Brain oscillations differentially encode noxious stimulus intensity and pain intensity

Abstract

Noxious stimuli induce physiological processes which commonly translate into pain. However, under certain conditions, pain intensity can substantially dissociate from stimulus intensity, e.g. during longer-lasting pain in chronic pain syndromes. How stimulus intensity and pain intensity are differentially represented in the human brain is, however, not yet fully understood. We therefore used electroencephalography (EEG) to investigate the cerebral representation of noxious stimulus intensity and pain intensity during 10min of painful heat stimulation in 39 healthy human participants. Time courses of objective stimulus intensity and subjective pain ratings indicated a dissociation of both measures. EEG data showed that stimulus intensity was encoded by decreases of neuronal oscillations at alpha and beta frequencies in sensorimotor areas. In contrast, pain intensity was encoded by gamma oscillations in the medial prefrontal cortex. Contrasting right versus left hand stimulation revealed that the encoding of stimulus intensity in contralateral sensorimotor areas depended on the stimulation side. In contrast, a conjunction analysis of right and left hand stimulation revealed that the encoding of pain in the medial prefrontal cortex was independent of the side of stimulation. Thus, the translation of noxious stimulus intensity into pain is associated with a change from a spatially specific representation of stimulus intensity by alpha and beta oscillations in sensorimotor areas to a spatially independent representation of pain by gamma oscillations in brain areas related to cognitive and affective-motivational processes. These findings extend the understanding of the brain mechanisms of nociception and pain and their dissociations during longer-lasting pain as a key symptom of chronic pain syndromes.

Keywords: Alpha; Beta; Gamma; Nociception; Oscillations; Pain; Tonic.

Fig. 1

Time courses of stimulus intensity and pain intensity. Group mean time courses of stimulus intensity and pain intensity during tonic pain left and tonic pain right conditions. The blue and red shaded areas depict the standard error of the mean. VAS, visual analogue scale. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article).

Fig. 2

Brain oscillations encoding stimulus intensity and pain intensity. Linear mixed model-based whole-brain t-maps of the fixed effects showing the encoding of stimulus and pain intensity for different frequency bands. T-maps were thresholded at p<0.05, false discovery rate corrected for the whole brain.

Fig. 3

Differences and similarities between tonic pain left and tonic pain right in the encoding of stimulus intensity and pain intensity. A) T-maps showing significant differences between tonic pain left and tonic pain right in the encoding of pain intensity and stimulus intensity for different frequency bands. T-maps were masked for sensorimotor cortices and thresholded at p<0.05, false discovery rate corrected for the sensorimotor cortices. B) Whole-brain t-maps showing significant similarities (conjunction analysis) between tonic pain left and tonic pain right in the encoding of stimulus intensity and pain intensity for different frequency bands. T-maps were thresholded at p<0.05, false discovery rate corrected for the whole brain.

Fig. 4

Similarities between tonic pain left and tonic pain right in the encoding of stimulus intensity controlled for pain intensity and vice versa. Whole-brain t-maps for the gamma frequency band showing significant similarities between tonic pain left and tonic pain right in the encoding of stimulus intensity when controlled for pain intensity (upper panel) and in the encoding of pain intensity when controlled for stimulus intensity (lower panel). T-maps were thresholded at p<0.05, false discovery rate corrected for the whole brain. The controlled conjunction analysis indicates that prefrontal gamma activity was more closely related to pain intensity than to stimulus intensity.