@article{Sandström2023,

title = {[11C]-PBR28 positron emission tomography signal as an imaging marker of joint inflammation in knee osteoarthritis},

author = {Angelica Sandström and Angel Torrado-Carvajal and Erin J. Morrissey and Minhae Kim and Zeynab Alshelh and Yehui Zhu and Matthew D. Li and Connie Y. Chang and Mohamed Jarraya and Oluwaseun Akeju and Andrew Schrepf and Richard E. Harris and Young-Min Kwon and Hany Bedair and Antonia F. Chen and Nathaniel D. Mercaldo and Norman Kettner and Vitaly Napadow and Nicola Toschi and Robert R. Edwards and Marco L. Loggia},

doi = {10.1097/j.pain.0000000000003114},

issn = {1872-6623},

year  = {2023},

date = {2023-11-28},

journal = {PAIN},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

abstract = {Abstract

          Although inflammation is known to play a role in knee osteoarthritis (KOA), inflammation-specific imaging is not routinely performed. In this article, we evaluate the role of joint inflammation, measured using [11C]-PBR28, a radioligand for the inflammatory marker 18-kDa translocator protein (TSPO), in KOA. Twenty-one KOA patients and 11 healthy controls (HC) underwent positron emission tomography/magnetic resonance imaging (PET/MRI) knee imaging with the TSPO ligand [11C]-PBR28. Standardized uptake values were extracted from regions-of-interest (ROIs) semiautomatically segmented from MRI data, and compared across groups (HC, KOA) and subgroups (unilateral/bilateral KOA symptoms), across knees (most vs least painful), and against clinical variables (eg, pain and Kellgren–Lawrence [KL] grades). Overall, KOA patients demonstrated elevated [11C]-PBR28 binding across all knee ROIs, compared with HC (all P's < 0.005). Specifically, PET signal was significantly elevated in both knees in patients with bilateral KOA symptoms (both P's < 0.01), and in the symptomatic knee (P < 0.05), but not the asymptomatic knee (P = 0.95) of patients with unilateral KOA symptoms. Positron emission tomography signal was higher in the most vs least painful knee (P < 0.001), and the difference in pain ratings across knees was proportional to the difference in PET signal (r = 0.74, P < 0.001). Kellgren–Lawrence grades neither correlated with PET signal (left knee r = 0.32, P = 0.19; right knee r = 0.18, P = 0.45) nor pain (r = 0.39, P = 0.07). The current results support further exploration of [11C]-PBR28 PET signal as an imaging marker candidate for KOA and a link between joint inflammation and osteoarthritis-related pain severity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Yoon2023,

title = {Graded brain fMRI response to somatic and visual acupuncture stimulation},

author = {Da-Eun Yoon and Seoyoung Lee and Jundong Kim and Kyuseok Kim and Hi-Joon Park and Vitaly Napadow and In-Seon Lee and Younbyoung Chae},

doi = {10.1093/cercor/bhad364},

issn = {1460-2199},

year  = {2023},

date = {2023-11-27},

volume = {33},

number = {23},

pages = {11269--11278},

publisher = {Oxford University Press (OUP)},

abstract = {Abstract

               Increased stimulation can enhance acupuncture clinical response; however, the impact of acupuncture stimulation as “dosage” has rarely been studied. Furthermore, acupuncture can include both somatic and visual components. We assessed both somatic and visual acupuncture dosage effects on sensory ratings and brain response. Twenty-four healthy participants received somatic (needle inserted, manually stimulated) and visual (needle video, no manual stimulation) acupuncture over the leg at three different dosage levels (control, low-dose, and high-dose) during functional magnetic resonance imaging (fMRI). Participants reported the perceived deqi sensation for each acupuncture dose level. Blood-oxygen-level dependent imaging data were analyzed by general linear model and multivariate pattern analysis. For both somatic and visual acupuncture, reported deqi sensation increased with increased dosage of acupuncture stimulation. Brain fMRI analysis demonstrated that higher dosage of somatic acupuncture produced greater brain responses in sensorimotor processing areas, including anterior and posterior insula and secondary somatosensory cortex. For visual acupuncture, higher dosage of stimulation produced greater brain responses in visual-processing areas, including the middle temporal visual areas (V5/MT+) and occipital cortex. Psychophysical and psychophysiological responses to both somatic and visual acupuncture were graded in response to higher doses. Our findings suggest that acupuncture response may be enhanced by the dosage of needling-specific and nonspecific components, represented by different neural mechanisms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lee2023,

title = {A Randomized Controlled Neuroimaging Trial of Cognitive Behavioral Therapy for Fibromyalgia Pain},

author = {Jeungchan Lee and Asimina Lazaridou and Myrella Paschali and Marco L. Loggia and Michael P. Berry and Dan‐Mikael Ellingsen and Kylie Isenburg and Alessandra Anzolin and Arvina Grahl and Ajay D. Wasan and Vitaly Napadow and Robert R. Edwards},

doi = {10.1002/art.42672},

issn = {2326-5205},

year  = {2023},

date = {2023-11-21},

journal = {Arthritis & Rheumatology},

publisher = {Wiley},

abstract = {ObjectiveFibromyalgia (FM) is characterized by pervasive pain‐related symptomatology and high levels of negative affect. Mind–body treatments such as cognitive behavioral therapy (CBT) appear to foster improvement in FM via reductions in pain‐related catastrophizing, a set of negative, pain‐amplifying cognitive and emotional processes. However, the neural underpinnings of CBT's catastrophizing‐reducing effects remain uncertain. This randomized controlled mechanistic trial was designed to assess CBT's effects on pain catastrophizing and its underlying brain circuitry.MethodsOf 114 enrolled participants, 98 underwent a baseline neuroimaging assessment and were randomized to 8 weeks of individual CBT or a matched FM education control (EDU) condition.ResultsCompared with EDU, CBT produced larger decreases in pain catastrophizing post treatment (P < 0.05) and larger reductions in pain interference and symptom impact. Decreases in pain catastrophizing played a significant role in mediating those functional improvements in the CBT group. At baseline, brain functional connectivity between the ventral posterior cingulate cortex (vPCC), a key node of the default mode network (DMN), and somatomotor and salience network regions was increased during catastrophizing thoughts. Following CBT, vPCC connectivity to somatomotor and salience network areas was reduced.ConclusionOur results suggest clinically important and CBT‐specific associations between somatosensory/motor‐ and salience‐processing brain regions and the DMN in chronic pain. These patterns of connectivity may contribute to individual differences (and treatment‐related changes) in somatic self‐awareness. CBT appears to provide clinical benefits at least partially by reducing pain‐related catastrophizing and producing adaptive alterations in DMN functional connectivity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Napadow2023,

title = {Birth of the Topological Atlas and Repository for Acupoint Research},

author = {Vitaly Napadow and Richard E. Harris and Karl G. Helmer},

doi = {10.1089/jicm.2023.0592},

issn = {2768-3613},

year  = {2023},

date = {2023-11-08},

journal = {Journal of Integrative and Complementary Medicine},

publisher = {Mary Ann Liebert Inc},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Toschi2023,

title = {Causal influence of brainstem response to transcutaneous vagus nerve stimulation on cardiovagal outflow},

author = {Nicola Toschi and Andrea Duggento and Riccardo Barbieri and Ronald G. Garcia and Harrison P. Fisher and Norman W. Kettner and Vitaly Napadow and Roberta Sclocco},

doi = {10.1016/j.brs.2023.10.007},

issn = {1935-861X},

year  = {2023},

date = {2023-11-00},

journal = {Brain Stimulation},

volume = {16},

number = {6},

pages = {1557--1565},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Weerasekera2023,

title = {Thalamic neurometabolite alterations in chronic low back pain: a common phenomenon across musculoskeletal pain conditions?},

author = {Akila Weerasekera and Paulina C. Knight and Zeynab Alshelh and Erin J. Morrissey and Minhae Kim and Yi Zhang and Vitaly Napadow and Alessandra Anzolin and Angel Torrado-Carvajal and Robert R. Edwards and Eva-Maria Ratai and Marco L. Loggia},

doi = {10.1097/j.pain.0000000000003002},

issn = {1872-6623},

year  = {2023},

date = {2023-08-11},

journal = {PAIN},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

abstract = {Abstract

          Recently, we showed that patients with knee osteoarthritis (KOA) demonstrate alterations in the thalamic concentrations of several metabolites compared with healthy controls: higher myo-inositol (mIns), lower N-acetylaspartate (NAA), and lower choline (Cho). Here, we evaluated whether these metabolite alterations are specific to KOA or could also be observed in patients with a different musculoskeletal condition, such as chronic low back pain (cLBP). Thirty-six patients with cLBP and 20 healthy controls were scanned using 1H-magnetic resonance spectroscopy (MRS) and a PRESS (Point RESolved Spectroscopy) sequence with voxel placement in the left thalamus. Compared with healthy controls, patients with cLBP demonstrated lower absolute concentrations of NAA (P = 0.0005) and Cho (P < 0.05) and higher absolute concentrations of mIns (P = 0.01) when controlling for age, as predicted by our previous work in KOA. In contrast to our KOA study, mIns levels in this population did not significantly correlate with pain measures (eg, pain severity or duration). However, exploratory analyses revealed that NAA levels in patients were negatively correlated with the severity of sleep disturbance (P < 0.01), which was higher in patients compared with healthy controls (P < 0.001). Additionally, also in patients, both Cho and mIns levels were positively correlated with age (P < 0.01 and P < 0.05, respectively). Altogether, these results suggest that thalamic metabolite changes may be common across etiologically different musculoskeletal chronic pain conditions, including cLBP and KOA, and may relate to symptoms often comorbid with chronic pain, such as sleep disturbance. The functional and clinical significance of these brain changes remains to be fully understood.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37339198,

title = {Brain-to-brain mechanisms underlying pain empathy and social modulation of pain in the patient-clinician interaction},

author = {Dan-Mikael Ellingsen and Kylie Isenburg and Changjin Jung and Jeungchan Lee and Jessica Gerber and Ishtiaq Mawla and Roberta Sclocco and Arvina Grahl and Alessandra Anzolin and Robert R Edwards and John M Kelley and Irving Kirsch and Ted J Kaptchuk and Vitaly Napadow},

