Sensorimotor Peak Alpha Frequency Is a Reliable Biomarker of Prolonged Pain Sensitivity

Furman, Andrew J.; Prokhorenko, Mariya; Keaser, Michael L.; Zhang, Jing; Chen, Shuo; Mazaheri, Ali; Seminowicz, David A.

doi:10.1093/cercor/bhaa124

Cited by 73 publications

(93 citation statements)

References 59 publications

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“…Importantly, we could not identify any EEG channels where the expanded mixed effects model including a Session X Visit term provided a better fit to the data. Consistent with our prior studies that used a wider frequency range for PAF calculation (Furman et al, 2020), performing these analyses with 8-12 Hz PAF estimates yielded qualitatively similar, albeit weaker, results (Supplementary Figure 2) and PAF changes during PHPOn were not correlated with participant slider activity (Supplementary Figure 3).…”

Section: Resultssupporting

confidence: 85%

“…Next, a room temperature thermode was placed onto the left forearm while eyes closed, pain-free EEG was collected for 5 minutes. The relationship of PAF recorded this eyes-closed, pain-free session to pain sensitivity was reported in an earlier publication (Furman et al, 2020).…”

Section: Methodsmentioning

confidence: 70%

“…individuals with fast PAF). Although this might be interpreted to reflect an active pain process, our earlier work on pain-free PAF using this same dataset has identified these individuals as the least pain sensitive (Furman et al, 2020). As such, diminishment of "fast" alpha power may reflect something like a pain management resource that is depleted over time.…”

Section: Discussionmentioning

confidence: 88%

“…This study was approved by the University of Maryland, Baltimore Institutional Review Board, and informed written consent was obtained from each participant prior to any study procedures. The study was pre-registered on ClinicalTrials.gov (NCT02796625), and the primary and secondary outcomes were previously reported, demonstrating a reliable relationship between pain-free PAF and prolonged pain sensitivity (Furman et al, 2020).…”

Section: Participantsmentioning

confidence: 99%

“…their pain sensitivity). This relationship exists across several different pain modalities and paradigms and is reliable across multiple timepoints (Furman et al, 2018(Furman et al, , 2019(Furman et al, , 2020. Clarifying these two alternatives can determine whether slow PAF is better served as a prospective diagnostic of risk or a metric of ongoing chronic pain.…”

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confidence: 99%

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Prolonged Pain Reliably Slows Peak Alpha Frequency by Reducing Fast Alpha Power

Furman

Prokhorenko

Keaser

et al. 2021

Preprint

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The relationship between the 8-12 Hz alpha rhythm, the predominant oscillatory activity of the brain, and pain remains unclear. In healthy individuals, acute, noxious stimuli suppress alpha power while patients with chronic pain demonstrate both enhanced alpha power and slowing of the peak alpha frequency (PAF). To investigate these apparent differences, EEG was recorded from healthy individuals while they completed two models of prolonged pain, Phasic Heat Pain and Capsaicin Heat Pain, at two testing visits occurring roughly 8 weeks apart. We report that PAF is reliably slowed and that alpha power is reliably decreased in response to prolonged pain. Furthermore, we show that alpha power changes, but not PAF changes, are fully reversed with stimulus removal suggesting that PAF slowing reflects pain associated states such as sensitization rather than the presence of ongoing pain. Finally, we provide evidence that changes to alpha power and PAF are due to power decreases in the fast (10-12 Hz) range of the alpha rhythm. This frequency dependent pain response aligns with the hypothesis that the alpha rhythm is composed of multiple, independent oscillators, and suggest that modulation of a putative fast oscillator may represent a promising therapeutic target for treating ongoing pain. In sum, we provide strong evidence that PAF is reliably slowed during prolonged pain and additionally identify a mechanism, fast alpha Power, which is responsible for these PAF changes.

