Author name cluster

Ted J. Kaptchuk

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10 papers

1 author row

YNICL Journal 2020 Journal Article

Corrigendum to “Multivariate resting-state functional connectivity predicts responses to real and sham acupuncture treatment in chronic low back pain” [Neuroimage Clinical 23 (2019) 101885]

Yiheng Tu
Ana Ortiz
Randy L. Gollub
Jin Cao
Jessica Gerber
Courtney Lang
Joel Park
Georgia Wilson

The authors regret to find several errors that do not influence the main findings or conclusions.Specifically, we have found that the values of pre-and post-treatment clinical sub-scores for 'physical function' and 'sleep' in Fig. 4 contain errors.The corrected Fig. 4 is shown below: As a result, the Results section 3.3 (Page 6, right column): "Real and sham acupuncture significantly reduced PROMIS sub-scores in

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YNIMG Journal 2020 Journal Article

Impaired mesocorticolimbic connectivity underlies increased pain sensitivity in chronic low back pain

Siyi Yu
Wen Li
Wei Shen
Robert R. Edwards
Randy L. Gollub
Georgia Wilson
Joel Park
Ana Ortiz

Chronic low back pain (cLBP) is a prevalent disorder. A growing body of evidence linking the pathology of the reward network to chronic pain suggests that pain sensitization may contribute to cLBP chronification via disruptions of mesocortical and mesolimbic circuits in the reward system. Resting-state (RS) functional magnetic resonance imaging (fMRI) data was acquired from 90 patients with cLBP and 74 matched pain-free controls (HCs) at baseline and after a manipulation for back pain intensification. The ventral tegmental area (VTA) was chosen as a seed region to perform RS functional connectivity (FC) analysis. Baseline rsFC of both the mesocortical (between the VTA and bilateral rostral anterior cingulate cortex (rACC)/and medial prefrontal cortex (mPFC)) and mesolimbic (between the VTA and bilateral hippocampus/parahippocampus) pathways was reduced in patients with cLBP (vs. HCs). In addition, patients exhibiting higher back pain intensity (compared to the relatively lower back pain intensity condition) also showed increases in both mesocortical and mesolimbic connectivity, implicating these pathways in pain downregulation in cLBP. Mediation analysis further isolated the mesolimbic (VTA-hippocampus/parahippocampus) dysconnectivity as a neural mechanism mediating the association between mechanical pain sensitivity (indexed by P40 pressure) and cLBP severity. In sum, the current study demonstrates deficient mesocorticolimbic connectivity in cLBP, with mesolimbic dysconnectivity potentially mediating the contribution of pain sensitization to pain chronification. These reward network dysfunctions and purportedly, dopaminergic dysregulations, may help us to identify key brain targets of neuromodulation in the treatment of cLBP.

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YNIMG Journal 2020 Journal Article

Reduced tactile acuity in chronic low back pain is linked with structural neuroplasticity in primary somatosensory cortex and is modulated by acupuncture therapy

Hyungjun Kim
Ishtiaq Mawla
Jeungchan Lee
Jessica Gerber
Kathryn Walker
Jieun Kim
Ana Ortiz
Suk-Tak Chan

Prior studies have shown that patients suffering from chronic Low Back Pain (cLBP) have impaired somatosensory processing including reduced tactile acuity, i. e. reduced ability to resolve fine spatial details with the perception of touch. The central mechanism(s) underlying reduced tactile acuity are unknown but may include changes in specific brain circuitries (e. g. neuroplasticity in the primary somatosensory cortex, S1). Furthermore, little is known about the linkage between changes in tactile acuity and the amelioration of cLBP by somatically-directed therapeutic interventions, such as acupuncture. In this longitudinal neuroimaging study, we evaluated healthy control adults (HC, N = 50) and a large sample of cLBP patients (N = 102) with structural brain imaging (T1-weighted MRI for Voxel-Based Morphometry, VBM; Diffusion Tensor Imaging, DTI) and tactile acuity testing using two-point discrimination threshold (2PDT) over the lower back (site of pain) and finger (control) locations. Patients were evaluated at baseline and following a 4-week course of acupuncture, with patients randomized to either verum acupuncture, two different forms of sham acupuncture (designed with or without somatosensory afference), or no-intervention usual care control. At baseline, cLBP patients demonstrated reduced acuity (greater 2PDT, P = 0. 01) over the low back, but not finger (P = 0. 29) locations compared to HC, suggesting that chronic pain affects tactile acuity specifically at body regions encoding the experience of clinical pain. At baseline, Gray Matter Volume (GMV) was elevated and Fractional Anisotropy (FA) was reduced, respectively, in the S1-back region of cLBP patients compared to controls (P < 0. 05). GMV in cLBP correlated with greater 2PDT-back scores (ρ = 0. 27, P = 0. 02). Following verum acupuncture, tactile acuity over the back was improved (reduced 2PDT) and greater improvements were associated with reduced S1-back GMV (ρ = 0. 52, P = 0. 03) and increased S1-back adjacent white matter FA (ρ = −0. 56, P = 0. 01). These associations were not seen for non-verum control interventions. Thus, S1 neuroplasticity in cLBP is linked with deficits in tactile acuity and, following acupuncture therapy, may represent early mechanistic changes in somatosensory processing that track with improved tactile acuity.