doi = {10.1073/pnas.2212910120},

issn = {1091-6490},

year  = {2023},

date = {2023-06-01},

journal = {Proc Natl Acad Sci U S A},

volume = {120},

number = {26},

pages = {e2212910120},

abstract = {Social interactions such as the patient-clinician encounter can influence pain, but the underlying dynamic interbrain processes are unclear. Here, we investigated the dynamic brain processes supporting social modulation of pain by assessing simultaneous brain activity (fMRI hyperscanning) from chronic pain patients and clinicians during video-based live interaction. Patients received painful and nonpainful pressure stimuli either with a supportive clinician present (Dyadic) or in isolation (Solo). In half of the dyads, clinicians performed a clinical consultation and intake with the patient prior to hyperscanning (Clinical Interaction), which increased self-reported therapeutic alliance. For the other half, patient-clinician hyperscanning was completed without prior clinical interaction (No Interaction). Patients reported lower pain intensity in the Dyadic, relative to the Solo, condition. In Clinical Interaction dyads relative to No Interaction, patients evaluated their clinicians as better able to understand their pain, and clinicians were more accurate when estimating patients' pain levels. In Clinical Interaction dyads, compared to No Interaction, patients showed stronger activation of the dorsolateral and ventrolateral prefrontal cortex (dlPFC and vlPFC) and primary (S1) and secondary (S2) somatosensory areas (Dyadic-Solo contrast), and clinicians showed increased dynamic dlPFC concordance with patients' S2 activity during pain. Furthermore, the strength of S2-dlPFC concordance was positively correlated with self-reported therapeutic alliance. These findings support that empathy and supportive care can reduce pain intensity and shed light on the brain processes underpinning social modulation of pain in patient-clinician interactions. Our findings further suggest that clinicians' dlPFC concordance with patients' somatosensory processing during pain can be boosted by increasing therapeutic alliance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36657520,

title = {Assessing the potential anti-neuroinflammatory effect of minocycline in chronic low back pain: Protocol for a randomized, double-blind, placebo-controlled trial},

author = {Erin J Morrissey and Zeynab Alshelh and Paulina C Knight and Atreyi Saha and Minhae Kim and Angel Torrado-Carvajal and Yi Zhang and Robert R Edwards and Chelsea Pike and Joseph J Locascio and Vitaly Napadow and Marco L Loggia},

doi = {10.1016/j.cct.2023.107087},

issn = {1559-2030},

year  = {2023},

date = {2023-03-01},

journal = {Contemp Clin Trials},

volume = {126},

pages = {107087},

abstract = {INTRODUCTION: Both preclinical studies, and more recent clinical imaging studies, suggest that glia-mediated neuroinflammation may be implicated in chronic pain, and therefore might be a potential treatment target. However, it is currently unknown whether modulating neuroinflammation effectively alleviates pain in humans. This trial tests the hypothesis that minocycline, an FDA-approved tetracycline antibiotic and effective glial cell inhibitor in animals, reduces neuroinflammation and may reduce pain symptoms in humans with chronic low back pain.nnMETHODS AND ANALYSIS: This study is a randomized, double-blind, placebo-controlled clinical trial. Subjects, aged 18-75, with a confirmed diagnosis of chronic (≥ six months) low back pain (cLBP) and a self-reported pain rating of at least four out of ten (for at least half of the days during an average week) are enrolled via written, informed consent. Eligible subjects are randomized to receive a 14-day course of either active drug (minocycline) or placebo. Before and after treatment, subjects are scanned with integrated Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) using [C]PBR28, a second-generation radiotracer for the 18 kDa translocator protein (TSPO), which is highly expressed in glial cells and thus a putative marker of neuroinflammation. Pain levels are evaluated via daily surveys, collected seven days prior to the start of medication, and throughout the 14 days of treatment. General linear models will be used to assess pain levels and determine the treatment effect on brain (and spinal cord) TSPO signal.nnTRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03106740).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chae2023b,

title = {Editorial: Neural substrates of acupuncture: From peripheral to central nervous system mechanisms, volume II},

author = {Younbyoung Chae and Florian Beissner and Hee-Young Kim and Richard E. Harris and Vitaly Napadow},

doi = {10.3389/fnins.2022.1119829},

issn = {1662-453X},

year  = {2023},

date = {2023-01-19},

journal = {Front. Neurosci.},

volume = {16},

publisher = {Frontiers Media SA},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36989853,

title = {Attenuated facial movement in depressed women is associated with symptom severity, and nucleus accumbens functional connectivity},

author = {Changjin Jung and Jieun Kim and Sunyoung Choi and Young Kyung Seo and Ki-Sun Park and Youngeun Choi and Sung Min Choi and Ojin Kwon and Youngkyu Song and Jooyeon Kim and Gyunggoo Cho and Chaejoon Cheong and Vitaly Napadow and In Chul Jung and Hyungjun Kim},

doi = {10.1016/j.nicl.2023.103380},

issn = {2213-1582},

year  = {2023},

date = {2023-01-01},

journal = {Neuroimage Clin},

volume = {38},

pages = {103380},

abstract = {It is assumed that mood can be inferred from one's facial expression. While this association may prove to be an objective marker for mood disorders, few studies have explicitly evaluated this linkage. The facial movement responses of women with major depressive disorder (n = 66) and healthy controls (n = 46) under emotional stimuli were recorded using webcam. To boost facial movements, the naturalistic audio-visual stimuli were presented. To assess consistent global patterns across facial movements, scores for facial action units were extracted and projected onto principal component using principal component analysis. The associations of component for facial movements with functional brain circuitry was also investigated. Clusters of mouth movements, such as lip press and stretch, identified by principal component analysis, were attenuated in depressive patients compared to those in healthy controls. This component of facial movements was associated with depressive symptoms, and the strengths of resting brain functional connectivity between nucleus accumbens and both posterior insular cortex and thalamus. The evaluation of facial movements may prove to be a promising quantitative marker for assessing depressive symptoms and their underlying brain circuitry.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mawla2023,

title = {Large-scale momentary brain co-activation patterns are associated with hyperalgesia and mediate focal neurochemistry and cross-network functional connectivity in fibromyalgia},

author = {Ishtiaq Mawla and Zirui Huang and Chelsea M. Kaplan and Eric Ichesco and Noah Waller and Tony E. Larkin and Helge J. Zöllner and Richard A.E. Edden and Steven E. Harte and Daniel J. Clauw and George A. Mashour and Vitaly Napadow and Richard E. Harris},

doi = {10.1097/j.pain.0000000000002973},

issn = {1872-6623},

year  = {2023},

date = {2023-00-00},

journal = {PAIN},

volume = {164},

number = {12},

pages = {2737--2748},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

abstract = {Abstract

          Fibromyalgia has been characterized by augmented cross-network functional communication between the brain's sensorimotor, default mode, and attentional (salience/ventral and dorsal) networks. However, the underlying mechanisms of these aberrant communication patterns are unknown. In this study, we sought to understand large-scale topographic patterns at instantaneous timepoints, known as co-activation patterns (CAPs). We found that a sustained pressure pain challenge temporally modulated the occurrence of CAPs. Using proton magnetic resonance spectroscopy, we found that greater basal excitatory over inhibitory neurotransmitter levels within the anterior insula orchestrated higher cross-network connectivity between the anterior insula and the default mode network through lower occurrence of a CAP encompassing the attentional networks during sustained pain. Moreover, we found that hyperalgesia in fibromyalgia was mediated through increased occurrence of a CAP encompassing the sensorimotor network during sustained pain. In conclusion, this study elucidates the role of momentary large-scale topographic brain patterns in shaping noxious information in patients with fibromyalgia, while laying the groundwork for using precise spatiotemporal dynamics of the brain for the potential development of therapeutics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36308976,

title = {Increased insula response to interoceptive attention following mindfulness training is associated with increased body trusting among patients with depression},

author = {Michael Datko and Jacqueline Lutz and Richa Gawande and Alexandra Comeau and My Ngoc To and Tenzin Desel and Jenny Gan and Gaelle Desbordes and Vitaly Napadow and Zev Schuman-Olivier},

doi = {10.1016/j.pscychresns.2022.111559},

issn = {1872-7506},

year  = {2022},

date = {2022-12-01},

journal = {Psychiatry Res Neuroimaging},

volume = {327},

pages = {111559},

abstract = {Interoceptive dysfunction is often present in anxiety and depression. We investigated the effects of an 8-week intervention, Mindfulness Training for Primary Care (MTPC), on brain mechanisms of interoceptive attention among patients with anxiety and/or depression. We hypothesized that fMRI brain response to interoception in the insula, a region known for interoceptive processing, would increase following the MTPC intervention, and that such increases would be associated with post-intervention changes in self-reported measures of interoceptive awareness. Adults (n = 28) with anxiety and/or depression completed baseline and post-intervention fMRI visits, including a task in which they alternated between focusing on their heartbeat (interoception (INT)) and a control visual attention task (exteroception (EXT)). Following MTPC, we observed increased evoked fMRI response (relative to baseline) in left anterior insula during the INT-EXT task contrast (z > 3.1, p < 0.001 corrected). In patients with moderate-to-severe depression as defined by the Patient Reported Outcomes Measurement Information System (PROMIS), increased post-intervention insula response was associated with increased Body Trusting, a subscale of the Multidimensional Assessment of Interoceptive Awareness (z > 3.1, p = 0.007 corrected). This study demonstrates that patients with mood disorders may respond differentially to mindfulness-based treatment depending on depression severity, and that among those who are more depressed, increased trusting in one's own body sensations and experiencing the body as a safe place to attend to may be necessary components of positive responses to mindfulness-based interventions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35560690,

title = {Cine gastric MRI reveals altered Gut-Brain Axis in Functional Dyspepsia: gastric motility is linked with brainstem-cortical fMRI connectivity},

author = {Roberta Sclocco and Harrison Fisher and Rowan Staley and Kyungsun Han and April Mendez and Andrew Bolender and Jaume Coll-Font and Norman W Kettner and Christopher Nguyen and Braden Kuo and Vitaly Napadow},

