All Publications

  • Brain Responses to Noxious Stimuli in Patients With Chronic Pain A Systematic Review and Meta-analysis JAMA NETWORK OPEN Xu, A., Larsen, B., Henn, A., Baller, E. B., Scott, J., Sharma, V., Adebimpe, A., Basbaum, A. I., Corder, G., Dworkin, R. H., Edwards, R. R., Woolf, C. J., Eickhoff, S. B., Eickhoff, C. R., Satterthwaite, T. D. 2021; 4 (1): e2032236


    Functional neuroimaging is a valuable tool for understanding how patients with chronic pain respond to painful stimuli. However, past studies have reported heterogenous results, highlighting opportunities for a quantitative meta-analysis to integrate existing data and delineate consistent associations across studies.To identify differential brain responses to noxious stimuli in patients with chronic pain using functional magnetic resonance imaging (fMRI) while adhering to current best practices for neuroimaging meta-analyses.All fMRI experiments published from January 1, 1990, to May 28, 2019, were identified in a literature search of PubMed/MEDLINE, EMBASE, Web of Science, Cochrane Library, PsycINFO, and SCOPUS.Experiments comparing brain responses to noxious stimuli in fMRI between patients and controls were selected if they reported whole-brain results, included at least 10 patients and 10 healthy control participants, and used adequate statistical thresholding (voxel-height P < .001 or cluster-corrected P < .05). Two independent reviewers evaluated titles and abstracts returned by the search. In total, 3682 abstracts were screened, and 1129 full-text articles were evaluated.Thirty-seven experiments from 29 articles met inclusion criteria for meta-analysis. Coordinates reporting significant activation differences between patients with chronic pain and healthy controls were extracted. These data were meta-analyzed using activation likelihood estimation. Data were analyzed from December 2019 to February 2020.A whole-brain meta-analysis evaluated whether reported differences in brain activation in response to noxious stimuli between patients and healthy controls were spatially convergent. Follow-up analyses examined the directionality of any differences. Finally, an exploratory (nonpreregistered) region-of-interest analysis examined differences within the pain network.The 37 experiments from 29 unique articles included a total of 511 patients and 433 controls (944 participants). Whole-brain meta-analyses did not reveal significant differences between patients and controls in brain responses to noxious stimuli at the preregistered statistical threshold. However, exploratory analyses restricted to the pain network revealed aberrant activity in patients.In this systematic review and meta-analysis, preregistered, whole-brain analyses did not reveal aberrant fMRI activity in patients with chronic pain. Exploratory analyses suggested that subtle, spatially diffuse differences may exist within the pain network. Future work on chronic pain biomarkers may benefit from focus on this core set of pain-responsive areas.

    View details for DOI 10.1001/jamanetworkopen.2020.32236

    View details for Web of Science ID 000610371800003

    View details for PubMedID 33399857

    View details for PubMedCentralID PMC7786252

  • Convergent neural representations of experimentally-induced acute pain in healthy volunteers: A large-scale fMRI meta-analysis NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS Xu, A., Larsen, B., Baller, E. B., Scott, J., Sharma, V., Adebimpe, A., Basbaum, A. I., Dworkin, R. H., Edwards, R. R., Woolf, C. J., Eickhoff, S. B., Eickhoff, C. R., Satterthwaite, T. D. 2020; 112: 300–323


    Characterizing a reliable, pain-related neural signature is critical for translational applications. Many prior fMRI studies have examined acute nociceptive pain-related brain activation in healthy participants. However, synthesizing these data to identify convergent patterns of activation can be challenging due to the heterogeneity of experimental designs and samples. To address this challenge, we conducted a comprehensive meta-analysis of fMRI studies of stimulus-induced pain in healthy participants. Following pre-registration, two independent reviewers evaluated 4,927 abstracts returned from a search of 8 databases, with 222 fMRI experiments meeting inclusion criteria. We analyzed these experiments using Activation Likelihood Estimation with rigorous type I error control (voxel height p < 0.001, cluster p < 0.05 FWE-corrected) and found a convergent, largely bilateral pattern of pain-related activation in the secondary somatosensory cortex, insula, midcingulate cortex, and thalamus. Notably, these regions were consistently recruited regardless of stimulation technique, location of induction, and participant sex. These findings suggest a highly-conserved core set of pain-related brain areas, encouraging applications as a biomarker for novel therapeutics targeting acute nociceptive pain.