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Section: Resultssupporting

confidence: 85%

Section: Methodsmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 88%

Section: Participantsmentioning

confidence: 99%

mentioning

confidence: 99%

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Prolonged Pain Reliably Slows Peak Alpha Frequency by Reducing Fast Alpha Power

Furman

Prokhorenko

Keaser

et al. 2021

Preprint

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Pain‐free default mode network connectivity contributes to tonic experimental pain intensity beyond the role of negative mood and other pain‐related factors

Alhajri

Boudreau

Mouraux

et al. 2023

European Journal of Pain

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BackgroundAlterations in the default mode network (DMN) connectivity across pain stages suggest a possible DMN involvement in the transition to persistent pain.AimThis study examined whether pain‐free DMN connectivity at lower alpha oscillations (8‐10 Hz) accounts for a unique variation in experimental peak pain intensity beyond the contribution of factors known to influence pain intensity.MethodsPain‐free DMN connectivity was measured with electroencephalography prior to 1 h of capsaicin‐evoked pain using a topical capsaicin patch on the right forearm. Pain intensity was assessed on a (0–10) numerical rating scale and the association between peak pain intensity and baseline measurements was examined using hierarchical multiple regression in 52 healthy volunteers (26 women). The baseline measurements consisted of catastrophizing (helplessness, rumination, magnification), vigilance, depression, negative and positive affect, sex, age, sleep, fatigue, thermal and mechanical pain thresholds and DMN connectivity (medial prefrontal cortex [mPFC]‐posterior cingulate cortex [PCC], mPFC‐right angular gyrus [rAG], mPFC‐left Angular gyrus [lAG], rAG‐mPFC and rAG‐PCC).ResultsPain‐free DMN connectivity increased the explained variance in peak pain intensity beyond the contribution of other factors (ΔR2 = 0.10, p = 0.003), with the final model explaining 66% of the variation (R2 = 0.66, ANOVA: p < 0.001). In this model, negative affect (β = 0.51, p < 0.001), helplessness (β = 0.49, p = 0.007), pain‐free mPFC‐lAG connectivity (β = 0.36, p = 0.003) and depression (β = −0.39, p = 0.009) correlated significantly with peak pain intensity. Interestingly, negative affect and depression, albeit both being negative mood indices, showed opposing relationships with peak pain intensity.ConclusionsThis work suggests that pain‐free mPFC‐lAG connectivity (at lower alpha) may contribute to individual variations in pain‐related vulnerability.SignificanceThese findings could potentially lead the way for investigations in which DMN connectivity is used in identifying individuals more likely to develop chronic pain.

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Peak alpha frequency differs between chronic back pain and chronic widespread pain

McLain,

Cavaleri,

Kutch

2024

European Journal of Pain

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BackgroundLow peak alpha frequency (PAF) is an electroencephalography (EEG) outcome associated reliably with high acute pain sensitivity. However, existing research suggests that the relationship between PAF and chronic pain is more variable. This variability could be attributable to chronic pain groups typically being examined as homogenous populations, without consideration being given to potential diagnosis‐specific differences. Indeed, while emerging work has compared individuals with chronic pain to healthy controls, no previous studies have examined differences in PAF between diagnoses or across chronic pain subtypes.MethodsTo address this gap, we reanalysed a dataset of resting state EEG previously used to demonstrate a lack of difference in PAF between individuals with chronic pain and healthy controls. In this new analysis, we separated patients by diagnosis before comparing PAF across three subgroups: chronic widespread pain (n = 30), chronic back pain (n = 38), and healthy controls (n = 87).ResultsWe replicate the original finding of no significant difference between chronic pain groups and controls, but also find that individuals with widespread pain had significantly higher global average PAF values than those of people with chronic back pain [p = 0.028, β = 0.25 Hz] after controlling for age, sex, and depression.ConclusionsThese novel findings reveal PAF values in individuals with chronic pain may be diagnosis‐specific and not uniformly shifted from the values of healthy controls. Future studies should account for diagnosis and be cautious with exploring homogenous ‘chronic pain’ classifications during investigations of PAF.SignificanceOur work suggests that, contrary to previous hypotheses, inter‐individual differences in PAF reflect diagnosis‐specific mechanisms rather than the general presence of chronic pain, and therefore may have important implications for future work regarding individually‐tailored pain management strategies.

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Sensorimotor Peak Alpha Frequency Is a Reliable Biomarker of Prolonged Pain Sensitivity

Cited by 73 publications

References 59 publications

Prolonged Pain Reliably Slows Peak Alpha Frequency by Reducing Fast Alpha Power

Prolonged Pain Reliably Slows Peak Alpha Frequency by Reducing Fast Alpha Power

Pain‐free default mode network connectivity contributes to tonic experimental pain intensity beyond the role of negative mood and other pain‐related factors

Peak alpha frequency differs between chronic back pain and chronic widespread pain

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