doi = {10.1111/nmo.14396},

issn = {1365-2982},

year  = {2022},

date = {2022-10-01},

journal = {Neurogastroenterol Motil},

volume = {34},

number = {10},

pages = {e14396},

abstract = {BACKGROUND: Functional dyspepsia (FD) is a disorder of gut-brain interaction, and its putative pathophysiology involves dysregulation of gastric motility and central processing of gastric afference. The vagus nerve modulates gastric peristalsis and carries afferent sensory information to brainstem nuclei, specifically the nucleus tractus solitarii (NTS). Here, we combine MRI assessment of gastric kinematics with measures of NTS functional connectivity to the brain in patients with FD and healthy controls (HC), in order to elucidate how gut-brain axis communication is associated with FD pathophysiology.nnMETHODS: Functional dyspepsia and HC subjects experienced serial gastric MRI and brain fMRI following ingestion of a food-based contrast meal. Gastric function indices estimated from 4D cine MRI data were compared between FD and HC groups using repeated measure ANOVA models, controlling for ingested volume. Brain connectivity of the NTS was contrasted between groups and associated with gastric function indices.nnKEY RESULTS: Propagation velocity of antral peristalsis was significantly lower in FD compared to HC. The brain network defined by NTS connectivity loaded most strongly onto the Default Mode Network, and more strongly onto the Frontoparietal Network in FD. FD also demonstrated higher NTS connectivity to insula, anterior cingulate and prefrontal cortices, and pre-supplementary motor area. NTS connectivity was linked to propagation velocity in HC, but not FD, whereas peristalsis frequency was linked with NTS connectivity in patients with FD.nnCONCLUSIONS & INFERENCES: Our multi-modal MRI approach revealed lower peristaltic propagation velocity linked to altered brainstem-cortical functional connectivity in patients suffering from FD suggesting specific plasticity in gut-brain communication.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36123113,

title = {Study protocol for a phase II, double-blind, randomised controlled trial of cannabidiol (CBD) compared with placebo for reduction of brain neuroinflammation in adults with chronic low back pain},

author = {Chelsea K Pike and Minhae Kim and Kristina Schnitzer and Nathaniel Mercaldo and Robert Edwards and Vitaly Napadow and Yi Zhang and Erin Janas Morrissey and Zeynab Alshelh and A Eden Evins and Marco L Loggia and Jodi M Gilman},

doi = {10.1136/bmjopen-2022-063613},

issn = {2044-6055},

year  = {2022},

date = {2022-09-01},

journal = {BMJ Open},

volume = {12},

number = {9},

pages = {e063613},

abstract = {INTRODUCTION: Chronic pain is a debilitating medical problem that is difficult to treat. Neuroinflammatory pathways have emerged as a potential therapeutic target, as preclinical studies have demonstrated that glial cells and neuroglial interactions play a role in the establishment and maintenance of pain. Recently, we used positron emission tomography (PET) to demonstrate increased levels of 18 kDa translocator protein (TSPO) binding, a marker of glial activation, in patients with chronic low back pain (cLBP). Cannabidiol (CBD) is a glial inhibitor in animal models, but studies have not assessed whether CBD reduces neuroinflammation in humans. The principal aim of this trial is to evaluate whether CBD, compared with placebo, affects neuroinflammation, as measured by TSPO levels.nnMETHODS AND ANALYSIS: This is a double-blind, randomised, placebo-controlled, phase II clinical trial. Eighty adults (aged 18-75) with cLBP for >6 months will be randomised to either an FDA-approved CBD medication (Epidiolex) or matching placebo for 4 weeks using a dose-escalation design. All participants will undergo integrated PET/MRI at baseline and after 4 weeks of treatment to evaluate neuroinflammation using [C]PBR28, a second-generation radioligand for TSPO. Our primary hypothesis is that participants randomised to CBD will demonstrate larger reductions in thalamic [C]PBR28 signal compared with those receiving placebo. We will also assess the effect of CBD on (1) [C]PBR28 signal from limbic regions, which our prior work has linked to depressive symptoms and (2) striatal activation in response to a reward task. Additionally, we will evaluate self-report measures of cLBP intensity and bothersomeness, depression and quality of life at baseline and 4 weeks.nnETHICS AND DISSEMINATION: This protocol is approved by the Massachusetts General Brigham Human Research Committee (protocol number: 2021P002617) and FDA (IND number: 143861) and registered with ClinicalTrials.gov. Results will be published in peer-reviewed journals and presented at conferences.nnTRIAL REGISTRATION NUMBER: NCT05066308; ClinicalTrials.gov.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35148407,

title = {The Effects of Combined Respiratory-Gated Auricular Vagal Afferent Nerve Stimulation and Mindfulness Meditation for Chronic Low Back Pain: A Pilot Study},

author = {Samantha M Meints and Ronald G Garcia and Zev Schuman-Olivier and Michael Datko and Gaelle Desbordes and Marise Cornelius and Robert R Edwards and Vitaly Napadow},

doi = {10.1093/pm/pnac025},

issn = {1526-4637},

year  = {2022},

date = {2022-08-01},

journal = {Pain Med},

volume = {23},

number = {9},

pages = {1570--1581},

abstract = {OBJECTIVE: Respiratory-gated Auricular Vagal Afferent Nerve stimulation (RAVANS) is a safe nonpharmacological approach to managing chronic pain. The purpose of the current study was to examine (1) the feasibility and acceptability of RAVANS, combined with mindful meditation (MM) for chronic low back pain (CLBP), (2) the potential synergy of MM+RAVANS on improving pain, and (3) possible moderators of the influence of MM+RAVANS on pain.nnDESIGN: Pilot feasibility and acceptability study.nnSETTING: Pain management center at large academic medical center.nnSUBJECTS: Nineteen adults with CLBP and previous MM training.nnMETHODS: Participants attended two sessions during which they completed quantitative sensory testing (QST), rated pain severity, and completed a MM+stimulation session. Participants received RAVANS during one visit and sham stimulation during the other, randomized in order. Following intervention, participants repeated QST.nnRESULTS: MM+RAVANS was well tolerated, acceptable, and feasible to provide relief for CLBP. Both MM+stimulation sessions resulted in improved back pain severity, punctate pain ratings, and pressure pain threshold. Individuals with greater negative affect showed greater back pain improvement from MM+RAVANS while those with greater mindfulness showed greater back pain improvement from MM+sham.nnCONCLUSIONS: Results suggest that for CLBP patients with prior MM training, the analgesic effects of MM may have overshadowed effects of RAVANS given the brief single session MM+RAVANS intervention. However, those with greater negative affect may benefit from combined MM+RAVANS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zhou2022,

title = {Challenges and Perspectives of Mapping Locus Coeruleus Activity in the Rodent with High-Resolution fMRI},

author = {Xiaoqing Alice Zhou and Yuanyuan Jiang and Vitaly Napadow and Xin Yu},

doi = {10.3390/brainsci12081085},

issn = {2076-3425},

year  = {2022},

date = {2022-08-00},

journal = {Brain Sciences},

volume = {12},

number = {8},

publisher = {MDPI AG},

abstract = {The locus coeruleus (LC) is one of the most commonly studied brainstem nuclei when investigating brain–behavior associations. The LC serves as a major brainstem relay for both ascending bottom-up and descending top-down projections. Specifically, noradrenergic (NA) LC neurons not only connect globally to higher-order subcortical nuclei and cortex to mediate arousal and attention but also directly project to other brainstem nuclei and to the spinal cord to control autonomic function. Despite the extensive investigation of LC function using electrophysiological recordings and cellular/molecular imaging for both cognitive research and the contribution of LC to different pathological states, the role of neuroimaging to investigate LC function has been restricted. For instance, it remains challenging to identify LC-specific activation with functional MRI (fMRI) in animal models, due to the small size of this nucleus. Here, we discuss the complexity of fMRI applications toward LC activity mapping in mouse brains by highlighting the technological challenges. Further, we introduce a single-vessel fMRI mapping approach to elucidate the vascular specificity of high-resolution fMRI signals coupled to LC activation in the mouse brainstem.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35475679,

title = {Skin Temperature of Acupoints in Health and Disease: A Systematic Review},

author = {EunMee Yang and Weidong Lu and Dennis Muñoz-Vergara and Esme Goldfinger and Ted J Kaptchuk and Vitaly Napadow and Andrew C Ahn and Peter M Wayne},

doi = {10.1089/jicm.2021.0437},

issn = {2768-3613},

year  = {2022},

date = {2022-07-01},

journal = {J Integr Complement Med},

volume = {28},

number = {7},

pages = {552--568},

abstract = { Despite substantial progress made in the field of acupuncture research, the existence and specificity of acupoints remain controversial. In recent years, the concept of acupoint sensitization has emerged as a theoretical framework for understanding acupoints as dynamic functional entities that are sensitized in pathological conditions. Based on this premise, some have claimed that specific acupoints are thermally distinct between healthy and clinical populations, but no systematic review has been conducted to synthesize and evaluate the quality of studies supporting such claims. In this review, we provide a summary and quality assessment of the existing literature addressing the question of whether changes in skin temperature at specific acupoints are indicative of pathological conditions.  A systematic literature search was performed in PubMed, EMBASE, and AltHealthWatch (EBSCO Host), by combining variations of search terms relevant to acupoints and temperature. The search was limited to the English language, and publication dates ranged from database inception to December 2020. Two authors independently screened all resulting abstracts and subsequently read full-text articles for eligibility. Information on study design, sample, acupoints, parameters of skin temperature assessments, and main findings were extracted from included studies. Quality of the thermal sensing methodology was evaluated using a thermal assessment checklist, adapted from the Thermographic Imaging in Sports and Exercise Medicine (TISEM) consensus checklist, and a modified Newcastle-Ottawa Scale (NOS) for case-control studies.  The search strategy yielded a total of 1771 studies, of which 10 articles met the eligibility criteria. Eight studies compared skin temperature at acupoints in healthy versus clinical populations, and two studies assessed within-subject changes in temperature of acupoints in relation to changes in health status. There were seven clinical conditions examined in the included studies: chronic bronchial asthma, chronic hepatitis, hyperplasia of mammary glands, infertility, intracranial hypertension, obesity, and primary dysmenorrhea. There were numerous methodological quality issues related to skin temperature measurements. Eight studies with case-control designs reported significant differences between healthy and clinical populations in temperature at certain acupoints. Two studies with pre-post designs reported that changes in health-disease status could be associated with changes in temperature at specific acupoints.  A review of the available literature suggests that certain acupoints may be thermally distinct between healthy and unhealthy states. However, given the methodological limitations and heterogeneity across included studies, no definitive conclusion could be drawn as to whether changes in skin temperature at specific acupoints are indicative of pathological conditions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35773702,

title = {The impact of COVID-19 pandemic on mental and physical wellbeing in women with fibromyalgia: a longitudinal mixed-methods study},

author = {Asimina Lazaridou and Myrella Paschali and Eric S Vilsmark and Timothy Wilkins and Vitaly Napadow and Robert Edwards},

