolfi, T.J. Kaptchuk, V. Napadow – “Patient-Clinician Brain Response During Clinical Encounter and Pain Treatment”. In 2020 42nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 306527-1610
Ellingsen DM, Isenburg K, Jung C, Lee J, Gerber J, Mawla I, Sclocco R, Jensen K, Edwards RR, Kelley JM, Kirsch I, Kaptchuk T, Napadow V. Dynamic brain to brain concordance and behavioral mirroring as a mechanism of the patient/clinician interaction. Science advances 6, no. 43 (2020): eabc1304.
Ellingsen DM, Isenburg K, Jung C, Lee J, Gerber J, Mawla I, Sclocco R, Grahl A, Anzolin A, Edwards RR, Kelley JM, Kirsch I, Kaptchuk TJ, Napadow V. Brain-to-brain mechanisms underlying pain empathy and social modulation of pain in the patient-clinician interaction. Proc Natl Acad Sci U S A. 2023 Jun 27;120(26):e2212910120. PMID: 37339198, PMCID: PMC10293846, https://doi.org/10.1073/pnas.2212910120.
Anzolin A, Das P, Garcia RG, Chen A, Grahl A, Ellis S, Purdon P, Napadow V. Delta power during sleep is modulated by EEG-gated auricular vagal afferent nerve stimulation (EAVANS). Annu Int Conf IEEE Eng Med Biol Soc. 2023 Jul;2023:1-4. 10.1109/EMBC40787.2023.10340971. PMID: 38082663.

53:T41b,Richard Harris is a Susan Samueli Endowed Chair and Professor in the Department of Anesthesiology and Perioperative Care in the School of Medicine at the University of California at Irvine. His background is in basic science and clinical research in alternative medicine. He received his B.S. degree in Genetics from Purdue University in 1992 and his Ph. D. in Molecular and Cell Biology from UC Berkeley in 1997. Following his graduate work, he completed a postdoctoral fellowship at NIH. He is a graduate of the Maryland Institute of Traditional Chinese Medicine and has received an MS degree in Clinical Research Design and Statistical Analysis at the University of Michigan. Dr. Harris is currently investigating mechanisms of chronic pain and its treatment with acupuncture and shamanism. His recent investigations have focused on the role of brain neurotransmitters and brain network behavior in chronic pain. He was a member of the National Advisory Council for NIH/NCCIH and is a current co-President for the Society for Acupuncture Research.54:T7fd1,

Energy Healing Brain Hyper Scanning in Fibromyalgia

Energy Healing Brain Hyper Scanning in Fibromyalgia

Peer Reviews

DOI