A neuroimaging biomarker for sustained experimental and clinical pain

Lee, Jae‐Joong; Kim, Hong Ji; Čeko, Marta; Park, Bo‐yong; Lee, Soo Ahn; Park, Hyunjin; Roy, Mathieu; Kim, Seong‐Gi; Wager, Tor D.; Woo, Choong‐Wan

doi:10.1038/s41591-020-1142-7

Cited by 152 publications

(154 citation statements)

References 67 publications

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“…Third, while our tonic heat pain paradigm models some aspects of a sustained pain experience, 31 tonic pain is not identical with chronic pain. It is conceivable that tACS may not modulate pain in healthy participants but only in patients when altered neural circuits can be restored, for example by reversing a slowing of the dominant frequency.…”

Section: Discussionmentioning

confidence: 99%

Modulating Brain Rhythms of Pain Using Transcranial Alternating Current Stimulation (tACS) - A Sham-Controlled Study in Healthy Human Participants

Hohn

Nickel

et al. 2021

The Journal of Pain

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Chronic pain is a major health care problem. A better mechanistic understanding and new treatment approaches are urgently needed. In the brain, pain has been associated with neural oscillations at alpha and gamma frequencies, which can be targeted using transcranial alternating current stimulation (tACS). Thus, we investigated the potential of tACS to modulate pain and painrelated autonomic activity in an experimental model of chronic pain in 29 healthy participants. In 6 recording sessions, participants completed a tonic heat pain paradigm and simultaneously received tACS over prefrontal or somatosensory cortices at alpha or gamma frequencies or sham tACS. Concurrently, pain ratings and autonomic responses were collected. Using the present setup, tACS did not modulate pain or autonomic responses. Bayesian statistics confirmed a lack of tACS effects in most conditions. The only exception was alpha tACS over somatosensory cortex where evidence was inconclusive. Taken together, we did not find significant tACS effects on tonic experimental pain in healthy humans. Based on our present and previous findings, further studies might apply refined stimulation protocols targeting somatosensory alpha oscillations.Trial registration: The study protocol was pre-registered at ClinicalTrials.gov (NCT03805854). Perspective: Modulating brain oscillations is a promising approach for the treatment of pain. We therefore applied transcranial alternating current stimulation (tACS) to modulate experimental pain in healthy participants. However, tACS did not modulate pain, autonomic responses, or EEG oscillations. These findings help to shape future tACS studies for the treatment of pain.

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Section: Discussionmentioning

confidence: 99%

Modulating Brain Rhythms of Pain Using Transcranial Alternating Current Stimulation (tACS) - A Sham-Controlled Study in Healthy Human Participants

Hohn

Nickel

et al. 2021

The Journal of Pain

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“…Analytic approaches can also improve reliability, with multivariate markers likely providing a broader base of support relative to single regions of interest 6,55 . In addition, methods for improved inter-subject alignment 56,57 and systematic approaches for developing biomarker pipelines 58,59 will improve performance. Finally, spatial resolution is an additional consideration, especially for smaller structures like the amygdala, and effective resolution will be determined by the smoothing kernel applied.…”

Section: Discussionmentioning

confidence: 99%

Brain markers predicting response to cognitive‐behavioral therapy for social anxiety disorder: an independent replication of Whitfield-Gabrieli et al. 2015

Ashar¹,

Clark²,

Gunning³

et al. 2021

Transl Psychiatry

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Predictive brain markers promise a number of important scientific, clinical, and societal applications. Over 600 predictive brain markers have been described in published reports, but very few have been tested in independent replication attempts. Here, we conducted an independent replication of a previously published marker predicting treatment response to cognitive-behavioral therapy for social anxiety disorder from patterns of resting-state fMRI amygdala connectivity1. The replication attempt was conducted in an existing dataset similar to the dataset used in the original report, by a team of independent investigators in consultation with the original authors. The precise model described in the original report positively predicted treatment outcomes in the replication dataset, but with marginal statistical significance, permutation test p = 0.1. The effect size was substantially smaller in the replication dataset, with the model explaining 2% of the variance in treatment outcomes, as compared to 21% in the original report. Several lines of evidence, including the current replication attempt, suggest that features of amygdala function or structure may be able to predict treatment response in anxiety disorders. However, predictive models that explain a substantial amount of variance in independent datasets will be needed for scientific and clinical applications.