doi = {10.1186/s12905-022-01840-9},

issn = {1472-6874},

year  = {2022},

date = {2022-06-01},

journal = {BMC Womens Health},

volume = {22},

number = {1},

pages = {267},

abstract = {OBJECTIVE: The COVID-19 pandemic has strongly influenced psychological and physical health worldwide. The aim of this study was to examine the impact of the pandemic on women with fibromyalgia.nnMETHODS: This mixed methods pilot study explored measures of pain severity and interference, as well as pain catastrophizing and level of fibromyalgia impact among women with fibromyalgia before and during the COVID-19 pandemic in the USA. Fibromyalgia patients completed demographic, pain-related, and other validated psychosocial questionnaires prior to the onset of the COVID-19 pandemic, and then were re-assessed with those questionnaires, as well as a pandemic-related questionnaire assessing the impact of the pandemic on the patients' life, during the pandemic.nnRESULTS: When comparing data reported before the pandemic to data collected 3-6 months into the pandemic, women with fibromyalgia reported a general worsening of their pain and pain-related symptoms. During the pandemic, pain catastrophizing (p ≤ 0.05) and fibromyalgia impact (p ≤ 0.05) increased significantly compared to before the pandemic. The increase in pain catastrophizing scores was highly correlated with the impact of the pandemic on the participants' ability to cope with pain and on their mental health. Qualitative analysis corroborated the significant impact of the pandemic on patients' mental health, with the vast majority reporting a worsening of their mood. Other impacted domains included anxiety, level of activity and sleep.nnCONCLUSIONS: Collectively, the pandemic appears to have produced a substantive worsening of pain-related symptomatology among women with fibromyalgia, which should be addressed by targeted interventions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35366813,

title = {Comparison of test-retest reliability of BOLD and pCASL fMRI in a two-center study},

author = {James W Ibinson and Andrea G Gillman and Vince Schmidthorst and Conrad Li and Vitaly Napadow and Marco L Loggia and Ajay D Wasan},

doi = {10.1186/s12880-022-00791-9},

issn = {1471-2342},

year  = {2022},

date = {2022-04-01},

journal = {BMC Med Imaging},

volume = {22},

number = {1},

pages = {62},

abstract = {BACKGROUND: The establishment of test-retest reliability and reproducibility (TRR) is an important part of validating any research tool, including functional magnetic resonance imaging (fMRI). The primary objective of this study is to investigate the reliability of pseudo-Continuous Arterial Spin Labeling (pCASL) and Blood Oxygen Level Dependent (BOLD) fMRI data acquired across two different scanners in a sample of healthy adults. While single site/single scanner studies have shown acceptable repeatability, TRR of both in a practical multisite study occurring in two facilities spread out across the country with weeks to months between scans is critically needed.nnMETHODS: Ten subjects were imaged with similar 3 T MRI scanners at the University of Pittsburgh and Massachusetts General Hospital. Finger-tapping and Resting-state data were acquired for both techniques. Analysis of the resting state data for functional connectivity was performed with the Functional Connectivity Toolbox, while analysis of the finger tapping data was accomplished with FSL. pCASL Blood flow data was generated using AST Toolbox. Activated areas and networks were identified via pre-defined atlases and dual-regression techniques. Analysis for TRR was conducted by comparing pCASL and BOLD images in terms of Intraclass correlation coefficients, Dice Similarity Coefficients, and repeated measures ANOVA.nnRESULTS: Both BOLD and pCASL scans showed strong activation and correlation between the two locations for the finger tapping tasks. Functional connectivity analyses identified elements of the default mode network in all resting scans at both locations. Multivariate repeated measures ANOVA showed significant variability between subjects, but no significant variability for location. Global CBF was very similar between the two scanning locations, and repeated measures ANOVA showed no significant differences between the two scanning locations.nnCONCLUSIONS: The results of this study show that when similar scanner hardware and software is coupled with identical data analysis protocols, consistent and reproducible functional brain images can be acquired across sites. The variability seen in the activation maps is greater for pCASL versus BOLD images, as expected, however groups maps are remarkably similar despite the low number of subjects. This demonstrates that multi-site fMRI studies of task-based and resting state brain activity is feasible.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36570845,

title = {Optimization of respiratory-gated auricular vagus afferent nerve stimulation for the modulation of blood pressure in hypertension},

author = {Ronald G Garcia and Rachel Staley and Sarah Aroner and Jessica Stowell and Roberta Sclocco and Vitaly Napadow and Riccardo Barbieri and Jill M Goldstein},

doi = {10.3389/fnins.2022.1038339},

issn = {1662-4548},

year  = {2022},

date = {2022-01-01},

journal = {Front Neurosci},

volume = {16},

pages = {1038339},

abstract = {BACKGROUND: The objective of this pilot study was to identify frequency-dependent effects of respiratory-gated auricular vagus afferent nerve stimulation (RAVANS) on the regulation of blood pressure and heart rate variability in hypertensive subjects and examine potential differential effects by sex/gender or race.nnMETHODS: Twenty hypertensive subjects (54.55 ± 6.23 years of age; 12 females and 8 males) were included in a within-person experimental design and underwent five stimulation sessions where they received RAVANS at different frequencies (i.e., 2 Hz, 10 Hz, 25 Hz, 100 Hz, or sham stimulation) in a randomized order. EKG and continuous blood pressure signals were collected during a 10-min baseline, 30-min stimulation, and 10-min post-stimulation periods. Generalized estimating equations (GEE) adjusted for baseline measures were used to evaluate frequency-dependent effects of RAVANS on heart rate, high frequency power, and blood pressure measures, including analyses stratified by sex and race.nnRESULTS: Administration of RAVANS at 100 Hz had significant overall effects on the reduction of heart rate (β = -2.03,  = 0.002). It was also associated with a significant reduction of diastolic (β = -1.90,  = 0.01) and mean arterial blood pressure (β = -2.23,  = 0.002) in Black hypertensive participants and heart rate in female subjects (β = -2.83,  = 0.01) during the post-stimulation period when compared to sham.nnCONCLUSION: Respiratory-gated auricular vagus afferent nerve stimulation exhibits frequency-dependent rapid effects on the modulation of heart rate and blood pressure in hypertensive patients that may further differ by race and sex. Our findings highlight the need for the development of optimized stimulation protocols that achieve the greatest effects on the modulation of physiological and clinical outcomes in this population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36382222,

title = {Correcting cardiorespiratory noise in resting-state functional MRI data acquired in critically ill patients},

author = {Suk-Tak Chan and William R Sanders and David Fischer and John E Kirsch and Vitaly Napadow and Yelena G Bodien and Brian L Edlow},

doi = {10.1093/braincomms/fcac280},

issn = {2632-1297},

year  = {2022},

date = {2022-01-01},

journal = {Brain Commun},

volume = {4},

number = {6},

pages = {fcac280},

abstract = {Resting-state functional MRI is being used to develop diagnostic, prognostic and therapeutic biomarkers for critically ill patients with severe brain injuries. In studies of healthy volunteers and non-critically ill patients, prospective cardiorespiratory data are routinely collected to remove non-neuronal fluctuations in the resting-state functional MRI signal during analysis. However, the feasibility and utility of collecting cardiorespiratory data in critically ill patients on a clinical MRI scanner are unknown. We concurrently acquired resting-state functional MRI (repetition time = 1250 ms) and cardiac and respiratory data in 23 critically ill patients with acute severe traumatic brain injury and in 12 healthy control subjects. We compared the functional connectivity results from two approaches that are commonly used to correct cardiorespiratory noise: (i) denoising with cardiorespiratory data (i.e. image-based method for retrospective correction of physiological motion effects in functional MRI) and (ii) standard bandpass filtering. Resting-state functional MRI data in 7 patients could not be analysed due to imaging artefacts. In 6 of the remaining 16 patients (37.5%), cardiorespiratory data were either incomplete or corrupted. In patients ( = 10) and control subjects ( = 10), the functional connectivity results corrected with the image-based method for retrospective correction of physiological motion effects in functional MRI did not significantly differ from those corrected with bandpass filtering of 0.008-0.125 Hz. Collectively, these findings suggest that, in critically ill patients with severe traumatic brain injury, there is limited feasibility and utility to denoising the resting-state functional MRI signal with prospectively acquired cardiorespiratory data.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35733704,

title = {Percutaneous electric nerve field stimulation alters cortical thickness in a pilot study of veterans with fibromyalgia},

author = {Anna Woodbury and Lisa C Krishnamurthy and Anastasia Bohsali and Venkatagiri Krishnamurthy and Jeremy L Smith and Melat Gebre and Kari Tyler and Mark Vernon and Bruce Crosson and Jerry P Kalangara and Vitaly Napadow and Jason W Allen and Daniel Harper},

doi = {10.1016/j.ynpai.2022.100093},

issn = {2452-073X},

year  = {2022},

date = {2022-01-01},

journal = {Neurobiol Pain},

volume = {12},

pages = {100093},

abstract = {OBJECTIVE: To evaluate changes in cortical thickness and right posterior insula (r-pIns) gamma-aminobutyric acid (GABA) concentrations in veterans with fibromyalgia treated with auricular percutaneous electric nerve field stimulation (PENFS).nnMATERIALS & METHODS: This was a randomized, controlled, open label investigation conducted in a government hospital. Twenty-one veterans with fibromyalgia were randomized to receive either standard therapy (ST; i.e., 4 weekly visits with a pain practitioner) or ST with auricular PENFS (ST + PENFS). Neuroimaging data was collected at baseline (i.e. before the first treatment session) and again within 2 weeks post-treatment.​ Clinical pain and physical function were also assessed at these timepoints. Single-voxel magnetic resonance spectroscopy was carried out in r-pIns to assess changes in r-pIns GABA concentrations and high-resolution T1-weighted images were collected to assess changes in regional gray matter volume using cortical thickness.nnRESULTS: Both the ST + PENFS and ST groups reported a decrease in pain with treatment.  Cortical thickness significantly decreased in the left middle posterior cingulate (p = 0.018) and increased in the left cuneus (p = 0.014) following ST + PENFS treatment. These findings were significant following FDR correction for multiple comparisons. ST group right hemisphere insula cortical thickness increased post-treatment and was significantly (p = 0.02) inversely correlated with pain scores. ST + PENFS group right hemisphere posterior dorsal cingulate size significantly (p = 0.044) positively correlated with pain scores. : There were no significant correlations with GABA, though a trend was noted towards increased GABA following treatment in both groups (p = 0.083) using a linear mixed effects model.nnCONCLUSIONS: Results suggest a novel effect of PENFS reflected by differential volumetric changes compared to ST. The changes in GABA that occur in both groups are more likely related to ST. Insular GABA and cortical thickness in key regions of interest may be developed as potential biomarkers for evaluating chronic pain pathology and treatment outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35091536,