    View details for DOI 10.1016/j.neubiorev.2020.01.004

    View details for Web of Science ID 000531016100019

    View details for PubMedID 31954149

    View details for PubMedCentralID PMC7755074

  • Distinct Insular Functional Connectivity Changes Related to Mood and Fatigue Improvements in Major Depressive Disorder Following Tai Chi Training: A Pilot Study FRONTIERS IN INTEGRATIVE NEUROSCIENCE Xu, A., Zimmerman, C. S., Lazar, S. W., Ma, Y., Kerr, C. E., Yeung, A. 2020; 14: 25


    Objective: Tai chi (TC), a contemplative practice combining slow movements and deep breathing, has been shown to be clinically effective in alleviating depressive symptoms. Feelings of fatigue or low vitality often accompany major depressive disorder (MDD) though they are commonly overlooked and not well understood neurologically. By using resting state functional connectivity (rs-FC) using the insula as the seed, this study examines the relationship between mood and vitality symptoms in MDD and how they are impacted by TC training. Methods: Patients (N = 16) with MDD participated in a 10-week TC intervention. Self-report scores of vitality (using the SF-36 scale) and depressed mood (using the Beck Depression Inventory) as well as rs-fMRI were collected pre- and post-intervention. A seed-to-voxel approach was used to test whether changes in insular rs-FC were related to therapeutic improvement in MDD-related symptoms resulting from TC practice. Results: We found decreased self-reported depressed mood and increased vitality following the TC intervention. Furthermore, decreases in depressed mood were associated with increased rs-FC between the right anterior insula (AIC) and superior temporal gyrus and caudate (cluster-corrected p < 0.05). Increased vitality was associated with increased rs-FC between the right posterior insula (PIC) and regions associated with sensorimotor processes (cluster-corrected p < 0.05). Conclusion: These results provide support for differential changes in insula connectivity as neural correlates of symptom improvement in MDD.

    View details for DOI 10.3389/fnint.2020.00025

    View details for Web of Science ID 000543373700001

    View details for PubMedID 32581734

    View details for PubMedCentralID PMC7295154

  • Epidemiology of chronic pain in Ukraine: Findings from the World Mental Health Survey PLOS ONE Xu, A., Hilton, E., Arkema, R., Tintle, N. L., Helming, L. M. 2019; 14 (10): e0224084


    Chronic pain can pose a serious challenge in everyday life for many individuals globally, especially in developing countries, but studies explicitly exploring risk factors of chronic pain beyond demographic characteristics using survey data have been scarce. To address this problem, this study analyzed World Health Organization data on chronic pain in Ukraine to explore demographic, psychological, and treatment perception-related risk factors to chronic pain. We replicated previous reports of older age, female sex, married status, inadequate financial resources, and comorbidity of other physical conditions as significant demographic risk factors for chronic pain diagnosis but not necessarily for severe pain. We also found evidence for psychological risk factors and treatment perceptions as significant predictors for chronic pain diagnosis and its severity. These results provide a first step in examining beyond demographic risk factors for chronic pain diagnosis and severity and, instead, assessing potential psychological risk factors.

    View details for DOI 10.1371/journal.pone.0224084

    View details for Web of Science ID 000532567300090

    View details for PubMedID 31622425

    View details for PubMedCentralID PMC6797182

  • Comparing embodiment experiences in expert meditators and non-meditators using the rubber hand illusion CONSCIOUSNESS AND COGNITION Xu, A., Cullen, B. H., Penner, C., Zimmerman, C., Kerr, C. E., Schmalzl, L. 2018; 65: 325–33


    One assessment of embodiment is the rubber hand illusion (RHI), a visuo-tactile illusion in which individuals attribute a sense of ownership to a rubber hand and disownership to their real hand. Interestingly, interoception seems to influence RHI susceptibility. In this study, we administered the RHI and the Multidimensional Assessment of Interoceptive Awareness (MAIA) to examine embodiment experiences and interoceptive awareness in experienced meditators (n = 15) and non-meditators (n = 15). We found that meditators reported less intensity in rubber hand ownership, but there was no significant difference between groups with respect to disownership of their real hand or drift in finger proprioception. Moreover, we found, from our MAIA results, that disownership experiences were associated with a feeling of trusting one's body in non-meditators and with the ability to maintain attention to unpleasant bodily sensations in meditators. These results suggest a unique relationship between interoceptive awareness and embodiment related to meditation.

    View details for DOI 10.1016/j.concog.2018.09.003

    View details for Web of Science ID 000449238300026

    View details for PubMedID 30336416