The effect of painful laser stimuli on EEG gamma-band activity in migraine patients and healthy controls

Highlights

• Central gamma-band oscillations (GBOs) seem to be related to pain perception in controls but not in migraine.

• No differences were found in nociceptive-related GBOs between interictal migraine patients and controls.

• We suggest the midcingulate cortex to be a source of nociceptive-related GBOs.

Abstract

Objective

Gamma-band oscillations (GBOs) induced by nociceptive stimuli were compared between migraine patients and controls in order to further characterize interictal pain processing in the brain of migraineurs. GBOs were related to subjective pain intensity, years of migraine history and migraine attack frequency and the sources of GBOs were investigated.

Methods

Twenty-three migraine patients without aura and 23 controls received a series of laser stimulations on their right forehead and right hand while recording electroencephalographic data (61 electrodes). After each series they indicated the perceived pain. A multitaper time-frequency method was used on artifact-cleaned scalp data and frequency domain beamforming was used to localize the GBOs.

Results

In both groups we observed increases in GBOs around central electrodes, which were not significantly different between groups. The central GBOs were positively associated with the subjective pain ratings in the control group, in accordance with previous studies, but not in the migraine group. Increases in gamma power were observed in the midcingulate cortex.

Conclusions

No evidence was found that GBOs differ between interictal migraine and controls nor that central GBOs represent a neurophysiological correlate of subjective pain in migraine.

Significance

We shed light on observations of GBOs during pain processing in interictal migraine.

Introduction

Previous studies using different brain functional analysis methods showed atypical pain processing in interictal migraine compared to control groups. This has been found with functional magnetic resonance imaging (fMRI) where impaired habituation to repeated painful stimuli has been found in the bilateral anterior insula, the midcingulate cortex and the thalamus (Stankewitz et al., 2013) as well as atypical activation of brain regions during painful stimulation (Schwedt et al., 2015). Using resting-state (RS) fMRI, several studies have shown that some intrinsic functional connections between regions in RS networks differ in migraine patients compared to healthy controls (Colombo et al., 2015). Colombo et al. (2015) summarized these findings, noting that in areas related to nociception, RS functional connectivity is mostly increased in migraine patients compared to healthy controls. In contrast, between regions related to pain modulation, RS functional connectivity seems to be mostly decreased. Several studies using electroencephalography (EEG) have also shown reduced habituation to repeated painful laser stimuli in migraine (de Tommaso et al., 2014, Valeriani et al., 2003). As interictal atypical pain processing in migraine may possibly indicate the readiness of the migrainous brain to generate attacks (Goadsby et al., 2017) it is important to further characterize the extent and features of this atypical interictal pain processing.

Most EEG studies examining pain processing in migraine using laser stimuli, have looked at the laser-evoked potential (LEP) components (i.e., N1, N2, P2). However, several studies show that LEPs are not a signature of pain perception but rather reflect stimulus saliency (Iannetti et al., 2008, Ronga et al., 2013). Although LEPs are very useful to study the nociceptive system (Treede et al., 2003), we could possibly improve the study of the nociceptive system in migraine by looking at other EEG features induced by laser stimuli. For example, in the pain literature, several studies have found an increase in high-frequency oscillations (gamma-band) between 150 and 350 ms after painful laser stimulations (Ploner et al., 2017). In EEG research, these gamma-band oscillations (GBOs) are mostly found between 70 and 90 Hz at central electrodes (Schulz et al., 2012, Schulz et al., 2011a, Schulz et al., 2011b). In addition to being related to pain perception (Gross et al., 2007, Schulz et al., 2011b, Zhang et al., 2012), it has been shown that GBOs assumed to be generated by the primary somatosensory region could reflect pain perception, rather than stimulus saliency (Zhang et al., 2012). An intracerebral EEG study showed that GBOs recorded from the insula are preferential for nociception as insular GBOs were more pronounced after painful laser stimulations than after equally arousing visual, auditory and vibrotactile stimuli (Liberati et al., 2018a). However, unlike GBOs recorded over the primary somatosensory region (Zhang et al., 2012), the insular GBOs can be dissociated from pain perception as insular GBOs habituated to repetitive stimulations while intensity ratings did not (Liberati et al., 2018b).

In the current study, we investigated GBOs related to nociception in episodic migraine patients without aura. The aims of the study were (1) to compare the increase in gamma-band power related to somatic and trigeminal laser stimulation between migraine without aura patients and controls, (2) to correlate the increase in GBOs at central electrodes with subjective pain ratings, (3) to correlate the increase in GBOs at central electrodes with years of migraine history and migraine attack frequency and (4) to localize the GBOs increases using a beamforming technique.