title = {Patient-clinician brain concordance underlies causal dynamics in nonverbal communication and negative affective expressivity},

author = {Dan-Mikael Ellingsen and Andrea Duggento and Kylie Isenburg and Changjin Jung and Jeungchan Lee and Jessica Gerber and Ishtiaq Mawla and Roberta Sclocco and Robert R Edwards and John M Kelley and Irving Kirsch and Ted J Kaptchuk and Nicola Toschi and Vitaly Napadow},

doi = {10.1038/s41398-022-01810-7},

issn = {2158-3188},

year  = {2022},

date = {2022-01-01},

journal = {Transl Psychiatry},

volume = {12},

number = {1},

pages = {44},

abstract = {Patient-clinician concordance in behavior and brain activity has been proposed as a potential key mediator of mutual empathy and clinical rapport in the therapeutic encounter. However, the specific elements of patient-clinician communication that may support brain-to-brain concordance and therapeutic alliance are unknown. Here, we investigated how pain-related, directional facial communication between patients and clinicians is associated with brain-to-brain concordance. Patient-clinician dyads interacted in a pain-treatment context, during synchronous assessment of brain activity (fMRI hyperscanning) and online video transfer, enabling face-to-face social interaction. In-scanner videos were used for automated individual facial action unit (AU) time-series extraction. First, an interpretable machine-learning classifier of patients' facial expressions, from an independent fMRI experiment, significantly distinguished moderately painful leg pressure from innocuous pressure stimuli. Next, we estimated neural-network causality of patient-to-clinician directional information flow of facial expressions during clinician-initiated treatment of patients' evoked pain. We identified a leader-follower relationship in which patients predominantly led the facial communication while clinicians responded to patients' expressions. Finally, analyses of dynamic brain-to-brain concordance showed that patients' mid/posterior insular concordance with the clinicians' anterior insula cortex, a region identified in previously published data from this study, was associated with therapeutic alliance, and self-reported and objective (patient-to-clinician-directed causal influence) markers of negative-affect expressivity. These results suggest a role of patient-clinician concordance of the insula, a social-mirroring and salience-processing brain node, in mediating directional dynamics of pain-directed facial communication during therapeutic encounters.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Citkovitz2021,

title = {Turning Point: A Review of Key Research and Engagement in 2021},

author = {Claudia Citkovitz and Lisa Jean Taylor-Swanson and Robert Davis and Richard E. Harris and Benjamin Kligler and Jiang-Ti Kong and Lixing Lao and Jun Mao and Ari Ojeda Ocampo Moré and Vitaly Napadow and Lee Hullender Rubin and Rosa Schnyer and Peter D. Wayne and Claudia M. Witt},

doi = {10.1089/acm.2021.0374},

issn = {1557-7708},

year  = {2021},

date = {2021-12-01},

journal = {The Journal of Alternative and Complementary Medicine},

volume = {27},

number = {12},

pages = {1018--1022},

publisher = {Mary Ann Liebert Inc},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lee2021,

title = {3D magnetic resonance spectroscopic imaging reveals links between brain metabolites and multidimensional pain features in fibromyalgia},

author = {Jeungchan Lee and Ovidiu C. Andronesi and Angel Torrado‐Carvajal and Eva‐Maria Ratai and Marco L. Loggia and Akila Weerasekera and Michael P. Berry and Dan‐Mikael Ellingsen and Laura Isaro and Asimina Lazaridou and Myrella Paschali and Arvina Grahl and Ajay D. Wasan and Robert R. Edwards and Vitaly Napadow},

doi = {10.1002/ejp.1820},

issn = {1532-2149},

year  = {2021},

date = {2021-10-00},

journal = {European Journal of Pain},

volume = {25},

number = {9},

pages = {2050--2064},

publisher = {Wiley},

abstract = {AbstractBackgroundFibromyalgia is a centralized multidimensional chronic pain syndrome, but its pathophysiology is not fully understood.MethodsWe applied 3D magnetic resonance spectroscopic imaging (MRSI), covering multiple cortical and subcortical brain regions, to investigate the association between neuro‐metabolite (e.g. combined glutamate and glutamine, Glx; myo‐inositol, mIno; and combined (total) N‐acetylaspartate and N‐acetylaspartylglutamate, tNAA) levels and multidimensional clinical/behavioural variables (e.g. pain catastrophizing, clinical pain severity and evoked pain sensitivity) in women with fibromyalgia (N = 87).ResultsPain catastrophizing scores were positively correlated with Glx and tNAA levels in insular cortex, and negatively correlated with mIno levels in posterior cingulate cortex (PCC). Clinical pain severity was positively correlated with Glx levels in insula and PCC, and with tNAA levels in anterior midcingulate cortex (aMCC), but negatively correlated with mIno levels in aMCC and thalamus. Evoked pain sensitivity was negatively correlated with levels of tNAA in insular cortex, MCC, PCC and thalamus.ConclusionsThese findings support single voxel placement targeting nociceptive processing areas in prior 1H‐MRS studies, but also highlight other areas not as commonly targeted, such as PCC, as important for chronic pain pathophysiology. Identifying target brain regions linked to multidimensional symptoms of fibromyalgia (e.g. negative cognitive/affective response to pain, clinical pain, evoked pain sensitivity) may aid the development of neuromodulatory and individualized therapies. Furthermore, efficient multi‐region sampling with 3D MRSI could reduce the burden of lengthy scan time for clinical research applications of molecular brain‐based mechanisms supporting multidimensional aspects of fibromyalgia.SignificanceThis large N study linked brain metabolites and pain features in fibromyalgia patients, with a better spatial resolution and brain coverage, to understand a molecular mechanism underlying pain catastrophizing and other aspects of pain transmission. Metabolite levels in self‐referential cognitive processing area as well as pain‐processing regions were associated with pain outcomes. These results could help the understanding of its pathophysiology and treatment strategies for clinicians.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sclocco2021,

title = {Non‐uniform gastric wall kinematics revealed by 4D Cine magnetic resonance imaging in humans},

author = {Roberta Sclocco and Christopher Nguyen and Rowan Staley and Harrison Fisher and April Mendez and Christopher Velez and Norman W. Kettner and Braden Kuo and Vitaly Napadow},

doi = {10.1111/nmo.14146},

issn = {1365-2982},

year  = {2021},

date = {2021-08-00},

journal = {Neurogastroenterology Motil},

volume = {33},

number = {8},

publisher = {Wiley},

abstract = {AbstractBackgroundAssessment of gastric function in humans has relied on modalities with varying degrees of invasiveness, which are usually limited to the evaluation of single aspects of gastric function, thus requiring patients to undergo a number of often invasive tests for a full clinical understanding. Therefore, the development of a non‐invasive tool able to concurrently assess multiple aspects of gastric function is highly desirable for both research and clinical assessments of gastrointestinal (GI) function. Recently, technological advances in magnetic resonance imaging (MRI) have provided new tools for dynamic (or “cine”) body imaging. Such approaches can be extended to GI applications.MethodsIn the present work, we propose a non‐invasive assessment of gastric function using a four‐dimensional (4D, volumetric cine imaging), free‐breathing MRI sequence with gadolinium‐free contrast enhancement achieved through a food‐based meal. In healthy subjects, we successfully estimated multiple parameters describing gastric emptying, motility, and peristalsis propagation patterns.Key ResultsOur data demonstrated non‐uniform kinematics of the gastric wall during peristaltic contraction, highlighting the importance of using volumetric data to derive motility measures.Conclusions & InferencesMRI has the potential of becoming an important clinical and gastric physiology research tool, providing objective parameters for the evaluation of impaired gastric function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mawla2021,

title = {Greater Somatosensory Afference With Acupuncture Increases Primary Somatosensory Connectivity and Alleviates Fibromyalgia Pain via Insular γ‐Aminobutyric Acid: A Randomized Neuroimaging Trial},

author = {Ishtiaq Mawla and Eric Ichesco and Helge J. Zöllner and Richard A. E. Edden and Thomas Chenevert and Henry Buchtel and Meagan D. Bretz and Heather Sloan and Chelsea M. Kaplan and Steven E. Harte and George A. Mashour and Daniel J. Clauw and Vitaly Napadow and Richard E. Harris},

doi = {10.1002/art.41620},

issn = {2326-5205},

year  = {2021},

date = {2021-07-00},

journal = {Arthritis & Rheumatology},

volume = {73},

number = {7},

pages = {1318--1328},

publisher = {Wiley},

abstract = {ObjectiveAcupuncture is a complex multicomponent treatment that has shown promise in the treatment of fibromyalgia (FM). However, clinical trials have shown mixed results, possibly due to heterogeneous methodology and lack of understanding of the underlying mechanism of action. The present study was undertaken to understand the specific contribution of somatosensory afference to improvements in clinical pain, and the specific brain circuits involved.MethodsSeventy‐six patients with FM were randomized to receive either electroacupuncture (EA), with somatosensory afference, or mock laser acupuncture (ML), with no somatosensory afference, twice a week over 8 treatments. Patients with FM in each treatment group were assessed for pain severity levels, measured using Brief Pain Inventory (BPI) scores, and for levels of functional brain network connectivity, assessed using resting state functional magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy in the right anterior insula, before and after treatment.ResultsFibromyalgia patients who received EA therapy experienced a greater reduction in pain severity, as measured by the BPI, compared to patients who received ML therapy (mean difference in BPI from pre‐ to posttreatment was −1.14 in the EA group versus −0.46 in the ML group; P for group × time interaction = 0.036). Participants receiving EA treatment, as compared to ML treatment, also exhibited resting functional connectivity between the primary somatosensory cortical representation of the leg (S1leg; i.e. primary somatosensory subregion activated by EA) and the anterior insula. Increased S1leg–anterior insula connectivity was associated with both reduced levels of pain severity as measured by the BPI (r = −0.44, P = 0.01) and increased levels of γ‐aminobutyric acid (GABA+) in the anterior insula (r = 0.48, P = 0.046) following EA therapy. Moreover, increased levels of GABA+ in the anterior insula were associated with reduced levels of pain severity as measured by the BPI (r = −0.59, P = 0.01). Finally, post–EA treatment changes in levels of GABA+ in the anterior insula mediated the relationship between changes in S1leg–anterior insula connectivity and pain severity on the BPI (bootstrap confidence interval −0.533, −0.037).ConclusionThe somatosensory component of acupuncture modulates primary somatosensory functional connectivity associated with insular neurochemistry to reduce pain severity in FM.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Farmer2021,