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“…Importantly, these authors show that by comparison, relying on static changes (e.g. static correlation averaged over scan duration) alone had lower predictive accuracy & had poor crossvalidation performance (Lee et al 2021).…”

Section: Pain Related Changes In Cbf Dynamicsmentioning

confidence: 98%

“…2016). A recent paper by Lee et al (2021) supports this by identified a neuroimaging biomarker for sustained experimental and clincal pain by focusing on dynamic changes in brain function (Lee et al 2021). Here, by using multiple BOLD FMRI datasets these authors employ a rigorous, data-driven approach to build a predictive algorithm for both experimental tonic and clinical pain that is based on whole-brain dynamic connectivity changes.…”

Section: Pain Related Changes In Cbf Dynamicsmentioning

confidence: 99%

Neural dynamics of parametrically modulated human mechanical pain determined using whole-brain quantitative perfusion imaging

Segerdahl

Kong

et al. 2021

Preprint

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Arterial spin labelling (ASL) FMRI is a powerful tool to non-invasively image tonic and ongoing pain states in both healthy participants and patients. We used ASL to image the neural correlates of extended, parametrically modulated mechanical pain in healthy human participants. The aims of this study were to: i) assess if force-calibrated pin-prick probes could safely and robustly evoke tonic mechanical pain; ii) determine the neural correlates of the parametric changes in both the force of the stimulus and the intensity of the perception that this elicits using ASL; and iii) provide an initial assessment of the capacity for amplitude of low-frequency fluctuation (ALFF) to differentiate painful versus non-painful tonic stimuli based on changes in the dynamics of the evoked signal. Our data confirm that it is possible to employ a stimulus force-locked design to induce robust, well maintained ongoing mechanical pain and to observe significant changes in rCBF relative to underlying component processes such as monitoring graded changes in the force applied to the skin (e.g., dACC, aMCC, pMCC, PCC, SI, SII, putamen, thalamus and the insula (anterior and posterior subsections); ipsilateral amygdala and hypothalamus; and the contralateral DLPFC) and tracking changes in the perceived intensity of the experience (e.g., bilateral dACC, aMCC, pMCC, PCC, thalamus, SII and the cerebellum; and contralateral SI, insula (including the dpIns). Further exploration of the data using an ALFF analysis reveals that a collection of regions (e.g. the contralateral VLPFC, inferior frontal gyrus, insula (anterior, mid and posterior subsections), SII, putamen, OFC, amygdala, and the hippocampus) exhibit unique perfusion dynamics during extended painful stimulation compared to non-painful touch. Results from this study provide further validation for the application of ASL to image experimental pain in healthy human subjects while interrogation of the data offers unique insight into the dynamic signal changes underlying the perception of a tonic mechanical pain experience.

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A neuroimaging biomarker for sustained experimental and clinical pain

Abstract: Peer review information Jerome Staal and Kate Gao were the primary editors on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team. Reprints and permissions information is available at www.nature.com/reprints.

Cited by 152 publications

References 67 publications

Modulating Brain Rhythms of Pain Using Transcranial Alternating Current Stimulation (tACS) - A Sham-Controlled Study in Healthy Human Participants

Modulating Brain Rhythms of Pain Using Transcranial Alternating Current Stimulation (tACS) - A Sham-Controlled Study in Healthy Human Participants

Brain markers predicting response to cognitive‐behavioral therapy for social anxiety disorder: an independent replication of Whitfield-Gabrieli et al. 2015

Neural dynamics of parametrically modulated human mechanical pain determined using whole-brain quantitative perfusion imaging

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