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YNICL Journal 2019 Journal Article

Corrigendum to ‘Multivariate resting-state functional connectivity predicts responses to real and sham acupuncture treatment in chronic low back pain’ Neuroimage Clinical, 23, 2019, 101885

Yiheng Tu
Ana Ortiz
Randy L. Gollub
Jin Cao
Jessica Gerber
Courtney Lang
Joel Park
Georgia Wilson

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YNICL Journal 2019 Journal Article

Multivariate resting-state functional connectivity predicts responses to real and sham acupuncture treatment in chronic low back pain

Yiheng Tu
Ana Ortiz
Randy L. Gollub
Jin Cao
Jessica Gerber
Courtney Lang
Joel Park
Georgia Wilson

Despite the high prevalence and socioeconomic impact of chronic low back pain (cLBP), treatments for cLBP are often unsatisfactory, and effectiveness varies widely across patients. Recent neuroimaging studies have demonstrated abnormal resting-state functional connectivity (rsFC) of the default mode, salience, central executive, and sensorimotor networks in chronic pain patients, but their role as predictors of treatment responsiveness has not yet been explored. In this study, we used machine learning approaches to test if pre-treatment rsFC can predict responses to both real and sham acupuncture treatments in cLBP patients. Fifty cLBP patients participated in 4 weeks of either real (N = 24, age = 39.0 ± 12.6, 16 females) or sham acupuncture (N = 26, age = 40.0 ± 13.7, 15 females) treatment in a single-blinded trial, and a resting-state fMRI scan prior to treatment was used in data analysis. Both real and sham acupuncture can produce significant pain reduction, with those receiving real treatment experiencing greater pain relief than those receiving sham treatment. We found that pre-treatment rsFC could predict symptom changes with up to 34% and 29% variances for real and sham treatment, respectively, and the rsFC characteristics that were significantly predictive for real and sham treatment differed. These results suggest a potential way to predict treatment responses and may facilitate the development of treatment plans that optimize time, cost, and available resources.

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YNICL Journal 2018 Journal Article

Enhancing treatment of osteoarthritis knee pain by boosting expectancy: A functional neuroimaging study

Jian Kong
Zengjian Wang
Jaclyn Leiser
Domenic Minicucci
Robert Edwards
Irving Kirsch
Ajay D. Wasan
Courtney Lang

Objectives: Expectation can significantly modulate pain and treatment effects. This study aims to investigate if boosting patients' expectancy can enhance the treatment of knee osteoarthritis (KOA), and its underlying brain mechanism. Methods: Seventy-four KOA patients were recruited and randomized to three groups: boosted acupuncture (with a manipulation to enhance expectation), standard acupuncture, or treatment as usual (TAU). Each patient underwent six treatments before being debriefed, and four additional treatments after being debriefed. The fMRI scans were applied during the first and sixth treatment sessions. Results: We found significantly decreased knee pain in the boosted acupuncture group compared to the standard acupuncture or TAU groups after both six and ten treatments. Resting state functional connectivity (rsFC) analyses using the nucleus accumbens (NAc) as the seed showed rsFC increases between the NAc and the medial prefrontal cortex (MPFC)/rostral anterior cingulate cortex (rACC) and dorsolateral prefrontal cortex in the boosted group as compared to the standard acupuncture group after multiple treatments. Expectancy scores after the first treatment were significantly associated with increased NAc-rACC/MPFC rsFC and decreased knee pain following treatment. Conclusions: Our study provides a novel method and mechanism for boosting the treatment of pain in patients with KOA. Our findings may shed light on enhancing outcomes of pharmacological and integrative medicines in clinical settings.

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YNIMG Journal 2015 Journal Article

Distinct neural representations of placebo and nocebo effects

Sonya Freeman
Rongjun Yu
Natalia Egorova
Xiaoyan Chen
Irving Kirsch
Brian Claggett
Ted J. Kaptchuk
Randy L. Gollub

