Prefrontal Gamma Oscillations Encode Tonic Pain in Humans

Enrico Schulz, Elisabeth S May, Martina Postorino, Laura Tiemann, Moritz M Nickel, Viktor Witkovsky, Paul Schmidt, Joachim Gross, Markus Ploner, Enrico Schulz, Elisabeth S May, Martina Postorino, Laura Tiemann, Moritz M Nickel, Viktor Witkovsky, Paul Schmidt, Joachim Gross, Markus Ploner

Abstract

Under physiological conditions, momentary pain serves vital protective functions. Ongoing pain in chronic pain states, on the other hand, is a pathological condition that causes widespread suffering and whose treatment remains unsatisfactory. The brain mechanisms of ongoing pain are largely unknown. In this study, we applied tonic painful heat stimuli of varying degree to healthy human subjects, obtained continuous pain ratings, and recorded electroencephalograms to relate ongoing pain to brain activity. Our results reveal that the subjective perception of tonic pain is selectively encoded by gamma oscillations in the medial prefrontal cortex. We further observed that the encoding of subjective pain intensity experienced by the participants differs fundamentally from that of objective stimulus intensity and from that of brief pain stimuli. These observations point to a role for gamma oscillations in the medial prefrontal cortex in ongoing, tonic pain and thereby extend current concepts of the brain mechanisms of pain to the clinically relevant state of ongoing pain. Furthermore, our approach might help to identify a brain marker of ongoing pain, which may prove useful for the diagnosis and therapy of chronic pain.

Keywords: electroencephalography; gamma oscillations; ongoing pain; pain perception; prefrontal cortex.

© The Author 2015. Published by Oxford University Press.

Figures

Figure 1.
Figure 1.
Time courses of pain intensity and stimulus intensity. Group mean time courses of subjective pain intensity and objective stimulus intensity during tonic painful heat stimulation of the left hand. Pain intensity was continuously rated on a VAS anchored at no pain and worst tolerable pain. Shaded areas around the curves depict the standard error of the mean. The light gray section indicates the time window used for the analysis. For display purposes, mean time courses were low-pass filtered at 0.1 Hz.
Figure 2.
Figure 2.
Neurophysiological encoding of pain intensity and stimulus intensity during tonic pain. (A) Topographies of the relationship between pain intensity/stimulus intensity and brain activity as assessed by LMMs. LMMs were calculated for theta (4–7 Hz), alpha (8–13 Hz), beta (14–29 Hz), and gamma (30–100 Hz) frequencies. Positive and negative relationships are depicted by warm and cold colors, respectively. Electrodes with a significant relationship between pain/stimulus intensity and brain activity after FDR correction for multiple testing are marked by bold black dots. (B) Frequency spectra of the relationship between pain/stimulus intensity and brain activity. LMMs were calculated for frequencies between 1 and 100 Hz for electrodes which had shown a significant relationship between pain/stimulus intensity and brain activity as displayed in (A). The strongest (positive) relationship between pain intensity and brain activity was observed at 84 Hz, and the strongest (negative) relationship between stimulus intensity and brain activity was found at 15 Hz.
Figure 3.
Figure 3.
Control conditions. Topographies of the relationship between brain activity and bar length rating in the visual control condition (upper row) and between brain activity and the inverted time course of pain intensity in the tonic pain condition (lower row) as assessed by LMMs. LMMs were calculated for theta (4–7 Hz), alpha (8–13 Hz), beta (14–29 Hz), and gamma (30–100 Hz) frequencies. Positive and negative relationships are depicted by warm and cold colors, respectively. No significant relationships were observed after FDR correction for multiple testing.
Figure 4.
Figure 4.
Neurophysiological encoding of pain intensity and stimulus intensity during phasic pain. (A) Group mean time–frequency representation of neuronal responses to phasic painful stimuli at electrode FCz. Neuronal responses are displayed as percent signal change relative to a pre-stimulus baseline (−1000 to 0 ms). Positive and negative signal changes are depicted by warm and cold colors, respectively. (B) Topographies of the relationship between stimulus/pain intensity and brain activity as assessed by LMMs. LMMs were calculated for time–frequency windows defined from previous studies (theta, 4–8 Hz, 0.15–0.35 s; alpha, 9–13 Hz, 0.47–0.70 s; beta, 14–29 Hz, 0.30–0.50 s; and gamma, 76–86 Hz, 0.20–0.30 s). Positive and negative relationships are depicted by warm and cold colors, respectively. Electrodes with a significant relationship between pain/stimulus intensity and brain activity after FDR correction for multiple testing are marked by bold black dots.
Figure 5.
Figure 5.
Brain sources encoding tonic pain. Locations of (A) the strongest relationship between subjective pain intensity and brain activity in the gamma band (30–100 Hz) and (B) the strongest relationship between objective stimulus intensity and brain activity in the beta band (14–29 Hz) as assessed by LMM in source space. Positive and negative relationships are depicted by warm and cold colors, respectively. MNI coordinates of strongest relationships (peak locations) were −4, 34, 36 in (A) and 8, −16, 68 in (B).

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