title = {International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020)},

author = {Adam D. Farmer and Adam Strzelczyk and Alessandra Finisguerra and Alexander V. Gourine and Alireza Gharabaghi and Alkomiet Hasan and Andreas M. Burger and Andrés M. Jaramillo and Ann Mertens and Arshad Majid and Bart Verkuil and Bashar W. Badran and Carlos Ventura-Bort and Charly Gaul and Christian Beste and Christopher M. Warren and Daniel S. Quintana and Dorothea Hämmerer and Elena Freri and Eleni Frangos and Eleonora Tobaldini and Eugenijus Kaniusas and Felix Rosenow and Fioravante Capone and Fivos Panetsos and Gareth L. Ackland and Gaurav Kaithwas and Georgia H. O'Leary and Hannah Genheimer and Heidi I. L. Jacobs and Ilse Van Diest and Jean Schoenen and Jessica Redgrave and Jiliang Fang and Jim Deuchars and Jozsef C. Széles and Julian F. Thayer and Kaushik More and Kristl Vonck and Laura Steenbergen and Lauro C. Vianna and Lisa M. McTeague and Mareike Ludwig and Maria G. Veldhuizen and Marijke De Couck and Marina Casazza and Marius Keute and Marom Bikson and Marta Andreatta and Martina D'Agostini and Mathias Weymar and Matthew Betts and Matthias Prigge and Michael Kaess and Michael Roden and Michelle Thai and Nathaniel M. Schuster and Nicola Montano and Niels Hansen and Nils B. Kroemer and Peijing Rong and Rico Fischer and Robert H. Howland and Roberta Sclocco and Roberta Sellaro and Ronald G. Garcia and Sebastian Bauer and Sofiya Gancheva and Stavros Stavrakis and Stefan Kampusch and Susan A. Deuchars and Sven Wehner and Sylvain Laborde and Taras Usichenko and Thomas Polak and Tino Zaehle and Uirassu Borges and Vanessa Teckentrup and Vera K. Jandackova and Vitaly Napadow and Julian Koenig},

doi = {10.3389/fnhum.2020.568051},

issn = {1662-5161},

year  = {2021},

date = {2021-03-23},

journal = {Front. Hum. Neurosci.},

volume = {14},

publisher = {Frontiers Media SA},

abstract = {Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Moré2021,

title = {Acupuncture Research in Animal Models: Rationale, Needling Methods and the Urgent Need for a Standards for Reporting Interventions in Clinical Trials of Acupuncture–Standards for Reporting Interventions in Acupuncture Using Animal Models Adaptation},

author = {Ari Ojeda Ocampo Moré and Richard E. Harris and Vitaly Napadow and Lisa Taylor-Swanson and Peter M. Wayne and Claudia M. Witt and Lixing Lao},

doi = {10.1089/acm.2021.0076},

issn = {1557-7708},

year  = {2021},

date = {2021-03-01},

journal = {The Journal of Alternative and Complementary Medicine},

volume = {27},

number = {3},

pages = {193--197},

publisher = {Mary Ann Liebert Inc},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34777225,

title = {S1 Brain Connectivity in Carpal Tunnel Syndrome Underlies Median Nerve and Functional Improvement Following Electro-Acupuncture},

author = {Harrison Fisher and Roberta Sclocco and Yumi Maeda and Jieun Kim and Cristina Malatesta and Jessica Gerber and Joseph Audette and Norman Kettner and Vitaly Napadow},

doi = {10.3389/fneur.2021.754670},

issn = {1664-2295},

year  = {2021},

date = {2021-01-01},

journal = {Front Neurol},

volume = {12},

pages = {754670},

abstract = {Carpal Tunnel Syndrome (CTS) is a median nerve entrapment neuropathy that alters primary somatosensory cortex (S1) organization. While electro-acupuncture (EA), a form of peripheral neuromodulation, has been shown to improve clinical and neurophysiological CTS outcomes, the role of EA-evoked brain response during therapy (within and beyond S1) for improved outcomes is unknown. We investigated S1-associated whole brain fMRI connectivity during both a resting and sustained EA stimulation state in age-matched healthy controls ( = 28) and CTS patients ( = 64), at baseline and after 8 weeks of acupuncture therapy (local, distal, or sham EA). Compared to healthy controls, CTS patients at baseline showed decreased resting state functional connectivity between S1 and thalamic pulvinar nucleus. Increases in S1/pulvinar connectivity strength following verum EA therapy (combined local and distal) were correlated with improvements in median nerve velocity ( = 0.38,  = 0.035). During sustained local EA, compared to healthy controls, CTS patients demonstrated increased functional connectivity between S1 and anterior hippocampus (aHipp). Following 8 weeks of local EA therapy, S1/aHipp connectivity significantly decreased and greater decrease was associated with improvement in patients' functional status ( = 0.64,  = 0.01) and increased median nerve velocity ( = -0.62,  = 0.013). Thus, connectivity between S1 and other brain areas is also disrupted in CTS patients and may be improved following EA therapy. Furthermore, stimulus-evoked fMRI connectivity adds therapy-specific, mechanistic insight to more common resting state connectivity approaches. Specifically, local EA modulates S1 connectivity to sensory and affective processing regions, linked to patient function and median nerve health.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Weng2021,

title = {Interventions and Manipulations of Interoception},

author = {Helen Y. Weng and Jack L. Feldman and Lorenzo Leggio and Vitaly Napadow and Jeanie Park and Cynthia J. Price},

doi = {10.1016/j.tins.2020.09.010},

issn = {0166-2236},

year  = {2021},

date = {2021-01-00},

journal = {Trends in Neurosciences},

volume = {44},

number = {1},

pages = {52--62},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ellingsen2020b,

title = {A picture is worth a thousand words: linking fibromyalgia pain widespreadness from digital pain drawings with pain catastrophizing and brain cross-network connectivity},

author = {Dan-Mikael Ellingsen and Florian Beissner and Tawfik Moher Alsady and Asimina Lazaridou and Myrella Paschali and Michael Berry and Laura Isaro and Arvina Grahl and Jeungchan Lee and Ajay D. Wasan and Robert R. Edwards and Vitaly Napadow},

doi = {10.1097/j.pain.0000000000002134},

issn = {1872-6623},

year  = {2021},

date = {2021-00-00},

journal = {PAIN},

volume = {162},

number = {5},

pages = {1352--1363},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

abstract = {Abstract

          Pain catastrophizing is prominent in chronic pain conditions such as fibromyalgia and has been proposed to contribute to the development of pain widespreadness. However, the brain mechanisms responsible for this association are unknown. We hypothesized that increased resting salience network (SLN) connectivity to nodes of the default mode network (DMN), representing previously reported pain-linked cross-network enmeshment, would be associated with increased pain catastrophizing and widespreadness across body sites. We applied functional magnetic resonance imaging (fMRI) and digital pain drawings (free-hand drawing over a body outline, analyzed using conventional software for multivoxel fMRI analysis) to investigate precisely quantified measures of pain widespreadness and the associations between pain catastrophizing (Pain Catastrophizing Scale), resting brain network connectivity (Dual-regression Independent Component Analysis, 6-minute multiband accelerated fMRI), and pain widespreadness in fibromyalgia patients (N = 79). Fibromyalgia patients reported pain in multiple body areas (most frequently the spinal region, from the lower back to the neck), with moderately high pain widespreadness (mean ± SD: 26.1 ± 24.1% of total body area), and high pain catastrophizing scale scores (27.0 ± 21.9, scale range: 0-52), which were positively correlated (r = 0.26, P = 0.02). A whole-brain regression analysis focused on SLN connectivity indicated that pain widespreadness was also positively associated with SLN connectivity to the posterior cingulate cortex, a key node of the DMN. Moreover, we found that SLN-posterior cingulate cortex connectivity statistically mediated the association between pain catastrophizing and pain widespreadness (P = 0.01). In conclusion, we identified a putative brain mechanism underpinning the association between greater pain catastrophizing and a larger spatial extent of body pain in fibromyalgia, implicating a role for brain SLN-DMN cross-network enmeshment in mediating this association.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Napadow2020b,

title = {Neuroimaging Somatosensory and Therapeutic Alliance Mechanisms Supporting Acupuncture},

author = {Vitaly Napadow},

doi = {10.1089/acu.2020.1497},

issn = {1933-6594},

year  = {2020},

date = {2020-12-01},

journal = {Medical Acupuncture},

volume = {32},

number = {6},

pages = {400--402},

publisher = {Mary Ann Liebert Inc},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ellingsen2020,

title = {Dynamic brain-to-brain concordance and behavioral mirroring as a mechanism of the patient-clinician interaction},

author = {Dan-Mikael Ellingsen and Kylie Isenburg and Changjin Jung and Jeungchan Lee and Jessica Gerber and Ishtiaq Mawla and Roberta Sclocco and Karin B. Jensen and Robert R. Edwards and John M. Kelley and Irving Kirsch and Ted J. Kaptchuk and Vitaly Napadow},

doi = {10.1126/sciadv.abc1304},

issn = {2375-2548},

year  = {2020},

date = {2020-10-23},

journal = {Sci. Adv.},

volume = {6},

number = {43},

publisher = {American Association for the Advancement of Science (AAAS)},

abstract = {Brain activity concordance between patients and clinicians supports therapeutic alliance and treatment relief of pain.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Berry2020,

title = {Brief Self-Compassion Training Alters Neural Responses to Evoked Pain for Chronic Low Back Pain: A Pilot Study},

author = {Michael P Berry and Jacqueline Lutz and Zev Schuman-Olivier and Christopher Germer and Susan Pollak and Robert R Edwards and Paula Gardiner and Gaelle Desbordes and Vitaly Napadow},

doi = {10.1093/pm/pnaa178},

issn = {1526-4637},

year  = {2020},

date = {2020-10-01},

volume = {21},

number = {10},

pages = {2172--2185},

publisher = {Oxford University Press (OUP)},

abstract = {Abstract

               

                  Objective

                  Self-compassion meditation, which involves compassion toward the self in moments of suffering, shows promise for improving pain-related functioning, but its underlying mechanisms are unknown. This longitudinal, exploratory pilot study investigated the effects of a brief (eight contact hours, two weeks of home practice) self-compassion training on pain-related brain processing in chronic low back pain (cLBP).