Expectations shape the way we experience the world. In this study, we used fMRI to investigate how positive and negative expectation can change pain experiences in the same cohort of subjects. We first manipulated subjects' treatment expectation of the effectiveness of three inert creams, with one cream labeled “Lidocaine” (positive expectancy), one labeled “Capsaicin” (negative expectancy) and one labeled “Neutral” by surreptitiously decreasing, increasing, or not changing respectively, the intensity of the noxious stimuli administered following cream application. We then used fMRI to investigate the signal changes associated with administration of identical pain stimuli before and after the treatment and control creams. Twenty-four healthy adults completed the study. Results showed that expectancy significantly modulated subjective pain ratings. After controlling for changes in the neutral condition, the subjective pain rating changes evoked by positive and negative expectancies were significantly associated. fMRI results showed that the expectation of an increase in pain induced significant fMRI signal changes in the insula, orbitofrontal cortex, and periaqueductal gray, whereas the expectation of pain relief evoked significant fMRI signal changes in the striatum. No brain regions were identified as common to both “Capsaicin” and “Lidocaine” conditioning. There was also no significant association between the brain response to identical noxious stimuli in the pain matrix evoked by positive and negative expectancies. Our findings suggest that positive and negative expectancies engage different brain networks to modulate our pain experiences, but, overall, these distinct patterns of neural activation result in a correlated placebo and nocebo behavioral response.

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YNICL Journal 2015 Journal Article

Evoked itch perception is associated with changes in functional brain connectivity

Gaëlle Desbordes
Ang Li
Marco L. Loggia
Jieun Kim
Peter C. Schalock
Ethan Lerner
Thanh N. Tran
Johannes Ring

Chronic itch, a highly debilitating condition, has received relatively little attention in the neuroimaging literature. Recent studies suggest that brain regions supporting itch in chronic itch patients encompass sensorimotor and salience networks, and corticostriatal circuits involved in motor preparation for scratching. However, how these different brain areas interact with one another in the context of itch is still unknown. We acquired BOLD fMRI scans in 14 atopic dermatitis patients to investigate resting-state functional connectivity before and after allergen-induced itch exacerbated the clinical itch perception in these patients. A seed-based analysis revealed decreased functional connectivity from baseline resting state to the evoked-itch state between several itch-related brain regions, particularly the insular and cingulate cortices and basal ganglia, where decreased connectivity was significantly correlated with increased levels of perceived itch. In contrast, evoked itch increased connectivity between key nodes of the frontoparietal control network (superior parietal lobule and dorsolateral prefrontal cortex), where higher increase in connectivity was correlated with a lesser increase in perceived itch, suggesting that greater interaction between nodes of this executive attention network serves to limit itch sensation via enhanced top-down regulation. Overall, our results provide the first evidence of itch-dependent changes in functional connectivity across multiple brain regions.

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YNIMG Journal 2009 Journal Article

An fMRI study on the interaction and dissociation between expectation of pain relief and acupuncture treatment

Jian Kong
Ted J. Kaptchuk
Ginger Polich
Irving Kirsch
Mark Vangel
Carolyn Zyloney
Bruce Rosen
Randy L. Gollub

It is well established that expectation can significantly modulate pain perception. In this study, we combined an expectancy manipulation model and fMRI to investigate how expectation can modulate acupuncture treatment. Forty-eight subjects completed the study. The analysis on two verum acupuncture groups with different expectancy levels indicates that expectancy can significantly influence acupuncture analgesia for experimental pain. Conditioning positive expectation can amplify acupuncture analgesia as detected by subjective pain sensory rating changes and objective fMRI signal changes in response to calibrated noxious stimuli. Diminished positive expectation appeared to inhibit acupuncture analgesia. This modulation effect is spatially specific, inducing analgesia exclusively in regions of the body where expectation is focused. Thus, expectation should be used as an important covariate in future studies evaluating acupuncture efficacy. In addition, we also observed dissociation between subjective reported analgesia and objective fMRI signal changes to calibrated pain in the analysis across all four groups. We hypothesize that as a peripheral-central modulation, acupuncture needle stimulation may inhibit incoming noxious stimuli; while as a top-down modulation, expectancy (placebo) may work through the emotional circuit.

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YNIMG Journal 2009 Journal Article

Expectancy and treatment interactions: A dissociation between acupuncture analgesia and expectancy evoked placebo analgesia

Jian Kong
Ted J. Kaptchuk
Ginger Polich
Irving Kirsch
Mark Vangel
Carolyn Zyloney
Bruce Rosen
Randy Gollub

Recent advances in placebo research have demonstrated the mind's power to alter physiology. In this study, we combined an expectancy manipulation model with both verum and sham acupuncture treatments to address: 1) how and to what extent treatment and expectancy effects — including both subjective pain intensity levels (pain sensory ratings) and objective physiological activations (fMRI) — interact; and 2) if the underlying mechanism of expectancy remains the same whether placebo treatment is given alone or in conjunction with active treatment. The results indicate that although verum acupuncture+high expectation and sham acupuncture+high expectation induced subjective reports of analgesia of equal magnitude, fMRI analysis showed that verum acupuncture produced greater fMRI signal decrease in pain related brain regions during application of calibrated heat pain stimuli on the right arm. We believe our study provides brain imaging evidence for the existence of different mechanisms underlying acupuncture analgesia and expectancy evoked placebo analgesia. Our results also suggest that the brain network involved in expectancy may vary under different treatment situations (verum and sham acupuncture treatment).

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