               

               

                  Methods

                  We evaluated functional magnetic resonance imaging (fMRI) response to evoked pressure pain and its anticipation during a self-compassionate state and compared altered brain responses following training with changes on self-reported measures of self-compassion (Self-Compassion Scale [SCS]), interoceptive awareness (Multidimensional Assessment of Interoceptive Awareness [MAIA]), and clinical pain intensity.

               

               

                  Results

                  In a sample of participants with cLBP (N = 20 total, N = 14 with complete longitudinal data) who underwent self-compassion training, we observed reduced clinical pain intensity and disability (P < 0.01) and increased trait self-compassion and interoceptive awareness (all P < 0.05) following training. Evoked pressure pain response in the right temporo-parietal junction (TPJ) was reduced following training, and decreases were associated with reduced clinical pain intensity. Further, increased fMRI responses to pain anticipation were observed in the right dorsolateral prefrontal cortex (dlPFC) and ventral posterior cingulate cortex (vPCC), and these increases were associated with mean post-training changes in SCS scores and scores from the body listening subscale of the MAIA.

               

               

                  Discussion

                  These findings, though exploratory and lacking comparison with a control condition, suggest that self-compassion training supports regulation of pain through the involvement of self-referential (vPCC), salience-processing (TPJ), and emotion regulatory (dlPFC) brain areas. The results also suggest that self-compassion could be an important target in the psychotherapeutic treatment of cLBP, although further studies using controlled experimental designs are needed to determine the specificity of these effects.

               },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Jung2020,

title = {Magnetic resonance imaging of neuroinflammation in chronic pain: a role for astrogliosis?},

author = {Changjin Jung and Eric Ichesco and Eva-Maria Ratai and Ramon Gilberto Gonzalez and Tricia Burdo and Marco L. Loggia and Richard E. Harris and Vitaly Napadow},

doi = {10.1097/j.pain.0000000000001815},

issn = {1872-6623},

year  = {2020},

date = {2020-00-00},

journal = {PAIN},

volume = {161},

number = {7},

pages = {1555--1564},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

abstract = {Abstract

          Noninvasive measures of neuroinflammatory processes in humans could substantially aid diagnosis and therapeutic development for many disorders, including chronic pain. Several proton magnetic resonance spectroscopy (1H-MRS) metabolites have been linked with glial activity (ie, choline and myo-inositol) and found to be altered in chronic pain patients, but their role in the neuroinflammatory cascade is not well known. Our multimodal study evaluated resting functional magnetic resonance imaging connectivity and 1H-MRS metabolite concentration in insula cortex in 43 patients suffering from fibromyalgia, a chronic centralized pain disorder previously demonstrated to include a neuroinflammatory component, and 16 healthy controls. Patients demonstrated elevated choline (but not myo-inositol) in anterior insula (aIns) (P = 0.03), with greater choline levels linked with worse pain interference (r = 0.41, P = 0.01). In addition, reduced resting functional connectivity between aIns and putamen was associated with both pain interference (whole brain analysis, pcorrected < 0.01) and elevated aIns choline (r = −0.37, P = 0.03). In fact, aIns/putamen connectivity statistically mediated the link between aIns choline and pain interference (P < 0.01), highlighting the pathway by which neuroinflammation can impact clinical pain dysfunction. To further elucidate the molecular substrates of the effects observed, we investigated how putative neuroinflammatory 1H-MRS metabolites are linked with ex vivo tissue inflammatory markers in a nonhuman primate model of neuroinflammation. Results demonstrated that cortical choline levels were correlated with glial fibrillary acidic protein, a known marker for astrogliosis (Spearman r = 0.49, P = 0.03). Choline, a putative neuroinflammatory 1H-MRS-assessed metabolite elevated in fibromyalgia and associated with pain interference, may be linked with astrogliosis in these patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Napadow2020,

title = {The mindful migraine: does mindfulness-based stress reduction relieve episodic migraine?},

author = {Vitaly Napadow},

doi = {10.1097/j.pain.0000000000001859},

issn = {1872-6623},

year  = {2020},

date = {2020-00-00},

journal = {PAIN},

volume = {161},

number = {8},

pages = {1685--1687},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31055043,

title = {The central autonomic network at rest: Uncovering functional MRI correlates of time-varying autonomic outflow},

author = {G Valenza and R Sclocco and A Duggento and L Passamonti and V Napadow and R Barbieri and N Toschi},

doi = {10.1016/j.neuroimage.2019.04.075},

issn = {1095-9572},

year  = {2019},

date = {2019-08-01},

journal = {Neuroimage},

volume = {197},

pages = {383--390},

abstract = {Peripheral measures of autonomic nervous system (ANS) activity at rest have been extensively employed as putative biomarkers of autonomic cardiac control. However, a comprehensive characterization of the brain-based central autonomic network (CAN) sustaining cardiovascular oscillations at rest is missing, limiting the interpretability of these ANS measures as biomarkers of cardiac control. We evaluated combined cardiac and fMRI data from 34 healthy subjects from the Human Connectome Project to detect brain areas functionally linked to cardiovagal modulation at rest. Specifically, we combined voxel-wise fMRI analysis with instantaneous heartbeat and spectral estimates obtained from inhomogeneous linear point-process models. We found exclusively negative associations between cardiac parasympathetic activity at rest and a widespread network including bilateral anterior insulae, right dorsal middle and left posterior insula, right parietal operculum, bilateral medial dorsal and ventrolateral posterior thalamic nuclei, anterior and posterior mid-cingulate cortex, medial frontal gyrus/pre-supplementary motor area. Conversely, we found only positive associations between instantaneous heart rate and brain activity in areas including frontopolar cortex, dorsomedial prefrontal cortex, anterior, middle and posterior cingulate cortices, superior frontal gyrus, and precuneus. Taken together, our data suggests a much wider involvement of diverse brain areas in the CAN at rest than previously thought, which could reflect a differential (both spatially and directionally) CAN activation according to the underlying task. Our insight into CAN activity at rest also allows the investigation of its impairment in clinical populations in which task-based fMRI is difficult to obtain (e.g., comatose patients or infants).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sclocco2019,

title = {The influence of respiration on brainstem and cardiovagal response to auricular vagus nerve stimulation: A multimodal ultrahigh-field (7T) fMRI study},

author = {Roberta Sclocco and Ronald G. Garcia and Norman W. Kettner and Kylie Isenburg and Harrison P. Fisher and Catherine S. Hubbard and Ilknur Ay and Jonathan R. Polimeni and Jill Goldstein and Nikos Makris and Nicola Toschi and Riccardo Barbieri and Vitaly Napadow},

doi = {10.1016/j.brs.2019.02.003},

issn = {1935-861X},

year  = {2019},

date = {2019-07-00},

journal = {Brain Stimulation},

volume = {12},

number = {4},

pages = {911--921},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lee2019,

title = {Brain Correlates of Continuous Pain in Rheumatoid Arthritis as Measured by Pulsed Arterial Spin Labeling},

author = {Yvonne C. Lee and Alexander Fine and Ekaterina Protsenko and Elena Massarotti and Robert R. Edwards and Ishtiaq Mawla and Vitaly Napadow and Marco L. Loggia},

doi = {10.1002/acr.23601},

issn = {2151-4658},

year  = {2019},

date = {2019-02-00},

journal = {Arthritis Care & Research},

volume = {71},

number = {2},

pages = {308--318},

publisher = {Wiley},

abstract = {ObjectiveCentral nervous system pathways involving pain modulation shape the pain experience in patients with chronic pain. The aims of this study were to understand the mechanisms underlying pain in patients with rheumatoid arthritis (RA) and to identify brain signals that may serve as imaging markers for developing targeted treatments for RA‐related pain.MethodsPatients with RA and matched control subjects underwent functional magnetic resonance imaging, using pulsed arterial spin labeling. The imaging conditions included 1) resting state, 2) low‐intensity stimulus, and 3) high‐intensity stimulus. Stimuli consisted of mechanical pressure applied to metacarpophalangeal (MCP) joints with an automated cuff inflator. The low‐intensity stimulus was inflation to 30 mm Hg. The high‐intensity stimulus was the amount of pressure required to achieve a pain intensity rating of 40 on a 100‐point scale for each RA patient, with the same amount of pressure used in the matched control.ResultsAmong RA patients, regional cerebral blood flow (rCBF) in the medial frontal cortex and dorsolateral prefrontal cortex increased during both low‐pressure and high‐pressure stimulation. No rCBF changes were observed in pain‐free controls. Region‐of‐interest analyses in RA patients showed that baseline rCBF in the medial frontal cortex was negatively correlated with the pressure required for the high‐intensity stimulus and positively correlated with pain induced by the low‐intensity stimulus. Baseline rCBF was also marginally correlated with disease activity). Regional CBF during high pain was positively correlated with pain severity and pain interference.ConclusionIn response to clinically relevant joint pain evoked by pressure applied to the MCP joint, neural processing in the medial frontal cortex increases and is directly associated with clinical pain in patients with RA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lee2018c,

title = {Machine learning–based prediction of clinical pain using multimodal neuroimaging and autonomic metrics},

author = {Jeungchan Lee and Ishtiaq Mawla and Jieun Kim and Marco L. Loggia and Ana Ortiz and Changjin Jung and Suk-Tak Chan and Jessica Gerber and Vincent J. Schmithorst and Robert R. Edwards and Ajay D. Wasan and Chantal Berna and Jian Kong and Ted J. Kaptchuk and Randy L. Gollub and Bruce R. Rosen and Vitaly Napadow},

doi = {10.1097/j.pain.0000000000001417},

issn = {1872-6623},

year  = {2019},

date = {2019-00-00},

journal = {PAIN},

volume = {160},

number = {3},

pages = {550--560},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

abstract = {Abstract

          Although self-report pain ratings are the gold standard in clinical pain assessment, they are inherently subjective in nature and significantly influenced by multidimensional contextual variables. Although objective biomarkers for pain could substantially aid pain diagnosis and development of novel therapies, reliable markers for clinical pain have been elusive. In this study, individualized physical maneuvers were used to exacerbate clinical pain in patients with chronic low back pain (N = 53), thereby experimentally producing lower and higher pain states. Multivariate machine-learning models were then built from brain imaging (resting-state blood-oxygenation-level-dependent and arterial spin labeling functional imaging) and autonomic activity (heart rate variability) features to predict within-patient clinical pain intensity states (ie, lower vs higher pain) and were then applied to predict between-patient clinical pain ratings with independent training and testing data sets. Within-patient classification between lower and higher clinical pain intensity states showed best performance (accuracy = 92.45%, area under the curve = 0.97) when all 3 multimodal parameters were combined. Between-patient prediction of clinical pain intensity using independent training and testing data sets also demonstrated significant prediction across pain ratings using the combined model (Pearson's r = 0.63). Classification of increased pain was weighted by elevated cerebral blood flow in the thalamus, and prefrontal and posterior cingulate cortices, and increased primary somatosensory connectivity to frontoinsular cortex. Our machine-learning approach introduces a model with putative biomarkers for clinical pain and multiple clinical applications alongside self-report, from pain assessment in noncommunicative patients to identification of objective pain endophenotypes that can be used in future longitudinal research aimed at discovery of new approaches to combat chronic pain.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Meints2018,

title = {The relationship between catastrophizing and altered pain sensitivity in patients with chronic low-back pain},

author = {Samantha M. Meints and Ishtiaq Mawla and Vitaly Napadow and Jian Kong and Jessica Gerber and Suk-Tak Chan and Ajay D. Wasan and Ted J. Kaptchuk and Christina McDonnell and Junie Carriere and Bruce Rosen and Randy L. Gollub and Robert R. Edwards},

doi = {10.1097/j.pain.0000000000001461},

issn = {1872-6623},

year  = {2019},

date = {2019-00-00},

journal = {PAIN},

volume = {160},

number = {4},

pages = {833--843},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

abstract = {Abstract

          Changes in central pain processing have been shown in patients with chronic low-back pain (cLBP). We used quantitative sensory testing methods to identify differences in pain sensitization between patients with cLBP (N = 167) and healthy controls (N = 33). Results indicated that, compared with healthy pain-free controls, cLBP patients showed increased sensitivity and greater painful aftersensations for mechanical pressure and pin-prick stimuli and lower tactile spatial acuity in the 2-point discrimination task (ps < 0.05). Then, we examined the role of pain catastrophizing as a mediator of the group differences in pain sensitization. We found that catastrophizing partially accounted for group differences in pressure required to produce moderate pain. Finally, we examined the relationship between pain sensitization, catastrophizing, and clinical pain among patients with cLBP. We found that catastrophizing and deep-tissue pressure pain were associated with greater pain intensity in the past month, week, and at the visit as well as low-back pain bothersomeness. Furthermore, deep-tissue pressure pain mediated the associations between catastrophizing and both pain in the past month and low-back pain severity. Taken together, these results indicate that not only do patients with cLBP demonstrate increased pain sensitization and decreased sensitivity to innocuous stimuli, but these changes are also linked with increased catastrophizing. Furthermore, both catastrophizing and sensitization are associated with increased clinical pain among cLBP patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kim2019,

title = {Somatotopically specific primary somatosensory connectivity to salience and default mode networks encodes clinical pain},

author = {Jieun Kim and Ishtiaq Mawla and Jian Kong and Jeungchan Lee and Jessica Gerber and Ana Ortiz and Hyungjun Kim and Suk-Tak Chan and Marco L. Loggia and Ajay D. Wasan and Robert R. Edwards and Randy L. Gollub and Bruce R. Rosen and Vitaly Napadow},

doi = {10.1097/j.pain.0000000000001541},

issn = {1872-6623},

year  = {2019},

date = {2019-00-00},

journal = {PAIN},

volume = {160},

number = {7},

pages = {1594--1605},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

abstract = {Abstract

          Although several studies have found that chronic pain is characterized by increased cross-network connectivity between salience network, sensorimotor network, and default mode network (DMN), a large sample-size investigation allowing for a more reliable evaluation of somatotopic specificity and subgroup analyses with linkage to clinical pain intensity has been lacking. We enrolled healthy adults and a large cohort of patients (N = 181) suffering from chronic low back pain (cLBP). To specifically link brain connectivity with clinical pain intensity, patients were scanned at baseline and after performing physical maneuvers that exacerbated pain. Compared with healthy adults, patients with cLBP demonstrated increased connectivity between the functionally localized back representation in the primary somatosensory cortex (S1back) and both salience network and DMN. Pain exacerbation maneuvers increased S1back connectivity to salience network regions, but decreased connectivity to DMN, with greater pain intensity increase associated with greater shifts in these connectivity patterns. Furthermore, only in patients with cLBP reporting high pain catastrophizing, DMN connectivity was increased to a cardinal node of the salience network, anterior insula cortex, which was correlated with increased postmaneuver pain in this cLBP subgroup. Hence, increased information transfer between salience processing regions, particularly anterior insula, and DMN may be strongly influenced by pain catastrophizing. Increased information transfer between the salience network and S1 likely plays an important role in shifting nociceptive afference away from self-referential processing, reallocating attentional focus, and affective coding of nociceptive afference from specific body areas. These results demonstrate S1 somatotopic specificity for cross-network connectivity in encoding clinical back pain and moderating influence of catastrophizing for DMN/insula connectivity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ellingsen2018,

title = {Brain Mechanisms of Anticipated Painful Movements and Their Modulation by Manual Therapy in Chronic Low Back Pain},

author = {Dan-Mikael Ellingsen and Vitaly Napadow and Ekaterina Protsenko and Ishtiaq Mawla and Matthew H. Kowalski and David Swensen and Deanna O'Dwyer-Swensen and Robert R. Edwards and Norman Kettner and Marco L. Loggia},

doi = {10.1016/j.jpain.2018.05.012},

issn = {1526-5900},

year  = {2018},

date = {2018-11-00},

journal = {The Journal of Pain},

volume = {19},

number = {11},

pages = {1352--1365},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lee2018b,

title = {Encoding of Self‐Referential Pain Catastrophizing in the Posterior Cingulate Cortex in Fibromyalgia},

author = {Jeungchan Lee and Ekaterina Protsenko and Asimina Lazaridou and Olivia Franceschelli and Dan‐Mikael Ellingsen and Ishtiaq Mawla and Kylie Isenburg and Michael P. Berry and Laura Galenkamp and Marco L. Loggia and Ajay D. Wasan and Robert R. Edwards and Vitaly Napadow},

doi = {10.1002/art.40507},

issn = {2326-5205},

year  = {2018},

date = {2018-08-00},

journal = {Arthritis & Rheumatology},

volume = {70},

number = {8},

pages = {1308--1318},

publisher = {Wiley},

abstract = {ObjectivePain catastrophizing is a common feature of chronic pain, including fibromyalgia (FM), and is strongly associated with amplified pain severity and disability. While previous neuroimaging studies have focused on evoked pain response modulation by catastrophizing, the brain mechanisms supporting pain catastrophizing itself are unknown. We designed a functional magnetic resonance imaging (fMRI)–based pain catastrophizing task whereby patients with chronic pain engaged in catastrophizing‐related cognitions. We undertook this study to test our hypothesis that catastrophizing about clinical pain would be associated with amplified activation in nodes of the default mode network (DMN), which encode self‐referential cognition and show altered functioning in chronic pain.MethodsDuring fMRI, 31 FM patients reflected on how catastrophizing (CAT) statements (drawn from the Pain Catastrophizing Scale) impact their typical FM pain experience. Response to CAT statements was compared to response to matched neutral (NEU) statements.ResultsDuring statement reflection, higher fMRI signal during CAT statements than during NEU statements was found in several DMN brain areas, including the ventral (posterior) and dorsal (anterior) posterior cingulate cortex (vPCC and dPCC, respectively). Patients’ ratings of CAT statement applicability were correlated solely with activity in the vPCC, a main DMN hub supporting self‐referential cognition (r = 0.38, P < 0.05). Clinical pain severity was correlated solely with activity in the dPCC, a PCC subregion associated with cognitive control and sensorimotor processing (r = 0.38, P < 0.05).ConclusionThese findings provide evidence that the PCC encodes pain catastrophizing in FM and suggest distinct roles for different PCC subregions. Understanding the brain circuitry encoding pain catastrophizing in FM will prove to be important in identifying and evaluating the success of interventions targeting negative affect in chronic pain management.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lee2018,

title = {Editorial: Functional Connectivity: Dissecting the Relationship Between the Brain and “Pain Centralization” in Rheumatoid Arthritis},

author = {Yvonne C. Lee and Vitaly Napadow and Marco L. Loggia},

doi = {10.1002/art.40454},

issn = {2326-5205},

year  = {2018},

date = {2018-07-00},

journal = {Arthritis & Rheumatology},

volume = {70},

number = {7},

pages = {977--980},

publisher = {Wiley},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Napadow2018,

title = {When a White Horse is a Horse: Embracing the (Obvious?) Overlap Between Acupuncture and Neuromodulation},

author = {Vitaly Napadow},

doi = {10.1089/acm.2018.29047.vtn},

issn = {1557-7708},

year  = {2018},

date = {2018-07-00},

journal = {The Journal of Alternative and Complementary Medicine},

volume = {24},

number = {7},

pages = {621--623},

publisher = {Mary Ann Liebert Inc},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28232189,

title = {Challenges and opportunities for brainstem neuroimaging with ultrahigh field MRI},

author = {Roberta Sclocco and Florian Beissner and Marta Bianciardi and Jonathan R Polimeni and Vitaly Napadow},

doi = {10.1016/j.neuroimage.2017.02.052},

issn = {1095-9572},

year  = {2018},

date = {2018-03-01},

journal = {Neuroimage},

volume = {168},

pages = {412--426},

abstract = {The human brainstem plays a central role in connecting the cerebrum, the cerebellum and the spinal cord to one another, hosting relay nuclei for afferent and efferent signaling, and providing source nuclei for several neuromodulatory systems that impact central nervous system function. While the investigation of the brainstem with functional or structural magnetic resonance imaging has been hampered for years due to this brain structure's physiological and anatomical characteristics, the field has seen significant advances in recent years thanks to the broader adoption of ultrahigh-field (UHF) MRI scanning. In the present review, we focus on the advantages offered by UHF in the context of brainstem imaging, as well as the challenges posed by the investigation of this complex brain structure in terms of data acquisition and analysis. We also illustrate how UHF MRI can shed new light on the neuroanatomy and neurophysiology underlying different brainstem-based circuitries, such as the central autonomic network and neurotransmitter/neuromodulator systems, discuss existing and foreseeable clinical applications to better understand diseases such as chronic pain and Parkinson's disease, and explore promising future directions for further improvements in brainstem imaging using UHF MRI techniques.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}